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Rationale: Multiple primary malignant neoplasms with tuberculosis are rare. The interaction between tuberculosis and tumor remains unclear. Moreover, the treatment of multiple primary tumors combined with tuberculosis is relatively complicated. Herein, we report a case of metachronous triple primary carcinoma complicated with pulmonary tuberculosis., Objective: This report aims to analyze the clinical characteristics of 3 primary tumors combined with tuberculosis. We report the long-term survival of this patient after personalized treatment and this patient have a good quality of life., Diagnoses and Interventions: A 55-year-old male patient was diagnosed with squamous cell carcinoma of the lower thoracic esophagus (cT4bN1M0 IVA) and received concurrent chemoradiotherapy, followed by 2 cycles consolidate chemotherapy. During the follow-up, he was diagnosed with secondary tuberculosis (TB) and accepted anti-TB treatment. During anti-TB treatment, he was diagnosed with squamous cell carcinoma of the oropharynx (cT1N0M0 I P16(-)), then he received radical radiation therapy. However, within a year, the patient was diagnosed with oral squamous cell carcinoma (cT3N0M0 IIIA). He accepted an individualized chemotherapy with paclitaxel combined with capecitabine. Moreover, immunohistochemistry of the patient's 3 biopsies indicated positive P53 expression., Outcomes: Since the patient suffered from esophageal cancer, oropharyngeal cancer, and oral floor cancer, no tumor recurrence or metastasis was observed. And he has a good quality of life. Tuberculosis, TP53 mutation, radiotherapy, smoking, and drinking history may be risk factors for multiple primary tumors., Lessons: The treatment of multiple primary tumors combined with pulmonary tuberculosis is complicated. Individualized treatment allows patients to achieve long-term survival while also having a good quality of life. Limitations in this case: surgery may be an alternative strategy for the patient, but the patient refused surgery., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Liposuction of the face and neck is a common treatment for fat deposition. If conventional methods are used for tumescent anesthesia, patients will experience pain, affecting their surgery experience. Using general anesthesia for liposuction of the face and neck can increase the cost to the patient and cause various adverse effects., Methods: The authors selected appropriate parts of the patient's neck, angle of the mandible, and face as needle entry points, and performed nerve block in different directions. Afterward, we performed facial liposuction on these patients and evaluated their level of pain., Results: This study included a total of 20 female participants who underwent facial liposuction after a nerve block. The Visual Analog Scale score of the 20 participants was 0.55 (±0.60). There were no significant adverse reactions during the treatment process, and all patients expressed satisfaction with this treatment., Conclusions: In this article, the authors present a method of tumescent anesthesia based on facial and cervical nerve block that significantly reduces the pain associated with facial and neck liposuction, eliminating the need for general anesthesia and enhancing the patient's comfort during the procedure., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Objective: To investigate the value of intraoperative assessment of spread through air spaces (STAS) on frozen sections (FS) in peripheral small-sized lung adenocarcinoma., Background: Surgical decision-making based on FS diagnosis of STAS may be useful to prevent local control failure after sublobar resection., Methods: We conducted a multicenter prospective observational study of consecutive patients with cT1N0M0 invasive lung adenocarcinoma to evaluate the accuracy of FS for the intraoperative detection of STAS. The final pathology (FP) diagnosis of STAS was based on corresponding permanent paraffin sections., Results: This study included 878 patients with cT1N0M0 invasive lung adenocarcinoma. A total of 833 cases (95%) were assessable for STAS on FS. 26.4% of the cases evaluated positive for STAS on FP, whereas 18.2% on FS. The accuracy, sensitivity, and specificity of FS diagnosis of STAS were 85.1%, 56.4%, and 95.4%, respectively, with moderate agreement (κ=0.575). Inter-observer agreement was substantial (κ=0.756) among the three pathologists. Subgroup analysis based on tumor size or consolidation-to-tumor ratio all showed moderate agreement for concordance. After rigorous reassessment of false-positive cases, the presence of artifacts may be the main cause of interpretation errors. Additionally, true positive cases showed more high-grade histological patterns and more advanced p-TNM stages than false negative cases., Conclusions: This is the largest prospective observational study to evaluate STAS on FS in patients with cT1N0M0 invasive lung adenocarcinoma. FS is highly specific with moderate agreement, but is not sensitive for STAS detection. While appropriately reporting STAS on FS may provide surgeons with valuable information for intraoperative decision-making, better approaches are needed., Competing Interests: Disclosure: The authors declare no relevant conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Uterus transplantation (UTx) is an emerging treatment for uterine factor infertility. Determining the maximum tolerable cold ischemia time is crucial for successful UTx. However, the limit for cold ischemia in the uterus is unclear. This study aimed to examine cold ischemia's effects on mouse uteri and identify the maximum cold ischemia duration that uteri can endure., Methods: We systematically assessed the tolerance of mouse uteri to extended cold ischemia, 24 h, 36 h, and 48 h, using the cervical heterotopic UTx model. Multiple indicators were used to evaluate ischemia-reperfusion injury, including reperfusion duration, macroscopic examination, oxidative stress, inflammation, and histopathology. The function of transplants was evaluated through estrous cycle monitoring and embryo transfer., Results: Mouse uteri subjected to 48 h of cold ischemia exhibited significant delays and insufficiencies in reperfusion, substantial tissue necrosis, and loss of the estrous cycle. Conversely, uteri that underwent cold ischemia within 36 h showed long survival, regular estrous cycles, and fertility., Conclusions: Our study demonstrated that mouse uteri can endure at least 36 h of cold ischemia, extending the known limits for cold ischemia and providing a pivotal reference for research on the prevention and treatment of cold ischemic injury in UTx., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Spinal cord stimulation (SCS) is an effective modality for pain treatment, yet its underlying mechanisms remain elusive. Neurokinin 1 receptor-positive (NK1R+) neurons in spinal lamina I play a pivotal role in pain transmission. To enhance our mechanistic understanding of SCS-induced analgesia, we investigated how different SCS paradigms modulate the activation of NK1R+ neurons, by developing NK1R-Cre;GCaMP6s transgenic mice and using in vivo calcium imaging of superficial NK1R+ neurons under anesthesia (1.5% isoflurane). Neurokinin 1 receptor-positive neurons in the lumbar spinal cord (L4-5) showed a greater activation by electrical test stimulation (TS, 3.0 mA, 1 Hz) at the hindpaw at 2 weeks after tibia-sparing nerve injury (SNI-t) than in naïve mice. Spinal cord stimulation was then delivered through a bipolar plate electrode placed epidurally at L1-2 level. The short-term 50-Hz high-intensity SCS (80% motor threshold [MoT], 10 minutes) induced robust and prolonged inhibition of NK1R+ neuronal responses to TS in both naïve and SNI-t mice. The 30-minute 50-Hz and 900-Hz SCS applied at moderate intensity (50% MoT) also significantly inhibited neuronal responses in SNI-t mice. However, at low intensity (20% MoT), the 30-minute 900-Hz SCS only induced persistent neuronal inhibition in naïve mice, but not in SNI-t mice. In conclusion, both 10-minute high-intensity SCS and 30-minute SCS at moderate intensity inhibit the activation of superficial NK1R+ neurons, potentially attenuating spinal nociceptive transmission. Furthermore, in vivo calcium imaging of NK1R+ neurons provides a new approach for exploring the spinal neuronal mechanisms of pain inhibition by neuromodulation pain therapies., (Copyright © 2024 International Association for the Study of Pain.)

Background: The long-term postoperative outcomes of two different orbicularis oris muscle reconstruction techniques in patients with unilateral incomplete cleft lip were compared., Methods: Forty-seven patients with unilateral incomplete cleft lip were assessed in this study, where 23 underwent a traditional method of reconstruction and 24 underwent a novel method. Preoperative measurements, postoperative results, and 3-year follow-up outcomes were measured by photographic anthropometric analysis. Five upper lip measurement indices and 8 nostril indices were included., Results: The postoperative outcomes showed that the shape of the lip and nose was more symmetric with the new surgical method compared with the conventional technique. Long-term outcomes after 3 years, although characterized by minimal changes during maxillofacial development, showed better maintenance of lip and nostril symmetry in the novel-method group., Conclusion: The novel technique seeks to balance the perinasal and perioral muscles, resulting in improved symmetry compared with the traditional reconstruction technique., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: This study aimed to investigate the timing of and indications for the Tajima reverse U incision for correcting secondary unilateral cleft nasal deformities., Methods: Non-syndromic patients with secondary cleft lip and nasal deformity who received Tajima reverse-U incision rhinoplasty were grouped by age (4-13 years, n=56;13-18 years, n=22; >18 years, n=18) and severity of deformity (mild deformity, n=7; moderate deformity=22; severity deformity=67) during 5-year follow-up. Face-Q assessment, a rating scale, and nasal symmetry measurements were employed in this study., Results: Ninety-six patients completed the FACE-Q assessment for the nose and nostril. The results showed higher satisfaction with nostril appearance 1-week after surgery (85.95±13.01) compared with pre-operation (79.72±11.89) and maintained 5-year follow-up (82.61±14.06). Significant differences were observed in five nasal parameters (nasal height ratio, one-fourth media part of nostril height ratio, nasal sill height ratio, columellar angle, and inner nostril height-to-width ratio (cleft)) for 1-week postoperatively and the corrected outcome of the Tajima technique was maintained 5 years after surgery in aged 4-13 years group. The same statistically significant changes were found in nasal sill height ratio in mild deformity group and nostril width ratio, one-fourth media part of nostril height ratio, columellar angle, and inner nostril height-to-width ratio (cleft) in moderate deformity group., Conclusion: The Tajima procedure was beneficial for preadolescent children and children with mild to moderate unilateral cleft nasal deformities., Competing Interests: Financial Disclosure Statement: There are no financial conflicts of interest to disclose., (Copyright © 2024 by the American Society of Plastic Surgeons.)

Malignant hyperthermia (MH) is a fatal hyperthermia with a high mortality, which usually occurs during induction of general anesthesia. Dantrolene sodium is a wonder drug currently used for treating malignant hyperthermia. However, preparing, storing, and maintaining dantrolene sodium are crucially expensive, thus making it financially unsatisfactory and difficult for clinicians to acquire in time. Monitoring patients' condition closely and intervening promptly when early signs of malignant hyperthermia occur can effectively prevent the condition from worsening and win over time for the arrival of dantraline sodium. This article is to report a case in which we successfully rescued a child occurring malignant hyperthermia without using dantrolene sodium., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 by Mutaz B. Habal, MD.)

Patients with intracranial hemorrhage (ICH) usually have an imbalance in the gut microbiota (GM); however, whether this is a causal correlation remains unclear. This study used summary data from an open genome-wide association study to conduct double-sample Mendelian randomization (MR) to test the causal correlation between GM and ICH. First, we used a cutoff value of P < 10E-5 to select single nucleotide polymorphisms critical for each GM. Inverse variance weighted, weighted median, and MR-PRESSO methods were used to evaluate the strength of this causal association. Finally, functional maps and annotations from genome-wide association studies were used to determine the biological functions of the genes. MR analysis revealed that Rikenellaceae RC9 gut group was significantly positively correlated with ICH risk. For every unit increase in Rikenellaceae RC9 gut group, the relative risk of ICH increased by 34.4%(P = 4.62E-04). Rhodospirillales, Terrisporobacter, Veillonellaceae, Coprococcus 3, unknown genus, Alphaproteobacteria, and Allisonella groups were negatively correlated with the risk of ICH, while Anaerofilum, Eubacteriumbrachy group, Clostridia, Howardella, and Romboutsia were negatively correlated with the risk of ICH. Nonetheless, the specific role of single nucleotide polymorphisms gene enrichment requires further investigation. This study suggests the causal effect on ICH. The discovery of >10 GMs associated with ICH could be used to prevent and treat ICH., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Bladder Urothelial Carcinoma (BLCA), a prevalent and lethal cancer, lacks understanding regarding the roles and prognostic value of cuproptosis-related lncRNAs (CRLs), a novel form of cell death induced by copper. We collected RNA-seq data, clinical information, and prognostic data for 414 BLCA samples and 19 matched controls from The Cancer Genome Atlas. Using multivariate and univariate Cox regression analyses, we identified CRLs to create a prognostic signature. Patients were then divided into low- and high-risk groups based on their risk scores. We analyzed overall survival using the Kaplan-Meier method, evaluated stromal and immune scores, and explored functional differences between these risk groups with gene set enrichment analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were also conducted to understand the links between CRLs and BLCA development. We developed a prognostic signature using 4 independent CRLs: RC3H1-IT1, SPAG5-AS1, FAM13A-AS1, and GNG12-AS1. This signature independently predicted the prognosis of BLCA patients. High-risk patients had worse outcomes, with gene set enrichment analysis revealing enrichment in tumor- and immune-related pathways in the high-risk group. Notably, high-risk patients exhibited enhanced responses to immunotherapy and conventional chemotherapy drugs like sunitinib, paclitaxel, and gemcitabine. The independent prognostic signature variables RC3H1-IT1, SPAG5-AS1, FAM13A-AS1, and GNG12-AS1 predicted the prognoses of BLCA patients and provided a basis for the study of the mechanism of CRLs in BLCA development and progression, and the guidance of clinical treatments for patients with BLCA., Competing Interests: The Cancer Genome Atlas is a public database and patients included in the database have provided informed consent for the use of their data. Users can freely download the relevant data for research purposes and publish relevant articles. As our study is based on open-source data, no ethical issues or conflicts of interest are reported. The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Introduction: Accurate and real-time monitoring of surgical blood loss is essential for ensuring intraoperative safety. However, there is currently no standard way to assess the amount of blood lost in patients during surgery. This study aims to evaluate the accuracy and precision of a new automatic intraoperative blood loss monitor, which can measure both free blood volume and blood content in sponges in real time. Methods: The monitor uses an integrated photoelectric probe to gauge hemoglobin levels in both free blood and blood taken from surgical sponges. These data, combined with initial hemoglobin levels, are processed using specific calculations to determine blood volume. We created 127 diverse free blood samples and 160 blood-containing sponge samples by using fresh pig blood and physiological saline. The monitor then measured these samples. We subsequently compared its measurements with actual values acquired through physical measurements, detecting both agreement and measurement errors. Repeated measurements were performed to calculate the coefficient of variation, thereby evaluating the monitor's precision. Results: The estimated blood loss percentage error of the monitor was 5.2% for free blood, -5.7% for small sponge, -6.3% for medium sponge, and -6.6% for large sponge. The coefficient of variation of free blood with different hemoglobin concentrations measured by the monitor was less than 10%. Bland-Altman analysis showed that the limits of agreement between the monitor and the reference method were all within the acceptable clinical range. Conclusion: The new automatic intraoperative blood loss monitor is an accurate and reliable device for monitoring both free blood and surgical sponge blood, and shows high performance under various clinical simulation conditions., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by the Shock Society.)

Rationale: Hepatic sinusoidal obstruction syndrome (HSOS), which includes hepatic stasis and portal hypertension, is a rare vascular disorder of the liver. It is often associated with hematopoietic stem cell transplantation. It is also possible to treat this disease using Chinese herbal medicines that contain pyrrolizidine alkaloids (PAs). This disease is extremely rare in children and poses a serious threat to their health. To our knowledge, this is the first case of HSOS in a child with PAs., Patient Concerns: We report a 4-year-old boy suffering from abdominal pain, hepatomegaly, massive ascites, elevated liver enzyme level, and severe portal hypertension as a result of the consumption of Gynura segetum (also known as Tusanqi in Chinese, a traditional herbal medicine containing PAs)., Diagnoses: The child was finally diagnosed with PA-HSOS based on pathological diagnosis and imaging examination., Intervention: With active symptomatic and supportive care and sequential anticoagulation therapy, the abdominal distension and liver function improved in the patient., Outcomes: The patient was eventually recovered. The levels of liver enzymes, hemoglobin, and bilirubin were normal, and the international normalized ratio fluctuated between 2.0 and 3.0 during 1-year follow-up after discharge., Lessons: This case report emphasizes the prevention of Chinese herb-induced liver injury in children and the importance of active long-term sequential anticoagulant therapy to reduce the progressive damage of PA-HSOS in the liver., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study aims to investigate the relationship between benign thyroid disease and breast cancer. The clinical study includes a total of 600 participants, divided into 2 groups: the control group (N = 300), which consists of individuals from the checkup population during the same periods, and the experimental group (N = 300), which consists of patients with breast cancer. General data of the participants, including age, tumor diameter, tumor staging, pathological classification, lymph node metastasis, and classification of benign thyroid disease, were collected and analyzed. The levels of TT3, TT4, FT3, FT4, TSH, TPOAb, and TgAb in blood samples from the experimental and control groups were determined using a radioimmune method. The levels of TPOAb, TgAb, and TSH in the experimental group were significantly higher than those in the control group, while the levels of TT3, TT4, FT3, and FT4 in the experimental group were significantly lower. The general data of the participants contributed to the appropriate sample size and allocation. Furthermore, benign thyroid disease contributes to the development of breast cancer by regulating the levels of TT3, TT4, FT3, FT4, TSH, TPOAb, and TgAb., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Phenylephrine may cause a reduction in maternal cerebral tissue oxygen saturation (SctO2) during Caesarean birth to prevent spinal hypotension; however, the effect of norepinephrine has not been assessed. We hypothesized that norepinephrine was more effective than phenylephrine in maintaining SctO2 when preventing spinal hypotension during Caesarean birth., Methods: We conducted a randomized, double-blind, controlled study. Sixty patients were randomly assigned to prophylactic norepinephrine or phenylephrine to maintain blood pressure during spinal anesthesia for Caesarean birth. SctO2, systolic blood pressure, and heart rate were recorded. The primary outcome was the incidence of a 10% reduction of intraoperative SctO2 from baseline or more during Caesarean birth., Results: The norepinephrine group had a lower incidence of more than 10% reduction of intraoperative SctO2 from baseline than that of the phenylephrine group (13.3% vs 40.0%, P = .02). The change in SctO2 after 5 minutes of norepinephrine infusion was higher than that after phenylephrine infusion (-3.4 ± 4.7 vs -6.2 ± 5.6, P = .04). The change in SctO2 after 10 minutes of norepinephrine infusion was higher than that after phenylephrine infusion (-2.5 ± 4.4 vs -5.4 ± 4.6, P = .006). The norepinephrine group showed greater left- and right-SctO2 values than the phenylephrine group at 5 to 10 minutes. However, the change in systolic blood pressure was comparable between the 2 groups., Conclusion: Norepinephrine was more effective than phenylephrine in maintaining SctO2 when preventing spinal hypotension during Caesarean birth. However, the changes in clinical outcomes caused by differences in SctO2 between the 2 medications warrant further studies., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Age-related hearing loss (ARHL), also known as presbycusis, is a debilitating sensory impairment that affects the elderly population. There is currently no ideal treatment for ARHL. Long-term caffeine intake was reported to have anti-aging effects in many diseases. This study is to identify whether caffeine could ameliorate ARHL in mice and analyze its mechanism., Methods: Caffeine was administered in drinking water to C57BL/6J mice from the age of 3 months to 12 months. The body weight, food intake and water intake of the mice were monitored during the experiment. The metabolic indicators of serum were detected by ELISA. The function of the hearing system was evaluated by ABR and hematoxylin and eosin staining of the cochlea. Genes' expression were detected by Q-PCR, immunofluorescencee and Western blot., Results: The results showed that the ARHL mice exhibited impaired hearing and cochlear tissue compared with the young mice. However, the caffeine-treated ARHL mice showed improved hearing and cochlear tissue morphology. The expression of inflammation-related genes, such as TLR4, Myd88, NF-κB, and IL-1β, was significantly increased in the cochleae of ARHL mice compared with young mice but was down-regulated in the caffeine-treated cochleae., Conclusions: Inflammation is involved in ARHL of mice, and long-term caffeine supplementation could ameliorate ARHL through the down-regulation of the TLR4/NF-κB inflammation pathway. Our findings provide a new idea for preventing ARHL and suggest new drug targets for ARHL treatment., Competing Interests: The authors disclose no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of Otology & Neurotology, Inc.)

The present study was conducted to characterize the clinicopathologic characteristics, immunohistochemical staining results, and immune checkpoint inhibitors (ICIs) efficacy in patients with SMARCA4-deficient/TP53 mutant lung cancer. Patients diagnosed with advanced or metastatic undifferentiated lung cancer harboring SMARCA4-deficient and TP53 mutations, however, without targetable sensitive mutations were retrieved from the electronic medical record system. Descriptive statistics were used to describe the baseline characteristics and clinical features including age, gender, eastern cooperative oncology group performance status, disease stage, smoking status, chief complaint, site of the primary mass, tumor size, gross type, symptoms, local invasion, and metastatic sizes. Immunological markers and potential drive genes were detected by immunohistochemical staining and next generation sequencing. Efficacy and safety profile of ICIs in included patients was evaluated with progression-free survival and overall survival. Between January 2019 and September 2022, there were 4 patients included within the inclusion criteria in the present study. Biomarkers including CK, CK7, and integrase interactor 1 were detected positive, however, other immunological markers including CK20, CD56, P63, P40, NapsinA, TTF-1, CgA, Syn, BRG1, or PD-L1 were detected negative among them. Results of next generation sequencing panel were failed to discover any targetable sensitive mutations. A total of 4 mutation types of TP53, including p.C141Y, p.S240G, p.E339X (terminator acquired), and p.L130F detected for the patients, respectively. Microsatellite stability status, as well as low tumor mutation burden was identified among all the patients. Median progression-free survival for ICIs as first line treatment and median overall survival were 3.25 months (range from 1.3 to 6.8 months), and 6.0 months (range from 2.7 to 9.6 months), respectively. Our results indicated that advanced lung cancer patients harboring co-occurring SMARCA4-deficient/TP53 mutations might respond to ICIs treatment, though within negative programmed cell death-ligand 1 expression or low tumor mutation burden. However, hyperprogressive disease by ICIs may also happen for such patients. The mutation types of TP53 might play a role during the exposure of ICIs, however, need further identification in basic experiments., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: The purpose of this study was to describe a method to achieve a high success rate for nanothin (NT, ≤50 μm) Descemet stripping automated endothelial keratoplasty (DSAEK) graft preparation using anterior chamber pressurizer (ACP) with a modified setting and evaluate its postoperative efficacy., Methods: A prospective cohort (study group) of 24 patients with corneal endothelial dysfunction was consecutively enrolled and received DSAEK grafts using the modified ACP method from December 2021 to May 2022. The control group included 24 historical patients who received DSAEK grafts using conventional ACP procedure. Central graft thickness (CGT), graft regularity (3-mm and 5-mm diameter zones), best spectacle-corrected visual acuity, and endothelial cell density (ECD) were compared between 2 groups., Results: A 100% ultrathin (UT, ≤100 μm) DSAEK rate and 62.5% NT-DSAEK rate was achieved at 3 months postsurgery in the study group, with a 51.3 ± 14.8 μm CGT, while a 70.8% UT-DSAEK rate and 4.2% NT-DSAEK rate was achieved in the control group, with an 89.0 ± 15.4 μm CGT (P <0.001). At 3-month postoperative follow-up, the regularity of graft thickness was significantly better in the study group (central-to-peripheral thickness difference: P = 0.044 and 0.014 for 3-mm and 5-mm diameter zones, respectively, graft thickness uniformity: P <0.001 and 0.012, respectively). There was no statistical difference in the best spectacle-corrected visual acuity (P = 0.170) or ECD (P = 0.833) between 2 groups at 3-month postoperative follow-up., Conclusions: DSAEK grafts harvested using modified ACP method were thinner and more regular compared with the conventional ACP method., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

While Salvia chinensis Benth (commonly known as "Shijianchuan" in Chinese, and abbreviated as SJC) is commonly used in adjuvant therapy for colorectal cancer (CRC) in traditional Chinese medicine, its mechanism of action remains unclear. In this study, Initially, we examined the impact of SJC on CRC cells in an in vitro setting. Next, we initially retrieved the primary active components and targets of SJC from databases such as TCMSP and existing literature. Subsequently, we integrated differential gene expression data from the GEO database and collected CRC-related targets from resources like DisGeNET. The matching of these datasets enabled the identification of SJC-CRC targets. We constructed a protein-protein interaction network and identified core targets through topological analysis. GO and KEGG enrichment analyses were performed using clusterProfiler. We established networks linking traditional Chinese medicine components to targets and core targets to signaling pathways. Additionally, we performed molecular docking to validate interactions between the main compounds and targets, and employed Western blot analysis to explore how the major components of SJC affect crucial signaling pathways. In this study, SJC inhibited the viability of HCT-116 and HT-29 cells. We identified a total of 11 active components in SJC along with 317 target genes. Among these, there were 8612 target genes associated with CRC, and we successfully matched 276 SJC-CRC target genes. Through topological analysis of the protein-protein interaction network, we pinpointed 20 core targets. It was revealed that SJC effects are linked to genes governing processes like cell apoptosis, proliferation, hypoxia, oxidative stress, and signaling pathways such as PI3K-Akt through GO and KEGG pathway enrichment analyses. Additionally, we applied molecular docking techniques and observed that the majority of active compounds displayed robust binding affinity with the selected targets. In vitro experiments suggested that SJC and its key component, Ursolic acid, may exert its anti-CRC effects by modulating the core PI3K/AKT signaling pathway through inhibiting the phosphorylation of the target Akt1. This discovery is consistent with the predictions derived from network pharmacology methods. This study marks the inaugural utilization of bioinformatics methods in conjunction with in vitro experiments to comprehensively investigate the pharmacological and molecular mechanisms responsible for SJC anti-CRC effects., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Submucous cleft palate (SMCP) is a particular subtype of cleft deformity for which the optimal surgical timing and technique are still under debate. This study aimed to identify potential prognostic factors for the speech outcome of patients with SMCP and provide evidence for further management strategy optimization., Methods: The authors reviewed patients with nonsyndromic SMCP who received either Furlow palatoplasty (FP) or posterior pharyngeal flap (PPF) between 2008 and 2021 in a tertiary hospital-based cleft center. Both univariate and multivariate logistic regression models were used to screen preoperative variables, including cleft type (overt or occult), age at surgery, mobility of velum and pharyngeal wall, velopharyngeal closure ratio, and pattern. The receiver operating characteristic curve was used to determine the cutoff value of the significant predictors for subgroup comparison., Results: A total of 131 patients were enrolled, with 92 receiving FP and 39 receiving PPF. Age at operation and cleft type were identified as having significant effects on FP outcome. Patients operated on before 9.5 years of age had a significantly higher velopharyngeal competence (VPC) rate than those operated on after that age. The speech outcome among patients with occult SMCP was significantly worse than that of patients with overt SMCP after FP treatment. No preoperative variable was found to be correlated with PPF outcome. PPF yielded a higher VPC rate than did FP among patients operated on after 9.5 years of age., Conclusions: The prognosis of patients with SMCP treated with FP is sensitive to age at surgery and cleft type. PPF may be considered for older patients in settings with limited access to multiple surgical procedures, especially when occult SMCP is diagnosed., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Background: In developmental and pathological tissues, nascent vessel networks generated by angiogenesis require further pruning/regression to delete nonfunctional endothelial cells (ECs) by apoptosis and migration. Mechanisms underlying EC apoptosis during vessel pruning remain elusive. TMEM215 (transmembrane protein 215) is an endoplasmic reticulum-located, 2-pass transmembrane protein. We have previously demonstrated that TMEM215 knockdown in ECs leads to cell death, but its physiological function and mechanism are unclear., Methods: We characterized the role and mechanism of TMEM215 in EC apoptosis using human umbilical vein endothelial cells by identifying its interacting proteins with immunoprecipitation-mass spectrometry. The physiological function of TMEM215 in ECs was assessed by establishing a conditional knockout mouse strain. The role of TMEM215 in pathological angiogenesis was evaluated by tumor and choroidal neovascularization models. We also tried to evaluate its translational value by delivering a Tmem215 small interfering RNA (siRNA) using nanoparticles in vivo., Results: TMEM215 knockdown in ECs induced apoptotic cell death. We identified the chaperone BiP as a binding partner of TMEM215, and TMEM215 forms a complex with and facilitates the interaction of BiP (binding immunoglobin protein) with the BH (BCL-2 [B-cell lymphoma 2] homology) 3-only proapoptotic protein BIK (BCL-2 interacting killer). TMEM215 knockdown triggered apoptosis in a BIK-dependent way and was abrogated by BCL-2. Notably, TMEM215 knockdown increased the number and diminished the distance of mitochondria-associated endoplasmic reticulum membranes and increased mitochondrial calcium influx. Inhibiting mitochondrial calcium influx by blocking the IP 3 R (inositol 1,4,5-trisphosphate receptor) or MCU (mitochondrial calcium uniporter) abrogated TMEM215 knockdown-induced apoptosis. TMEM215 expression in ECs was induced by physiological laminar shear stress via EZH2 downregulation. In EC-specific Tmem215 knockout mice, induced Tmem215 depletion impaired the regression of retinal vasculature characterized by reduced vessel density, increased empty basement membrane sleeves, and increased EC apoptosis. Moreover, EC-specific Tmem215 ablation inhibited tumor growth with disrupted vasculature. However, Tmem215 ablation in adult mice attenuated lung metastasis, consistent with reduced Vcam1 expression. Administration of nanoparticles carrying Tmem215 siRNA also inhibited tumor growth and choroidal neovascularization injury., Conclusions: TMEM215 , which is induced by blood flow-derived shear stress via downregulating EZH2 , protects ECs from BIK-triggered mitochondrial apoptosis mediated by calcium influx through mitochondria-associated ER membranes during vessel pruning, thus providing a novel target for antiangiogenic therapy., Competing Interests: Disclosures None.

During the course of treating non-small cell lung cancer (NSCLC) with epithelial growth factor receptor (EGFR) mutant, gefitinib resistance (GR) is unavoidable. As the environment for tumor cells to grow and survive, tumor microenvironment (TME) can significantly affect therapeutic response and clinical outcomes, offering new opportunities for addressing GR. Dynamic changes within the TME were identified during the treatment of gefitinib, suggesting the close relationship between TME and GR. Various dynamic processes like angiogenesis, hypoxia-pathway activation, and immune evasion can be blocked so as to synergistically enhance the therapeutic effects of gefitinib or reverse GR. Besides, cellular components like macrophages can be reprogrammed for the same purpose. In this review, we summarized recently proposed therapeutic targets to provide an overview of the potential roles of TME in treating gefitinib-resistant NSCLC, and discussed the difficulty of applying these targets in cancer treatment., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Hyaluronic acid is a commonly used soft tissue filler. However, it has been associated with numerous complications including skin necrosis, loss of vision, and cerebral infarction. In this article, the authors have reported the case of a 25-year-old woman who presented with significant dizziness and pain in the temporal and intrahairline region after undergoing hyaluronic acid augmentation of the temple and inner temporal hairline regions. Subsequently, the patient received 4 doses of a hyaluronidase injection to dissolve the emboli. She demonstrated improvement in clinical symptoms after emboli dissolution. During the 10-month posttreatment follow-up, the patient experienced gradual relief from pain and dizziness. The use of hyaluronic acid fillers should be limited in the intrahairline region as the resulting complications can be difficult to manage., Competing Interests: The authors report no conflicts of interest., (Copyright © 2023 by Mutaz B. Habal, MD.)

Breast cancer (BRCA) is a highly heterogeneous malignancy with an urgent need to build a proper model to predict its prognosis. Cuproptosis is a recently discovered form of cell death, mediated by protein fatty acylation and tightly associated with mitochondrial metabolism. The role of cuproptosis-related genes (CRGs) in BRCA remains to be explored. We aimed to investigate the applications of CRGs in BRCA prognosis in different clinical contexts, including chemotherapy and immunotherapy, via bioinformatics analysis of the messenger RNA profiles and clinical data obtained from public databases. Molecular subtyping of CRGs was performed through consistent clustering analysis. Differentially expressed genes between different CRG clusters were identified. The differentially expressed genes were then used to build a risk assessment model using least absolute shrinkage and selection operator regression to predict patient survival with BRCA. The model was then validated with the data from the Molecular Taxonomy of Breast Cancer International Consortium, GSE96058, and GSE20685. Differences in somatic mutations, copy number variations, hallmark pathways, drug responses, and prognosis of immunotherapy and chemotherapy were analyzed by comparing the high-risk and low-risk groups. Patients with high-risk scores showed worse overall survival than those with low-risk scores. The results indicated significant differences between the 2 groups immune-related biological pathways and the variable immune status. It also suggests the differential sensitivity to chemotherapy between the 2 groups. The CRGs model showed the promise to predict the prognosis of BRCA patients and shed light on their treatment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: The association between depression and sarcopenia has been reported in observational studies but the causality of depression on sarcopenia remained unknown. We aimed to assess the causal effect between major depressive disorder (MDD) and sarcopenia using the two-sample Mendelian randomization (MR) method., Methods: A set of genetics instruments were used for analysis, derived from publicly available genetic summary data. Clinically, appendicular lean mass (ALM) and low hand grip strength (LHGS) have been widely used for the diagnosis of sarcopenia. Inverse-variance weighted method, weighted median method, MR-Egger, MR Pleiotropy RESidual Sum and Outlier test were used for the bidirectional MR analyses., Results: No evidence for an effect of MDD on sarcopenia risk was found. MDD was not associated with ALM [effect = -0.17 (-0.60 to 0.27), P = 0.449] and LHGS [effect = 0.24 (-0.46 to 0.93), P = 0.506]. Sarcopenia was not associated with MDD [ALM: odds ratio (OR) = 0.999 (0.996-1.001), P = 0.374; LHGS: OR = 0.999 (0.996-1.002), P = 0.556]., Conclusion: MDD and Sarcopenia might mutually have no causal effect on each other., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: A modified palatoplasty was established by incorporating the designs of both Sommerlad and Furlow techniques in addition to a novel incision on the medial pterygoid plate's surface, named the Sommerlad-Furlow modified technique. Thus, this study aimed to evaluate the clinical and functional outcomes of the Sommerlad-Furlow modified technique against an accepted standard, the Furlow technique., Methods: A retrospective review was conducted for 212 consecutive nonsyndromic cleft palate patients who underwent Sommerlad-Furlow ( n = 106) and Furlow ( n = 106) repairs without relaxing incision on the hard palate between 2011 and 2016. The success of surgical procedures was estimated by the rate of postoperative fistula, speech outcomes, and velopharyngeal insufficiency (VPI)-related quality of life. The demographic and surgical data, including sex, age, cleft type, cleft width, and follow-up period were recorded., Results: There was no statistically significant difference between the two treatment groups regarding demographic and surgical data, except the cleft width ( P < 0.001). The incidence of the fistula was 7.5% and 6.6% after the Sommerlad-Furlow and Furlow procedures, respectively. The two groups showed no significant differences in speech outcomes, and adequate velopharyngeal function was found in 84% and 82.1% in Sommerlad-Furlow and Furlow procedures, respectively. Besides, the rate of severe VPI was slightly lower in Sommerlad-Furlow (0.9%) than in Furlow (2.8%) procedures. Moreover, an adequate VPI-related quality of life was found in 80.4% of the Sommerlad-Furlow group and 78.6% of the Furlow group., Conclusion: The Sommerlad-Furlow technique has obtained acceptable postoperative outcomes and could be a choice for cleft palate repair, especially in wider clefts., Clinical Question/level of Evidence: Therapeutic, III., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Obesity is associated with cervicalgia and low back pain (LBP), but the specific role and how to reduce the risk of neck pain and low back pain are not clear. The Mendelian randomization analysis was used to investigate the causal relationship between obesity and cervicalgia and LBP, as well as the effect of possible mediating factors. Then, causal associations were estimated using sensitivity analysis. Educational level (odds ratio (OR) = 0.30, 0.23) was negatively associated with cervicalgia and LBP; Heavy physical work (HPW) (OR = 3.24, 2.18), major depression (MD) (OR = 1.47, 1.32), body mass index (BMI) (OR = 1.36, 1.32), and waist circumference (WC) (OR = 1.32, 1.35) were positively associated with cervicalgia and LBP; Leisure sedentary behavior (LSB) (OR = 1.96), smoking (OR = 1.32), and alcohol intake frequency (OR = 1.34) were positively associated only with LBP, but not with cervicalgia. Ranked by mediated proportions of selected mediators, the largest causal mediator from BMI and WC to cervicalgia was educational level (38.20%, 38.20%), followed by HPW (22.90%, 24.70%), and MD (9.20%, 17.90%); However, the largest causal mediator from BMI and WC to LBP was LSB (55.10%, 50.10%), followed by educational level (46.40%, 40.20%), HPW (28.30%, 20.90%), smoking initiation (26.60%, 32.30%), alcohol intake frequency (20.40%, 6.90%), and MD (10.00%, 11.40%). For obese individuals, avoiding HPW and maintaining a stable mood may be an effective approach to prevent cervicalgia; Additionally, reducing LSB, avoiding HPW, quitting smoking and drinking, and maintaining a stable mood may be an effective approach to prevent LBP., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Rationale: Anti- N -methyl- d -aspartate receptor (NMDAR) encephalitis is a rare disease of nervous system, which is mediated by autoimmune mechanisms. The treatment of anti-NMDAR encephalitis includes Immunotherapy, symptomatic and supportive treatment for seizures and psychiatric symptoms. There are many kinds of drugs, so drug treatment management and pharmaceutical care for children are particularly important. At present, there are few reports on pharmaceutical care for children with this disease. Clinical pharmacists participated in the pharmaceutical care of a child with refractory anti-NMDAR encephalitis treated with rituximab, conducted drug treatment management on the dosage, administration method, complications and other aspects of off-label use of rituximab, combined with the children's clinical manifestations, inflammatory indicators, pathogenic detection, blood concentration, liver and kidney functions, drug interactions and other factors. The treatment plan of anti-infective drugs shall be adjusted, and attention shall be paid to whether there are adverse reactions during the treatment., Patient Concerns: A 4-year-old girl presented with epileptic seizure, intermittent recurrent fever, high inflammatory markers, abnormal psychiatric function/cognitive impairment, language disorder, consciousness disturbance, and movement disorder/involuntary movement., Diagnosis: Refractory anti-NMDAR encephalitis., Interventions: The patient was given first-line (3 rounds of methylprednisolone pulse therapy and gamma globulin) and second-line (rituximab) immunotherapy. On the advice of a clinical pharmacist, the patient wasn't given Advanced antibacterial agents (voriconazole, vancomycin) therapy. On the 41st day of admission, the patient's temperature and inflammatory indicators were normal, CD19 + B cells were reduced to 0., Outcomes: The patient consciousness level, cognition and orientation were gradually improved, mental disorder was improved, involuntary movement was obviously controlled, no seizure occurred again, and the patient was discharged with stable condition., Lessons: Clinical pharmacists ensure the safety, effectiveness and economy of patients' medication by carrying out the whole process of individualized drug treatment management and care for patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Norepinephrine is effective in preventing spinal hypotension during cesarean birth; however, an optimal regimen has not been determined. We hypothesized that an initial bolus of norepinephrine improves efficacy of spinal hypotension prophylaxis beyond continuous norepinephrine alone., Methods: In this double-blind, controlled study, 120 patients scheduled for cesarean birth under spinal anesthesia were randomly allocated to receive a norepinephrine bolus at 0.05 or 0.10 μg/kg, followed by norepinephrine infusion at a rate of 0.05 μg·kg -1 ·min -1 . The primary outcome was the frequency of spinal hypotension during cesarean birth. The doses of the rescue drug (phenylephrine), frequency of nausea or vomiting, duration of hypotension, frequency of intraoperative hypertension, frequency of bradycardia, and fetal outcomes were also compared., Results: One-hundred-fifteen patients were included in the analysis. Compared with the 0.05 μg/kg group, the frequency of spinal hypotension was lower in the 0.10 μg/kg group (20.7% vs 45.6%; odds ratio [OR], 0.31; 95% confidence interval (CI), 0.14-0.71; P = .004). Fewer rescue doses of phenylephrine (0 [0,0] vs 0 [0,80]; 95% CI for the difference, 0 (0-0); P = .006) were required, and the frequency of nausea or vomiting was lower (5.2% vs 17.5%; OR, 0.26; 95% CI, 0.07-0.99; P = .04) in the 0.10 μg/kg group. The duration of hypotension was shorter in the 0.10 μg/kg group than that in the 0.05 μg/kg group (0 [0,0] vs 0 [0,2]; 95% CI for the difference, 0 [0-0]; P = .006). The incidence of intraoperative hypertension, frequency of bradycardia, and fetal outcomes were comparable between the 2 groups., Conclusions: With a fixed-rate norepinephrine infusion of 0.05 μg·kg -1 ·min -1 , the 0.10 μg/kg initial bolus was more effective in reducing the incidence of spinal hypotension compared with the 0.05 μg/kg initial bolus., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 International Anesthesia Research Society.)

Significance: This study investigated the potential perinatal risk factors associated with infantile esotropia in a Chinese population, including advanced parental age at childbirth and mode of delivery. The findings may be significant in developing better intervention strategies for infantile esotropia., Purpose: This study aimed to investigate the associations between gestational age, birth weight, parental age at childbirth, mode of delivery, family history of strabismus, and infantile esotropia in the Chinese population., Methods: Ninety-nine patients with infantile esotropia and 117 control subjects were enrolled between March 2018 and March 2021. Detailed questionnaires were administered to parents to collect relevant information. Univariate and multivariate logistic regression models were used to identify possible risk factors of infantile esotropia. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated., Results: Infantile esotropia was associated with low birth weight (<2500 g; OR, 4.235; 95% CI, 1.460 to 12.287; P = .008) and emergency cesarean delivery (OR, 2.230; 95% CI, 1.127 to 4.413; P = .02)., Conclusions: The findings suggest that low birth weight and emergency cesarean deliveries are risk factors for infantile esotropia, highlighting a need for collaborative care between obstetricians, pediatricians, and vision care providers., Competing Interests: Conflict of Interest Disclosure: The authors declare no conflict of interest., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Optometry.)

To investigate the effectiveness of metformin and atorvastatin in preventing in-stent restenosis (ISR) on coronary patients with type 2 diabetes mellitus with percutaneous coronary intervention within 8 to 12 months after rapamycin-eluting stent implantation. A total of 1278 consecutive patients implanted with rapamycin-eluting stent from January 2012 to December 2019, who underwent coronary computed tomography or coronary angiography within 8 to 12 months. The patients were categorized into atorvastatin 20 mg, or atorvastatin 20 mg + metformin 1.5/d, or atorvastatin 40 mg + metformin 1.5/d groups. The clinical characteristics of the 3 groups were compared. The correlation between variables and ISR was analyzed. A total of 701 patients participated in the study. The ratio of ISR/nonstenosis (P = .039) and fasting blood sugar (P = .001) differed significantly in the 3 groups. Logistic regression showed that d, L, different therapeutic agents, and dosage groups were independent risk factors of ISR. The longer L and smaller d may increase ISR incidence with 8 to 12 months after percutaneous coronary intervention. Both metformin and atorvastatin are beneficial in reducing stent restenosis by a dose-dependent manner. An increasing dose of atorvastatin and a combination of metformin decreases the incidence of ISR in patients., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: This study aimed to evaluate the application of oxycodone in anesthesia induction and overall management of Da Vinci robot-assisted nephrectomy., Methods: A total of 42 patients undergoing Da Vinci robot-assisted nephrectomy with general anesthesia were selected. They were randomly divided into 2 groups: patients were induced with oxycodone (oxycodone group) and were induced with sufentanil (sufentanil group). The vital signs at the following time points were recorded: after injection of induced drugs (T1), during glottis exposure (T2), immediately after intubation (T3), 1 minute (T4), 2 minute (T5), 3 minute (T6), 5 minute (T7), 10 minute (T8) after intubation, during skin incision (T9), at the end of suturing skin (T10), during extubation (T11), and during hemodynamic fluctuations intraoperatively (T`). Numerical rating scale, facial affective scale and monitoring of adverse events (visual analogue scale, NVAS) were evaluated postoperatively at 1 hour (T'"1), 3 hours (T""2), 6 hours (T""3), 12 hours (T""4), 24 hours (T""5), and 48 hours (T"'6)., Results: The systolic blood pressure, the diastolic blood pressure and the mean arterial blood pressure showed no statistically different changes between the 2 groups. There were no statistical differences in heart rate and respiratory rate among various timepoints intraoperatively. There were statistical differences in Bispectral index (BIS) scores in T6 between the 2 groups. The numerical rating scale and facial affective scale scores were significantly lower in oxycodone group. Anesthetized with oxycodone, the pain did not affect the sleep of patients after operation. Also, the postoperative QoR-40 scores were lower in oxycodone group., Conclusion: Compared with sufentanil, anesthesia induction with 0.3 mg/kg oxycodone in Da Vinci robot-assisted nephrectomy can achieve mild pain and mild adverse responses in patients postoperatively., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Monocyte chemoattractant protein-1 (MCP-1) rs1024611 (-2518 A > G) polymorphism are associated with inflammatory diseases. In this study, we investigate the relationship between MCP-1 rs1024611 polymorphism and genetic susceptibility of type 2 diabetes mellitus (T2DM) with sepsis. Two hundred eighty-five patients with T2DM are divided into the diabetes with sepsis group (combined group, 113 cases) and the diabetes group (172 cases). Blood samples and corresponding clinical data were collected. MCP-1 rs1024611 polymorphism in blood samples was detected by pyrosequencing. Meanwhile, the expressions of MCP-1, tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-6 in blood samples were detected by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay, respectively. The relationship between different genotypes of MCP-1 rs1024611 polymorphic locus and T2DM with sepsis was analyzed by combining with the clinical data of the patients. The frequencies of rs1024611 AG/GG genotypes and G allele in T2DM with sepsis group were significantly higher than those in T2DM patients without sepsis (P = .004 for AG/GG vs AA genotypes; P = .037 for G allele vs A allele). Subgroup analysis showed that the rs1024611 G allele frequency in the septic shock group was significantly higher than the general sepsis group (P = .02). The expressions of MCP-1 and TNF-α in GG genotypes in T2DM with sepsis group were significantly higher than AA or GA genotypes (P < .05). This study preliminarily showed that the rs1024611 A > G polymorphism within the promoter region of MCP-1 gene can upregulate the expression of MCP-1 gene and proinflammatory cytokine TNF-α, which ultimately contributed to the predisposition and progression of T2DM with sepsis., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aim: To quantitatively evaluate the relationship between nasal appearance and nasal septum deviation in unilateral complete cleft patients using cone-beam computed tomography.Method: Cone-beam computed tomography images of 180 patients with unilateral cleft lip/palate from June 2014 to June 2017 were used in the study. None of the subjects had undergone septoplasty. The data were compared between the 2 groups to elucidate the relationship between nasal appearance and deviated nasal septum in unilateral complete cleft patients., Results: The mean age of a total of 180 patients (126 males and 54 females) was 14.58 years, with a standard deviation of 7.10 years, ranged from 6 years old to 49 years old. Columella nasi symmetry parameters show slight positive significant association with angle of nasal septal deviation on transerve plan (r = 0.250, P < 0.001), TRSD (r = 0.323, P < 0.001) and coronal range of nasal septal deviation (r = 0.294, P < 0.001), and moderate positive significant association with coronal angle about septal deviation (r = 0.404, P < 0.001)., Conclusions: Columella nasi symmetry affected by septal deviation, whereas there is lack of evidence to say symmetry of nasal tip and base affected by septal deviation. The symmetry of nasal tip and alar base are not just determined by nasal septum deviation. The nasal septum deviation show difference in different cleft type., Competing Interests: The authors report no conflicts of interest., (Copyright © 2021 by Mutaz B. Habal, MD.)

Rationale: Viruses are the most common pathogens that can cause infection-related non-recurrent death after transplantation, occurring mostly from the early stages of hematopoietic stem cell transplantation (HSCT) to within 1 year after transplantation. Human coronavirus (HCoV)-NL63 is a coronavirus that could cause mortality among patients with underlying disease complications. Serological tests are of limited diagnostic value in immunocompromised hosts and cases of latent infection reactivation. In contrast, macro-genomic high-throughput (DNA and RNA) sequencing allows for rapid and accurate diagnosis of infecting pathogens for targeted treatment., Patient Concerns: In this report, we describe a patient who exhibited acute B-lymphocytic leukemia and developed complicated pulmonary HCoV-NL63 infection after a second allogeneic HSCT (allo-HSCT). Six months after the second allo-HSCT, he developed sudden-onset hyperthermia and cough with decreased oxygen saturation. Chest computed tomography (CT) suggested bilateral multiple rounded ground-glass opacities with the pulmonary lobules as units., Diagnoses: HCoV-NL63 was detected by metagenomic next-generation sequencing (NGS), and HCoV-NL63 viral pneumonia was diagnosed., Interventions: The treatment was mainly based on the use of antiviral therapy, hormone administration, and gamma-globulin., Outcomes: After the therapy, the body temperature returned to normal, the chest CT findings had improved on review, and the viral copy number eventually became negative., Lessons: The latest NGS is an effective method for early infection diagnosis. The HCoV-NL63 virus can cause inflammatory factor storm and alter the neutrophil-to-lymphocyte ratio (NLR). This case suggests that the patient's NLR and cytokine levels could be monitored during the clinical treatment to assess the disease and its treatment outcome in a timely manner., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: : Lumbar disc herniation (LDH) is a common disease in orthopedics. Surgery is shown to provide significant faster relief of pain compared to conservative therapy. However, due to the influence of surgical trauma, anesthesia and other perioperative stress factors, patients may have complications. Among them, postoperative fatigue syndrome (POFS) is a common complication. Traditional Chinese medicine or integrated traditional Chinese and Western medicine have been proved to be effective in improving postoperative fatigue., Methods: : This study is a randomized controlled trial. One hundred eighty Chinese patients with POFS of LDH will be randomly divided into control group, experimental group 1, experimental group 2 and experimental group 3 according to the ratio of 1:1:1:1. The patients in the control group will be treated with conventional treatment after operation, the patients in the experimental group 1 will be treated with acupoint massage, the patients in the experimental group 2 will be treated with relaxation therapy, and the patients in the experimental group 3 will be treated with acupoint massage combined with relaxation therapy. The whole treatment will last for 5 days. The main outcome measures will be fatigue visual analogue scale and identity-consequence fatigue scale, and the secondary outcome measures will be hospital anxiety and depression scale., Discussion: : This study is to observe the effects of acupoint massage comblined with relaxation therapy on reducing postoperative fatigue of lumbar disc herniation surgical patients., Trial Registration: : Chinese Clinical Trial Registry (http://www.chictr.org.cn/edit.aspx?pid=123978&htm=4), No. ChiCTR2100044788. Registered on March 27, 2021., Competing Interests: The authors have no conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: The systemic immune-inflammation index (SII) is an independent prognostic predictor of hepatocellular carcinoma (HCC). The present investigation examined whether an association exists between preoperative SII value and postoperative acute kidney injury (pAKI) in HCC patients.The study included 479 hepatitis B virus (HBV)-associated HCC patients undergoing hepatectomy. The SII was calculated as P × N/L, where P, N, and L represent the counts of platelets, neutrophils, and lymphocytes in routine blood test, respectively. After propensity score matching, logistic regression analysis was used to explore independent predictors of pAKI in HCC patients.pAKI was confirmed in 51 patients (10.8%). The average SII value was higher in patients with pAKI than patients without pAKI. After multivariate logistic regression analysis, SII, history of hypertension, and tumor size, among others, were found to be predictors of pAKI. The optimal threshold value of SII for predicting pAKI was found to be 547.84 × 109/L. Multivariate analysis performed after propensity score matching confirmed that SII ≥ 547.84 × 109/L was an independent predictor of pAKI.The preoperative SII qualifies as a novel, independent predictor of pAKI in HCC patients with HBV infection who underwent hepatectomy., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: Mechanisms of visceral pain sensitization and referred somatic hypersensitivity remain unclear. We conducted calcium imaging in Pirt-GCaMP6s mice to gauge responses of dorsal root ganglion (DRG) neurons to visceral and somatic stimulation in vivo. Intracolonic instillation of 2,4,6-trinitrobenzene sulfonic acid (TNBS) induced colonic inflammation and increased the percentage of L6 DRG neurons that responded to colorectal distension above that of controls at day 7. Colorectal distension did not activate L4 DRG neurons. TNBS-treated mice exhibited more Evans blue extravasation than did control mice and developed mechanical hypersensitivity in low-back skin and hind paws, which are innervated by L6 and L4 DRG neurons, respectively, suggesting that colonic inflammation induced mechanical hypersensitivity in both homosegmental and heterosegmental somatic regions. Importantly, the percentage of L4 DRG neurons activated by hind paw pinch and brush stimulation and calcium responses of L6 DRG neurons to low-back brush stimulation were higher at day 7 after TNBS than those in control mice. Visceral irritation from intracolonic capsaicin instillation also increased Evans blue extravasation in hind paws and low-back skin and acutely increased the percentage of L4 DRG neurons responding to hind paw pinch and the response of L6 DRG neurons to low-back brush stimulation. These findings suggest that TNBS-induced colitis and capsaicin-induced visceral irritation may sensitize L6 DRG neurons to colorectal and somatic inputs and also increase the excitability of L4 DRG neurons that do not receive colorectal inputs. These changes may represent a potential peripheral neuronal mechanism for visceral pain sensitization and referred somatic hypersensitivity., (Copyright © 2020 International Association for the Study of Pain.)

Purpose: Apolipoprotein B mRNA editing enzyme catalytic polypeptide-like 3B (APOBEC3B) is a recently discovered protein that is considered important in causing mutations in tumor cell genome bases. Whether APOBEC3B is expressed in nasopharyngeal carcinoma (NPC) still remains unknown. Studies have shown that programmed-cell-death receptor-1 ligand (PD-L1) is highly expressed in NPC, but its clinical significance has not been fully elucidated. We aimed to evaluate APOBEC3B and PD-L1 protein expression in NPC and also investigate their prognostic significance., Materials and Methods: One hundred and three patients with NPC were retrospectively collected in this study, and were followed-up for 5 years. The expression of APOBEC3B and PD-L1/PD-1 in NPC was detected by immunohistochemical staining., Results: High expression of APOBEC3B was observed in 42.7% of NPC patients. The high expression rate of APOBEC3B was 31.5% in patients without recurrence or metastasis within 5 years, and 55.1% in those patients with recurrence or metastasis, and the difference was statistically significant (P=0.016). There was no significant difference in APOBEC3B expression among patients with different sex, age group, and clinical stage (P>0.05). The positive expression rate of PD-L1 was 55.3% in all patients with NPC. There was no significant difference in PD-L1 expression among patients with different sex, age group, clinical stage, and tumor recurrence or metastasis condition (P> 0.05). There was no significant correlation between the expression of APOBEC3B and PD-L1 in NPC patients. The positive expression rate of PD-1 was 1.9% (2/103) in patients with NPC., Conclusions: APOBEC3B showed association with aggressive behavior and poor outcome in NPC, and is also considered as a potential marker for predicting NPC recurrence or metastasis. PD-L1 is not associated with the aggressive behavior and poor outcome in NPC., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To explore the accuracy and security of 3-dimensional (3D) printing technology combined with guide plates in the preoperative planning of thoracic tuberculosis and the auxiliary placement of pedicle screws during the operation., Methods: Retrospective analysis was performed on the data of 60 cases of thoracic tuberculosis patients treated with 1-stage posterior debridement, bone graft fusion, and pedicle screw internal fixation in the Department of Orthopedics, Zhejiang Chinese Medicine and Western Medicine Integrated Hospital from March 2017 to February 2019. There were 31 males and 29 females; age: 41 to 52 years old, with an average of (46.6 ± 2.0) years old. According to whether 3D printing personalized external guide plates are used or not, they are divided into 2 groups: 30 cases in 3D printing group (observation group), and 30 cases in pedicle screw placement group (control group). A 1:1 solid model of thoracic spinal tuberculosis and personalized pedicle guide plates was created using the 3D printing technology combined with guide plates in the observation group. Stability and accuracy tests were carried out in vitro and in vivo. 30 patients in the control group used conventional nail placement with bare hands. The amount of blood loss, the number of fluoroscopy, the operation time, and the occurrence of adverse reactions related to nail placement were recorded. After the operation, the patients were scanned by computed tomography to observe the screw position and grade the screw position to evaluate the accuracy of the navigation template. All patients were followed up for more than 1 year. Visual Analogue Scale scores, erythrocyte sedimentation rate, and C-reactive protein were evaluated before surgery, 6 months after surgery, and 12 months after surgery., Results: Sixty patients were followed up for 6 to 12 months after surgery. One hundred seventy-five and 177 screws were placed in the 3D printing group and the free-hand placement group, respectively. The rate of screw penetration was only 1.14% in the 3D-printed group (all 3 screws were grade 1) and 6.78% in the free-hand nail placement group (12 screws, 9 screws were grade 1 and 3 screws were grade 2). The difference was statistically significant (P = .047). The operation time of the 3D printing group ([137.67 ± 9.39] minutes), the cumulative number of intraoperative fluoroscopy ([4.67 ± 1.03] times), and the amount of intraoperative blood loss ([599.33 ± 83.37] mL) were significantly less than those in the manual nail placement group ([170.00 ± 20.48] minutes, [9.38 ± 1.76] times, [674.6 ± 83.61] mL). The differences were statistically significant (P < .05). There was no significant difference in VAS score and Oswestry disability index score between the 2 groups of patients before operation, 3 and 6 months after operation (P > .05)., Conclusion: The 3D printing technology combined with guide plate is used in thoracic spinal tuberculosis surgery to effectively reduce the amount of bleeding, shorten the operation time, and increase the safety and accuracy of nail placement., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Abstract: The evidence for associations between family history of prostate cancer and the risk of breast cancer and ovarian cancer is inconclusive. The first systematic review and meta-analysis of studies was conducted to assess the risk of breast cancer and ovarian cancer associated with a family history of prostate cancer.A literature search was conducted using MEDLINE, Embase and Web of science databases up to January 31, 2019. Data were screened and extracted independently by 2 reviewers. The pooled risk ratio (RR) and its 95% confidence interval (CI) were calculated using random-effects models. The GRADE approach was used to assess the quality of evidence.Nine observational studies including 8,011,625 individuals were included in the meta-analysis. The meta-analysis showed that family history of prostate cancer in first-degree relatives was associated with an increased risk of breast cancer (RR 1.12, 95%CI 1.09 to 1.14) with moderate quality evidence, subgroup analysis showed consistent results. Compared with no family history of prostate cancer, history of prostate cancer in first-degree relatives was associated with a slight risk of ovarian cancer (1.10, 95%CI 1.01 to 1.20) with moderate quality evidence. Family history of prostate cancer among sibling was associated with a 17% increased risk of ovarian cancer (95% CI 1.03 to 1.34), however, no significant association was found between family history of prostate cancer among parent and risk of ovarian cancer (RR 1.19, 95% CI 0.84 to 1.70).This review demonstrates that women with a family history of prostate cancer in first-degree relatives was associated with an increased risk of breast cancer and ovarian cancer. These findings may aid in screening, earlier detection and treatment of women with a family history of prostate cancer in first-degree relatives., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Patients' expectation to treatment response is one source of placebo effects. A number of randomized controlled trials (RCTs) reported that expectation benefits to acupuncture treatment, while some did not. Previous systematic reviews failed to draw a confirmative conclusion due to the methodological heterogeneity. It is necessary to conduct a new systematic review to find out whether expectation can influence acupuncture outcomes., Methods: We systematically search English and Chinese databases from their inception to 3rd October, 2020, including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), Chinese BioMedical Literature Database (CBM), Chinese National Knowledge Infrastructure (CNKI), and Chinese Science and Technology Periodical Database (VIP). RCTs that evaluated the relationship between expectation and treatment response following acupuncture for adults will be included. Study selection, data extraction, and risk of bias assessment will be conducted independently. Risk of bias will be assessed by the Cochrane risk of bias assessment tool. Data synthesis will be performed by Review Manager (RevMan) software if the data is suitable for synthesis., Results: This systematic review will provide evidence that whether patients' expectation impacts on the therapeutic effects of acupuncture. This protocol will be performed and reported according to the Preferred Reporting Items from Systematic Reviews and Meta-analysis Protocols (PRISMA-P) statement. The findings of this review will be disseminated through peer-reviewed publications and conference presentations., Conclusion: This systematic review aims to assess whether a higher level of patient's expectation contributes to a better outcome after acupuncture treatment, and in which medical condition this contribution will be more significant., Inplasy Registration Number: INPLASY2020100020 on International Platform of Registered Systematic Review and Meta-analysis Protocols., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Acupuncture has been recommended for the treatment of tension-type headache (TTH). However inconsistent findings on the efficacy of acupuncture impacts on the uptake of this effective therapy for TTH. This systematic review aims to 1) Evaluate the efficacy of acupuncture for TTH; and 2) Clarify the factors contributing to conflicting findings through conducting a meta-analysis and meta-regression of randomized controlled trials., Methods: Comprehensive literature search will be performed on PubMed, EMBASE, CINAHL, ProQuest, Cochrane Central Register of Controlled Trials, Acubriefs, ScienceDirect, Scopus, AMED, and 4 leading Chinese databases of the China National Knowledge Infrastructure, China Science and Technology Journal Database, Wanfang Data, and CBM (SinoMed). We will include Randomized controlled Trials or controlled trials of patients with TTH that compared acupuncture with sham interventions. The primary outcome is the number of days on headache (within 4 weeks) at the end of the treatment and follow-ups. Secondary outcomes include intensity of pain, frequency of attack, and the adverse effects resulting from the intervention. We will use pre-defined sub-group analysis and meta-regression to explore the influential factors of acupuncture effects. Heterogeneity assessment will be performed before carrying out meta-analysis, whereas the subgroup analyses and meta-regression will be used in verifying the possible factors of heterogeneity when significant heterogeneity detected., Results: Review Manager 5.3 software will be used for meta-analysis. The synthesis will be performed by generating forest plots. Meta-regression will be used to understand influential factors for acupuncture in patients with TTH., Conclusion: By utilizing techniques of meta-regression, this study will provide evidence toward to a more focused understanding of influential factors for acupuncture in patients with TTH. This systematic review will provide quality evidence for the optimization of acupuncture therapeutic regimen. It will facilitate the development of clinical practice guideline on acupuncture for TTH.

Background: When atherosclerosis occurs in the coronary artery, resulting in stenosis, occlusion, or spasm of the coronary artery, the supply of blood and oxygen to the myocardium will be reduced or even unavailable, resulting in myocardial necrosis and heart pain, chest tightness, dyspnea and other symptoms caused by myocardial necrosis are collectively referred to as coronary atherosclerotic heart disease. Coronary angiography can not only understand the degree of coronary artery damage, but also estimate the prognosis of coronary artery stenting, which provides a reliable reference for clinical treatment. Transradial coronary angiography (TCA) has the advantages of high success rate, small trauma, less complications, no bed rest, reduce hospital stay and other superiority, which accepted and used by physicians. Although the success rate of surgery is high, the postoperative complications will still affect the effect of surgery and the prognosis of patients. The main manifestations are radial artery occlusion (RAO), forearm hematoma formation, pseudoaneurysm formation, periosteal compartment syndrome, radial artery perforation, etc. Among the many ways to prevent RAO, anticoagulant therapy with common heparin is one of them, but the dosage of heparin is not clear. Therefore, we decided to use systematic evaluation to evaluate the clinical effectiveness and safety of different dose of heparin in preventing of RAO, and to provide clinical basis for the early prevention and treatment of RAO., Methods: Two reviewers independently searched PubMed, Embase, the Cochrance Library, Web of Science, Medline, CBM Disc, CNKI, and WANFANG Data to find the eligible research. The retrieval about the randomized controlled trials of different dose of heparin in preventing the occurrence of RAO after TCA in recent years. The retrieval time is set between January 1990 and June 2020. The retrieval language is Chinese/English. Two researchers independently searched, managed and screened the literature through the search terms. When the 2 parties have inconsistent opinions on the inclusion or not of certain literature, the literature will be referred to the third researcher for discussion and decision. The included studies are conducted bias risk assessment through bias risk assessment tool, which based on Cochrane Handbook 5.0. The extracted data uses RevMan5.3 software for statistical processing., Results: The research results of this systematic review will be published in peer-reviewed medical-related academic journals., Conclusion: This study adopts the Meta-analysis method and expands the sample size, which will give high-quality evidence-based medicine evidence on the clinical effectiveness and safety of different dose of heparin in preventing the occurrence of RAO., Trial Registration Number: OSF, DOI 10.17605/OSF.IO/CPXJ3.

Posterior pharyngeal flap palatoplasty is used to restore the function of velopharyngeal (VP) closure, after which 2 ports remain between the nasal and oral cavity. The authors hypothesized that the airflow dynamics of the upper airway is different in PPF patients compared to health subjects, who only has 1 movable port. Twenty adults who have multislice spiral computed tomography scan were included in this study. Two cylinders (radius, 2.00 mm; height, 4.5 mm) were used to recapitulate the 2-port VP structure after PPF palatoplasty. The areas of ports were modified by changing the radius of 2 cylinders. Real-time computational fluid dynamics simulation was used to capture the airflow velocity and pressures through the 2 ports. The airflow velocity and pressure of upper airway were recorded as the total areas of 2 VP ports increased. The total orifice areas of the 2-port VP closure for 4 VP conditions, including adequate closure, adequate/borderline closure, borderline/inadequate closure, and inadequate closure, were demonstrated. Significant differences between the 2-port VP function for demonstrating PPF reconstruction and the 1-port VP function were found. Airflow dynamics is dependent on the VP structure. The 2-port airflow model for mimicking VP closure after PPF palatoplasty demonstrated airflow characteristics that were significantly different from the 1-port model in normal VP closure.

Multiple factors, including increasing incidence, poor knowledge of stroke and lack of effective, noninvasive and convenient stroke risk prediction tools, make it more difficult for precautions against stroke in China. Effective prediction models for stroke may assist to establish better risk awareness and management, healthier lifestyle, and lower stroke incidence for people.The China Health and Retirement Longitudinal Survey was the development cohort. Logistic regression was applied to model's development, in which the candidate variables with statistically significant coefficient were included in the prediction model. The area under receiver operating characteristic curve (AUC) and 10-times cross-validation were used for internal validation. Cutoff point of high-risk group was measured by Youden index. The China Health and Nutrition Survey was the validation cohort.The development cohort and the validation cohort included 16557 and 5065 participants, and the incidence density was 358.207/100,000 person-year and 350.701/100,000 person-year, respectively. The model for 2-year new-onset stroke risk prediction included age, hypertension, diabetes, heart disease, and smoking. The AUC and cross-validation AUC were 0.707 (95% confidence interval[CI]: 0.664, 0.750) and the 0.710 (95% CI: 0.650, 0.736). The sensitivity, specificity and accuracy of the cutoff point were 0.774, 0.545, and 0.319. The AUC and cross-validation AUC were 0.800 (95% CI: 0.744, 0.856) and 0.811(95% CI:0.714, 0.847), and the sensitivity, specificity and accuracy of cutoff point being 0.857,0.569, and 0.426 in external validation.A simple prediction tool using 5 noninvasive and easily accessible factors can assist in 2-year new-onset stroke risk prediction in Chinese people over 45 years old, which is believed to be applicable in identifying high-risk individuals and health management in China.

Objective: The aim of the study was to explore the tendency of modified electroconvulsive therapy (MECT)-related working memory and subjective memory deficits in depressed patients., Methods: Sixty patients with unipolar/bipolar depression were prepared and enrolled for MECT and 56 subjects were enrolled as healthy controls (HCs). Their demographics (sex, age, body mass index, years of schooling, etc) and clinical characteristics (dosage and number of MECT, etc) were compared. Depression severity, working memory, and subjective memory were measured using the Hamilton Depression Rating Scale 17 (HAMD17), a Digit Span Backwards (DSB), and self-reported assessments, respectively. Measurements were taken at baseline, within 24 hours after each MECT session, and in every month for a 6-month follow-up period., Results: (a) The patients had poorer performance than the HCs on DSB and HAMD17 at baseline, and the DSB score and HAMD17 total scores were negatively correlated. However, after the second MECT session, the patients' HAMD17 score was significantly improved compared with that at the baseline (P < 0.05), whereas the DSB score showed no significant difference compared with the HCs (P > 0.05). (b) After the first MECT session, 62% of the patients reported subjective memory deficits, which were exacerbated over the subsequent sessions and relieved with antidepressant treatment during the follow-up period. (c) The risk factors for prolonged subjective memory deficits were overweight and the maximum MECT dosage/age (dosage/age = the percentage of output part of total dosage × 100/age, unit: 1/year) ≥ 1.5/year (odds ratio [OR] = 15.36 and 7.98)., Conclusions: Depressed patients showed poorer working memory than the HCs. Such memory deficit may be aggravated by MECT, although it may improve with the relief of depression. Although subjective memory deficits can occur after the first MECT session and gradually recover after the treatment, they may last for 6 months or longer. Persistent deficits may be related to being overweight and having a high MECT dosage.