Objective: To explore the effects of Cldn14 gene knockout on renal metabolism and stone formation in rats，so as to provide reference for research in the field of urinary calium metabolism and stone formation. Methods: Cldn14 gene knockout homozygous rats and wild-type rats of the same age were randomly divided into 4 groups：wild-type control (WC) group，wild-type ethylene glycol (WE) group，gene knockout control (KC) group and gene knockout ethylene glycol (KE) group，with 10 rats in each group.The WE and KE groups were induced with ethylene glycol + ammonium chloride to form kidney stones，while the WC and KC groups received normal saline gavage.After 4 weeks of standard maintenance feeding，the urine samples were collected to detect the venous blood.The kidneys were collected for HE，Pizzolatto's staining and transmission electron microscopy.The protein in renal tissues was extracted to detect the expressions of Claudin16 and Claudin19. Results: Crystal deposition was observed in the renal tubular lumen of the WE and the KE groups，and more crystals were detected in the KE group.The WE group had a large number of intracytoplasmic black crystalline inclusions observed in renal tubular epithelial cells under transmission electron microscope，followed by the KE and KC groups.Compared with WC and WE groups，KC and KE groups had significantly decreased serum calcium and magnesium levels but significantly increased urinary calcium level.In addition，the urinary calcium level was higher in the WE group than in the WC group and higher in the KE group than in the KC group.The KE group had lower level of Claudin16，but there was no significant difference in the level of Claudin19 among the 4 groups(P>0.05). Conclusion: Knockout of Cldn14 gene alone cannot effectively reduce urinary calcium excretion or reduce the risk of stone formation in rats，which may be related to the decrease of Claudin16 level.

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Objective:To investigate the clinical efficacy of 3D printed metal augment or tibial prosthesis for reconstruction of large bone defects in total knee arthroplasty (TKA) and knee revision surgery.Methods:A total of 7 patients (7 knees) with TKA or knee revision who were admitted to the Department of Orthopaedics of the Second Affiliated Hospital of Zhejiang University School of Medicine with large bone defects from July 2018 to December 2023 were retrospectively analyzed, including 4 patients with TKA and 3 patients with knee revision. There were 3 males and 4 females, aged 58.7±7.6 years (range, 54-68 years), 3 patients with left knee and 4 patients with right knee. All the patients had bone defects in the knee joint (AORI type III), 2 cases had bone defects only in the femur, 4 cases had bone defects only in the tibia, and 1 case had bone defects in both the tibia and femur, which were treated with personalized reconstruction using 3D printing. Hip-knee-ankle angles, American Knee Society score (KSS) before and after surgery were compared, and postoperative complications were observed.Results:All patients successfully completed the operation, and the operation time was 189.3±35.5 min (range, 125-240 min). Complex TKA was performed in 4 cases with surgical times of 175, 195, 210, and 240 min, and revision surgery was performed in 3 cases with surgical times of 125, 180, and 200 min, respectively. Intraoperative blood loss was 114±24.4 ml (range, 100-150 ml). Five cases used 3D printed metal augment, and two used 3D printed one-piece tibial components. All patients were followed up for 2, 2, 5, 6, 7, 20, 57 months, respectively. The KSS of the five patients at 3 months postoperatively were 56, 61, 66, 56, and 56 points, respectively, greater than the preoperative scores of 35, 44, 36, 27, and 41 points. The KSS functional scores of the five patients at 3 months postoperatively were 45, 45, 45, 30, and 45 points, respectively, which were greater than the preoperative scores of 30, 30, 15, 20, and 20 points. The hip-knee-ankle angle was 181.8°±3.4° (range, 177.9° to 188.0°) at the final follow-up and 175.8°±12.4° (range, 153.3° to 192.1°) before surgery, with no significant difference ( t=-1.230, P=0.242). At the final follow-up, the 3D printed component was well integrated with the bone surface, the prosthesis was securely positioned, and the force lines of the lower limbs were normal. There were no postoperative complications such as poor wound healing, infection, fat liquefaction, nerve injury, deep vein thrombosis of lower limbs, knee joint stiffness, periprosthesis infection and loosening. Conclusion:Using 3D printed metal augment or tibial prosthesis to reconstruct the huge bone defect in TKA and revision has a satisfactory early clinical effect, satisfactory joint function and good surgical safety.

Objective:To explore the classification and influencing factors of family resilience and post-traumatic growth in patients with spinal tumor.Methods:A cross-sectional investigation was conducted among 219 inpatients with spinal tumor admitted from July 2021 to July 2022. The General Demographic Information questionnaire, Chinese-Family Resilience Assessment Scale, Posttraumatic Growth Inventory, Family Crisis-Oriented Personal Evaluation Scales (F-COPES), and Social Support Rating Scale (SSRS) were used in the study. The ordinal and multivariate logistic regression analyses was applied to identify the factors associated with the classification of family resilience and post-traumatic growth.Results:Of the 219 patients, there were 62 cases of primary spinal tumors (28.3%). According to the results of latent profile analysis, the respondents were classified into three categories by family resilience and post-traumatic growth, namely family difficulty-resistant type ( n=38, 17.4%), general resilience-struggle type ( n=99, 45.2%) and family adaptation-growth type ( n=82, 37.4%). There were significant differences in occupational status, commitment to housework, family atmosphere( χ2=10.75, P=0.025; χ2=6.95, P=0.031; χ2=11.37, P=0.017), and total score of F-COPES and SSRS ( F=25.95, P<0.001; F=19.06, P<0.001)among three groups. Ordinal and multivariate logisitc regression analyses showed that retirement ( OR=2.928, 95% CI:1.098-7.808, P<0.05), family coping ( OR=1.113, 95% CI:1.063-1.165, P<0.05), and social support ( OR=1.226, 95% CI:1.103-1.362, P<0.05) were independently associated with family resilience and post-traumatic growth in patients with spinal tumor. Conclusion:Patients with spinal tumor have significant differences in characteristics by family resilience and post-traumatic growth. As a result, more targeted interventions should be provided for different categories of spinal tumor patients in the future.

BACKGROUND:Recent studies have shown that research on naringin anti-osteoporosis mostly stays in in vitro and in vivo experiments.Understanding the mechanism of related signaling pathways and the expression of related proteins and some specific genes is an important way to deeply understand naringin anti-osteoporosis.At present,traditional Chinese medicine has been confirmed to have a significant role in anti-osteoporosis.Naringin is one of the main active ingredients in Rhizoma Drynariae.Its effectiveness and mechanism of action against osteoporosis have been gradually recognized by scholars,and its clinical and basic research has been gradually emphasized. OBJECTIVE:To analyze and summarize the research progress of naringin in anti-osteoporosis in vitro and in vivo,thereby providing some ideas for the next step to study its related mechanism of action. METHODS:The relevant literatures included in CNKI and PubMed database were searched with the Chinese search terms of"naringin,osteoporosis,traditional Chinese medicine compound,pathogenesis,signaling pathway,bone marrow mesenchymal stem cells,osteoblasts,osteoclasts"in Chinese and English,respectively.The corresponding criteria were established according to the research needs,and finally 69 articles were included for review. RESULTS AND CONCLUSION:Naringin blocks the increase in the number of osteoclasts and adipocytes,the decrease in the number of osteocytes and osteocalcin(+)cells induced by fructose-rich diet,and promotes the secretion of Sema3A from osteoblasts and osteocytes,thereby enhancing local bone formation and inhibiting osteoclast production by activating the Wnt/β-catenin pathway.Naringin is an important way to induce autophagy of osteoblasts,but autophagy-related proteins participate in osteoblast differentiation and bone formation.Lack of autophagy in osteoblasts reduces mineralization and leads to an imbalance in the number of osteoblasts and osteoclasts,which results in bone loss and decreased bone density.The composite scaffold loaded with naringin can be used as a necessary carrier for bone defect repair and has excellent bone repair properties.Naringin can also accelerate the growth of new bone tissue by increasing the local contents of bone morphogenetic protein 2 and vascular endothelial growth factor.Naringin can regulate bone metabolism and inhibit oxidative stress via ERK,PI3K/Akt and Wnt signaling pathways to improve osteoporosis,which can play a good role in preventing and controlling the disease.However,the depth and breadth of the relevant research is insufficient.Based on the mechanism of the current study,we should investigate the specific mechanisms by which naringin regulates different pathways and inter-pathway interactions in the future,which will be beneficial to the multifaceted development of naringin used in the treatment of osteoporosis..

OBJECTIVE To study the effect of 60Co-γ irradiation on the sterilization effect and main components of Rubus chingii Hu. METHODS Irradiated Rubus chingii Hu by 0, 6, 10, 15, 30 kGy doses of 60Co-γ, used the microbial count method to determine the microbial level of Rubus chingii Hu before and after irradiation. Analyzed the components of Rubus chingii Hu by high resolution mass spectrometry, investigated the effects of irradiation on the quality of Rubus chingii Hu by comparing the components of Rubus chingii Hu samples before and after irradiation, analyzing the quantitative results of ellagic acid and kaempferol 3-O-yunxiangoside, and evaluating the similarity of fingerprints. RESULTS The results of microbial examination of Rubus chingii Hu after different doses of irradiation all met the requirements, cluster analysis and principal component analysis of 20 components showed no significant difference. And there was no significant difference in the contents of ellagic acid and kaempferol 3-O-glucoside before and after irradiation. The similarity of fingerprints before and after irradiation was between 0.995 and 1.000. CONCLUSION Irradiation can effectively control the microbial level in Rubus chingii Hu, and there is no significant effect on the chemical composition of Rubus chingii Hu, the results provide a basis for the application of irradiation in the sterilization process of Rubus chingii Hu.

OBJECTIVE To evaluate the quality and existing problems of Compound Paracetamol and Chlorphenamine Tablets for Infant. METHODS Using legal standards to inspect sampled samples, and several analytical methods were subsequently established or improved for the exploratory research on related substances, assay, dissolution, subdivision characteristics of scored tablets, and genotoxic impurities. RESULTS All samples met the regulatory specification, and the pass rate was 100%. However, the control for related substances was lacking, and the method for assay and content uniformity was defective. The exploratory studies showed that the assay and content uniformity met the requirements, and the risk of related substances and genotoxic impurities was acceptable. As a divisible tablet, the subdivision characteristics could not meet the requirements of the scored tablet, and the dissolution performance of some enterprise samples could not meet the requirements of similar products in foreign pharmacopoeias. CONCLUSION The overall quality of this product is adequate. However, due to the early time on the market, some quality attributes no longer meet the requirements of current regulations or relevant guidelines. The manufacturers should further optimize the prescription and production process, referring to foreign similar products. The current specification needs to be revised and improved.

ObjectiveTo investigate the impact of acute respiratory infections in children under 12 years old in Pudong New Area， Shanghai from 2019 to 2023. MethodsAcute respiratory infection samples of children under 12 years old from three sentinel hospitals in Pudong New Area， Shanghai from 2019 to 2023 were collected， and 42 respiratory infection pathogens， including influenza virus， adenovirus， parainfluenza virus， respiratory syncytial virus， human enterovirus/rhinovirus， human pulmonary virus， human bokavirus， coronavirus （229E， HKU1， NL63 and OC43）， and novel coronavirus， were detected with microfluidic chips. The situation of acute respiratory infections among outpatient and inpatient children in this area was analyzed for the before the implementation of non pharmacological intervention measures （2019.12‒2020.1）， during the period of non pharmacological intervention measures （2020.2‒2022.12）， and after non pharmacological intervention measures （2023.1‒2023.6）. ResultsFrom 2019 to 2023， a total of 1 770 samples were collected， and 445 pathogens were detected， with a detection rate of 25.14% （445/1 770）. The main pathogens detected during the study period were influenza virus： 8.70% （154/1 770）， respiratory syncytial virus： 4.41% （78/1 770）， human enterovirus/rhinovirus： 2.66% （47/1 770）， human adenovirus： 2.49% （44/1 770）， and parainfluenza virus： 2.20% （39/1 770）. Before the implementation of non pharmacological intervention measures， outpatients were primarily infected with influenza， parainfluenza virus， and respiratory syncytial virus， with detection rates of 8.09%， 4.49%， and 4.04%， respectively； inpatients were mainly infected with influenza， respiratory syncytial virus， and parainfluenza virus， with detection rates of 4.49%， 3.82%， and 3.15%， respectively. During the period of non pharmacological intervention measures， influenza， rhinovirus and respiratory syncytial virus were the main viruses detected in the samples of outpatient children， with detection rates of 4.04%， 3.60%， and 2.47%， respectively； inpatient samples mainly detected respiratory syncytial virus， rhinovirus， and influenza virus， with detection rates of 3.60%， 2.02%， and 1.80%， respectively. After non pharmacological intervention measures， influenza， rhinovirus and respiratory syncytial virus were the main pathogens detected in the outpatients， with detection rates of 9.89%， 2.92% and 2.02%， respectively； influenza， respiratory syncytial virus， and rhinovirus were the main pathogens detected in inpatient children， with detection rates of 6.29%， 1.57%， and 1.35%， respectively. ConclusionThe prevalence of pathogens related to acute respiratory infections in children is influenced by non pharmacological preventive measures.

ObjectiveTo understand the acceptance of sex-related behaviors， sexual safety awareness， and refusal skills among junior high school students and conduct association analysis， and to provide a reference for the implementation of sex and reproductive health education for adolescents. MethodsA questionnaire survey related to knowledge of sexual and reproductive health was conducted among 478 students from two junior high schools in Jiading District， Shanghai. ResultsThe pass rate for sex and reproductive health knowledge among junior high school students was only 36.6%， with acceptance rates for dating， watching pornography， engaging in sexual behavior， pregnancy， and artificial abortion at 24.5%， 11.1%， 5.6%， 4.8%， and 5.9%， respectively. Binary logistic regression analysis showed that students who passed the sexual and reproductive health assessment had a significantly lower acceptance rate of sex-related behaviors than those who did not （aOR=1.666， 95%CI： 1.124‒2.470， P=0.011）. Adolescents with a passing knowledge of sexual and reproductive health （aOR=1.607， 95%CI： 1.060‒2.438， P=0.026） or a lower acceptance of sex-related behaviors （aOR=4.199， 95%CI： 2.804‒6.289， P<0.001） had higher awareness of sexual safety. Adolescents with a passing knowledge of sexual and reproductive health （aOR=1.691， 95%CI： 1.066‒2.684， P=0.026）， a lower acceptance of sex-related behaviors （aOR=1.756， 95%CI： 1.130‒2.729， P=0.012）， or higher awareness of sexual safety （aOR=2.872， 95%CI： 1.826‒4.516， P<0.001） had stronger skills to refuse sex-related behaviors. ConclusionSexual and reproductive attitudes， sexual safety awareness， and refusal skills for sex-related behaviors among junior high school students in Jiading District need to be improved. Schools should focus on cultivating adolescents’ sexual and reproductive knowledge and related skills， and advocate for relevant institutions to provide appropriate sexual healthcare services to meet their needs for reproductive healthcare.

Objective:To investigate the status quo and influencing factors of social isolation of parents of children with autism spectrum disorder in order to provide theoretical basis for clinical intervention measures.Methods:A total of 340 parents of children with autism spectrum disorder who visited the Children′s Developmental Behavior Center of Third Affiliated Hospital of Sun Yat sen University were selected by the convenience sampling method as research objects during July to November 2023. A cross-sectional survey was investigated by a general information questionnaire, General Alienation Scale, Social Avoidance and Distress Scale, Affiliate Stigma Scale, Family APGAR Index, Chinese Simplified Version of Social Support Scale, and Social Responsiveness Scale.Results:A total of 323 valid questionnaires were collected, including 235 mothers and 88 fathers; 33 individuals aged 25-29 years, 233 individuals aged 30-39 years, and 57 individuals aged 40-60 years. The subjective social isolation score of parents of children with autism spectrum disorder was 33.24 ± 4.92 and the objective social isolation score was 4.00(2.00,7.00). The results of multiple linear regression analysis showed that the subjective social isolation of parents of children with autism spectrum disorder was influenced by factors including self-assessed health status, whether they worked full-time or not, whether they were satisfied with the division of labor in the family caring for their children, affiliate stigma, family care, and social support (all P<0.05); and the objective social isolation of parents was influenced by factors including the severity of autism symptoms, self-assessed health status, affiliate stigma, and family care (all p<0.05). Conclusions:Parents of children with autism spectrum disorder had some degree of social isolation, and the level of subjective social isolation was higher than objective social isolation. Healthcare professionals should pay attention to parents of autistic children who have high levels of symptom severity, poor self-rated health, do not work full-time, and are dissatisfied with the division of labor in the family caring for their child, and take measures to reduce the affiliate stigma, and to increase the level of family care and social support, so as to improve the social isolation of parents of children with autism spectrum disorder.