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Tiger pufferfish (Takifugu rubripes) is one of Asia's most economically valuable aquaculture species. However, winter production of this species in North China is limited by low water temperature and unavailability of high-quality feed, resulting in high mortality and low profitability. Therefore, the aim of this study was to evaluate the effect of feeding frequency (F1: one daily meal; F2: two daily meals; F3: four daily meals; F4: continuous diurnal feeding using a belt feeder) on the growth performance, plasma biochemistry, digestive and antioxidant enzyme activities, and expression of appetite-related genes in T. rubripes (initial weight: 266.80 ± 12.32 g) cultured during winter (18.0 ± 1.0 °C) for 60 days. The results showed that fish in the F3 group had the highest final weight, weight gain rate, specific growth rate, survival rate, and best feed conversion ratio. Additionally, daily feed intake increased significantly with increasing feeding frequency. The protein efficiency and lipid efficiency ratios of fish in the F3 group were significantly higher than those of fish in the other groups. Furthermore, total cholesterol, triglycerides, and glucose levels increased with increasing feeding frequency, peaking in the F2 group and decreasing under higher feeding frequencies. The antioxidant (superoxide dismutase, catalase, glutathione, and glutathione peroxidase) and digestive (trypsin, amylase, and lipase) enzyme activities of fish in the F1 group were significantly higher than those of fish in the F3 and F4 groups. Additionally, there was a decrease in orexin expression with increasing feeding frequency. In contrast, the expression levels of tachykinin, cholecystokinin, and leptin increased with increasing feeding frequency, peaking in the F4 group. Overall, the findings of this study indicated that a feeding frequency of four meals per day was optimal for improved growth performance of pufferfish juveniles cultured during winter.

Purpose: To establish recommended phase II dose (RP2D) in phase I and evaluate safety and efficacy of abivertinib in patients with EGFR Thr790Met point mutation (T790M)-positive(+) non–small cell lung cancer (NSCLC) with disease progression from prior EGFR inhibitors in phase II. Patients and Methods: This multicenter, open-label study included 367 adult Chinese patients. Abivertinib at doses of 50 mg twice a day to 350 mg twice a day was evaluated in phase I in continual 28-day cycles, and the RP2D of 300 mg twice a day was used in phase II in continual 21-day cycles. Primary endpoints include RP2D in phase I and objective response rate (ORR) at RP2D in phase II. Results: The RP2D of 300 mg twice a day for abivertinib was established based on pharmacokinetics, efficacy, and safety profiles across doses in phase I. In phase II, 227 patients received RP2D for a median treatment duration of 24.6 weeks (0.43–129). Among 209 response–evaluable patients, confirmed ORR was 52.2% [109/209; 95% confidence interval (CI): 45.2–59.1]. Disease control rate (DCR) was 88.0% (184/209; 95% CI: 82.9–92.1). The median duration of response (DoR) and progression-free survival (PFS) was 8.5 months (95% CI: 6.1–9.2) and 7.5 months (95% CI: 6.0–8.8), respectively. The median overall survival (OS) was 24.9 months [95% CI: 22.4–not reachable (NR)]. All (227/227) patients reported at least 1 adverse event (AE), with 96.9% (220/227) of treatment-related AEs. Treatment-related serious AEs were reported in 13.7% (31/227) of patients. Death was reported in 4.4% (10/227) of patients, and none was deemed as treatment-related. Conclusions: Abivertinib of 300 mg twice a day demonstrated favorable clinical efficacy with manageable side effects in patients with EGFR T790M+ NSCLC.

Background Consensus lacks regarding the association between diabetes mellitus (DM) and the prognosis of patients with non-Hodgkin lymphoma (NHL). We aimed to systematically evaluate the above association, as well as the potential influence of metformin use in a meta-analysis of cohort studies. Materials and Methods Cohort studies investigating the association between DM and survival outcomes of patients with NHL were included by search of electronic databases that included PubMed, Embase, and Web of Science. A random-effects model was adopted to combine the results. Results Eight cohort studies including 8652 patients with NHL were analyzed. Compared to non-DM patients with NHL, DM was associated with poor overall survival (OS, hazard ratio [HR] = 1.49, 95% confidence interval [CI]: 1.18-1.89, P .10). Conclusions DM is associated with poor survival outcomes in patients with B-cell NHL, which is consistent in patients with DLBCL. Concurrent metformin use in DM patients with NHL may be associated with improved survival outcomes.

Peritoneal carcinomatosis (PC) is considered incurable, and more effective therapies are needed. Herein we test the hypothesis that GPA33-directed intracompartmental pretargeted radioimmunotherapy (PRIT) can cure colorectal peritoneal carcinomatosis. Nude mice were implanted intraperitoneally with luciferase-transduced GPA33-expressing SW1222 cells for aggressive peritoneal carcinomatosis (e.g., resected tumor mass 0.369 ± 0.246 g; n = 17 on day 29). For GPA33-PRIT, we administered intraperitoneally a high-affinity anti-GPA33/anti-DOTA bispecific antibody (BsAb), followed by clearing agent (intravenous), and lutetium-177 (Lu-177) or yttrium-86 (Y-86) radiolabeled DOTA-radiohapten (intraperitoneal) for beta/gamma-emitter therapy and PET imaging, respectively. The DOTA-radiohaptens were prepared from S-2-(4-aminobenzyl)-1,4,7, 10-tetraazacyclododecane tetraacetic acid chelate (DOTA-Bn). Efficacy and toxicity of single- versus three-cycle therapy were evaluated in mice 26–27 days post-tumor implantation. Single-cycle treatment ([177Lu]LuDOTA-Bn 111 MBq; tumor dose: 4,992 cGy) significantly prolonged median survival (MS) approximately 2-fold to 84.5 days in comparison with controls (P = 0.007). With three-cycle therapy (once weekly, total 333 MBq; tumor dose: 14,975 cGy), 6/8 (75%) survived long-term (MS > 183 days). Furthermore, for these treated long-term survivors, 1 mouse was completely disease free (microscopic “cure”) at necropsy; the others showed stabilized disease, which was detectable during PET-CT using [86Y]DOTA-Bn. Treatment controls had MS ranging from 42–52.5 days (P < 0.001) and 19/20 mice succumbed to progressive intraperitoneal disease by 69 days. Multi-cycle GPA33 DOTA-PRIT significantly prolongs survival with reversible myelosuppression and no chronic marrow (929 cGy to blood) or kidney (982 cGy) radiotoxicity, with therapeutic indices of 12 for blood and 12 for kidneys. MTD was not reached.

BACKGROUND: Membranoproliferative glomerulonephritis (MPGN) is a rare histopathologic pattern of glomerular injury with limited studies in pediatric patients. Characteristics and outcomes of children with MPGN have also remained to be further explored. METHODS: We retrospectively reviewed the clinicopathological features, genetic findings, treatments and outcomes in 17 pediatric patients pathologically diagnosed with MPGN from 2007 to 2020 in the Children’s National Medical Center in China. RESULTS: Median age at disease onset was 9.9 years (IQR, 5.6–11.9 years). Most of the patients (12/17) had nephrotic range of proteinuria, and nephritic-nephrotic syndrome was the most common clinical presentation (35.2%). Secondary causes were identified in eight patients including hepatitis B virus (HBV) infection (n=4), methylmalonic acidemia (MMA, n=2), rheumatoid arthritis (RA, n=1) and Aymé-Gripp Syndrome (n=1). The nine patients with primary MPGN were further identified as immune-complex mediated MPGN (n=8), and unclassifiable MPGN (U-MGPN, n=1). Genetic analyses identified pathogenic variants of MMACHC gene in two cases of MMA and established the diagnosis for Aymé-Gripp syndrome in one case with a de novo variant of MAF gene. Comparing study between the complete or partial remission group (n=8) and non-response group (n=9) showed a significant difference in the timing of renal biopsy (P

OBJECTIVE We aimed to establish a standardized procedure for white light gastroscopy (WLG) to screen gastric lesions including early gastric cancer (EGC) in China and to verify its efficacy and feasibility in clinical practice. METHODS A standardized WLG procedure for outpatients at nine tertiary hospitals in Beijing was established. Clinical information of the participants and details of the endoscopic procedures were recorded. RESULTS A total of 1051 participants were enrolled in a baseline conventional endoscopic survey between March 2014 and December 2015, while 2156 patients were enrolled in the standardized WLG operation from January 2016 to June 2017. The procedure time of the standardized procedure was significantly longer than that of the baseline conventional procedure (P = 0.003). More images were obtained during the standardized procedure compared with the baseline conventional procedure (P

INTRODUCTION To improve compliance with voiding diaries in children with primary monosymptomatic nocturnal enuresis (PMNE), a new modified 3-day weekend frequency-volume chart (FVC) was designed, and the compliance and validity of this modified FVC was evaluated by comparing with the International Children's Continence Society (ICCS) recommended voiding diary. METHODS A total of 1200 patients with PMNE were enrolled in the study from 13 centers in China and were randomly assigned to record this modified FVC or the ICCS-recommended voiding diary. The primary outcome measure was the compliance, assessed by comparing the completing index and the quality score of diaries between two groups. The secondary outcome measure was the validity, evaluated by comparing the constituent of subtypes, micturition parameters and response rate to desmopressin. RESULTS Among the 1200 participants enrolled in the study, 447 patients completed the ICCS-recommended voiding diary and 469 completed the modified diary. The diurnal completing index and the quality score of the modified FVC group were better than those of the ICCS group. In addition, there was no significant difference between these two groups in the subtype classification, or in the response rate to desmopressin. CONCLUSIONS The modified FVC could be applied to obtain the voiding characteristics of children with PMNE as the ICCS-recommended voiding diary does and offers a reasonable and better choice for children with PMNE from the unselected population in the future.

Background Acupuncture combined with Chinese herbal medicine was performed on 24 patients with post-schizophrenia comorbid depressive disorder and insomnia admitted to the Psychiatry Department, Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine from 2016 to 2020, and provided satisfactory results. Considering post-schizophrenia comorbid depressive disorder and insomnia is not a common clinical disorder in hospital of traditional Chinese medicine, the treatment and follow-up cycle is long, and the dropout rate is high, a retrospective case series based on Joanna Briggs Institute (JBI) reporting checklist were conducted instead of a randomized controlled trial. Objective To retrospectively summary the short-, mid- and long-term effects of acupuncture combined with Chinese herbal medicine for post-schizophrenia comorbid depressive disorder and insomnia, and analyze the principles of the prescriptions. Methods A retrospective analysis based on case series JBI reporting checklist were performed to investigate effects of 24 patients with post-schizophrenia comorbid depressive disorder and insomnia undergoing 12-week combined acupuncture and Chinese herbal medicine treatment (patients did not receive full dosage treatments, or received western medicine or other physical and psychological therapies during the treatment period were excluded). The psychotic symptoms, depression, insomnia, and self-care ability for daily living were measured by the Positive and Negative Syndrome Scale (PANSS), Calgary Depression Scale for Schizophrenia (CDSS), Pittsburgh Sleep Quality Index (PSQI), and Activity of Daily Living Questionnaire (ADL-Q), respectively. Follow-ups were conducted at 8 and 16 weeks after treatment. Meanwhile, Acupuncture Beliefs Scale (ABS) was assessed at pre- and post- treatment as well as 16-week follow-up to investigate patients' beliefs and expectations for acupuncture treatment. Results (1) compared with pre-treatment, the PANSS global scores did not decrease significantly at post-treatment and follow-up periods (P> 0.05). (2) compared with pre-treatment, the global scores of CDSS and PSQI decreased significantly at post-treatment and follow-up periods (both P Conclusions Acupuncture combined with Chinese herbal medicine can significantly improve the insomnia and depressed mood following schizophrenia, with satisfactory short-, medium- and long-term effects; effective treatment experience can increase patients' beliefs and expectations for acupuncture therapy.

Yi-Hui Liu,1 Yan Guo,2 Hong Xu,1 Hui Feng,1 Dong-Ya Chen1 1Department of Digestive Hepatology, Hangzhou Red Cross Hospital, Hangzhou, Zhejiang, 310003, People’s Republic of China; 2Department of Gastroenterology, Hangzhou Third Hospital, Hangzhou, Zhejiang, 310009, People’s Republic of ChinaCorrespondence: Yi-Hui LiuDepartment of Digestive Hepatology, Hangzhou Red Cross Hospital, No. 208 of Huancheng East Road, Xiacheng District, Hangzhou, Zhejiang, 310003, People’s Republic of ChinaTel +8613588227972Email yhl_123drsea@163.comObjective: To observe the effect of non-alcoholic simple fatty liver disease on drug-induced liver injury caused by tuberculosis.Methods: We retrospectively analyzed the incidence, characteristics, and risk factors of antituberculosis drug-induced liver injury in 104 patients with initial treatment of tuberculosis complicated with non-alcoholic simple fatty liver disease. The patients were divided into two groups according to whether there was liver injury or not. The differences in age, gender, body mass index (BMI), cholesterol, and triglycerides were studied between the two groups.Results: Among the 104 patients with initial treatment of tuberculosis complicated with non-alcoholic fatty liver disease, 24 (23%) patients developed a drug-induced liver injury. The remaining 80 (77%) patients did not develop drug-induced liver injury (χ2 = 60.308, P < 0.05). In the liver injury group, there were 20 cases of mild liver injury, two cases of moderate liver injury, two cases of severe liver injury, 22 cases of hepatocellular injury, two cases of cholestasis, and no cases of mixed liver injury. The time of abnormal liver function in antituberculosis treatment was 16.42 ± 9.18 days from the beginning of the antituberculosis treatment. There were no significant differences in gender, age, BMI, or triglyceride between the liver injury group and the non-liver injury group (χ2 = 2.063, t = 0.179, t = 0.703, t = 1.12, P > 0.05 in all), but there were significant differences in cholesterol (t = 3.08, P < 0.05). By logistic regression analysis, cholesterol was a high-risk factor for liver injury.Conclusion: Non-alcoholic simple fatty liver disease may increase the risk of antituberculosis drug-induced liver injury.Keywords: non-alcoholic simple fatty liver disease, antituberculosis drugs, drug-induced liver injury

Aims Monocyte-lymphocyte ratio (MLR) or neutrophil-lymphocyte ratio (NLR) are useful for diagnosing periprosthetic joint infection (PJI), but their diagnostic values are unclear for screening fixation-related infection (FRI) in patients for whom conversion total hip arthroplasty (THA) is planned after failed internal fixation for femoral neck fracture. Methods We retrospectively included 340 patients who underwent conversion THA after internal fixation for femoral neck fracture from January 2008 to September 2020. Those patients constituted two groups: noninfected patients and patients diagnosed with FRI according to the 2013 International Consensus Meeting Criteria. Receiver operating characteristic (ROC) curves were used to determine maximum sensitivity and specificity of these two preoperative ratios. The diagnostic performance of the two ratios combined with preoperative CRP or ESR was also evaluated. Results The numbers of patients with and without FRI were 19 (5.6%) and 321 (94.4%), respectively. Areas under the ROC curve for diagnosing FRI were 0.763 for MLR, 0.686 for NLR, 0.905 for CRP, and 0.769 for ESR. Based on the Youden index, the optimal predictive cutoffs were 0.25 for MLR and 2.38 for NLR. Sensitivity and specificity were 78.9% and 71.0% for MLR, and 78.9% and 56.4% for NLR, respectively. The combination of CRP with MLR showed a sensitivity of 84.2% and specificity of 94.6%, while the corresponding values for the combination of CRP with NLR were 89.5% and 91.5%, respectively. Conclusion The presence of preoperative FRI among patients undergoing conversion THA after internal fixation for femoral neck fracture should be determined. The combination of preoperative CRP with NLR is sensitive tool for screening FRI in those patients. Cite this article: Bone Joint J 2021;103-B(9):1534–1540.

Background Postoperative moderate and severe anemia (PMSA) has been a serious perioperative complication in primary total knee arthroplasty (TKA). However, the ideal cutoff values to predict PMSA is still undetermined. The aim of this study was (1) to identify the risk factors associated with PMSA and (2) to establish the cutoff values of preoperative hemoglobin (HB) associated with increased PMSA in primary TKA. Methods We identified 474 patients undergoing primary TKA and separated those in which PMSA (HB was less than 110 g/L on postoperative day 1 and 3) was developed from those without PMSA. Multivariate logistic regression model was used to identify independent risk factors for PMSA. Area under the receiver-operator curve (AUC) was used to determine the best-supported preoperative HB cutoff across all the patients. Results The PMSA rate in primary TKA was 53.2%. Significant risk factors were lower preoperative HB (OR [odds ratio] = 1.138, 95% CI [confidence interval] = 1.107–1.170, p p A preoperative HB cutoff value that maximized the AUC was 138.5 g/L for men (sensitivity: 79.4%, specificity: 75.0%) and 131.5 g/L for women (sensitivity: 74.7%, specificity: 80.5%), respectively. Conclusion We should recognize and consider the related risk factors to establish specific, personalized risk assessment for PMSA, including preoperative HB and intraoperative blood loss. Of these, preoperative HB was a referable tool to predict PMSA in primary TKA.

Objectives Silicosis is a chronic occupational lung disease. As was previously found by the authors, some proteins increased in the lung tissue of activated rats, and protein tyrosine phosphatase non-receptor type 2 (PTPN2), factor B, and vaccinia-related kinase 1 (VRK1) showed highly differential expressions. Material and Methods In this study, serum and bronchoalveolar lavage fluid samples were collected from patients with silicosis and healthy people to verify the expression of PTPN2, factor B, and VRK1. The diagnostic value of differentially expressed proteins for silicosis was judged. Results The expression levels of serum PTPN2, VRK1, and factor B in patients with silicosis were significantly higher than those in the control group (p < 0.01). Higher serum PTPN2 and factor B concentrations significantly and negatively correlated with the ratio of forced expiratory volume in 1 s to forced vital capacity (FEV 1 /FVC), maximum vital capacity (VC max ), FEV 1 , and FVC, suggesting that the high expression of PTPN2 and factor B is associated with decreased pulmonary ventilation function and restrictive ventilatory impairment in patients with silicosis. All area under curve (AUC) measurements generated from single detection events were >0.744, with PTPN2 reaching the highest value (0.858). The AUC, sensitivity, and specificity for the combined diagnosis using factor B and PTPN2 were 0.907, 86.91% and 85.07%, respectively, for factor B and PTPN2. The 3 differentially expressed proteins are potential classes of predictive biomarkers for silicosis. Conclusions Regarding the economy and test practicality, the best diagnostic combination is factor B and PTPN2 for the analysis of AUC, sensitivity and specificity. Int J Occup Med Environ Health. 2021;34(4):527–40

BACKGROUND: The optimal duration of treatment for intestinal tuberculosis (TB), which remains a common disease worldwide, has not yet been established. The proposed randomized controlled study will aim to compare the efficacy of short-term six-month with nine-month anti-TB therapy for treating intestinal TB. METHODS: This multicenter, open-label, double-blinded, randomized controlled trial conducted in the Affiliated Hangzhou Chest Hospital of Zhejiang University will include a total of 80 patients. Patients who meet the inclusion criteria will be randomly assigned to either the six-month (n=40) or nine-month (n=40) treatment group. The primary outcome will be complete response, which is defined as endoscopy displaying active lesion healing at the end of treatment. Participants will be scheduled for follow-up visits once a month in the first three months, then once every three months until the end of the treatment. The last follow-up will be one year after the treatment. Recurrence will be assessed one year after the end of treatment, which is defined as endoscopy displaying recurrent lesions after complete response. DISCUSSION: In addition to the reports of tuberculous lymphadenitis and spinal TB, there are few appropriate randomized trials for the treatment of extrapulmonary TB with appropriate clinical endpoints. We believe that the proposed randomized controlled trial will provide further data on the efficacy of short-term six-month anti-TB therapy in intestinal TB patients. TRIAL REGISTRATION: This trial will be registered on ClinicalTrial.gov.

Background The serum surfactant protein D (SP-D) level is suggested to be a useful biomarker for acute lung injuries and acute respiratory distress syndrome. Whether the serum SP-D level could identify the severity of coronavirus disease 2019 (COVID-19) in the early stage has not been elucidated. Methods We performed an observational study on 39 laboratory-confirmed COVID-19 patients from The Fourth People’s Hospital of Yiyang, Hunan, China. Receiver operating characteristic (ROC) curve analysis, correlation analysis, and multivariate logistic regression model analysis were performed. Results In the acute phase, the serum levels of SP-D were elevated significantly in severe COVID-19 patients than in mild cases (mean value ± standard deviation (SD), 449.7 ± 125.8 vs 245.9 ± 90.0 ng/mL, PPP = 0.011), while markedly lower in the recovery period than those in the acute phase (median value, 2.0 vs 9.0, PP = 0.047), while positively correlated with CRP (r = 0.658, PP = 0.002), the duration of nucleic acid of throat swab turning negative (r = 0.668, PPP = 0.008). Multivariate logistic regression model analysis showed that age (P = 0.041, OR = 1.093) and SP-D (P = 0.008, OR = 1.018) were risk factors for severe COVID-19. Conclusions Elevated serum SP-D level was a potential biomarker for the severity of COVID-19; this may be useful in identifying patients whose condition worsens at an early stage.

BACKGROUND Lymphangioleiomyomatosis (LAM) is a rare cystic lung disease characterized by the proliferation, metastasis, and infiltration of smooth muscle cells in the lung and other tissues, which can be associated with tuberous sclerosis complex (TSC). The disorder of TSC has a variable expression, and there is great phenotypic variability. CASE SUMMARY A 32-year-old Chinese woman with a history of multiple renal angioleiomyolipoma presented with a productive cough persisting for over 2 wk. High-resolution chest computed tomography revealed interstitial changes, multiple pulmonary bullae, bilateral pulmonary nodules, and multiple fat density areas of the inferior mediastinum. Conventional and contrast ultrasonography revealed multiple high echogenic masses of the liver, kidneys, retroperitoneum, and inferior mediastinum. These masses were diagnosed as angiomyolipomas. Pathology through thoracoscopic lung biopsy confirmed LAM. Furthermore, high-throughput genome sequencing of peripheral blood DNA confirmed the presence of a heterozygous mutation, c.1831C>T (p.Arg611Trp), of the TSC2 gene. The patient was diagnosed with TSC-LAM. CONCLUSION We highlight a rare case of TSC-LAM and the first report of a mediastinum lymphangioleiomyoma associated with TSC-LAM.

This study aimed to develop and validate a bedside risk analysis system for predicting the clinical severity and prognosis of patients with coronavirus disease 2019 (COVID-19). In total, 444 COVID-19 patients were included and randomly assigned in a 2:1 ratio to 2 groups: derivation group and validation group. The new scoring system comprised of the following 8 variables: history of malignant diseases, history of diabetes mellitus, dyspnea, respiratory rate >24 breaths/min, C-reactive protein level >14 mg/L, white blood cell count >8×109/L, platelets count

Neuroimaging technique is a powerful tool to characterize the abnormality of brain networks in schizophrenia. However, the neurophysiological substrate of schizophrenia is still unclear. Here we investigated the patterns of brain functional and structural changes in female patients with schizophrenia using elastic net logistic regression analysis of resting-state functional magnetic resonance imaging data. Data from 52 participants (25 female schizophrenia patients and 27 healthy controls) were obtained. Using an elastic net penalty, the brain regions most relevant to schizophrenia pathology were defined in the models using the amplitude of low-frequency fluctuations (ALFF) and gray matter, respectively. The receiver operating characteristic analysis showed reliable classification accuracy with 85.7% in ALFF analysis, and 77.1% in gray matter analysis. Notably, our results showed eight common regions between the ALFF and gray matter analyses, including the Frontal-Inf-Orb-R, Rolandic-Oper-R, Olfactory-R, Angular-L, Precuneus-L, Precuenus-R, Heschl-L, and Temporal-Pole-Mid-R. In addition, the severity of symptoms was found positively associated with the ALFF within the Rolandic-Oper-R and Frontal-Inf-Orb-R. Our findings indicated that elastic net logistic regression could be a useful tool to identify the characteristics of schizophrenia -related brain deterioration, which provides novel insights into schizophrenia diagnosis and prediction.

Background Therapeutic developments have contributed to markedly improved clinical outcomes in peritoneal dialysis (PD) during the 1990s and 2000s. We investigated whether recent advances in PD treatment are implemented in routine Swedish care and whether their implementation parallels improved patient outcomes. Methods We conducted an observational study of 3122 patients initiating PD in Sweden from 2006 to 2015. We evaluated trends of treatment practices (medications, PD-related procedures) and outcomes [patient survival, major adverse cardiovascular events (MACEs), peritonitis, transfer to haemodialysis (HD) and kidney transplantation] and analysed associations of changes of treatment practices with changes in outcomes. Results Over the 10-year period, demographics (mean age 63 years, 33% women) and comorbidities remained essentially stable. There were changes in clinical characteristics (body mass index and diastolic blood pressure increased), prescribed drugs (calcium channel blockers, non-calcium phosphate binders and cinacalcet increased and the use of renin–angiotensin system inhibitors, erythropoietin and iron decreased) and dialysis treatment (increased use of automated PD, icodextrin and assisted PD). The standardized 1- and 2-year mortality and MACE risk did not change over the period. Compared with the general population, the risk of 1-year mortality was 4.1 times higher in 2006–2007 and remained stable throughout follow-up. However, the standardized 1- and 2-year peritonitis rate decreased and the incidence of kidney transplantation increased while transfers to HD did not change. Conclusions Over the last decade, treatment advances in PD patients were accompanied by a substantial decline in peritonitis frequency and an increased rate of kidney transplantations, while 1- and 2-year survival and MACE risk did not change., Graphical Abstract Graphical Abstract

Human serum albumin (HSA) is a non-glycosylated, negatively charged, single-chain polypeptide composed of 585 amino acid residues with a relative molecular mass of 66.438 kD. It is synthesized by the liver at a rate of approximately 200 mg·kg−1·day−1, with a half-life of 21 days, and subjected to catabolism in the muscles, liver, and kidneys at a rate of 4% per day.[1] Albumin, accounting for 60% of the total plasma protein, has various physiological functions,[2] such as maintaining 70% to 80% of effective plasma colloid osmotic pressure, coordinating vascular endothelial integrity, anti-oxidant and anti-inflammatory activities, maintaining the acid-base balance, and participating in the transport, distribution, and metabolism of a variety of endogenous and exogenous substances. The normal concentration of plasma albumin is 35 to 50 g/L. In clinical practice, hypoalbuminemia often occurs because of reduced albumin synthesis due to liver dysfunction, redistribution of serum albumin due to capillary leakage, or increased loss via the intestinal and renal routes. Hypoalbuminemia (defined as a serum albumin concentration less than 35 g/L) reportedly has an incidence of 24% to 87% in critically ill patients,[3] while severe hypoalbuminemia (a serum albumin concentration less than 25 g/L) has an incidence of 5.0–9.6%.[4] Hypoalbuminemia is an independent risk factor for increased short- and long-term mortality and an increased incidence of acute kidney injury (AKI) in patients with acute conditions such as trauma, cardiogenic shock, and sepsis.[5] A meta-analysis showed that for every 10 g/L decrease in the serum albumin concentration in critically ill patients, there was a 137% increase in in-hospital mortality, an 89% increase in the incidence of comorbidities, and a 72% increase in the length of hospital stay.[6] Hypoalbuminemia can also alter the pharmacokinetics of antibiotics, leading to either insufficient or excessively high blood concentrations, thereby resulting in treatment failure or excessive toxicity.[7] HSA is mainly used for fluid resuscitation and the treatment of hypoproteinemia in critically ill patients.[2] Existing studies have shown controversial results regarding whether the use of albumin in critically ill patients improves their clinical prognosis.[8] Albumin consumption varies greatly among countries,[9] and its inappropriate use is frequently seen, with 40% to 90% of reported HSA applications failing to follow clinical guidelines.[10] A tertiary hospital in China reported that hypoproteinemia was the most common indication for the use of HSA (35.6%); however, it was also used in 11.8% of patients with serum albumin concentrations more than 40 g/L. The reason for its use was not documented in 22% of cases.[11] In clinical practice, guidelines and consensus are lacking regarding the selection of HSA concentration, the timing of administration, dosage, and target concentration. Inappropriate use of HSA will cause adverse effects and increase medical costs inevitably, whereas guidance from clinical pharmacists or hospital standards can help reduce inappropriate HSA use by 30% and decrease medical costs without affecting patient prognosis.[12] To further strengthen the standardized application of HSA in critically ill patients and achieve optimal clinical outcomes, the Chinese Society of Critical Care Medicine convened a panel of relevant experts who reviewed and summarized data on the clinical use of HSA, outlined 11 relevant clinical problems, and formulated the “Expert Consensus on the Use of Human Serum Albumin in Critically Ill Patients” using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

Kidney disease is manifested in a wide variety of phenotypes, many of which have an important hereditary component. To delineate the genotypic and phenotypic spectrum of pediatric nephropathy, a multicenter registration system is being implemented based on the Chinese Children Genetic Kidney Disease Database (CCGKDD). In this study, all the patients with kidney and urological diseases were recruited from 2014 to 2020. Genetic analysis was conducted using exome sequencing for families with multiple affected individuals with nephropathy or clinical suspicion of a genetic kidney disease owing to early-onset or extrarenal features. The genetic diagnosis was confirmed in 883 of 2256 (39.1%) patients from 23 provinces in China. Phenotypic profiles showed that the primary diagnosis included steroid-resistant nephrotic syndrome (SRNS, 23.5%), glomerulonephritis (GN, 32.2%), congenital anomalies of the kidney and urinary tract (CAKUT, 21.2%), cystic renal disease (3.9%), renal calcinosis/stone (3.6%), tubulopathy (9.7%), and chronic kidney disease of unknown etiology (CKDu, 5.8%). The pathogenic variants of 105 monogenetic disorders were identified. Ten distinct genomic disorders were identified as pathogenic copy number variants (CNVs) in 11 patients. The diagnostic yield differed by subgroups, and was highest in those with cystic renal disease (66.3%), followed by tubulopathy (58.4%), GN (57.7%), CKDu (43.5%), SRNS (29.2%), renal calcinosis /stone (29.3%) and CAKUT (8.6%). Reverse phenotyping permitted correct identification in 40 cases with clinical reassessment and unexpected genetic conditions. We present the results of the largest cohort of children with kidney disease in China where diagnostic exome sequencing was performed. Our data demonstrate the utility of family-based exome sequencing, and indicate that the combined analysis of genotype and phenotype based on the national patient registry is pivotal to the genetic diagnosis of kidney disease.

Clinical practice guidelines (CPGs) are systematically developed statements backed by scientific evidence to assist practitioners in management in clinical practice. An international cross-sectional survey was conducted by the IPNA to examine the perceptions of pediatric nephrologists on guidelines and their usage and to identify important diseases for future clinical practice guidelines (CPGs). The survey found that the majority of pediatric nephrologists find CPGs useful in clinical practice and admitted to using them most of the time. Developing CPGs is challenging and there are standards available to develop trustworthy guidelines. While evidence-based global guidelines are ideal, pediatric nephrologists expressed the desire that they address regional differences. Most respondents (89.2%) to the survey agreed that adult guidelines did not cover the pediatric perspective adequately and 71.4% opined that consensus-based pediatric guidelines can be developed when evidence for the pediatric population is lacking. The development of high-quality practice guidelines requires substantial resources and may not be feasible in resource-poor countries. Adaptation of an existing guideline has been suggested as an alternative and the ADAPTE collaboration provides a systematic approach to adapting guidelines. Several diseases where pediatric guidelines are needed as a priority including IgA and C3 glomerulopathy were identified in the survey. Implementation of guideline-based care is challenging and the survey found that lack of availability of guidelines (43%) and resources (22.8%) are important reasons for poor implementation in lower-middle and low-income countries. Perceived complexity of guidelines, physician attitudes, and lack of training also contribute to non-adherence to guidelines.

Circulating tumor DNA (ctDNA) can be used to evaluate the prognosis of lymphoma. However, there is no uniform consensus about the mechanistic role that ctDNA plays in the prognosis of lymphoma. This meta-analysis explores the prognostic value of ctDNA in lymphoma, especially in diffuse large B cell lymphoma (DLBCL). All relevant reports published as of May 14, 2020, were retrieved by searching electronic databases in Pubmed, Embase and Cochrane Library. The prognostic value of ctDNA was evaluated using meta-analysis. Revman 5.3 software was used for prognostic data extraction and analysis. Eight studies, including a total of 767 lymphoma patients, were enrolled in this meta-analysis. Five out of eight studies investigated the association between ctDNA levels and progression-free survival (PFS) in 501 lymphoma patients, indicating that high levels of ctDNA were significantly associated with poor PFS (HR 2.24, 95%CI: 1.63–3.08, P

High rates of hospitalization in dialysis patients impose an increasing healthcare burden. We explored and compared hospital admission rates among patients starting hemodialysis (HD) and peritoneal dialysis (PD), and investigated causes of admission/readmission in search of potentially preventable risks. Observational study recruiting 8902 patients (3101 on PD) who started maintenance dialysis in Sweden between 2006 and 2016 and were followed-up for 2 years. We compared the Hazard Ratios (HR) for hospital admission and in-hospital death, and calculated the odds ratios (OR) of readmission within 30 days after discharge. Six thousand four hundred ninety-three (73%) patients were hospitalized at least once, and 246 admissions ended with in-hospital death. Compared with HD, patients on PD had a higher risk of hospitalization (HR 1.07; 95% CI 1.01–1.13), longer length of stay (mean difference of 2.06; 1.39–2.73 days), and higher risk of in-hospital death (HR 1.18; 1.03–1.37). Peritonitis and cardiovascular events were the most frequent causes of admission. Of 5810 patients discharged from the hospital, 1447 (25%) were readmitted and 124 (2%) died within 30 days. No differences in readmission risk were observed between dialysis modalities. There was frequently discordance between the cause of hospital admission and readmission, and we identified a consistent pattern of readmission attributed to complications from infections and their interplay with cardiovascular diseases. Our study illustrates a high burden of hospitalization in patients on dialysis, suggests the risk of longer hospitalizations for patients on PD, and identifies cardiovascular events and infections as complications that may benefit from closer post-discharge monitoring.

ObjectiveCommunity-based reports regarding the association between the estimated glomerular filtration rate (eGFR) and dementia risk show conflicting results. The aim of this study is to investigate the links among kidney function, kidney function decline, and dementia incidence.MethodsWe analyzed the association of eGFR with the risk of dementia (defined as a new dementia diagnosis or initiation of dementia treatments) among 329,822 residents of Stockholm who accessed health care during 2006 to 2011, were ≥65 years of age, had no history of dementia, or underwent kidney replacement therapy. We also estimated the rate of eGFR decline among 205,622 residents with repeated eGFR measurements during the first year of observation and investigated its association with subsequent dementia risk.ResultsWe detected 18,983 cases of dementia (5.8% of participants) over a median follow-up of 5 years. Dementia incidence rates were progressively higher with lower eGFR: from 6.56/1,000 person-years in those with eGFR of 90 to 104 mL/min to 30.28/1,000 person-years in those with eGFR 2 mL/min/1.73 m2/y) within 1 year was associated with higher dementia risk. Risk magnitudes were stronger for vascular dementia than for Alzheimer dementia. As many as 10% (95% CI 6%–14%) of dementia cases could be attributed to eGFR 2, a proportion higher than that attributed to other dementia risk factors such as cardiovascular disease and diabetes.ConclusionsBoth lower kidney function and steeper kidney function decline are associated with the development of dementia.

Objective To investigate the risk factors for, and outcomes of, preoperative asymptomatic pulmonary embolism (PE) in patients ≥60 years old following delayed operation for hip fracture. Methods From March 2017 to December 2018, 90 patients aged ≥60 years with hip fracture who suffered a delay in surgery were recruited to this prospective study following admission to our hospital. Computed tomography pulmonary angiography (CTPA) was used to detect preoperative asymptomatic PE and calculated its incidence. Time from injury to admission, baseline characteristics, medical comorbidities, and blood biomarker levels were evaluated as potential risk factors. Logistic regression analysis was used to identify risk factors. Mortality and major bleeding events were recorded and compared between individuals with PE and without. Data were analyzed by t‐test, Mann–Whitney U test, χ 2 test, Fisher's exact test, and logistic regression analysis. Results The incidence of preoperative asymptomatic PE was 18.9% (17/90 patients). In the univariate analysis, the risk factors for preoperative asymptomatic PE were male sex, hypertension, cerebrovascular accident, smoking, plasma D‐dimer level, potassium level, urea level, creatinine level, and cysteine level. Multivariate logistic regression analysis showed that the risk of preoperative asymptomatic PE was higher in patients with hypertension (odds ratio [OR] = 10.048; 95% confidence interval [CI], 1.118–90.333), cerebrovascular accident (OR = 20.135; 95% CI, 1.875–216.164), smoking (OR = 48.741; 95% CI, 4.155–571.788), high plasma D‐dimer levels (OR = 1.200; 95% CI, 1.062–157.300), and high plasma potassium levels (OR = 12.928; 95% CI, 1.062–157.300). All patients were followed up for 21.0 months (range, 2 to 36 months). Mortality within the first year postoperatively was higher in patients with PE (29.41% vs 9.59%, P = 0.046). Conclusions In view of the high incidence of preoperative asymptomatic PE and the inferior prognosis in individuals with PE, routine CTPA examination for preoperative asymptomatic PE could be useful for patients aged ≥60 years with hip fracture for whom surgery is delayed., The overall incidence of preoperative asymptomatic PE was 18.9% in patients ≥60 years old following delayed operation for hip fracture. Individuals with preoperative asymptomatic PE have an inferior prognosis. Hypertension, cerebrovascular accident, smoking, high plasma D‐dimer levels, and high plasma potassium levels were associated with preoperative asymptomatic PE in these patients.

Yes-associated protein (YAP), as a co-activator of transcription factors, is a downstream protein in the Hippo signaling pathway with important functions in cell proliferation, apoptosis, invasion and migration. YAP also plays a key role in the development of CCl4-induced liver fibrosis. However, the mechanism of YAP during hepatic fibrosis progression and reversion is still unclear. Mild liver fibrosis was developed after 4 months of high-fat diet (HFD) stimulation, and we found that the YAP signaling pathway was activated. Here, we aim to reveal whether specific knockout of Yap gene in the liver can improve liver fibrosis induced by insulin resistance (IR) stimulated by HFD, and further explain its specific mechanism. We found that liver-specific Yap gene knockout improved IR-induced liver fibrosis and liver dysfunction, and this mechanism is related to the inhibition of the insulin signal pathway at the FoxO1 level. These findings provide a new insight, and Yap is expected to be a new target to reverse the early stage of liver fibrosis induced by IR.

This study explored the safety of COVID-19 vaccine (Aikewei) and the role of clinical pharmacists in the implementation of COVID-19 vaccination. A total of 2305 hospital employees in Children’s Hospital of Fudan University in Shanghai, China received the COVID-19 vaccine. The whole process of vaccination was monitored by clinical pharmacists, and the occurrence, types, severity of adverse reactions were recorded in detail. Through the investigation and analysis on the safety of COVID-19 vaccination of the 2305 people, the important role and value of clinical pharmacists in the vaccination process was elaborated. Common adverse reactions included local pain, dizziness and fatigue, with the incidence rates of 2.09%, 0.67% and 0.49%, respectively. Others such as headache, nausea, skin itching, cough, palpitation, dry mouth, hand anesthesia, local induration, muscle soreness, local rash, and chill had incidence rates of less than 0.30%. Three cases of serious adverse events that occurred in this vaccination returned to normal after treatment, with no subsequent discomfort. Clinical pharmacists played an important role in the safety monitoring of COVID-19 vaccination. The safety of the inactivated COVID-19 vaccine is good. Most of the common adverse reactions were mild and tolerable, with generally low incidence. The work of clinical pharmacists is important and can be expanded in the future to ensure the safety of vaccination and to provide better health care service.

Objectives: This study compared the rate of graft success, as well as hearing improvement and dry ear time between dry ears and wet ears with otomycosis or without otomycosis in patients with chronic suppurative otitis media (CSOM) after endoscopic cartilage myringoplasty. Methods: This retrospective study was conducted in a tertiary hospital in Shanghai. In total, 83 patients with CSOM (43 with dry ears and 40 with wet ears) were included. Among the 40 patients with CSOM and wet ears, 25 exhibited otomycosis. All patients underwent endoscopic myringoplasty, and perforations were repaired using tragal cartilage with a single-sided perichondrium. Patients were followed up for at least 6 months. Pure-tone hearing was examined preoperatively and at 3 months postoperatively. The graft uptake rate, hearing improvement, and dry ear time were compared between the groups. Results: The graft success rate did not differ significantly between the dry-ear and wet-ear groups (95.35% and 90.00%, respectively). Furthermore, the graft success rate also did not differ significantly between patients with wet ears and otomycosis and those with wet ears without otomycosis (92.00% and 86.67%, respectively). Hearing gain did not differ significantly between the dry-ear and wet-ear groups. No significant difference in hearing gain was also found in patients with wet ears with or without otomycosis. However, the time to dry ear was significantly longer in the wet-ear group than in the dry-ear group. Conclusion: Patients with CSOM and wet ears required more time to achieve a completely healthy status. However, the graft success rate and hearing improvement were not affected by a wet middle ear and otomycosis. Thus, endoscopic myringoplasty using tragus cartilage is an effective treatment for refractory CSOM in patients with wet ears and otomycosis.

The diagnostic potential of D‐dimer and fibrinogen to detect periprosthetic joint infection (PJI) of the hip and knee is not well‐understood. The aim of this study was to determine whether D‐Dimer and fibrinogen can be used as effective biomarkers to screen PJI. A systematic review of the literature indexed in Web of Science, PubMed, Cochrane Library, Embase, and Google Scholar databases was performed. All studies using D‐dimer levels in serum or plasma, or fibrinogen levels in plasma, for the diagnosis of PJI were included. Meta‐analysis estimates, including sensitivity, specificity, diagnostic odds ratios (DOR), and the area under the summary receiver operating characteristic curve (AUSROC), were calculated using a random‐effects model, and used to assess the diagnostic accuracy of these biomarkers. A total of nine studies were analyzed, and their quality was considered to be acceptable. D‐dimer gave a limited diagnostic value if serum and plasma combined: sensitivity (0.77, 95% confidence interval [CI] [0.63 to 0.87]), specificity (0.67, 95% CI [0.54 to 0.78]), DOR (6.81, 95% CI [2.67 to 17.37]), and AUSROC (0.78, 95% CI [0.74 to 0.82]). Plasma D‐dimer levels were associated with less satisfactory sensitivity (0.65, 95% CI 0.57 to 0.71), specificity (0.58, 95% CI 0.50 to 0.66), DOR (2.52, 95% CI 1.64 to 3.90), and AUSROC (0.65, 95% CI 0.61 to 0.69). Serum D‐dimer levels showed higher corresponding values of 0.89 (95% CI 0.79 to 0.94), 0.76 (95% CI 0.55 to 0.89), 24.24 (95% CI 10.07 to 58.32), and 0.91 (95% CI 0.88 to 0.93). Plasma fibrinogen showed acceptable corresponding values of 0.79 (95% CI 0.70 to 0.85), 0.73 (95% CI 0.57 to 0.85), 10.14 (95% CI 6.16 to 16.70), and 0.83 (95% CI 0.79 to 0.86). Serum D‐dimer may be an effective marker for the diagnosis of PJI in hip and knee arthroplasty patients, and it may show higher diagnostic potential than plasma fibrinogen. Plasma D‐dimer may have limited diagnostic potential.

BACKGROUND: Telemedicine is becoming an emerging innovative supplement to the traditional medical system in China. In the present study, we described the rapid implementation of the telemedicine in pediatrics during the coronavirus disease 2019 (COVID-19) outbreak and explored its value in response to the demand for pediatric medical services during the epidemic. METHODS: An Internet-based platform for multidisciplinary online medical consultation was established on February 8, 2020, by a national children’s medical center in China. The medical data of the traditional hospital visits and novel online visits from the first two months (February 8 to March 31) after the establishment of the platform were collected and analyzed. The demographic features, changes in the disease spectrum and characteristics of online medical services were described. RESULTS: The total number of visits was significantly lower (by 75.3%) than that of in the same period in the previous year. The disease spectrum was different with a significant decrease of >95% in the number of patients with infectious or contagious diseases. The online visits accounted for 14.7% of all visits. Online patients came from all over the country, covering 91% of the administrative regions of China, and the largest proportion of inquiries were for infants (33.7%) (P

Adenomyosis is associated with dysmenorrhea, infertility, and lesional fibrosis. The pathogenesis of adenomyosis is still unclear. Plasminogen activator inhibitor 1 (PAI-1) plays important roles in pathological activities like tumor metastasis and endometriosis. Our objective was to investigate the expression and localization of PAI-1 in eutopic and ectopic endometrium with adenomyosis and in endometrium without adenomyosis. We also sought to determine the relationship between PAI-1 immunoreactivity and the severity of dysmenorrhea and the extent of lesional fibrosis in adenomyosis. PAI-1 expression was significantly higher in the ectopic endometrium of patients with adenomyosis than in both the eutopic endometrium of patients with adenomyosis and the endometrium of controls. Ectopic PAI-1 expression correlated positively with dysmenorrhea visual analog scale (VAS) scores and the extent of lesional fibrosis in adenomyosis. High PAI-1 expression increased the likelihood of moderate to severe dysmenorrhea in adenomyosis. These results suggest that PAI-1 is involved in the adenomyosis-associated dysmenorrhea and lesional fibrosis, which provide a potential target in treating symptomatic adenomyosis. Supplementary Information The online version contains supplementary material available at 10.1007/s43032-021-00513-6.

Peutz-Jeghers syndrome (PJS) is a polygenic autosomal dominant disease characterized by multiple gastrointestinal polyps and pigmentation of the mucosa and skin. While there are a few reports regarding successful treatment of intestinal polyps in PJS, there is little research regarding treatment of mucocutaneous melanosis. This study investigated the many advantages of using a Q-switched alexandrite laser to treat mucocutaneous melanosis. In this case, a 19-year-old male with PJS presented with labial lentigines and received two Q-switched alexandrite laser treatments in 2018. Subsequently, the efficacy of the treatment was evaluated. The result of the evaluation was that, after the two laser treatments, the labial lentigines were successfully removed, and there were no complications.

Severe hand, foot, and mouth disease (HFMD) caused by enterovirus 71 (EV71) infection is associated with high mortality and disability. DC-SIGN, a receptor for EV71, is widely distributed in dendritic cells and may influence the severity of HFMD caused by EV71 infection. This observational study attempts to explore whether single-nucleotide polymorphisms (SNPs) in DC-SIGN are related to the severity of EV71-associated HFMD. Based on linkage disequilibrium and functional predictions, two DC-SIGN SNPs were selected and tested to explore their potential association with the severity of HFMD caused by EV71 infection. Two hundred sixteen Han Chinese children with HFMD caused by EV71 were enrolled to obtain clinical data, including the severity of HFMD, serum DC-SIGN levels, and DC-SIGN SNPs. We found a significant association between the rs7248637 polymorphism (A vs. G: OR = 0.644, 95% CI = 0.515-0.806) and the severity of HFMD caused by EV71 infection, as well as the rs4804800 polymorphism (A vs. G: OR = 1.539, 95% CI =1.229-1.928). These two DC-SIGN SNPs may have an effect on the severity of HFMD caused by EV71 infection.

Based on the Chinese Children Genetic Kidney Disease Database (CCGKDD), we established a pediatric Gitelman syndrome (GS) cohort to explore the phenotype and genotype characteristics. Thirty-two patients with SLC12A3 gene variants were collected. Five cases (16%) were homozygous, 16 (50%) were compound heterozygous, 10 (31%) carried only a single variant, and the other one harbored two de novo variants beyond classification. p.(T60M) was found in eight patients. The average diagnosis age was 7.79 ± 3.54 years. A total of 31% of the patients were asymptomatic. Muscle weakness was the most common symptom, accounting for 50%. Earlier age of onset (4.06 ± 1.17 yr vs. 8.10 ± 3.46 yr vs. 8.61 ± 3.56 yr, p< 0.05) and lower urinary calcium-creatinine ratio (p = 0.024) were found in the homozygous group than those in the heterozygous and compound heterozygous group. Patients with p.(T60M) variant had an earlier age of onset (4.01 ± 2.83 yr vs. 6.92 ± 3.07 yr, p = 0.025) and lower urinary calcium-creatinine ratio (p = 0.056). Thus, more than 30% of GS children have no clinical symptoms. Homozygous variant and the p.(T60M) variant may be associated with earlier onset and lower urinary calcium excretion in Chinese pediatric GS.

α-Klotho is known for its aging-related functions and is associated with neurodegenerative diseases, accelerated aging, premature morbidity, and mortality. Recent literature suggests that α-Klotho is also involved in the regulation of mental functions, such as cognition and psychosis. While most of studies of α-Klotho are focusing on its anti-aging functions and protective role in dementia, increasing evidence showed many shared symptoms between depression and dementia, while depression has been proposed as the preclinical stage of dementia such as Alzheimer's disease (AD). To see whether and how α-Klotho can be a key biological link between depression and dementia, in this review, we first gathered the evidence on biological distribution and function of α-Klotho in psychiatric functions from animal studies to human clinical investigations with a focus on the regulation of cognition and mood. Then, we discussed and highlighted the potential common underlying mechanisms of α-Klotho between psychiatric diseases and cognitive impairment. Finally, we hypothesized that α-Klotho might serve as a neurobiological link between depression and dementia through the regulation of oxidative stress and inflammation.

Background: Gen1 mutation can cause various phenotypes of congenital anomaly of the kidney and urinary tract (CAKUT). An intrauterine low-protein isocaloric diet can also cause CAKUT phenotypes in offspring. However, single factors such as gene mutation or abnormal environmental factor during pregnancy can only explain part of the pathogenesis of CAKUT. Objectives: A low-protein isocaloric diet was fed to Gen1-mutant mice throughout pregnancy to establish a Gen1-mutant mouse model exposed to a low-protein isocaloric intrauterine environment. The mice were divided into 4 groups: normal (22%) protein diet (ND) + wild-type mice (CON group), ND + Gen1PB/+ mice (Gen1PB/+ group), low (6%)-protein isocaloric diet (LD) + wild-type mice (LD group), and the LD + Gen1PB/+ groups. Methods: The experimental design included observing proportion and distribution of CAKUT phenotypes of neonatal mice; evaluating the number of ureteric buds (UBs) on embryonic day (E) 11.5, the location of UBs on E11.5, and length of the common nephric duct (CND); isolating embryonic kidneys on E11.5 from the Gen1PB/+ group and culturing embryonic kidneys in medium containing 10% serum or serum-free medium to observe the branching of UBs; and detecting the p-PLCγ, p-Akt, and p-ERK1/2 in UBs and CND on E11.5, as well as the apoptosis and proliferation of tissues by immunofluorescence staining. Results: We found that the incidence of CAKUT in offspring of Gen1PB/+ mice under an intrauterine low-protein isocaloric diet environment was significantly increased, and a duplicated collecting system was the dominant phenotype of CAKUT. During the early stage of metanephric development, ectopic protrusion of UBs may appear and lower locations of UBs in Gen1PB/+ mice under an intrauterine low-protein isocaloric diet environment and the number of UB branches in the serum-free culture condition significantly decreased. Further examination revealed that p-PLCγ signaling and tissue apoptosis were abnormal in UBs and the CND at the early stage of kidney development. Conclusions: The aforementioned findings suggest that an intrauterine low-protein isocaloric diet can aggravate the occurrence of CAKUT in Gen1-mutant mice, which might affect key steps in the metanephric development, such as the protrusion of UBs, which might be related to mediate UBs and CND apoptosis through p-PLCγ signaling.

Cold injury refers to local or systemic injury caused by a rapid, massive loss of body heat in a cold environment. The incidence of cold injury is high. However, the current situation regarding the diagnosis and treatment of cold injury in our country is not ideal. To standardize and improve the level of clinical diagnosis and treatment of cold injury in China, it is necessary to make a consensus that is practical and adapted to the conditions in China. We used the latest population-level epidemiological and clinical research data, combined with relevant literature from China and foreign countries. The consensus was developed by a joint committee of multidisciplinary experts. This expert consensus addresses the epidemiology, diagnosis, on-site emergency procedures, in-hospital treatment, and prevention of cold injury.

BACKGROUND: Despite increasing incidence of CKD, no evidence-based lifestyle recommendations for CKD primary prevention apparently exist. METHODS: To evaluate the consistency of evidence associating modifiable lifestyle factors and CKD incidence, we searched MEDLINE, Embase, CINAHL, and references from eligible studies from database inception through June 2019. We included cohort studies of adults without CKD at baseline that reported lifestyle exposures (diet, physical activity, alcohol consumption, and tobacco smoking). The primary outcome was incident CKD (eGFR

Background: Icariin has been shown to enhance bone formation. Objective: The present study aimed to investigate whether icariin also promotes bone fracture healing and its mechanisms. Methods: First, we isolated and cultured rat bone marrow stromal cells (rBMSCs) with icariincontaining serum at various concentrations (0%, 2.5%, 5% and 10%) and then measured alkaline phosphatase (ALP) activity and the expression of Core-binding factor, alpha 1 (Cbfα1), bone morphogenetic protein-2 (BMP-2) and bone morphogenetic protein-4 (BMP-4) in the rBMSCs. Second, we established a model of fracture healing in rats and performed gavage treatment for 20 days. Then, we detected bone biochemical markers (ELISA kits) in the serum, fracture healing (digital radiography, DR), and osteocalcin expression (immunohistochemistry). Results: Icariin treatment increased ALP activity and induced the expression of Cbfα1, BMP-2 and BMP-4 in rBMSCs in a dose-dependent manner. In addition, Icariin increased the serum levels of osteocalcin (OC), bone-specific alkaline phosphatase (BAP), N-terminal telopeptides of type I collagen (NTX-1), C-terminal telopeptide of type I collagen (CTX-1) and tartrate-resistant acid phosphatase 5b (TRACP-5b); promoted osteocalcin secretion at the fracture site; and accelerated fracture healing. Conclusions: Icariin can promote the levels of bone-formation markers, accelerate fracture healing, and activate the WNT1/β-catenin osteogenic signaling pathway.

BackgroundThe recent years have witnessed significant therapeutic advances for patients on haemodialysis (HD). We evaluated temporal changes in treatments practices and survival rates among incident HD patients.MethodsThis was an observational study of patients initiating HD in Sweden in 2006–15. Trends of HD-related practices, medications and routine laboratory biomarkers were evaluated. The incidence of death and major cardiovascular events (MACEs) across calendar years were compared against the age- and sex-matched general population. Via Cox regression, we explored whether adjustment for implementation of therapeutic advances modified observed survival and MACE risks.ResultsAmong 6612 patients, age and sex were similar, but the burden of comorbidities increased over time. The proportion of patients receiving treatment by haemodiafiltration, ≥3 sessions/week, lower ultrafiltration rate and working fistulas increased progressively, as did use of non-calcium phosphate binders, cinacalcet and vitamin D3. The standardized 1-year mortality decreased from 13.2% in 2006–07 to 11.1% in 2014–15. The risk of death decreased by 6% [hazard ratio (HR) = 0.94, 95% confidence interval (CI) 0.90–0.99] every 2 years, and the risk of MACE by 4% (HR = 0.96, 95% CI 0.92–1.00). Adjustment for changes in treatment characteristics abrogated these associations (HR = 1.00, 95% CI 0.92–1.09 for death and 1.00, 0.94–1.06 for MACE). Compared with the general population, the risk of death declined from 6 times higher in 2006–07 [standardized incidence rate ratio (sIRR) = 6.0, 95% CI 5.3–6.9] to 5.6 higher in 2014–15 (sIRR = 5.57, 95% CI 4.8–6.4).ConclusionsGradual implementation of therapeutic advances over the last decade was associated with a parallel reduction in short-term risk of death and MACE among HD patients.

AIMS The purpose of this study is to examine the safety and efficacy of eltrombopag as first-line treatment for thrombocytopenia among paediatric patients after haematopoietic stem cell transplantation (HSCT). METHODS Forty-three childhood patients with thrombocytopenia after HSCT who received eltrombopag were retrospectively analysed. RESULT Eltrombopag was began at the median of 27 days after HSCT and lasted for 24 days. Thirty-five children responded to eltrombopag therapy, and the cumulative platelet recovery rate was 88.9%. The cumulative incidence of platelet recovery was lower (83.9 vs 100%; P = .035) in patients with decreased numbers of megakaryocytes before starting eltrombopag than in those with normal. Factors associated with a significantly elevated response to eltrobopag from univariate analysis were donor type. Results from the multiple regression analysis found that weight (hazard ratio [HR] = 0.7, 95% confidence interval [CI] 0.5-0.9, P = .022), platelet engraftment time (HR = 1.0, 95%CI 1.0-1.0, P = .012) and bone marrow megakaryocytes (HR = 8.0, 95%CI 1.5-43.3, P = .016) before starting eltrombopag were the independent risk factors. Based on Youden's index algorithm in the receiver-operating characteristic curve, the optimal cut-off value of the maintenance dose of eltrombopag in predicting nonresponders was 4 mg/kg. The area under the receiver-operating characteristic curve was 0.923 with sensitivity of 97.8%, specificity of 87.9%, positive predictive value of 72.3%, and negative predictive value of 92%. None of the paediatric patients stopped using eltrombopag due to side effect or intolerability. CONCLUSION Eltrombopag is effective and safe in paediatric patients with thrombocytopenia after HSCT. The number of megakaryocytes in bone marrow before eltrombopag treatment may serve as a predictor of the response to eltrombopag. We recommend that the maintenance dose of eltrombopag should not exceed 4 mg/kg/d.

Background Central line-associated bloodstream infections (CLABSI) are largely preventable when evidence-based guidelines are followed. However, it is not clear how well these guidelines are followed in intensive care units (ICUs) in China. This study aimed to evaluate Chinese ICU nurses’ knowledge and practice of evidence-based guidelines for prevention of CLABSIs issued by the Centers for Disease Control and Prevention, US and the Department of Health UK. Method Nurses completed online questionnaires regarding their knowledge and practice of evidence-based guidelines for the prevention of CLABSIs from June to July 2019. The questionnaire consisted of 11 questions, and a score of 1 was given for a correct answer (total score = 0–11). Results A total of 835 ICU nurses from at least 104 hospitals completed the questionnaires, and 777 were from hospitals in Guangdong Province. The mean score of 11 questions related to evidence-based guidelines for preventing CLABSIs was 4.02. Individual total scores were significantly associated with sex, length of time as an ICU nurse, educational level, professional title, establishment, hospital grade, and incidence of CLABSIs at the participant’s ICU. Importantly, only 43% of nurses reported always using maximum barrier precautions, 14% of nurses reported never using 2% chlorhexidine gluconate for antisepsis at the insertion site, only 40% reported prompt removal of the catheter when it was no longer necessary, and 33% reported frequently and routinely changing catheters even if there was no suspicion of a CLABSI. Conclusion Chinese ICU nurses in Guangdong Province lack of knowledge and practice of evidence-based guidelines for the prevention of CLABSIs. National health administrations should adopt policies to train ICU nurses to prevent CLABSIs.

Aims The efficacy and safety of intrawound vancomycin for preventing surgical site infection in primary hip and knee arthroplasty is uncertain. Methods A systematic review of the literature was conducted, indexed from inception to March 2020 in PubMed, Web of Science, Cochrane Library, Embase, and Google Scholar databases. All studies evaluating the efficacy and/or safety of intrawound vancomycin in patients who underwent primary hip and knee arthroplasty were included. Incidence of periprosthetic joint infection (PJI), superficial infection, aseptic wound complications, acute kidney injury, anaphylactic reaction, and ototoxicity were meta-analyzed. Results were reported as odds ratios (ORs) and 95% confidence intervals (CIs). The quality of included studies was assessed using the risk of bias in non-randomized studies of interventions (ROBINS-I) assessment tool. Results Nine studies involving 4,607 patients were included. Intrawound vancomycin was associated with lower incidence of PJI (30 patients (1.20%) vs 58 control patients (2.75%); OR 0.44, 95% CI 0.28 to 0.69) and simultaneous acute kidney injury (four patients (0.28%) vs four control patients (0.35%), OR 0.71, 95% CI 0.19 to 2.55). However, it did not reduce risk of superficial infection (four patients (0.67%) vs six control patients (1.60%), OR 0.60, 95% CI 0.17 to 2.12) and was associated with higher incidence of aseptic wound complications (23 patients (2.15%) vs eight in control patients (0.96%), OR 2.39, 95% CI 1.09 to 5.23). Four studies reported no anaphylactic reactions and three studies reported no ototoxicity in any patient group. Conclusion The current literature suggests that intrawound vancomycin used in primary hip and knee arthroplasty may reduce incidence of PJI, but it may also increase risk of aseptic wound complications. Cite this article: Bone Joint Res 2020;9(11):778–788.

Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in children. Human 16p11.2 deletions have been associated with CAKUT, but the responsible molecular mechanism remains to be illuminated. To explore this, we investigated 102 carriers of 16p11.2 deletion from multi-center cohorts, among which we retrospectively ascertained kidney morphologic and functional data from 37 individuals (12 Chinese and 25 Caucasian/Hispanic). Significantly higher CAKUT rates were observed in 16p11.2 deletion carriers (about 25% in Chinese and 16% in Caucasian/Hispanic) than those found in the non-clinically ascertained general populations (about 1/1000 found at autopsy). Furthermore, we identified seven additional individuals with heterozygous loss-of-function variants in TBX6, a gene that maps to the 16p11.2 region. Four of these seven cases showed obvious CAKUT. To further investigate the role of TBX6 in kidney development, we engineered mice with mutated Tbx6 alleles. The Tbx6 heterozygous null (i.e., loss-of-function) mutant (Tbx6(+/−)) resulted in 13% solitary kidneys. Remarkably, this incidence increased to 29% in a compound heterozygous model (Tbx6(mh/‒)) that reduced Tbx6 gene dosage to below haploinsufficiency, by combining the null allele with a novel mild hypomorphic allele (mh). Renal hypoplasia was also frequently observed in these Tbx6-mutated mouse models. Thus, our findings in patients and mice establish TBX6 as a novel gene involved in CAKUT and its gene dosage insufficiency as a potential driver for kidney defects observed in the 16p11.2 microdeletion syndrome.

Background The effectiveness of acupuncture for insomnia and insomnia-related anxiety and depression has been widely investigated in clinical trials. However, whether higher dosage (more frequent) acupuncture can bring greater responses (a greater size of effect) is less understood. Objective This study is designed to investigate whether a five-times weekly (5 Ts/w) electroacupuncture (EA) treatment is better than a three-times weekly (3 Ts/w) EA in alleviating sleep deprivation, and sleep disturbance-induced cognitive dysfunctions and negative emotions in rats through four various behavioral tests. Methods Forty-six male Sprague-Dawley rats were randomly divided into control group (n = 10), model group (n = 12), EA-3 Ts/w group (n = 12), and EA-5 Ts/w group (n = 12). Except for the control group, the other three groups were established as chronic sleep deprivation models via the modified multi-platform water environment methodology. Then, rats in both EA-3 Ts/w group and EA-5 Ts/w group received corresponding dosage of EA therapy, respectively. After modeling and interventions, all four groups received four behavioral tests as follows: (1) sleep behavioral monitoring and evaluation was achieved by Comprehensive Lab Animal Monitoring System (CLAMS). (2) Cognitive functions were assessed by Novel Object Recognition (NOR) test. (3) Depressive-like behaviors was evaluated by Open-Field (OF) test. (4) Anxiety-like behaviors was appraised by Elevated Plus-Maze (EPM) test. After finishing the behavioral tests, the hippocampus of each rat was removed and its synaptic structure changes were observed under electron microscope. Results (1) CLAMS: two EA groups derived more sleep time within 24 h than the model group (both P 0.05). (2) NOR test: NOR ratio in the EA-3 Ts/w group was higher than that of the model group (P 0.05), although both of them were lower than that of the control group (both P 0.05) but was found in both the model group (P Conclusion (1) Five-week EA treatment can partially mitigate cognitive dysfunctions, anxiety-like behaviors, and depressive behaviors in rats with sleep deprivation, and this effect might be associated with the repairs on mitochondrial damage in hippocampal neurons. (2) There is insufficient evidence supporting 3 Ts/w EA treatment is less effective than 5 Ts/w EA treatment in mitigating sleep deprivation symptoms and depressive behaviors induced by sleep deprivation among rats. (3) 5 Ts/w EA treatment might be more effective than 3Ts/w EA treatment in attenuating sleep deprivation-induced cognitive impairments while it might further increase rat's anxiety-like behaviors at the same time.

Carrier screening of Duchenne muscular dystrophy (DMD) has not been widely evaluated. To identify definite DMD female carriers prior to or in early pregnancy, we studied a large population of reproductive age females and provided informed reproductive options to DMD carriers. 37268 females were recruited from the Hangzhou Family Planning Publicity and Technology Guidance Station/Hangzhou Health Service Center for Children and Women, Hangzhou, China, between October 10, 2017, and December 16, 2018. CK activity was measured with follow-up serum DMD genetic testing in subjects with hyperCKemia, defined as CK>200 U/L. The calculated upper reference limit (97.5th percentile) of serum creatine kinase (CK) for females aged 20-50 years in this study was near the reference limit recommended by the manufacturer (200 U/L), above which was defined as hyperCKemia. 427 females (1.2%) harbored initially elevated CK, among which 281 females (response rate of 65.8%) accepted CK retesting. DMD genetic testing was conducted on 62 subjects with sustained serum CK>200 U/L and 16 females with a family history of DMD. Finally, 6 subjects were confirmed to be DMD definite carriers. The estimated DMD female carrier rate in this study was 1 : 4088 (adjusting for response rate), an underestimated rate, since only 50% to 70% of DMD female carriers manifest elevated serum CK, and carriers in this study may have been missed due to lack of follow-up or inability to detect all DMD pathogenic variants by current genetic testing.

Background The effect of calcium channel blockers (CCB) on mortality and ischaemic stroke risk in dementia patients is understudied. Objectives To calculate the risk of death and ischaemic stroke in dementia patients treated with CCBs, considering individual agents and dose response. Methods Longitudinal cohort study with 18 906 hypertensive dementia patients from the Swedish Dementia Registry (SveDem), 2008–2014. Other Swedish national registries contributed information on comorbidities, dispensed medication and outcomes. Individual CCB agents and cumulative defined daily doses (cDDD) were considered. Results In patients with hypertension and dementia, nifedipine was associated with increased mortality risk (aHR 1.32; CI 1.01–1.73; P

To investigate the effect of electroacupuncture (EA) on cognitive function in D-galactose (D-gal)-induced aging rats, and the correlation between the effect and nucleotide-binding oligomerization domain (NOD)-like receptor protein 3 (NLRP3)-ASC-Caspase-1 signaling pathway. Forty-six male Sprague-Dawley (SD) rats were randomly divided into a control group (n=10), a model group (n=12), an EA-7 d group (n=12) and an EA-21 d group (n=12). Except the control group, the other three groups received 42 consecutive days of intraperitoneal injection of D-gal to establish aging rat models with cognitive dysfunction. The control group received the same amount of normal saline via intraperitoneal injection. Two EA groups were given EA therapy for 21 consecutive days (began from the 22nd day of modeling) or 7 consecutive days (began from the 36th day of modeling) accordingly at Dazhui (GV 14), Baihui (GV 20), Shenshu (BL 23) and Zusanli (ST 36). After modeling/intervention, all four groups received behavioral evaluations by Morris water maze (MWM) test, novel object recognition (NOR) test and step-down passive avoidance (SDPA) test followed by the Western blot (WB) detection of the expression levels of hippocampal NLRP3 inflammasome-associated proteins NLRP3, ASC and Caspase-1. MWM (place navigation test, PNT) results showed that the escape latency in the model group was significantly longer than that in the other three groups (P 0.05). From the 2nd day to the 4th day of the test, there was no significant difference between the EA-21 d group and the control group (P>0.05) in the escape latency; the escape latency was significantly shorter in the EA-21 d group than in the model group and the EA-7 d group (P 0.05). NOR results showed that there was no significant difference in the recognition ratio between the EA-7 d group and the EA-21 d group (P>0.05), and the recognition ratio was significantly higher in the two EA groups than in the model group (P 0.05). The model group had the shortest step-down latency, followed by the EA-7 d group, the EA-21 d group and the control group in order (P 0.05). NLRP3 inflammasome may be involved in the development of cognitive decline in aging rats; 7 consecutive days of EA intervention can partially improve the cognitive impairment in aging rats though the effect is rather limited; 21 consecutive days of EA intervention may improve the learning and memory abilities in aging rats via down-regulating the expression levels of NLRP3 inflammasome-associated proteins in hippocampus.