Circadian rhythm is one of the biorhythms formed by organisms in the process of evolution to adapt to the rotation of the earth,which is manifested as a cyclical biorhythm of about 24 hours produced by the body under the control of the internal biological clock,coordinating sleep/wakefulness,body temperature regulation,endocrine time and other activities.Long-term circadian rhythm disorders can cause increased risk of metabolic disorders,gastrointestinal diseases,neurodegenerative diseasesand other illnesses.As a typical model animal,the aquatic organism zebrafish(Danio rerio)has been widely used in experimental studies of circadian rhythm.This paper introduces in detailthe operating mechanism of zebrafish circadian clock,the influencing factors of the input system,the genes and pathways of the circadian clock,and the physiological output,summarizes the application and advantages in circadian rhythm research,finally looks forward to future research and development,in order to provide theoretical support for circadian rhythm regulation mechanism research,related drug development and disease treatment strategies.

As the incidence of chronic kidney disease (CKD) increases year by year, the number of patients with CKD is increasing year by year before or during pregnancy. Pregnancy management is increasingly important for patients with kidney disease, and women with CKD face a number of challenges during pregnancy, such as the risk of kidney disease progression, fetal growth restriction, the potential teratogenicity of medications, and an increased risk of complications such as preeclampsia and preterm birth. In order to ensure a good outcome for pregnant women and the fetus, it is necessary for multidisciplinary physicians in the department of nephrology, obstetrics, reproductive health and other departments to assess the risk of pregnancy in patients with CKD in a standardized manner, adjust medication in a timely manner, and closely monitor to detect maternal and fetal complications early, stabilize the patient′s condition, and determine the safest time for pregnancy and delivery.

Objective:To identify the risk factors for poor prognosis following interventional treatment in the patients with postherpetic neuralgia (PHN) and construct a predictive model.Methods:The medical records from patients with PHN undergoing interventional therapy at the First Affiliated Hospital of Soochow University from March 2020 to August 2023 were retrospectively collected, including basic characteristics, past medical and surgical history, symptoms, medication therapy, clinical pain score, neutrophil/lymphocyte ratio (NLR) before interventional treatment and interventional treatment methods. Logistic regression analysis was used to identify the risk factors associated with poor prognosis following interventional treatment in PHN patients, and a nomogram predictive model for poor prognosis was constructed. The discrimination and calibration of the nomogram predictive model were evaluated using the C-index and Hosmer-Lemeshow test. Calibration curves and clinical decision curves were drawn to further verify the accuracy of the predictive model.Results:The results of the multivariate logistic regression analysis show that increasing age, prolonged disease duration, elevated NLR, use of immunosuppressants and use of pulsed radiofrequency were independent risk factors for poor prognosis following intervention treatment in PHN patients ( P<0.05). The nomogram predictive model for poor prognosis following PHN interventional treatment constructed based on these factors had a C-index of 0.844. Calibration curves showed good consistency between predicted probability of poor prognosis and actual incidence of poor prognosis. Clinical decision curves indicated that the predictive model provided good accuracy and net benefit. Conclusions:Increasing age, prolonged disease course, elevated NLR, use of immunosuppressants and use of pulsed radiofrequency are independent risk factors for poor prognosis following interventional treatment in the patients with PHN. The nomogram predictive model based on these factors can effectively predict the occurrence of poor prognosis in PHN patients undergoing interventional treatment.

Objective:Based on Web of Science database, this study aimed to explore the current status, research hotspots and development trends of countries regarding clinical management of osteoporotic fractures using bibliometrics and visualized analysis.Methods:We collected literatures in the field of clinical management of osteoporotic fractures included in Web of Science database, and applied bibliometrics to analyze the publication dates, countries, institutions, journals, authors, highly cited literatures and research hotspots. Visualization was drawn by VOSviewer software.Results:Analysis of the 2 508 articles revealed 3 types of data. (1) The analysis of basic information of the literature showed that: ①The country with the largest number of publications was the United States, which published 672 articles, followed by the United Kingdom and Canada, and China ranked fourth; ②The top three authors in the number of publications were Kanis JA, Cooper C and McCloskey EV respectively; ③The institution with the highest number of publications was the University of Sheffield, UK, followed by the University of Southampton, UK and the University of Toronto, Canada. (2) Network visualization of highly cited literatures showed that 118 highly cited literatures were mainly divided into 5 clusters, which were related to osteoporotic fracture diagnosis, treatment, medication adherence, management consensus and strategies of preventing refracture. (3) Temporal overlay visualization of research hotspots showed that early research mainly focused on traditional therapeutic drugs, and current research hotspots were mainly molecular targeted drugs, trabecular bone score and fracture liaison services.Conclusion:This study shows that the research activity of clinical management of osteoporotic fractures is increasing worldwide, and there is still a huge gap between China and Europe or the United States. Current research hotspots and development trends mainly focus on molecular targeted drugs, osteoporotic fracture treatment concepts, emerging fracture risk assessment tools, and fracture prevention and management models.

OBJECTIVE To study the effects and potential mechanism of anaphylactoid reaction induced by nonapeptide IVQKIKHCF activating mast cells. METHODS Using human mast cell line LAD2 as subject， and substance P as positive control， the activation effects of 25， 50 and 100 μmol/L IVQKIKHCF on mast cells were investigated by determining the release rate of β-aminohexosidase， histamine release， and the contents of inflammatory factors； using MrgprX2-knockdown LAD2 cells and Mas- related G protein-coupled receptor X2 （MRGPRX2） high-expression human embryonic kidney cell line HEK293 （MRGPRX2/ HEK293 cells） as subject， the correlation between the activation effect of IVQKIKHCF and MRGPRX2 was investigated by determining the release rate of β-aminohexosidase， and intracellular calcium ion concentration. RESULTS IVQKIKHCF with 25， 50， 100 μmol/L could significantly increase the release rate of β-aminohexosidase and histamine release in LAD2 cells （P＜0.05）， and promote the release of tumor necrosis factor-α， interleukin-8， macrophage inflammatory protein-1β and monocyte chemotactic protein-1 to varying degrees （P＜0.05）. After knocking down MrgprX2， the effects of 25， 50， 100 μmol/L IVQKIKHCF promoting the release of β-aminohexosidase in LAD2 cells were reversed significantly （P＜0.05）， resulting in an increase of calcium ion concentration in MRGPRX2/HEK293 cells. CONCLUSIONS Nonapeptide IVQKIKHCF can promote mast cells to release granular matter and inflammatory mediators by activating MRGPRX2 thus inducing anaphylactoid reaction.

OBJECTIVE: To evaluate the value of pharmacogenetic testing for improving the efficacy and safety of treatment with cyclosporine, tacrolimus, and cyclophosphamide (CTX) for PLA2R-related membranous nephropathy and for determing individualized and precise treatment plans for the patients. METHODS: A total of 63 patients with PLA2R-related membranous nephropathy hospitalized in the Department of Nephrology at our hospital from January, 2019 to October, 2021 were enrolled in this study. Thirty-three of the patients underwent pharmacogenetic testing before taking the immunosuppressive drugs selected based on the results of genetic screening for sensitive targets, and the other 30 patients were empirically given immunosuppressive drugs according to the guidelines (control group). The clinical efficacy and adverse effects of the immunosuppressive drugs were analyzed for all the patients. The two groups of patients were compared for demographic and biochemical parameters including 24-h urine protein, serum albumin, renal function, and serum anti-phospholipase A2 receptor antibody both before and at 3 months after the beginning of the treatment. RESULTS: Among the 33 patients undergoing pharmacogenetic testing, 51.5% showed a GG genotype for cyclosporine, and 61.6% had an AG genotype for tacrolimus; for CTX, 51.5% of the patients showed a homozygous deletion and 63.6% had an AA genotype. After treatment for 3 months, serum anti-phospholipase A2 receptor antibody, 24-h urine protein, and serum albumin levels were significantly improved in pharmacogenetic testing group as compared with the control group (P < 0.05). CONCLUSION Individualized and precise administration of immunosuppressive drugs based on pharmacogenetic testing better controls proteinuria and serum antiphospholipase A2 receptor antibodies and increases serum albumin level in patients with PLA2R-related membranous nephropathy.
Humans ; Autoantibodies ; Cyclosporine/therapeutic use* ; Glomerulonephritis, Membranous/diagnosis* ; Homozygote ; Immunosuppressive Agents/therapeutic use* ; Pharmacogenomic Testing ; Receptors, Phospholipase A2 ; Sequence Deletion ; Serum Albumin ; Tacrolimus/therapeutic use*

Objective:To explore the risk factors for death within 1 year after hip fracture surgery in the elderly.Methods:A case control study was made on the clinical data of 551 elderly patients with hip fracture treated in Second Affiliated Hospital of Soochow University from January 2019 to December 2020, including 182 males and 369 females; aged 65-100 years [80(73,86)years]. Joint replacement, cannulated screw fixation or proximal femoral nail fixation were performed. The patients were divided into survival group ( n=494) and death group ( n=57) based on the death within 1 year after surgery recorded at postoperative telephone follow-up. The gender, age, hypertension, diabetes, cardiovascular diseases, chronic respiratory diseases, neurological diseases, chronic renal failure, anemia on admission, fracture types, American anesthesiologist Association (ASA) classification, operative methods, preoperative waiting time, duration of operation and perioperative blood transfusion were recorded in two groups. Univariate Cox regression was used to analyze the correlation between the above indexes and death within 1 year after surgery. All indexes with P<0.2 in the univariate analysis were included in multivariate Cox regression analysis to clarify the independent risk factors for death within 1 year after surgery. Results:Univariate Cox regression analysis showed that death within 1 year after surgery correlated with gender, age chronic respiratory diseases, chronic renal failure and anemia on admission (all P<0.01), but not with hypertension, diabetes, cardiovascular diseases, neurological diseases, fracture types, ASA classification, operative methods, preoperative waiting time, duration of operation or perioperative blood transfusion (all P>0.05). Multivariate Cox regression analysis showed that male ( HR=2.08, 95% CI 1.20, 3.61, P<0.01), age ≥ 80 years ( HR=2.22, 95% CI 1.15, 4.28, P<0.05), chronic respiratory diseases ( HR=2.54, 95% CI 1.19, 5.40, P<0.05), chronic renal failure ( HR=4.57, 95% CI 1.27, 16.44, P<0.05), anemia on admission ( HR=2.82, 95% CI 1.38, 5.76, P<0.01) were significantly associated with death within 1 year after surgery. Conclusion:Male age≥ 80 years, chronic respiratory disease, chronic renal failure and anemia on admission are independent risk factors for death within 1 year after hip fracture surgery in the elderly.

Objective:To investigate the early clinical outcomes of a minimally invasive anterolateral approach (Orthopadische chirurgie munchen, OCM) versus a conventional (posterolateral approach, PLA) hemiarthroplasty in the treatment of senior femoral neck fractures.Methods:A retrospective analysis was performed on 90 elderly patients with femoral neck fractures who received anterolateral and posterolateral approaches for hemiarthroplasty in the Second Affiliated Hospital of Soochow University from December 2019 to June 2021 and were followed up. In the OCM group, there were 45 cases, including 18 males and 27 females, aged 83.33±5.29 years (range, 76-96 years); In the PLA group, there were 45 cases, including 13 males and 32 females, aged 81.87±5.00 years (range, 75-94 years). Postoperative, surgical indices, perioperative bleeding, and soft tissue injury were assessed; pain was assessed using the visual analogue scale (VAS), and hip function was evaluated using the Harris score and the University of California at Los Angeles (UCLA) score.Results:The incision length, postoperative hospital stay, hemoglobin reduction, and occult blood loss were lower in the OCM group than in the PLA group ( P<0.05), but there was no significant difference in intraoperative bleeding and postoperative transfusion rate ( P>0.05). Serum creatine kinase and C-reactive protein levels (232.98±83.70 IU/L and 81.67±48.85 mg/L) were lower in the OCM group than in the PLA group (296.93±124.58 IU/L and 104.79±36.75 mg/L) 1 day after surgery, and the differences were statistically significant ( t=2.86, P=0.005; t=2.54, P=0.013). Postoperative pain was significantly improved in all patients, and VAS scores were lower in the OCM group than in the PLA group at 12 h, 24 h, and 48 h postoperatively ( P<0.05). The time to get out of bed after surgery was 20.73±4.99 h in the OCM group compared with 41.69±13.58 h in the PLA group, with a statistically significant difference ( t=9.71, P<0.001). Harris scores (63.31±6.21 and 75.76±4.91) and UCLA scores (1.84±0.42 and 3.69±0.76) were higher in the OCM group on the day of discharge and at 1 month postoperatively than in the PLA group (52.69±10.01 and 71.33±3.66); (1.62±0.54 and 3.16±0.80) points, all with statistically significant differences ( P<0.05). However, the differences in Harris score and UCLA score between the two groups at 6 months postoperatively were not statistically significant ( P>0.05). There were two cases of intermuscular vein thrombosis in the OCM group, with a complication rate of 4% (2/45), and one case of dislocation in the PLA group, with a complication rate of 2% (1/45), there was no significant difference between the two groups ( P=1.000). Conclusion:The minimally invasive anterolateral approach is a more ideal procedure for elderly patients with femoral neck fractures undergoing hemiarthroplasty. It has the advantages of a short incision, small soft tissue damage, low occult blood loss, early removal from bed, a short postoperative hospital stay, an improvement in pain, and a good early recovery of hip function.

Objective:To evaluate the relationship between preoperative plasma trimethylamine oxide (TMAO) concentrations and postoperative delirium (POD) in elderly patients.Methods:One hundred and eighty patients, aged ≥65 yr, of American Society of Anesthesiologists Physical Status classification Ⅱ or Ⅲ, with body mass index of 17-30 kg/m 2, scheduled for elective hip replacement, were enrolled in this study. Venous blood samples were collected at 1 day before surgery, and the plasma TMAO concentrations were measured by high throughput liquid chromatography-tandem mass spectrometry. The patients were divided into 3 groups according to the concentrations of TMAO: low-concentration TMAO group (group L, ≤1.2 μmol/L), moderate-concentration TMAO group (group M, 1.3-1.9 μmol/L), and high-concentration TMAO group (group H, ≥2.0 μmol/L). All patients received superior inguinal fascia iliaca compartment block combined with intravenous general anesthesia. POD was identified by the Confusion Assessment Method-Chinese Reversion scale at 1, 2, 3 and 7 days after operation. The patients were divided into POD group and non-POD group according to whether POD occurred. Binary logistic regression analysis was used to evaluate the relationship between different plasma TMAO concentrations and POD. The receiver operating characteristic curve was used to evaluate the efficacy of plasma TMAO concentrations in predicting the occurrence of POD. Results:There were 60 cases in L group, 67 cases in M group and 53 cases in H group, and the incidence of POD was 12%, 22% and 32% in L, M and H groups, respectively. The incidence of POD was significantly higher in group H than in group L ( P<0.05). The plasma TMAO concentration was significantly higher in POD group than in non-POD group ( P<0.05). Logistic regression analysis showed that the risk of POD was 3.91 times higher in group H than in group L ( P<0.05). The area under the receiver operating characteristic curve of preoperative plasma TMAO concentrations in predicting POD was 0.754 (95% confidence interval 0.671-0.838, P<0.05). When the Youden index was 0.426, the optimal cut-off value of plasma TMAO concentrations was 1.625 μmol/L, and the specificity and sensitivity were 0.795 and 0.631, respectively. Conclusions:Elevated preoperative plasma TMAO concentration is associated with an increased risk of POD in elderly patients, and it has a good predictive value for POD.

The incidence of osteoporosis and its resulting osteoporotic fractures is increasing year by year. More and more scholars pay attention to the fact that the 2 years after osteoporotic fractures is a high-risk period for re-fractures and the key window period for secondary fracture prevention. Osteoporotic fractures are important risk factors for re-fractures, and many other factors, such as the time interval after fracture and fracture site, affect the occurrence of re-fractures. Therefore, traditional fracture risk assessment tools are not suitable for the re-fracture risk assessment, while preliminary reports of emerging re-fracture risk assessment tools have been available. In recent years, with the worldwide promotion of fracture liaison service (FLS), the comprehensive management strategies have effectively improved the diagnosis rate, treatment rate and drug compliance of patients with osteoporotic fractures, while reducing the risk of re-fractures. However, there are a variety of FLS projects with different models around the world, clinicians in some countries and regions have insufficient understanding and attention to the absence of management after osteoporotic fractures, and the risk of re-fractures is still imminent. Therefore, this article systematically elaborated the latest status of re-fractures after osteoporotic fractures, risk factors affecting re-fractures and new re-fracture risk assessment tools. The prevention and management strategies of re-fractures are summarized from three aspects: the standardized anti-osteoporosis drug therapy, the multidisciplinary FLS, as well as the early and personalized rehabilitation therapy, in order to provide references for clinical management of osteoporotic fractures in China.