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Objective: To compare the effects of general anesthesia between remimazolam and propofol in pediatric patients undergoing binocular strabismus day surgery. Methods: Prospectively, 60 pediatric patients, American Society of Anesthesiologists (ASA) grade Ⅰ-Ⅱ, scheduled to undergo binocular strabismus daytime surgery in Beijing Tongren Hospital under general anesthesia with laryngeal mask airway from December 2021 to May 2022 were selected. They were randomly divided into Remimazolam group and Propofol group with 30 cases in each group, according to the ratio of 1∶1 by SPSS program. Patients in Remimazolam group were induced by remimazolam, remifentanil and micuronium chloride, and maintained by remimazolam and remifentanil. Patients in Propofol group were induced by propofol, remifentanil and micuronium chloride, and maintained by propofol and remifentanil. Patients in Remimazolam group were given 0.1 mg of flumazenil for antagonism 3 minutes after operation, while children in Propofol group waited for natural awakening. The primary outcome was the time from drug withdrawal to laryngeal mask removal after operation. The secondary outcomes included the time for consciousness loss during induction, intraoperative hemodynamic data [mean arterial pressure (MAP) and heart rate], the success rate of sedation, the awareness rate during operation, and the incidence of adverse events after admission to postanesthesia care unit(PACU). Results: The Remimazolam group included 12 males and 18 females, aged (5.0±1.4) years. There were 14 males and 16 females in the Propofol group, aged (5.3±1.3) years. The time from drug withdrawal to laryngeal mask removal in Remimazolam group was (6.5±1.2) min, which was shorter than that in Propofol group of (10.7±1.9) min ( P <0.001). The time for consciousness loss during induction was (38.1±4.8) s in Remimazolam group, which was longer than that in Propofol group of (31.6±4.9) s ( P <0.001). The variability of MAP and heart rate of patients during operation in Remimazolam group was lower than that in Propofol group (all P <0.05). There was no significant difference in sedation success rate, intraoperative awareness and adverse reactions in PACU between the two groups (all P >0.05). Conclusion: In pediatric patients with binocular strabismus during daytime surgery, general anesthesia with remimazolam can shorten the time from drug withdrawal to laryngeal mask removal after operation without increasing the incidence of postoperative adverse reactions and can provide more stable hemodynamics.

To investigate the clinical assessment of dual-enhanced antiplatelet therapy after cerebrovascular intervention to reduce the risk of cerebral infarction recurrence, and to provide a reference for the prevention and treatment of cerebral infarction recurrence risk. 202 patients with cerebral infarction who underwent cerebrovascular intervention in Tianjin Fifth Central Hospital from January 2018 to October 2022 were selected as study subjects. The patients were divided into a treatment group ( n =104) based on randomized controlled single-blind method with 61 males and 43 females with a mean age of (62.33±2.57) years old and a control group ( n =98) with 56 males and 42 females with a mean age of (62.49±2.36) years old. The control group was given aspirin mono-antiplatelet therapy, and the treatment group was given clopidogrel doublet augmented antiplatelet therapy on the basis of the control group, and both groups continued the treatment for 2 months. Platelet counts, coagulation indexes and inflammatory factors were compared between the two groups before and after treatment, and the America National Institutes of Health Stroke Scale (NIHSS) score was used to assess the neurological functions of the two groups before and after treatment, and the recurrence of cerebral infarction in the two groups was counted within 6 months after treatment. In addition, the patients in the treatment group were divided into the cerebral infarction recurrence group and the cerebral infarction non-recurrence group according to whether they had cerebral infarction recurrence within 6 months after treatment, and the clinical data of the patients in the treatment group were collected to analyze the influencing factors of the dual-enhancement antiplatelet therapy for the recurrence of cerebral infarction in patients with cerebral infarction after cerebral vascular intervention by multifactorial logistic regression. The results showed that after treatment, patients in the treatment group had an international normalized ratio (INR) of (1.76±0.38), a platelet activation rate of (39.52±4.79)%, a platelet aggregation rate of (48.54±5.21)%, a tumor necrosis factor-alpha (TNF-alpha) of (28.37±4.47)ng/L, an interleukin 6 (IL-6) of (24.77±3.52)ng/L, a high-sensitivity C-reactive protein (hs-CRP) of (7.39±1.53)mg/L and an NIHSS score of (6.11±1.39) were lower than those of the control group (2.32±0.41), (44.81±6.37)%, (51.39±5.58)%, (39.66±4.51) ng/L, (29.25±4.04) ng/L, (9.03±1.78) mg/L and (9.93±1.46) points (all P <0.05). At 6-month follow-up of all patients, cerebral infarction recurred in 16 (15.38%) patients in the treatment group and in 33 (33.67%) patients in the control group ( χ 2 =9.185, P <0.05). Kaplan-Meier results showed a statistically significant difference in the rate of recurrence without cerebral infarction in the treatment group compared with the control group(LogRank χ 2 =4.595, P <0.05). Logistic regression analysis showed that smoking history, cervical vascular plaque, post-treatment NIHSS score, post-treatment stenosis score, post-treatment INR, post-treatment hs-CRP and CYP2C19 gene polymorphism were independent influences on the recurrence of cerebral infarction in cerebral infarction patients with cerebral vascular interventions followed by doublet augmentation of antiplatelet therapy (all P< 0.05). In conclusion, dual-enhanced antiplatelet therapy may be an effective measure to reduce the risk of cerebral infarction recurrence after cerebrovascular intervention in patients with cerebral infarction, but it is still influenced by more factors.

In the realm of animal phenotyping, manual measurements are frequently utilised. While machine-generated data show potential for enhancing high-throughput breeding, additional research and validation are imperative before incorporating them into genetic evaluation processes. This research presents a method for managing meat sheep and collecting data, utilising the Sheep Data Recorder system for data input and the Sheep Body Size Collector system for image capture. The study aimed to investigate the genetic parameter changes of growth traits in Ujumqin sheep by comparing machine-generated measurements with manual measurements. The dataset consisted of 552 data points from the offspring of 75 breeding rams and 399 breeding ewes. Six distinct random regression models were assessed to pinpoint the most suitable model for estimating genetic parameters linked to growth traits. These models were distinguished based on the inclusion or exclusion of maternal genetic effects, maternal permanent environmental effects, and covariance between maternal and direct genetic effects. Fixed factors such as individual age, individual sex, and ewe age were taken into account in the analysis. The genetic parameters for the yearling growth traits of Ujumqin sheep were calculated using ASReml software. The Akaike information criterion, the Bayesian information criterion, and fivefold cross-validation were employed to identify the optimal model. Research findings indicate that the most accurate models for manually measured data revealed heritability estimates of 0.12 ± 0.15 for BW, 0.05 ± 0.07 for body slanting length, 0.03 ± 0.07 for withers height, 0.15 ± 0.12 for hip height, 0.11 ± 0.11 for chest depth, 0.13 ± 0.13 for shoulder width, and 0.53 ± 0.15 for chest circumference. The optimal models for machine-predicted data showed heritability estimates of 0.1 ± 0.09 for body slanting length, 0.14 ± 0.12 for withers height, 0.55 ± 0.15 for hip height, 0.34 ± 0.15 for chest depth, 0.26 ± 0.15 for shoulder width, and 0.47 ± 0.16 for chest circumference. In manually measured data, genetic correlations ranged from 0.35 to 0.99, while phenotypic correlations ranged from 0.07 to 0.90. In machine data, genetic correlations ranged from -0.05 to 0.99, while phenotypic correlations ranged from 0.03 to 0.84. The results suggest that machine-based estimations may lead to an overestimation of heritability, but this discrepancy does not impact the selection of breeding models., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

The spread of antimicrobial-resistant bacteria is a significant concern, as it can lead to increased morbidity and mortality in both humans and animals. Whole-genome sequencing (WGS) is a powerful tool that can be used to conduct a comprehensive analysis of the genetic basis of antimicrobial resistance (AMR). We compared the phenotypic and genotypic AMR profiles of 97 Salmonella isolates derived from chicken and turkey diagnostic samples. We focused AMR analysis on 5 antimicrobial classes: aminoglycoside, beta-lactam, phenicol, tetracycline, and trimethoprim. The overall sensitivity and specificity of WGS in predicting phenotypic antimicrobial resistance in the Salmonella isolates were 93.4% and 99.8%, respectively. There were 16 disagreement instances, including 15 that were phenotypically resistant but genotypically susceptible; the other instance involved phenotypic susceptibility but genotypic resistance. Of the isolates examined, 67 of 97 (69%) carried at least 1 resistance gene, with 1 isolate carrying as many as 12 resistance genes. Of the 31 AMR genes analyzed, 16 were identified as aminoglycoside-resistance genes, followed by 4 beta-lactam-resistance, 3 tetracycline-resistance, 2 sulfonamide-resistance, and 1 each of fosfomycin-, quinolone-, phenicol-, trimethoprim-, bleomycin-, and colistin-resistance genes. Most of the resistance genes found were located on plasmids., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To analyze the clinicopathological features of salivary carcinoma showing thymus-like differentiation(CASTLE). Methods: Cases diagnosed with salivary CASTLE from January 2020 to December 2023 were collected and selected from the Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine. A total of 7 cases of salivary CASTLE were identified. All the cases originated from parotid. There were 3 males and 4 females. The patients' age range was 11-70 years.The clinical, microscopic, immunohistochemical and prognostic features of these cases were analyzed. Results: The duration of disease ranged from 1 month to 1 year, and 1 patient had facial numbness and 1 with swelling sensation occasionally. Radiographically, 4 cases showed malignant signs. Microscopically, 4 cases involved in parotid gland, and all the tumors had different degrees of lymphoid tissue background. The tumor cells arranged in nests, 5 cases with lymphoepithelial carcinoma-like and 2 cases with squamous cell carcinoma morphology. The tumor cells expressed CD5 and CD117 proteins diffusely in lymphoepithelial carcinoma-like cases. However, the tumor cells expressed CD5 diffusely and CD117 focally in cases with squamous cell carcinoma morphology. All the cases had no Epstein-Barr virus infection. Among the 6 patients with follow-up information, all of them underwent postoperative radiotherapy, and none of them had local recurrence and lymph node metastasis. Conclusions: Salivary CASTLE is a rare tumor, it should be distinguished from lymphoepithelial carcinoma and squamous cell carcinoma. The patients often have better prognosis and CD5 protein expression has a valuable role in the differential diagnosis.

Objective: To investigate the effect and safety of transnasal humidified rapid insufflation ventilatory exchange (THRIVE) technique in hysteroscopic diagnostic and therapeutic surgery. Methods: This study was a randomized controlled trial. A total of 100 female patients undergoing hysteroscopy surgery at Beijing Tongren Hospital from September to December 2023 were selected and randomly divided into two groups by the random number table method: the THRIVE group and the mask oxygen group, with 50 patients in each group. Patients in both groups were given total intravenous anesthesia with propofol combined with remifentanil and preserved spontaneous respiration. The THRIVE group was given oxygen by the THRIVE device with an oxygen flow rate of 50 L/min, while the mask oxygen group was given oxygen by the mask with an oxygen flow rate of 5 L/min; the oxygen concentration of both groups was set at 100%. The general condition of the patients, vital signs during the operation, the amount of anesthesia drugs used and the operation time were recorded. The primary observation index was the incidence of hypoxic events in the two groups; the secondary observation indexes were the incidence and time of intraoperative apnea as well as the corresponding oxygenation interventions and the incidence of non-hypoxic adverse events. Results: The age of the THRIVE group was (42±14) years, and the age of the mask oxygen group was (43±15) years. The duration of surgery in the THRIVE group was (15.9±3.4) min, which was statistically lower than that of the mask oxygen group (16.3±4.5) min ( P =0.041), and there were no differences observed in the duration of awakening time and anesthesia time (both P >0.05). There was no significant difference in the dosage of propofol, remifentanil, and intraoperative vasoactive drugs between the two groups (all P >0.05). The SpO 2 of the patients in the THRIVE group at the end of the operation was (99.7±1.1) %, which was higher than that of the mask-oxygen group (99.1±1.1) % ( P <0.05). There was no difference in SpO 2 of the two groups at the other time points (all P >0.05). There were no differences in HR and MAP of two group patients at each time point (all P >0.05). The incidence of hypoxic events in the THRIVE group was 12.0% (6/50), which was lower than that of 28.0% (14/50) in the mask oxygen group ( P =0.045). The difference in the incidence and duration of apnea between the two groups was not statistically significant (all P >0.05). There were no cases of temporary need for laryngeal mask or tracheal intubation during surgery in both groups. There was no statistically significant difference in the incidence of intraoperative body movement, dizziness, nausea and vomiting between the two groups (all P >0.05), and no cardiac, cerebral, renal or other important organ insufficiency occurred in the two weeks after surgery. Conclusion: THRIVE technology can provide effective oxygenation for patients undergoing hysteroscopic diagnosis and treatment, maintain patients' circulatory stability, and improve the safety and efficiency of surgery.

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of ( M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) μmol/L(range: 5.4 to 722.8 μmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 μmol/L to 85.5 μmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ ( P =0.009), hemi-hepatectomy and extended resection ( P =0.001),T1 and T2 patients without vascular invasion (T2 vs. T1: OR =1.43 (0.61-3.35), P =0.413;T3 vs. T1: OR =2.57 (1.03-6.41), P =0.010;T4 vs. T1, OR =3.77 (1.37-10.38), P <0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

Objective: To construct a novel dual-specific antibody targeting human CD123 (CD123 DuAb) and study its effects in acute myeloid leukemia (AML) . Methods: Based on the variable region of the CD123 monoclonal antibody independently developed at our institution, the CD123 DuAb expression plasmid was constructed by molecular cloning and transfected into ExpiCHO-S cells to prepare the antibody protein. Through a series of in vitro experiments, its activation and proliferation effect on T cells, as well as the effect of promoting T-cell killing of AML cells, were verified. Results: ① A novel CD123 DuAb plasmid targeting CD123 was successfully constructed and expressed in the Expi-CHO eukaryotic system. ②The CD123 DuAb could bind both CD3 on T cells and CD123 on CD123(+) tumor cells. ③When T cells were co-cultured with MV4-11 cells with addition of the CD123 DuAb at a concentration of 1 nmol/L, the positive expression rates of CD69 and CD25 on T cells were 68.0% and 44.3%, respectively, which were significantly higher than those of the control group ( P <0.05). ④Co-culture with CD123 DuAb at 1 nmol/L promoted T-cell proliferation, and the absolute T-cell count increased from 5×10(5)/ml to 3.2×10(6)/ml on day 9, and CFSE fluorescence intensity decreased significantly. ⑤ With the increase in CD123 DuAb concentration in the culture system, T-cell exhaustion and apoptosis increased. When the CD123 DuAb was added at a concentration of 1 nmol/L to the culture system, the proportion of CD8(+) PD-1(+) LAG-3(+) T cells was 10.90%, and the proportion of propidium iodide (PI) (-) Annexin Ⅴ(+) T cells and PI(+) Annexin Ⅴ(+) T cells was 18.27% and 11.43%, respectively, which were significantly higher than those in the control group ( P <0.05). ⑥ The CD123 DuAb significantly activated T cells, and the activation intensity was positively correlated with its concentration. The expression rate of CD107a on T cells reached 16.05% with 1 nmol/L CD123 DuAb, which was significantly higher than that of the control group ( P <0.05). ⑦The CD123 DuAb promoted cytokine secretion by T cells at a concentration of 1 nmol/L, and the concentration of IFN-γ and TNF-α in the supernatant of the co-culture system reached 193.8 pg/ml and 169.8 pg/ml, respectively, which was significantly higher than that of the control group ( P <0.05). ⑧When CD123 DuAb was added at a concentration of 1 nmol/L to the co-culture system of T cells and CD123(+) tumor cells, the killing intensity of T cells significantly increased, and the residual rates of CD123(+) MV4-11 cells, CD123(+) Molm13 cells, and CD123(+) THP-1 cells were 7.4%, 6.7%, and 14.6% on day 3, respectively, which were significantly lower than those in the control group ( P <0.05) . Conclusion: In this study, a novel CD123 DuAb was constructed and expressed. In vitro experiments verified that the DuAb binds to CD123(+) tumor cells and T cells simultaneously, promotes T-cell activation and proliferation, and facilitates their anti-leukemia effect, which provides a basis for further clinical research.

Objectives: This study aimed to assess the associations between blood heavy metal concentrations and hearing loss., Study Design: This was a systematic review and meta-analysis., Methods: A comprehensive literature search was performed using Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature, Wanfang and Weipu databases. Ten studies were included, and a random or fixed-effects model was used for the meta-analysis. Review Manager 5.4 software was used for data synthesis, and Stata 15.1 software was used for the publication bias and sensitivity analyses., Results: Blood lead concentrations were significantly and substantially associated with hearing loss (mean difference (MD) = 1.14; 95% confidence interval [CI] = 0.03, 2.26; P = 0.04; I 2  = 81%), and iron deficiency was significantly related to hearing loss (MD = -0.42; 95% CI = -0.66, -0.18; P = 0.12; I 2  = 60%)., Conclusions: These results suggest an association between blood heavy metal concentrations and hearing loss. However, there were limitations: confounding factors, lack of description for the specific methods of blinding and independent verification of case definition, limited sample size, Chinese publications comprising half of the primary data and the lack of assessment of the relationship between different blood heavy metal concentrations and the severity of hearing loss. Therefore, larger and well-designed prospective cohort studies are required for further exploration., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: To analyze the reported incidence and epidemiological characteristics of pulmonary tuberculosis (PTB) among healthcare workers (HCWs) nationwide from 2011 to 2020. Methods: The national surveillance data of PTB from 2011 to 2020 were used to analyze the reported incidence and epidemiological characteristics of PTB among HCWs, and the average annual change trends were calculated. Results: The reported incidence of PTB among HCWs in China first decreased and then increased, with an average annual percentage change (AAPC) of -1.1%, from 37.0/100 000 in 2011 to 30.0/100 000 in 2015, and then to 33.4/100 000 in 2020. From 2011 to 2019, the risk of PTB in males was 1.02-1.37 times higher than that in females, and in 2020, the risk of PTB in males was 0.86 times higher than that in females. The risk of pulmonary tuberculosis in males showed a rapid downward trend, and the AAPC was -3.8%. Taking the 45-<55 age group as a reference, the risk of PTB in the <25, 25-<35, 55-<60 and≥60 age groups was 4.64, 1.97, 1.28 and 1.47 times, respectively. There was no significant difference between the 35-<45 age group and the 44-<55 age group. The reported incidence rates in the eastern, central and western China were 25.0/100 000, 33.2/100 000 and 44.0/100 000, respectively. The incidence rates in the central and western China were 1.33 and 1.76 times higher than that in the eastern China, and the AAPCs were -1.2%, -0.2%, and -1.6% in the eastern, central, and western China, respectively. Conclusions: From 2011 to 2020, the reported incidence of PTB among HCWs in China was generally at a low level, but there was an upward trend since 2015. It is necessary to strengthen TB prevention and control among this group, especially focusing on key provinces in the central and western China. At the same time, it is necessary to strengthen the entry-level and routine training for young HCWs in TB infection control.

Objective: This study aims to explore the causal relationship between obstructive sleep apnea (OSA) and type 2 diabetes (T2D) using bidirectional Mendelian randomization (MR). Methods: The genetic data related to OSA were obtained from the FinnGen Biobank (Ncase=16, 761, Ncontrol=201, 194) in the Genome-wide association study (GWAS). Three single nucleotide polymorphism (SNP) were screened out as instrumental variable (IV) of OSA. The genetic data related to T2D were derived from a large Meta-analysis of GWAS (Ncase=62, 892, Ncontrol=596, 424), 114 SNP were selected as IV of T2D. Multiple MR methods were used for analysis and inverse variance weighted (IVW) was performed as main method. The sensitivity of MR analytic results was analyzed using MR-Egger and other methods, and the IV was evaluated using F -value statistics. Results: MR analysis showed that OSA was significantly associated with increased risk of T2D ( OR =2.016, 95% CI : 1.185-3.429, P <0.05). There was no significant relationship between T2D and OSA risk ( OR =1.030, 95% CI : 0.980-1.082, P =0.238). There was heterogeneity in both-way results (OSA➝T2D, P =1.808×10 -11 ; T2D➝OSA, P =1.729×10 -7 ), and no horizontal pleiotropy (OSA➝T2D, P =0.477; T2D➝OSA, P =0.349). IV of OSA and T2D-selected in the study were strong instrumental variables ( F statistics of OSA=20.543; F statistics of T2D=30.117). Conclusion: Our results supported that OSA was a risk factor for T2D, but T2D had no significant impact on the incidence of OSA. Blood glucose monitoring and diabetes screening in OSA patients might be beneficial to the early detection and intervention of T2D.

The development of antimicrobial agents with novel model of actions is a promising strategy to combat multiple resistant bacteria. Here, three ruthenium-based complexes, which acted as potential antimicrobial agents, were synthesized and characterized. Importantly, three complexes all showed strong bactericidal potency against Staphylococcus aureus. In particular, the most active one has a MIC of 6.25 μg/mL. Mechanistic studies indicated that ruthenium complex killed S. aureus by releasing ROS and damaging the integrity of bacterial cell membrane. In addition, the most active complex not only could inhibit the biofilm formation and hemolytic toxin secretion of S. aureus, but also serve as a potential antimicrobial adjuvant as well, which showed synergistic effects with eight traditional antibiotics. Finally, both G. mellonella larva infection model and mouse skin infection model all demonstrated that ruthenium complex also showed significant efficacy against S. aureus in vivo. In summary, our study suggested that ruthenium-based complexes bearing a phenyl hydroxide are promising antimicrobial agents for combating S. aureus., (© 2023 Wiley-VCH GmbH.)

Objective: To preliminarily analyze the application experience of veno-arterio-venous extracorporeal membrane oxygenation (VAV-ECMO).The VAV-ECMO is a rescue strategy for patients with extremely critical respiratory failure combined with refractory shock. Methods: From February 2016 to February 2022, the characteristics and outcomes of patients who were started on either veno-venous or veno-arterial ECMO due to respiratory or hemodynamic failure, and then converted to VAV-ECMO in respiratory intensive care unit (ICU) of Beijing Chaoyang Hospital were analyzed. Results: A total of 15 patients underwent VAV-ECMO, aged 53 (40, 65) years, and 11 of whom were male. Within the group, VV-ECMO was initially used in 12 patients due to respiratory failure, but then VAV-ECMO was used due to cardiogenic shock (7/12) and septic shock (4/12), while VAV-ECMO was established in two patients due to lung transplantation. One patient was diagnosed with pneumonia complicated by septic shock, which was initially determined to be VA-ECMO, but then switched to VAV-ECMO because it was difficult to maintain oxygenation. The time from the establishment of VV or VA-ECMO to the switch to VAV-ECMO was 3 (1, 5) days and the VAV-ECMO support time was 5 (2, 8) days. ECMO-related complications were bleeding, mostly in the digestive tract ( n =4) and airway hemorrhage ( n =4), without intracranial hemorrhage, and poor arterial perfusion of the lower limbs ( n =2). Among these 15 patients, the overall ICU mortality was 53.3%. The mortality of patients who received VAV-ECMO due to septic shock and cardiogenic shock was 100% (4/4) and 42.8% (3/7), respectively. Two patients who received VAV-ECMO due to lung transplantation all survived. Conclusion: VAV-ECMO may be a safe and effective treatment for carefully selected patients with critical respiratory failure associated with cardiogenic shock or end-stage lung disease lung transplantation transition, however, patients with septic shock may benefit the least.

This experiment investigated the effects of different dietary starch sources on the growth and glucose metabolism of geese. A total of 240 healthy 35-day-old male geese were selected and randomly divided into 4 groups, with 6 replicates per group and 10 geese per replicate. Four types of diets were prepared, with glutinous rice (rapidly-digestible starch), corn, indica rice and high amylose as their starch sources, and fed for 28 d. Results showed that after consuming different feeds, the blood glucose of geese first increased and then decreased, reaching its maximum value 0.5 h after feeding, and there were significant differences between the groups (P < 0.05). The body weight of the corn and indica rice group geese at 63 d was higher than that of the high amylose group (P < 0.05). The serum total cholesterol (TCHO) content in the glutinous rice and corn groups was higher than in the high amylose group (P < 0.05). The serum insulin content in the glutinous rice group was lower than in the corn and high amylose groups (P < 0.05), while the glucagon content was higher (P < 0.05). The α-amylase activities of the pancreas, jejunal chyme, and jejunal mucosa in the glutinous rice group were higher than in the indica rice and high amylose groups (P < 0.05). The liver glycogen content in the glutinous rice group was higher than the other groups (P < 0.05). The liver glucose-6-phosphate dehydrogenase (G-6-PD) content in the glutinous rice group was higher than the high amylose group's (P < 0.05), but the glycogen synthase kinase-3 β (GSK-3β) content was lower (P < 0.05). In conclusion, the corn and indica rice diets had a positive effect on the growth performance of the geese, while the high amylose diet had a negative effect. The glutinous rice diet leads to rapid release of glucose, strengthening glucose metabolism pathways such as glycogen synthesis and the pentose phosphate pathway, and further influencing lipid metabolism., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: To investigate the difference of programmed death-ligand 1 (PD-L1) expression between primary lesions and lymph node metastatic lesions in oral squamous cell carcinoma. Methods: Eighty-two patients diagnosed with oral squamous cell carcinoma from December 2020 to July 2021 in Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine & College of Stomatology, Shanghai Jiao Tong University, were enrolled in this study. All the patients underwent neck dissection concurrently and had lymph node metastasis. Among them, there were 28 females and 54 males. The age range was 24-79 years old [(58.6±11.7) years old]. The expression of PD-L1 protein in primary tumors and lymph node metastatic lesions was detected by immunohistochemistry. Combined positive score (CPS) was used to evaluate the PD-L1 expression. And the difference of PD-L1 expression between primary tumors and metastatic lesions was analyzed. Results: Among 82 primary tumors, 9 cases (11%) had PD-L1 CPS<1, 31 cases (38%)≥ 1 and <20, and 42 cases (51%)≥20. Cases with perineural invasion had lower CPS (χ 2 =6.35, P =0.042). Among 82 matched lymph node metastatic lesions, 9 cases (11%) had CPS<1, 38 cases (46%)≥1 and<20, and 35 cases (43%)≥20. The CPS of 27 pairs (33%) of primary and metastatic lesions were discordant. The statistical results showed that the Kappa value of consistency evaluation was 0.446, indicating that the consistency of PD-L1 CPS in primary and metastatic lesions of OSCC was medium. Conclusions: There are differences in PD-L1 expression between the primary lesion of OSCC and cervical lymph node metastatic lesions, and the consistency is medium. In the routine practice, lymph node metastatic lesions should be carefully used to replace the primary lesion for PD-L1 CPS evaluating.

Objective: To establish an in vitro organoid model of human salivary gland basal cell adenoma (BCA). Methods: Fresh tumor sample from a 66-year-old female patient diagnosed with salivary gland BCA was collected from the Dpartment of Oral pathology, Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine in October 2021. And the organoid culture was performed in vitro in a culture medium based on solid droplets of matrix gel, and the growth of the organoid was observed by inverted microscopy. After 14 days, the organoid was fixed in 10% neutral formalin and made into paraffin blocks by agar pre-embedding paraffin embedding method, sectioned. HE staining, morphological observation and immunohistochemical staining of p63, Ki-67, cytokeratin14 (CK14), β-catenin, S-100 and calponin were used for organoids identification. Results: The established BCA organoids were lobulated nodular locally under light microscopy, with deposition of eosinophilic glass-like material around the nests of organoid cells, similar to the morphological architectures of the parental BCA. Immunohistochemistry showed that organoids expressed CK14, p63, and β-catenin in various degree, which was consistent with the immunophenotypic characteristics of the parental BCA tumor cells. Conclusions: An in vitro culture system of BCA organoids was preliminarily established which provides a new model for the study of the pathogenesis of salivary gland tumors.

Objective: To explore the effect of polyethylene glycol loxenatide (long-acting GLP-1R agonist) on the lipid, glucose levels, and weight in type 2 diabetes mellitus patients with obesity., Patients and Methods: A total of 40 obese patients with type 2 diabetes mellitus in our hospital from July 2019 to June 2020 were randomly divided into a control group and a study group. The study group was treated with metformin and polyethylene glycol loxenatide injection, while the control group was treated with metformin., Results: Before treatment, there was no significant difference in FPG (Fasting Blood Glucose) and PPG (Post Prandial Glycaemia) levels between the study group and the control group (p>0.05). After a treatment period, the FPG and PPG levels in the study group were significantly lower than those in the control group (p<0.05). With the longer treatment time, the patient's weight and BMI were lower (p<0.05). The weight and BMI of patients changed the least after one month of treatment, and the weight and BMI changed the most after more than seven months of treatment. After a period of treatment, the levels of FPG and PPG in the blood of male patients in the study group were significantly lower than those of female patients (p<0.05). After treatment, the TG level of the study group was significantly lower than that of the control group (p<0.05). In comparison, the HDL-C level was significantly higher than that of the control group (p<0.05)., Conclusions: Lipid and glucose levels of type 2 diabetes mellitus patients with obesity have decreased after 12 weeks of polyethylene glycol loxanatide use. The weight of type 2 diabetes mellitus patients with obesity has changed after using polyethylene glycol loxenatide for a period of treatment. Among them, there is a certain relationship between body weight and treatment time, gender, and original body weight, which is worthy of further research and promotion in clinical practice.

Objective: To analyze the disease spectrums underlying orthostatic intolerance (OI) and sitting intolerance (SI) in Chinese children, and to understand the clinical empirical treatment options., Methods: The medical records including history, physical examination, laboratory examination, and imagological examination of children were retrospectively studied in Peking University First Hospital from 2012 to 2021. All the children who met the diagnostic criteria of OI and SI were enrolled in the study. The disease spectrums underlying OI and SI and treatment options during the last 10 years were analyzed., Results: A total of 2 110 cases of OI and SI patients were collected in the last 10 years, including 943 males (44.69%) and 1 167 females (55.31%) aged 4－18 years, with an average of (11.34±2.84) years. The overall case number was in an increasing trend over the year. In the OI spectrum, postural tachycardia syndrome (POTS) accounted for 826 cases (39.15%), followed by vasovagal syncope (VVS) (634 cases, 30.05%). The highest proportion of SI spectrum was sitting tachycardia (STS) (8 cases, 0.38%), followed by sitting hypertension (SHT) (2 cases, 0.09%). The most common comorbidity of OI and SI was POTS coexisting with STS (36 cases, 1.71%). The highest proportion of treatment options was autonomic nerve function exercise (757 cases, 35.88%), followed by oral rehydration salts (ORS) (687 cases, 32.56%), metoprolol (307 cases, 14.55%), midodrine (142 cases, 6.73%), ORS plus metoprolol (138 cases, 6.54%), and ORS plus midodrine (79 cases, 3.74%). The patients with POTS coexisting with VVS were more likely to receive pharmacological intervention than the patients with POTS and the patients with VVS (41.95% vs. 30.51% vs . 28.08%, χ 2 = 20.319, P < 0.01), but there was no significant difference in the proportion of treatment options between the patients with POTS and the patients with VVS., Conclusion: POTS and VVS in children are the main underlying diseases of OI, while SI is a new disease discovered recently. The number of children with OI and SI showed an increasing trend. The main treatment methods are autonomic nerve function exercise and ORS. Children with VVS coexisting with POTS were more likely to take pharmacological treatments than those with VVS or POTS only.

RUNX2 is a master osteogenic transcription factor, and mutations in RUNX2 cause the inherited skeletal disorder cleidocranial dysplasia (CCD). Studies have revealed that RUNX2 is not only a downstream target of the bone morphogenetic protein (BMP) pathway but can also regulate the expression of BMPs. However, the underlying mechanism of the regulation of BMPs by RUNX2 remains unknown. In this project, we diagnosed a CCD patient with a 7.86-Mb heterozygous deletion on chromosome 6 containing all exons of RUNX2 by multiplex ligation-dependent probe amplification (MLPA) and whole-genome sequencing (WGS). Bone marrow mesenchymal stem cells (BMSCs) were further extracted from patient alveolar bone fragments (CCD-BMSCs), an excellent natural model to explore the possible mechanism. The osteogenic differentiation ability of CCD-BMSCs was severely affected by RUNX2 heterozygous deletion. Also, BMP4 decreased most in BMP ligands, and CHRDL1, a BMP antagonist, was abnormally elevated in CCD-BMSCs. Furthermore, BMP4 treatment essentially rescued the osteogenic capacity of CCD-BMSCs, and RUNX2 overexpression reversed the abnormal expression of BMP4 and CHRDL1. Notably, we constructed CRISPR/Cas9 Runx2 +/m MC3T3-E1 cells, which simulated a variant in CCD-BMSCs, to exclude the interference of other gene deletions and the heterogeneity of the genetic background of primary cells, and verified all findings from the CCD-BMSCs. Moreover, the luciferase reporter experiment showed that RUNX2 could inhibit the transcription of CHRDL1 . Through immunofluorescence, the inhibitory effect of CHRDL1 on BMP4/Smad signaling was confirmed in MC3T3-E1 cells. These results revealed that RUNX2 regulated the BMP4 pathway by inhibiting CHRDL1 transcription. We collectively identified a novel RUNX2/CHRDL1/BMP4 axis to regulate osteogenic differentiation and noted that BMP4 might be a valuable therapeutic option for treating bone diseases.

Objective: To study the surgical safety and efficacy of preoperative neoadjuvant therapy with immune checkpoint inhibitors combined with anti-angiogenic drugs in patients with China liver cancer staging(CNLC)-Ⅱb and Ⅲa resectable hepatocellular carcinoma. Methods: The data of 129 patients with Ⅱb and Ⅲa hepatocellular carcinoma who underwent surgery at the First Affiliated Hospital of Nanjing Medical University from January 2018 to December 2020 were analyzed. All patients were divided into two groups: the neoadjuvant therapy group( n =14,13 males and 1 female,aged (55.4±12.6)years(range:34 to 75 years)) received immune combined targeted therapy before surgery,immune checkpoint inhibitor camrelizumab was administered intravenously at a dose of 200 mg each time,every 2 weeks for 3 cycles,anti-angiogenesis drug apatinib was taken orally and continuously with a dose of 250 mg for 3 weeks and the conventional surgery group( n =115,103 males and 12 females,aged (55.8±12.0)years(range:21 to 83 years)) did not receive antitumor systemic therapy before surgery. There were 3 patients with CNLC-Ⅱb,11 with CNLC-Ⅲa in the neoadjuvant group;28 patients with CNLC-Ⅱb,87 with CNLC-Ⅲa in the conventional group. Student's t test or rank-sum test was used to compare the differences between two groups for quantitative data, Fisher's exact probability method was used to compare the differences of proportions between two groups, and Log-rank test was used to compare survival differences between two groups. Results: The 1-year recurrence rate in the neoadjuvant group was 42.9%,and the 1-year recurrence rate in the conventional group was 64.0%,with a statistically significant difference between the two groups(χ²=3.850, P =0.050);The 1-year survival rate in the neoadjuvant group was 100% and that in the conventional group was 74.2%,with a statistically significant difference between the two groups(χ²=5.170, P =0.023). According to the stratified analysis of the number of tumors,for single tumor,the 1-year recurrence rate in the neoadjuvant group was 25.0%,and that in the conventional surgery group was 71.0%,and the difference between the two groups was statistically significant(χ²=5.280, P =0.022). For multiple tumors, the 1-year recurrence rate in the neoadjuvant group was 66.7%,and the 1-year recurrence rate in the conventional surgery group was 58.9%,with no significant difference between the two groups(χ²=0.110, P =0.736). The operative time,intraoperative blood loss,and postoperative hospital stay in the neoadjuvant group were similar to those in the conventional group,and their differences were not statistically significant. Conclusions: Immune checkpoint inhibitors combined with anti-angiogenic targeted drugs as a neoadjuvant therapy for resectable hepatocellular carcinoma can reduce the 1-year recurrence rate and improve the 1-year survival rate,especially for those with solitary tumor. Limited by the sample size of the neoadjuvant group,the safety of immune combined targeted therapy before surgery cannot be observed more comprehensively,and further studies will be explored.

Work-related musculoskeletal disorders (WMSDs) refer to musculoskeletal disorders caused by work or work as the main cause, which are characterized by high prevalence and heavy burden of disease as a global problem. The classification and catalog of occupational diseases is of great significance for guiding the prevention and control of occupational diseases and safeguarding the rights and interests of workers. The types of WMSDs included in the list of occupational diseases vary greatly from country to country, and the regulations on specific pathogenic factors are also inconsistent. By sorting out and analyzing the lists and characteristics of WMSDs at home and abroad, and using the International Statistical Classification of Diseases and Related Health Problems (ICD-10) in occupational health to standardize of WMSDs in various countries, which would lay the foundation for future multi-country WMSDs occupational health registration and disease burden research, and provide a reference for China to revise the WMSDs list.

A total of 16 detrusor hyperactivity with impaired contractility (DHIC) patients who received 12 weeks remote variable frequency stimulation (VFS) were enrolled at the First Affiliated Hospital of Zhengzhou University from September 2020 to February 2021. The voiding diary, symptom score scales and incidence of complications were completed and recorded at baseline, constant frequency stimulation (CFS) and VFS phases. Compared with the CFS phase, voiding times, urge incontinence times and daily catheterization volume were reduced; average voiding amount and functional bladder capacity increased; and the quality of life score and mental health questionnaire assessment were improved in the VFS phase(all P <0.05). In the end, among all 16 patients, there were 14 whose symptoms had improved, and there were no new complications such as pain or infection at the implantation site, electrode displacement, and electric shock sensation in the stimulation area. VFS-SNM can not only improve the DHIC patients' lower urinary tract symptoms during storage and urination period, but also improve the patients' quality of life and satisfaction of the therapy.

Spatial deviations of the temporomandibular joint (TMJ) after oncological mandibular reconstruction are important to the aesthetic and functional rehabilitation. The aim of this study was to clarify whether and how three dimensionally (3D) printed patient-specific surgical plates, and the preservation of the condyle or ramus, affect spatial deviations of the TMJ. A total of 33 patients who underwent mandibular reconstruction via computer-assisted surgery were included. Regarding absolute deviations, patients in the 3D-printed plate group showed smaller TMJ deviations compared to those in the conventional plate group. There was no difference in absolute deviations of the TMJ regardless of whether the condyle or ramus was preserved. Regarding physiological deviations, the impact on the contralateral TMJ was smaller in the 3D-printed plate group. Patients with both the condyle and ramus removed had significantly higher deviations of the condyle and joint space. In summary, 3D-printed patient-specific surgical plates improved the spatial accuracy of the TMJ. Under physiological conditions, TMJ deviations on the operated side were mainly affected by the preservation of the condyle. Removal of both the condyle and ramus caused more severe spatial interference to the TMJ; this should be further confirmed., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: This study aimed to investigate the effects of hydrothermal treatment on four types of monolithic, translucent, yttria-stabilized, tetragonal zirconia polycrystals (Y-TZPs)., Methods and Materials: Two commercially available Y-TZP brands-SuperfectZir High Translucency (Aidite Technology Co, China) and Katana HT (Kuraray Noritake Dental, Japan) were assessed. For each brand of Y-TZP, materials of four coloring types, including noncolored (NC), colored by staining (CS), precolored (PC), and multilayered (ML) specimens were investigated after hydrothermal aging in an autoclave at 134°C/0.2 MPa for 0 (control group), 5, 10, and 20 hours. The tetragonal-to-monoclinic phase transformation, surface roughness, flexural strength, and structural reliability (Weibull analysis) were measured and statistically analyzed (α=0.05). The subsurface microstructure was analyzed with scanning electron microscopy., Results: The group ML exhibited the lowest flexural strength and Weibull characteristic strength among the four coloring types (p<0.05). Slight increases in the monoclinic phase volume, flexural strength, and Weibull characteristic strength were observed after hydrothermal aging (pall<0.05). Regardless of coloring type, no significant effects of aging on the Weibull modulus or surface roughness were found for the tested materials. Compared with the Katana HT cross-sections, the SuperfectZir High Translucency cross-sections exhibited a similar but thicker transformation zone., Conclusions: The coloring procedure and material type were found to affect the mechanical properties and aging resistance of translucent monolithic Y-TZP ceramics. Regardless of the aging time, the surface roughness of the tested Y-TZP ceramics remained unchanged., (©Operative Dentistry, 2022.)

Objective: To provide insight into the diagnosis for clinicians, the clinical characteristics, diagnosis and treatment history of 3 patients with 21-hydroxylase deficiency (21-OHD) and testicular adrenal rest tumors (TART) were analyzed. Methods: The clinical, laboratory and imaging data of 3 male patients with 21-OHD and TART, confirmed with CYP21 gene sequencing, from May 2010 to May 2021 in the First Medical Center of Chinese PLA General Hospital were analyzed retrospectively. The treatment strategy and clinical outcome were followed up. Results: All the 3 patients were first diagnosed with bilateral adrenal mass at the age of 27-42 years old. They were 145-162 cm tall. The levels of progesterone, 17-hydroxyprogesterone, and adrenocorticotropic hormone (ACTH) of the 3 patients were relatively high, and that of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) of the 3 patients were low. Testosterone level of 1 patient was significantly elevated, and that of the other 2 patients was below the lower limit of normal range. Testicular ultrasound showed heterogeneous hyperechoic masses in both testes. CT of the adrenal glands showed bilateral adrenal enlargement with mass. All 3 patients were treated with dexamethasone. After 4-96 months of follow-up, 17-hydroxyprogesterone level was kept above the median normal level. One of the patients got married and had a baby after treatment. The sizes of adrenal hyperplasia and testicular masses reduced to various degrees with the change of the testicular masses being proportional to that of adrenal hyperplasia. Conclusions: Patients with 21-OHD are prone to have TART, leading to the impaired testicular function. Early glucocorticold therapy is beneficial to the reduction of TART and restoration of testicular function.

Objective: To study the expression of programmed death ligand-1 (PD-L1) in tumor cells and CD8 + T lymphocytes in tumor infiltrating lymphocytes, and to analyze the correlation of PD-L1 expression with infiltration of CD8 + T lymphocytes and clinicopathologic features in salivary gland lymphoepithelial carcinoma (LEC). Methods: Forty-two cases of primary salivary LECs and 21 cases of secondary salivary LECs were enrolled at the Department of Oral Pathology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University between 2015 and 2017. The expression of Epstein-Barr (EB) virus, PD-L1 and CD8 was examined using chromogenic in situ hybridization (CISH) and immunohistochemistry (IHC) staining. The data were analyzed using SPSS 23.0 software package. Results: EB virus was detected in 61 cases (61/63, 96.8%), including 42 (42/42, 100%) primary LECs and 19 (19/21, 90.5%) secondary LECs. The PD-L1 positive rate (score ≥1) was 97.6% (41/42), and its high-expression rate (score ≥20) was 78.6% (33/42) in primary LECs. The PD-L1 positive rate (score ≥1) was 71.4% (15/21), and its high-expression rate (≥20) was 38.1% (8/21) in secondary LECs. However, the PD-L1 positive rate (score ≥1, P =0.004) and high-expression rate (score ≥20, P =0.001) in primary LECs were higher than those in secondary LECs. There was no difference in the infiltration degree of CD8 + T lymphocytes between primary and secondary LECs. There was a significant correlation between the expression of PD-L1 and CD8 in primary LECs ( P =0.001) and in secondary LECs ( P =0.048), respectively. Conclusions: There is PD-L1 expression in primary and secondary salivary LECs, while the expression rate is higher in primary LECs than secondary LECs. The combination of PD-L1 expression and CD8 + T lymphocytes' presence suggest that most LEC patients might be responsive to immunotherapy, and primary LECs might be more significantly responsive than secondary LECs.

In order to solve the problem of dust hazard of vibrating screen machine and difficult treatment in catalyst production process, computational fluid dynamics software Fluent was used to carry out numerical simulation calculation of the local exhaust dust removal system for the main dust dispersing points of the vibrating screen machine, including fine/coarse particles outlet and product outlet blowing and cleaning the dust points. The optimal design scheme and key technical parameters of local ventilation and dust removal system of vibrating screen machine were proposed. The results showed that the dust diffusion could be prevented by setting up an upper suction hood without air blowing, but the exhaust air volume needed to be calculated accurately. On the premise of purge, it is necessary to control the air volume to form a wind speed band of 8 m/s with a height of 15 cm at the feed port, so as to effectively remove the dust on the surface of solid particles of catalyst products and ensure that the catalyst products will not be blown away when falling into the feed barrel. The simulated design was applied to the vibrating sieve powder machine of a catalyst company, and the maximum dust concentration in the workplace was reduced from 45.80 mg/m(3) to 5.46mg/m(3), which effectively improved the working environment in the workplace.

Background: Accurate and robust pathological image analysis for colorectal cancer (CRC) diagnosis is time-consuming and knowledge-intensive, but is essential for CRC patients' treatment. The current heavy workload of pathologists in clinics/hospitals may easily lead to unconscious misdiagnosis of CRC based on daily image analyses., Methods: Based on a state-of-the-art transfer-learned deep convolutional neural network in artificial intelligence (AI), we proposed a novel patch aggregation strategy for clinic CRC diagnosis using weakly labeled pathological whole-slide image (WSI) patches. This approach was trained and validated using an unprecedented and enormously large number of 170,099 patches, > 14,680 WSIs, from > 9631 subjects that covered diverse and representative clinical cases from multi-independent-sources across China, the USA, and Germany., Results: Our innovative AI tool consistently and nearly perfectly agreed with (average Kappa statistic 0.896) and even often better than most of the experienced expert pathologists when tested in diagnosing CRC WSIs from multicenters. The average area under the receiver operating characteristics curve (AUC) of AI was greater than that of the pathologists (0.988 vs 0.970) and achieved the best performance among the application of other AI methods to CRC diagnosis. Our AI-generated heatmap highlights the image regions of cancer tissue/cells., Conclusions: This first-ever generalizable AI system can handle large amounts of WSIs consistently and robustly without potential bias due to fatigue commonly experienced by clinical pathologists. It will drastically alleviate the heavy clinical burden of daily pathology diagnosis and improve the treatment for CRC patients. This tool is generalizable to other cancer diagnosis based on image recognition.

Objective: To explore the clinical value of ambulatory urodynamics monitoring (AUM) in the diagnosis and treatment of children with refractory monosymptomatic nocturnal enuresis (RMNE) by comparing the urodynamic parameters of AUM with those of conventional urodynamics (CUD). Methods: A total of 40 children (22 males and 18 females) diagnosed with RMNE in the First Affiliated Hospital of Zhengzhou University from May 2017 to September 2019 were collected. They were aged 9-16 years, and their frequency of nocturnal bed-wetting was≥2 times per week. CUD and one sleep cycle AUM were performed, respectively. Then, the urodynamic parameters were recorded and analyzed. Results: Five of the 40 children dropped out of the study because of the poor compliance. The age of children with RMNE was(12.6±2.1)years old, the ratio of male to female was 19∶16, and the severity of enuresis (enuresis frequency) was(4.2±1.7) times per week. Compared to the CUD group, the bladder compliance (BC) [(28.4±7.7) ml/cmH 2 O vs (23.6±6.1) ml/cmH 2 O(1 cmH 2 O=0.098 kPa)] and maximum detrusor pressure (Pmax.det) [(44.6±9.1) cmH 2 O vs (36.8±8.3) cmH 2 O] in the AUM group were significantly higher ( P <0.05). The maximum flow rate (Qmax) [(19.6±7.2) ml/s vs (20.9±5.4) ml/s] and post void residual (PVR) [(9.5±5.7) ml vs (10.9±5.3) ml] between the two groups showed no statistically significant differences ( P >0.05). Detrusor overactivity (DO) was detected in 27 cases (77.1%) during AUM and in 16 cases (45.7%) during CUD; the difference was statistically significant ( P <0.05). Among them, 15 cases (42.9%) with DO were detected both in CUD and AUM, while 12 (34.3%) with DO were not detected in CUD. For the 15 cases with DO detected by both CUD and AUM, the frequency [(3.1±1.0) times/h vs (2.4±0.8) times/h] and maximum value of DO [(22.9±4.5) cmH 2 O vs (19.2±4.0) cmH 2 O] in the AUM group were both higher than those in the CUD group ( P <0.05). Conclusions: Bladder dysfunction can be diagnosed in children with RMNE using AUM. Furthermore, AUM is more accurate than CUD in evaluating BC, Pmax.det, DO, and other parameters. For children with RMNE and with unsatisfactory CUD results, further AUM examination is recommended to clarify the etiology.

Background: The use of mesh is controversial in the treatment of female pelvic organ prolapse., Objectives: To systematically review the outcomes of sacrocolpopexy compared with transvaginal mesh surgery and to provide evidence-based suggestions., Search Strategy: The MEDLINE, EMBASE, Cochrane Library and clinicaltrials.gov databases were searched on 21 November 2018., Selection Criteria: Randomised controlled trials and prospective and retrospective cohort studies were included., Data Collection and Analysis: Data were extracted by one reviewer and examined by a second reviewer for accuracy. Odds ratios and 95% CI were calculated using random-effects models., Main Results: Twenty comparative studies were included. The meta-analysis was performed with subgroups. The summary odds ratios of the randomised controlled group were 1.84 (95% CI 0.79-4.29, I 2  = 75%) for anatomical success, 1.41 (95% CI 0.47-4.24, I 2  = 38%) for subjective success, 0.42 (95% CI 0.18-0.98, I 2  = 0%) for mesh complications, 0.61 (95% CI 0.20-1.91, I 2  = 0%) for prolapse reoperation and 0.44 (95% CI 0.23-0.88, I 2  = 0%) for de novo dyspareunia. The mean differences were 0.77 (95% CI 0.31-1.23, I 2  = 66%) for total vaginal length and -1.28 (95% CI -2.00 to -0.55, I 2  = 66%) for point C after surgery., Conclusions: Very-low-quality evidence indicated that the anatomical and subjective success rates of sacrocolpopexy were similar to those of transvaginal mesh surgery; sacrocolpopexy might be more beneficial than transvaginal mesh surgery in terms of mesh-related complication rates, prolapse recurrence and de novo dyspareunia. However, additional high-quality randomised trials with long-term follow-up durations are needed., Tweetable Abstract: Sacrocolpopexy is beneficial after surgical anatomical changes and has decreased rates of mesh-related complications and dyspareunia., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Objective: To summarize the experience of surgical treatment of primary liver cancer. Methods: The clinical data of 10 966 surgically managed cases with primary liver cancer, from January 1986 to December 2019 at Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, were retrospectively analyzed. The life table method was used to calculate the survival rate and postoperative recurrence rate. Log-rank test was used to compare the survival process of different groups, and the Cox regression model was used for multivariate analysis. In addition, 2 884 cases of hepatocellular carcinoma(HCC) with more detailed follow-up data from 2009 to 2019 were selected for survival analysis. Among 2 549 patients treated with hepatectomy, there were 2 107 males and 442 females, with an age of (56.6±11.1) years (range: 20 to 86 years). Among 335 patients treated with liver transplantation, there were 292 males and 43 females, with an age of (51.0±9.7) years (range: 21 to 73 years). The outcomes of hepatectomy versus liver transplantation, anatomic versus non-anatomic hepatectomy were compared, respectively. Results: Of the 10 966 patients with primary liver cancer, 10 331 patients underwent hepatectomy and 635 patients underwent liver transplantation. Patients with liver resection were categorized into three groups: 1986－1995(712 cases), 1996－2008(3 988 cases), 2009‒2019(5 631 cases). The 5-year overall survival rate was 32.9% in the first group(1986－1995). The 5-year overall survival rate of resected primary liver cancer was 51.7% in the third group(2009-2019), among which the 5-year overal survival rates of hepatocellular carcinoma, intrahepatic cholangiocarcinoma and mixed liver cancer were 57.4%, 26.6% and 50.6%, respectively. Further analysis was performed on 2 549 HCC patients with primary hepatectomy. The 1-, 3-, 5-, and 10-year overall survival rates were 88.1%, 71.9%, 60.0%, and 41.0%, respectively, and the perioperative mortality rate was 1.0%. Two hundred and forty-seven HCC patients underwent primary liver transplantation, with 1-, 3-, 5-, and 10-year overall survival rates of 84.0%, 64.8%, 61.9%, and 57.6%, respectively. Eighty-eight HCC patients underwent salvage liver transplantation, with the 1-, 3-, 5-, and 10-year overall survival rates of 86.8%, 65.2%, 52.5%, and 52.5%, respectively. There was no significant difference in survival rates between the two groups with liver transplantation ( P >0.05). Comparing the overall survival rates and recurrence rates of primary hepatectomy (2 549 cases) with primary liver transplantation (247 cases), the 1-, 3-, 5-, and 10-year overall survival rates in patients within Milan criteria treated with hepatectomy and transplantation were 96.3%, 87.1%, 76.9%, 54.7%, and 95.4%, 79.4%, 77.4%, 71.7%, respectively ( P =0.754). The 1-, 3-, 5-year recurrence rates were 16.3%, 35.9%, 47.6% and 8.1%, 11.7%, 13.9%, respectively( P <0.01). The 1-, 3-, 5-, 10-year overall survival rates in patients with no large vessels invasion beyond the Milan criteria treated with liver resection and transplantation were 87.2%, 65.9%, 53.0%, 33.0% and 87.6%, 71.8%, 71.8%, 69.3%, respectively( P =0.003); the 1-, 3-, 5-year recurrence rate were 39.2%, 57.8%, 69.7% and 29.7%, 36.7%, 36.7%, respectively ( P <0.01). The 1-, 3-, 5-, and 10-year overall survival rates in patients with large vessels invasion treated with liver resection and transplantation were 62.1%, 36.1%, 22.2%, 15.0% and 62.9%, 31.8%,19.9%, 0, respectively ( P =0.387); the 1-, 3-, 5-year recurrence rates were 61.5%, 74.7%, 80.8% and 59.7%, 82.9%, 87.2%, respectively( P =0.909). Independent prognostic factors for both overall survival and recurrence-free survival rates of HCC patients treated with liver resection included gender, neoadjuvant therapy, symptoms, AST, intraoperative or postoperative blood transfusion, tumor number, tumor size, cirrhosis, macrovascular invasion, microvascular invasion, and pathological differentiation. Propensity score matching analysis of 443 pairs further showed that there was no significant difference in overall survival rate between anatomical liver resection and non-anatomical liver resection( P =0.895), but the recurrence rate of non-anatomical liver resection was higher than that of anatomical liver resection( P =0.035). Conclusions: In the past decade, the overall survival rate of HCC undergoing surgical treatment is significantly higher than before. For HCC patients with good liver function reservation, surgical resection can be performed first, and salvage liver transplantation can be performed after recurrence. The effect of salvage liver transplantation is comparable to that of primary liver transplantation. As for the choice of liver resection approaches, non-anatomical resection can reserve more liver tissue and can be selected as long as the negative margin is guaranteed.

Objective: To compare and analyze the diagnostic value of prostate imaging reporting and data system (PI-RADS) version 2.1 and version 2 for prostate transitional zone lesions. Methods: The imaging data of 159 patients with major prostate lesions located in the transitional zone collected by the Department of Radiology of the Second Affiliated Hospital of Suzhou University from January to December 2017 were retrospectively analyzed. Two radiologists used PI-RADS V2.1 and V2 scoring system respectively to perform diagnostic scores on the enrolled cases. The weighted Kappa test was used to evaluate the consistency of PI-RADS V2.1 and V2 scores between the two radiologists. The receiver operating characteristic (ROC) curve was used to evaluate and compare the diagnostic efficiency of two radiologists using two scoring systems for transitional zone prostate cancer (PCa) and clinically significant PCa (csPCa). Results: The weighted Kappa values between the scores of all lesions, benign lesions, PCa lesions, and csPCa lesions by the two radiologists using PI-RADS V2.1 and V2 scoring systems were 0.754, 0.643, 0.734, 0.782 and 0.808, 0.738, 0.775, 0.826, respectively. The PI-RADS V2.1 scoring system had a better consistency. There were no statistically significant differences in sensitivity, specificity, area under the ROC curve (AUC) between the PI-RADS V2.1 and V2 scoring system for PCa and csPCa (all P> 0.05). However, in this set of data, the sensitivity and AUC value of PI-RADS V2.1 scoring system in diagnosing PCa and csPCa were higher than those of P-RADS V2. The diagnostic sensitivity of PI-RADS V2.1 and V2 for PCa were 86.7% and 80.0%, the diagnostic sensitivity for csPCa were 94.4% and 88.9%, the diagnostic AUC for PCa were 0.857 and 0.816, and the diagnostic AUC of csPCa were 0.917 and 0.886, respectively. Conclusion: The consistency of PI-RADS V2.1 in scoring prostate transitional zone lesions was better than PI-RADS V2. The diagnostic efficiency of PI-RADS V2.1 for transitional carcinoma was not lower than or slightly higher than PI-RADS V2.

Objective: Through 16S rDNA technology, we aimed at separating adults aging 20-50 years old into a few groups and processing the high-throughput sequencing analysis, in order to explore the features and differences of intestinal flora in each age group in a microcosmic perspective., Patients and Methods: 120 stool specimens were collected strictly in accordance with acceptance criteria and exclusion criteria. 49 subjects aging 20-29 years old (Group AGE1), 51 subjects aging 30-39 years old (Group AGE2), and 20 subjects aging 40-49 years old (Group AGE3) were divided into 3 groups. Bacteria DNA from fresh stool specimens of 3 groups were abstracted. Illumina MiSeq high-throughput sequencing platform was applied to process 16S rDNA sequencing in Area 338F&#95;806R for intestinal flora detection. I-Sanger Bio-cloud platform was applied for the analysis of intestinal flora structure changes in phylum level and genus level., Results: Among the age of 20-50, with older age, the abundance of intestinal flora decreased among healthy adults more than 40 years old. In addition, the diversity and sample dispersion of intestinal flora is significantly different from people among 20-40 years old. The decrease ratio of Firmicutes/Bacteroidetes indicated that as the age grows, glucose tolerance might decrease. Comparing with people among 20-40 years old, the amount of Bifidobacterium and Eubacterium in people over 40 years old have significantly decreased. The decrease of Bifidobacterium and Eubacterium may increase the risks of cognitive impairment and lower the anti-inflammation and anti-cancer efficacy in human body, respectively. Subdoligranulum relates to poor metabolism and chronic inflammation and it happens more in people aged over 40 than young people who are among 20-40 years old., Conclusions: There are differences in the intestinal flora of healthy adults aged 20-50. Effective intervention of the intestinal flora may play a role in delaying aging and preventing diseases.

Objective: To observe the status of the sinus membrane using fiber optic endoscope during the lateral window approach sinus floor elevation to provide a reference for clinicians when evelvating the sinus mucoperiosteum. Methods: Sixty-six patients (72 sides) who underwent maxillary sinus floor elevation in Beijing Ruicheng Stomatology Hospital from September 2016 to December 2019 were selected, including 40 males and 26 females, aged 26-80 years old [(56.2±11.5) years]. And fiber optic endoscopy was used to observe the maxillary mucoperiosteum during the operation. Results: The status of maxillary sinus mucoperiosteal during lateral window approach sinus floor elevation can be divided into four categories: ① Class Ⅰ, complete periosteal, no damage to mucoperiosteum; ②Class Ⅱ, periosteal injury, unexposed laminae propria; ③Class Ⅲ, periosteal Rupture, exposed lamina propria; ④ Class Ⅳ, mucoperiosteum perforation, rupture of periosteum, lamina propria and epithelial layer. A total of 72 operations were performed, including 18 cases of class I, 28 cases of class Ⅱ, 4 cases of class Ⅲ, and 22 cases of class Ⅳ. Conclusions: The status of maxillary sinus mucoperiosteal during lateral window approach sinus floor elevation can be divided into four categories. Fiberoptic endoscopy as a clinical auxiliary examination method can improve the operator's control of the status of the maxillary sinus membrane and assist the peeling of the mucosa.

Objective: To evaluate the airway and voice quality improvement in patients with bilateral vocal fold paralysis (BVFP) who underwent selective laryngeal reinnervation surgery. Methods: From January 2012 to December 2016, a retrospective study was conducted in 39 patients with BVFP who underwent selective laryngeal reinnervation surgery in Department of Otorhinolaryngology Head and Neck Surgery, the First Affiliated Hospital of Navy Medical University. All patients were examined by videostroboscopy, vocal function assessment, laryngeal electromyography and pulmonary function test before and after the surgery, and followed up for at least 2 years to evaluate the efficacy and safety of the surgery.Wilcoxon signed rank test was used to analyze the G score and VHI-10 score data. Paired t -test was used to analyze acoustic parameters, MPT values and pulmonary function parameters. Results: Postoperative infection and hemorrhage occurred in one patient separately.Videostroboscopic videos showed that at 4-8 months postoperatively, vocal folds in 35 patients achieved moderate or severe abduction during inspiration, 2 patients only achieved mild abduction, 2 patients showed no abduction,while all patients achieved adduction in bilateral vocal cords during phonation. The recovery rate of moderate-to-severe abduction was 89.7% (35/39), and these patients were decannulated successfully. At 12 months after operation, G score and VHI-10 score were significantly lower than those before operation ( P< 0.05), and the acoustic parameters jitter, shimmer, HNR and MPT were significantly improved ( P< 0.05). Most of the parameters of the pulmonary function test at 3 months postoperatively returned to the normal reference level, while the maximum inspiratory pressure (PImax) at 12 months after operation was still slightly lower than the normal level, but it was significantly improved compared with preoperative value ( P< 0.05). The EMG data at 12 months postoperatively showed full interference potentials in 37 patients in bilateral posterior cricoarytenoid muscles during inspiration, and full interference potentials in bilateralthyroarytenoid muscles during phonation. Obvious misdirected regeneration electric activitieswere found in two of them. Potentials in posterior cricoarytenoid muscle were weak in 2 cases with poor abduction. During long-term follow-up, only one case showed decreased abduction, but did not affect respiratory function. Conclusions: The selective laryngeal reinnervation procedure applied in the present study can restore physiological motion of vocal cords. The success rate was high, the curative effect was stable, and the complications were rare. It is worth of promotion.

High-level sensory and motor cortical areas are activated when processing the meaning of language, but it is unknown whether, and how, words share a neural substrate with corresponding sensorimotor representations. We recorded from single neurons in human posterior parietal cortex (PPC) while participants viewed action verbs and corresponding action videos from multiple views. We find that PPC neurons exhibit a common neural substrate for action verbs and observed actions. Further, videos were encoded with mixtures of invariant and idiosyncratic responses across views. Action verbs elicited selective responses from a fraction of these invariant and idiosyncratic neurons, without preference, thus associating with a statistical sampling of the diverse sensory representations related to the corresponding action concept. Controls indicated that the results are not the product of visual imagery or arbitrary learned associations. Our results suggest that language may activate the consolidated visual experience of the reader., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Preoperative staging is essential for the planning of treatment of cancer. This study was designed to evaluate the accuracy of computed tomography (CT) in predicting the local stage of tongue cancer by comparing it with the gold standard of histopathology. A total of 233 patients with newly-diagnosed tongue cancer was retrospectively reviewed, and the size of the tumour and the status of the cervical lymph node were compared between CT images and histopathological results. Patients with stage II cancer were followed up to assess the influence of inaccurate preoperative staging on prognosis. The accuracy of local staging by CT was 47.6% (111/233), with 59.7% (139/233) for tumour stage, and 70.4% (164/233) for nodal stage. The greatest dimension of the tumour on the CT image was about 2mm less than that measured by histopathology. The estimated volume of tumour was a quarter smaller. The accuracy of predicting malignant lymph nodes by CT was 68.9% (n=161). Among patients with stage II disease, simultaneous neck dissection was less likely in the understaged group than in the accurately staged one. The reoperation rate was a little higher but not significantly so. We conclude that the accuracy of CT in predicting local staging for tongue cancer was only moderate, because it underestimated the size of the tumour and needed to improve the criteria for detecting malignant lymph nodes. Understaging on CT images may influence the prognosis of patients with early stage tongue cancer., (Copyright © 2020 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: To investigate the clinical characteristics and outcomes of monochorionic monoamniotic (MCMA) twin pregnancy. Methods: The clinical data of 60 MCMA twin pregnant women who were terminated in Peking University Third Hospital from January 2011 to December 2019 were collected, and the general clinical data, prenatal examination and pregnancy outcomes were analyzed retrospectively. Results: The age of 60 MCMA twin pregnant women was (31.0±4.1) years old, among which 44 cases were primiparas (73%, 44/60) and 16 cases were multiparas (27%, 16/60). Fifty-eight cases were diagnosed as MCMA twin pregnancy prenatally and were confirmed after delivery. Median ultrasonic diagnosis of gestational age was 12 weeks (range: 8-30 weeks). In the 60 MCMA twin pregnancies, 6 cases were conjoined twins, 5 cases were complicated with twin reversed arterial perfusion sequence (TRAPS), and 10 cases were diagnosed as other fetal malformation by prenatal ultrasound examination. Among the 60 MCMA twin pregnant women, 19 cases had spontaneous abortion or induced abortion due to fetal malformation, fetal death or other reasons within 28 weeks of pregnancy, 41 cases entered the perinatal period, a total of 70 newborns survived. The main cause of perinatal fetal or neonatal death was fetal dysplasia. Conclusions: There is a high incidence of fetal abnormality and perinatal mortality in MCMA twin pregnancy. Accurate early diagnosis, enhanced management and monitoring during pregnancy, and individualized treatment are the keys to improve MCMA twin pregnancy outcomes.

Objective: To explore the application of axillary reverse mapping (ARM) in breast cancer sentinel lymph node biopsy (SLNB), and to collect and record patient's data during operation. Through the specific experimental data, the anatomical location and morphology of the intercostal brachial nerve (ICBN) and the anatomic relationship of the axillary lymph nodes were analyzed to accurately locate the anatomical division of the axillary fossa of sentinel lymph node (SLN) and ARM lymph nodes. Methods: The technique of methylene blue staining for SLN combined with indocyanine green fluorescent staining for axillary reverse mapping was used to analyze the patients of Tianjin Central Hospital of Gynecology Obstetrics from June 2017 to June 2018. The clinical data of 35 patients with T1-2N0M0 breast cancer were analyzed. Results: Of the 35 patients, two cases were excluded from metastatic carcinoma of the SLN. Thirty-three cases were included in the data analysis. Three cases of ICBN were located 0-2.0 cm (9.09%) from the lower edge of the iliac vein, 27 cases were located at 2.0-4.0 cm (81.82%), and 3 cases of ICBN were located greater than 4.0 cm (9.09%). In the region of 0-2.0 cm from the lower edge of the iliac vein, 1-2 ARM lymph nodes were found in 5 cases; in the 2.0-4.0 cm area, SLN was found in 33 cases, 4 of which found 1 coincident lymph node; at>4.0 cm ARM lymph nodes and overlapping lymph nodes were not found in the cm region, and 1-2 SLNs were found in 3 cases. Conclusions: Individual ICBNs vary greatly, with different shapes and distances from the lower edge of the axillary vein. The axillary region below the iliac vein can be divided into three regions: ARM region (0-2.0 cm); SLN region (2.0-4.0 cm); and sentinel gate region (>4.0 cm). The position 2.0 cm from the lower edge of the iliac vein can be used as the boundary between the ARM lymph node and the SLN. 4. There is a certain proportion of coincidence rate between SLN and ARM lymph nodes.

Background: Esophageal squamous cell carcinoma (ESCC) is a kind of cancer with heterogeneous biological characteristics, which is affected by a complex network of gene interactions. Identification of molecular biomarkers paves the way for individualized therapy based on gene expression profiles, which can overcome the heterogeneity of ESCC., Methods: In this study, GSE20347, GSE23400 and GSE45670 datasets were retrieved from Gene Expression Omnibus (GEO) database, and the overlapping differentially expressed genes (DEGs) in three datasets were screened. Then the overlapping DEGs function was annotated by Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway-enrichment analysis. The prognostic value of the top five KEGG pathway-related genes were further validated in The Cancer Genome Atlas (TCGA) database. After extensive statistical analysis, four genes (CDC25B, CXCL8, FZD6 and MCM4) were identified as potential prognostic markers. Among the four candidate genes, the prognostic value of FZD6 in ESCC patients has not been evaluated. Therefore, we finally used immunohistochemistry method to evaluate the effect of FZD6 on the prognosis of patients with ESCC. Additionally, we detected the expression level of FZD6 in ESCC cell line and normal esophageal epithelial cell line, and observed the cell viability of ESCC cell line after FZD6 knockdown., Results: The results showed that the overexpression of FZD6 predicted poor overall survival (OS) (P = 0.005) and progression-free survival (PFS) (P = 0.004) in ESCC patients. COX regression analysis showed that N stage (P = 0.026) and FZD6 expression level (P = 0.001) were independent prognostic factors of OS for ESCC patients. Furthermore, compared with normal esophageal epithelial cell line, the up-regulation of FZD6 was detected in ESCC cell line. Knockdown of FZD6 could significantly inhibit the proliferation of ESCC cells (P < 0.001)., Conclusion: CDC25B, CXCL8, FZD6 and MCM4 were screened as candidate genes for prognosis assessment of patients with ESCC. The prognostic role of FZD6 in ESCC patients was confirmed in current study.

Objectives: To summarize the clinical and genetic characteristics of the patients with isolated methylmalonic acidemia and investigate the strategies for the diagnosis, treatment and prevention. Methods: Three hundred and fourteen patients (180 males, 134 females) with isolated methylmalonic acidemia were ascertained from 26 provinces or cities across the mainland of China during January 1998 to March 2020. Genetic analysis was performed by Sanger sequencing, gene panel sequencing, whole exome sequencing, multiplex ligation-dependent probe amplification or quantitative PCR. According to the age of onset, the patients were divided to early-onset group (≤12 months of age) and the late-onset group (>12 months of age). They were treated by cobalamin, L-carnitine and (or) special diet and symptomatic treatment. Statistical analysis was done using Chi-square test. Results: Fifty-eight of 314 (18.5%) patients were detected by Newborn screening using liquid chromatography tandem mass spectrometry. Five cases (1.6%) had a postmortem diagnosis. Two hundred and fifty-one patients (79.9%) were clinically diagnosed with an age of onset ranged from 3 hours after birth to 18 years. One hundred and fifty-nine patients (71.0%) belonged to early-onset groups, 65 patients (29.0%) belonged to the late-onset group. The most common symptoms were metabolic crises, psychomotor retardation, epilepsy, anemia and multiple organ damage. Metabolic acidosis and anemia were more common in early-onset patients than that in late-onset patients (20.8%(33/159) vs. 9.2% (6/65), 34.6% (55/159) vs. 16.9% (11/165), χ(2)=4.261, 6.930, P= 0.039, 0.008). Genetic tests were performed for 236 patients (75.2%), 96.2%(227/236) had molecular confirmation. One hundred and twenty-seven variants were identified in seven genes (MMUT, MMAA, MMAB, MMADHC, SUCLG1, SUCLA2, and MCEE), of which 49 were novel. The mut type, caused by the deficiency of methylmalonyl-CoA mutase, was the most common ( n= 211, 93%) cause of this condition. c.729&#95;730insTT, c.1106G>A and c.914T>C were the three most frequent mutations in MMUT gene. The frequency of c.914T>C in early-onset patients was significantly higher than that in late-onset patients (8.3% (18/216) vs. 1.6% (1/64), χ(2)=3.859, P= 0.037). Metabolic crisis was more frequent in mut type than the other types (72.6% (114/157) vs. 3/13, χ(2)=13.729, P= 0.001),developmental delay and hypotonia were less frequent in mut type (38.2% (60/157) vs. 9/13, 25.5% (40/157) vs. 8/13, χ(2)=4.789, 7.705, P= 0.030, 0.006). Of the 58 patients identified by newborn screening, 44 patients (75.9%) who were treated from asymptomatic phase developed normally whereas 14 patients (24.1%) who received treatment after developing symptoms exhibited varying degrees of psychomotor retardation. Conclusions: The characteristics of phenotypes and genotypes among Chinese patients with isolated methylmalonic acidemia were analyzed. Expanded the mutation spectrum of the associated genes. Because of the complex clinical manifestations and severe early onset of isolated methylmalonic acidemia, Newborn screening is crucial for early diagnosis and improvement of prognosis. MMUT gene is recommended for carrier screening as an effort to move the test earlier as a part of the primary prevention of birth defects.

Objective: Neuroblastoma (NB) is a type of extracranial solid tumor that usually occurs in children. Drug resistance has become a major obstacle in NB chemotherapy. Long non-coding RNA small nucleolar RNA host gene 7 (SNHG7) is an oncogene in many cancers, including NB. This study aimed to investigate the role of SNHG7 in cisplatin sensitivity of NB and the underlying mechanism., Patients and Methods: Cell Counting Kit-8 (CCK-8) assay was used to detect cell viability, and the IC50 of cisplatin was calculated. The protein levels of autophagy markers were measured by Western blot assay. The levels of SNHG7, miR-329-3p and myosin X (MYO10) were examined by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blot assay. The interaction among SNHG7, miR-329-3p and MYO10 was confirmed by Dual-Luciferase reporter assay., Results: Cisplatin curbed the viability of NB cells in a dose-dependent manner and facilitated autophagy in NB cells. Silencing of SNHG7 reduced cisplatin resistance and suppressed cisplatin-induced autophagy. SNHG7 was a sponge of miR-329-3p and modulated chemosensitivity and autophagy by regulating miR-329-3p. In addition, SNHG7 upregulated MYO10 by sponging miR-329-3p. MYO10 restored the effect of miR-329-3p on cisplatin sensitivity and autophagy. Moreover, suppression of autophagy blocked SNHG7-induced cisplatin resistance., Conclusions: Depletion of SNHG7 potentiated cisplatin sensitivity through inhibition of autophagy by modulating miR-329-3p/MYO10 axis, providing a new therapeutic approach to overcome cisplatin resistance in NB chemotherapy.

Objective: To investigate the relationship between SNP and noise-induced hearing loss (NIHL) susceptibility in occupational noise exposure population in China. Methods: From 6297 for a certain steel works in contact with noise, contact length of 3 years or more and workplace noise exposure intensity of 80 dB (A) , ears or high frequency (3 000, 4 000, 6 000 Hz) average of hearing acuity 40 dB (HL) , or high frequency loss in both ears, on the basis of single whisper frequency (500, 1, 000, 2 000 Hz) average threshold of 26 dB (HL) or object as case group. A case-control study was designed with 1:1 matching. Subjects with the same gender, the same type of work, age ±5 years old, and working age ±2 years after noise exposure were selected as the control group. Subjects with any whisper frequency (500, 1, 000, 2, 000 Hz) whose hearing threshold in any frequency band was ≤25 dB (A) and whose average high-frequency hearing threshold in pure tone hearing test was <35 dB (A) were selected as the control group. Four sites of PON2 gene were genotyped by medium-and high-throughput SNP genotyping. Univariate logistic regression was used to analyze the relationship between single SNP polymorphism and NIHL. Results: A total of 286 case-control pairs were included. Smoking was statistically significant difference between cases and controls ( P <0.001) . Conclusion: No statistical difference has been found between single SNP polymorphism and NIHL. At the level of greater than 92 dB of high noise exposure, rs7785846 (CT+TT) genotype is a risk factor for occupational noise deafness, and its OR is 2.74 (95% CI : 1.09-6.89) compared with wild homozygous type (CC) . Conclusion. The rs7785846 (CT+TT) genotype carriers of PON2 gene are more susceptible to hearing impairment when exposed to high noise intensity.

Objective: Diabetic nephropathy (DN) is one of the primary complications of diabetes. Long non-coding RNA cancer susceptibility candidate 2 (CASC2) has been established to function in DN, while its role in high glucose (HG)-induced human mesangial cells (HMCs) remains limited., Materials and Methods: The expression level of CASC2 and miR-133b was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation was assessed using cell counting kit-8 (CCK-8) assay. Extracellular matrix (ECM) accumulation was monitored through the expression levels of collagen IV (Col IV) and fibronectin (FN) using qRT-PCR and western blot analyses. Oxidative stress was observed through the expression of NADPH oxidase2 (NOX2) and the activity of malondialdehyde (MDA) and superoxide dismutase (SOD) using western blot or corresponding detection kit. The expression of forkhead box P1 (FOXP1) at mRNA and protein levels was determined by qRT-PCR and Western blot, respectively. The relationship between miR-133b and CASC2 or FOXP1 was predicted by online bioinformatics tools and verified by dual-luciferase reporter assay or RNA pull-down., Results: The expression of CASC2 was reduced in serum from DN patients and HG-induced HMCs. CASC2 upregulation inhibited HG-induced HMCs proliferation, ECM accumulation and oxidative stress. MiR-133b was a target of CASC2 with a high level in serum from DN patients and HG-induced HMCs, and its enrichment reversed the effects of CASC2 upregulation. Besides, FOXP1 was a target of miR-133b with a low level in HG-induced HMCs, and its knockdown abolished the impacts of CASC2 upregulation., Conclusions: CASC2 upregulation suppressed HG-induced proliferation, ECM accumulation and oxidative stress of HMCs through miR-133b /FOXP1 regulatory axis, suggesting that CASC2 was a novel biomarker for DN treatment.

Three-dimensionally (3D) printed patient-specific surgical plates have been proposed to facilitate mandibular reconstruction and are attracting extensive attention. We have recently reported the high accuracy of 3D-printed patient-specific surgical plates used in head and neck reconstruction. Based on this previous work, the current study proposes a novel 'surgeon-dominated' approach to the design of 3D-printed patient-specific surgical plates. The aim of this proof-of-concept study was to explore the workflow and technical procedures of the surgeon-dominated approach. The workflow includes virtual surgery, the design and printing of patient-specific surgical devices, and real surgery. The prototype of the patient-specific surgical plate was designed by surgeons and further optimized for 3D printing by engineers. Different types of mandibular defect were tested to confirm the wide applicability of this approach. Cases in which this approach was used were reviewed and the duration of time spent on each case studied. Based on a total of 16 patients, the time spent on virtual surgery and plate design was 18.83±13.19hours, and the time taken for 3D printing, post-processing, and product delivery was 162.9±55.15hours. Therefore, this novel surgeon-dominated approach is feasible and time-saving, which would likely promote the wide application of patient-specific surgical plates and lead to a new era of 'digitization and precision' in mandibular reconstruction. ClinicalTrials.gov registration: NCT03057223., (Copyright © 2019 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Objective: To explore the new mechanism of spectomycin B1 in inhibiting angiogenesis of nasopharyngeal carcinoma and to provide a theoretical basis for targeted gene therapy of nasopharyngeal carcinoma. Method: Human nasopharyngeal carcinoma CNE1 cells were divided into two groups, the control group and spectomycin B1 group. Western blot was used to detect the expression levels of small ubiquitin-related modified protein（SUMO） 1 and vascular endothelial growth factor receptor 2（VEGFR2）. The angiogenesis assay was used to detect the angiogenic ability of CNE1 cells, and the apoptosis was detected by flow cytometry. The model of nasopharyngeal carcinoma-bearing mice was established, spectomycin B1 was administered, tumor volume and weight were measured, and protein expression of CD31 was detected by immunohistochemistry and microvessel density was compared. Result: Spectomycin B1 could reduce deSUMOylation of VEGFR2 protein by 4.05 times, significantly reduce the angiogenic ability of CNE1 cells, and increase the apoptosis rate by 20.68%. In the tumor-bearing mouse model, spectomycin B1 treatment could inhibit subcutaneous tumor growth rate and weight, and the blood vessel density decreased by 40.04%. Conclusion: Spectomycin B1 can inhibit neovascularization of nasopharyngeal carcinoma by inducing deSUMOylation of VEGFR2 protein., Competing Interests: The authors of this article and the planning committee members and staff have no relevant financial relationships with commercial interests to disclose., (Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.)

Objective: The pathogenesis of diabetes is closely related to islet β-cell dysfunction. Lnc-NTF3-5 participates in the occurrence and development of various diseases. However, Lnc-NTF3-54's effect on islet β-cell dysfunction in high glucose environment remains unclear., Materials and Methods: The islet β cell MIN6 cells were cultured in vitro and randomly divided into control group, high glucose group, NTF3-5 siRNA group, and NTF3-5 group, which was respectively transfected with Lnc-NTF3-5 siRNA and Lnc-NTF3-5 plasmid under high glucose condition. Lnc-NTF3-5 expression was measured by real time PCR and cell proliferation was assessed by MTT assay. In addition, Caspase 3 activity, SOD activity, and ROS content were also detected along with the secretion of IL-10 and IL-1 by enzyme-linked immunosorbent assay (ELISA)., Results: Compared with control group, Lnc-NTF3-5 expression in MIN6 cells was significantly increased in high glucose environment (p<0.05). In high glucose environment, Lnc-NTF3-5 plasmid transfection up-regulated Lnc-NTF3-5 expression, inhibited cell proliferation, increased Caspase 3 activity, and decreased SOD activity. Meanwhile, Lnc-NTF3-5 plasmid also increased ROS content and IL-1 level, and decreased IL-10 level and insulin secretion. Compared with high glucose group, the differences were statistically significant (p<0.05). However, transfection of Lnc-NTF3-5 siRNA down-regulated Lnc-NTF3-5 expression under high glucose environment and reversed the above changes. Compared with high glucose group, the differences were statistically significant (p<0.05)., Conclusions: Lnc-NTF3-5 expression is increased in high glucose environment. Targeting Lnc-NTF3-5 can inhibit islet cell apoptosis, oxidative stress, and promote islet cell proliferation and insulin secretion.