Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

Objective:Investigating the migration pattern of microorganisms in the oil-water phase during the prep-aration of sterile test solutions for drugs by extraction method,providing reference for the pre-treatment of oil-based matrix test samples.Methods:Inoculate 6 strains of test bacteria separately into sterile isopropyl tetradecanoate,simulate the sample preparation process of extraction method,and detect the growth status of microorganisms in oil-water phase;Detect the recovery ratio of each test bacterium in the aqueous phase using the extraction method.Select semi-solid oily matrix samples and prepare the test solution using extraction method.Establish a sterility test method according to Part 1101 of the 2020 edition of the Chinese Pharmacopoeia.Results:After extraction,the recovery ratio of each test bacteria in the water phase is in the range of 0.64-0.89.After the oily matrix sample is extracted,the water phase is taken for microbial test,which effectively solves the problems of filter membrane blockage and difficult antibacterial removal,and is beneficial to the subsequent microbial inspection.Conclusion:The extraction method can improve the accuracy and sensitivity of microbial detection in the prepara-tion of test solutions for oily matrix samples.The applicability test of the established sterile inspection method meets the requirements of the Chinese Pharmacopoeia.

Objective: To assess the dynamic changes of microcirculation at acupoints in patients with primary dysmenorrhea and cold congelation and blood stasis syndrome using laser speckle blood flow imaging. Methods: Patients with primary dysmenorrhea and cold coagulation and blood stasis syndrome (primary dysmenorrhea group, n=53) and healthy female college students(control group, n=57) who met the inclusion and exclusion criteria from October 2020 to July 2022 were enrolled at Hebei University of Chinese Medicine. On the premenstrual and first day of menstruation, a laser speckle blood flow imaging system was used to measure the microcirculation blood flow perfusion on the surface of acupoints related to the conception, thoroughfare, and governor vessels, and stomach, spleen, and bladder meridians in the abdomen and lumbosacral regions. The dynamic changes in microcirculation were calculated based on the difference in average blood flow perfusion at each acupoint before and after menstruation. Receiver operating curve (ROC) analysis was used to analyze the diagnostic efficacy of dynamic changes in microcirculation on the surface of each acupoint. The microcirculation sensitization rate of acupoints was calculated. Results: Compared with the control group, the dynamic changes in microcirculation at the following acupoints in the primary dysmenorrhea group were increased (P<0.05): conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]); left thoroughfare vessel (left Huangshu[KI16], left Zhongzhu[KI15], left Siman[KI14], left Qixue[KI13], left Dahe[KI12], left Henggu[KI11]); left stomach meridian (left Tianshu[ST25], left Wailing[ST26], left Qichong[ST30]); left spleen meridian (left Daheng[SP15], left Fujie[SP14]); right thoroughfare vessel (right Huangshu[KI16], right Zhongzhu[KI15], right Siman[KI14], right Qixue[KI13], right Dahe[KI12], right Henggu[KI11]); right stomach meridian (right Wailing[ST26], right Daju[ST27], right Shuidao[ST28], right Guilai[ST29], right Qichong[ST30]); and right spleen meridian (right Fujie[SP14]). The area under the ROC curve of conception vessel (Yinjiao[CV7], Qihai[CV6], Shimen[CV5], Guanyuan[CV4]), thoroughfare vessel (right Siman[KI14], left Huangshu[KI16], right Qixue[KI13], right Zhongzhu[KI15], right Dahe[KI12], left Zhongzhu[KI15], left Siman[KI14], right Huangshu[KI16], left Qixue[KI13], right Henggu[KI11], left Henggu[KI11], left Dahe[KI12]); stomach meridian (left Tianshu[ST25], right Guilai[ST29], left Wailing[ST26], right Shuidao[ST28], right Daju[ST27], right Wailing[ST26], right Qichong[ST30], left Qichong[ST30]), and spleen meridian (left Daheng[SP15], left Fujie[SP14], right Fujie[SP14]) was 0.610-0.682 (P<0.05). Compared with the control group, the sensitization rate of some acupoints in the primary dysmenorrhea group increased (P<0.05). Conclusion With the onset of menstruation, the blood flow perfusion of some acupoints in the abdomen (thoroughfare, and conception vessels, and stomach and spleen meridians) of patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome increased, and the status of acupoints changed from a resting state to an active state. These acupoints are sensitive in patients with primary dysmenorrhea and cold blood coagulation and blood stasis syndrome and have a certain diagnostic efficacy, providing a basis for further analyzing the efficacy and mechanism of acupuncture and moxibustion to treat primary dysmenorrhea with cold blood coagulation and blood stasis syndrome.

ObjectiveTo explore the current situation， causes， and countermeasures of medical disputes in a tertiary A comprehensive hospital in Xi’an from 2018 to 2023. MethodsA total of 804 medical dispute cases that had been processed in a tertiary A hospital in Xi’an from January 2018 to December 2023 were collected. The occurrence， current characteristics， and cause distribution of medical disputes were retrospectively analyzed. ResultsThe cumulative incidence rate of medical disputes was 4.408/100，000， and the compensation rate was 31.59% （254/804）. The incidence and compensation rate of medical disputes showed an overall increasing trend year by year from 2018 to 2023 （P<0.05）. The proportion of deceased patients in dispute cases in the past 6 years showed an increasing trend annually （χ²=30.396， P=0.011）. Medical dispute cases mainly came from hospitalized patients （65.17%） and patients undergoing surgical treatment （55.35%）， and the top five departments with medical dispute cases were the hepatobiliary surgery department， cardiovascular medicine department， obstetrics and gynecology department， emergency department， and gastroenterology department. The number of in-hospital mediations showed a decreasing trend annually， while the number of people’s mediations showed an increasing trend annually from 2018 to 2023 （χ²=34.523， P<0.001）. The top five causes of medical disputes in this hospital were surgical/operational complications （29.10%）， disease condition assessment/disease diagnosis （10.45%）， diagnosis and treatment plan （9.45%）， diagnosis and treatment effectiveness （8.83%）， and medical insurance reimbursement （7.59%）. ConclusionThe number of medical disputes and compensation cases in comprehensive hospitals is increasing annually， and high-risk departments such as the surgical department and emergency department need to be given high attention. The handling of medical disputes has shown diversification， with people’s mediation gradually taking the dominant position. The causes of medical disputes mainly concentrated on diagnosis and treatment technology， doctor-patient communication， medical insurance， and other aspects. It is necessary to continuously improve the level of clinical diagnosis and treatment technology， strengthen doctor-patient communication， improve the medical insurance system， strengthen hospital connotation management， alleviate doctor-patient conflicts， and builds a harmonious doctor-patient relationship.

Polygonati Rhizoma demonstrates significant potential for addressing both chronic and hidden hunger. The supply of high-quality seedlings is a primary factor influencing the development of the Polygonati Rhizoma industry. Warm water soaking is often used in agriculture to promote the rapid germination of seeds, while its application and molecular mechanism in Polygonati Rhizoma have not been reported. To rapidly obtain high-quality seedlings, this study treated Polygonatum kingianum var. grandifolium seeds with sand storage at low temperatures, warm water soaking, and cultivation temperature gradients. The results showed that the culture at 25 ℃ or sand storage at 4 ℃ for 2 months rapidly broke the seed dormancy of P. kingianum var. grandifolium, while the culture at 20 ℃ or sand storage at 4 ℃ for 1 month failed to break the seed dormancy. Soaking seeds in 60 ℃ warm water further increased the germination rate, germination potential, and germination index. Specifically, the seeds soaked at 60 ℃ and cultured at 25 ℃ without sand storage treatment(Aa25) achieved a germination rate of 78. 67%±1. 53% on day 42 and 83. 40%±4. 63% on day 77. The seeds pretreated with sand storage at 4 ℃ for 2 months, soaked in 60 ℃ water, and then cultured at 25 ℃ achieved a germination rate comparable to that of Aa25 on day 77. Transcriptomic analysis indicated that warm water soaking might promote germination by triggering reactive oxygen species( ROS), inducing the expression of heat shock factors( HSFs) and heat shock proteins( HSPs), which accelerated DNA replication, transcript maturation, translation, and processing, thereby facilitating the accumulation and turnover of genetic materials. According to the results of indoor controlled experiments and field practices, maintaining a germination and seedling cultivation environment at approximately 25 ℃ was crucial for the one-year seedling cultivation of P. kingianum var. grandifolium.
Germination ; Seedlings/genetics* ; Water/metabolism* ; Seeds/metabolism* ; Polygonatum/genetics* ; Temperature ; Plant Proteins/genetics* ; Plant Dormancy

Objective To analyze the characteristics of oral and maxillofacial injuries from military training and provide references for related prevention and treatment.Methods A retrospective analysis was conducted of the medical records of 111 patients with oral and maxillofacial military training injuries treated between 2014 and 2023.Results From 2014 to 2023,the number of hospitalized patients with maxillofacial military training injuries in the hospital trended upward.The top 3 training injuries in the spectrum of diseases were maxillofacial fractures(45.08％),maxillofacial space infections(28.83％),and temporomandibular joint injuries(18.92％).The average number of hospitalizations for all maxillofacial military training injuries was 1.33(1-4),and the median length of hospital stay was 8(5,12)days.The median hospitalization cost was 14 793.23(5236.18,24 255.25)yuan,and the improvement rate was 95.50％.Conclusion The number of patients hospitalized due to oral and maxillofacial military training injuries in this hospital is increasing year by year,and the injuries are mostly jaw fractures.Precautions should be taken to prevent maxillofacial training injuries.

OBJECTIVE: To establish and validate a novel diabetic retinopathy (DR) risk-prediction model using a whole-exome sequencing (WES)-based machine learning (ML) method. METHODS: WES was performed to identify potential single nucleotide polymorphism (SNP) or mutation sites in a DR pedigree comprising 10 members. A prediction model was established and validated in a cohort of 420 type 2 diabetic patients based on both genetic and demographic features. The contribution of each feature was assessed using Shapley Additive explanation analysis. The efficacies of the models with and without SNP were compared. RESULTS: WES revealed that seven SNPs/mutations ( rs116911833 in TRIM7, 1997T>C in LRBA, 1643T>C in PRMT10, rs117858678 in C9orf152, rs201922794 in CLDN25, rs146694895 in SH3GLB2, and rs201407189 in FANCC) were associated with DR. Notably, the model including rs146694895 and rs201407189 achieved better performance in predicting DR (accuracy: 80.2%; sensitivity: 83.3%; specificity: 76.7%; area under the receiver operating characteristic curve [AUC]: 80.0%) than the model without these SNPs (accuracy: 79.4%; sensitivity: 80.3%; specificity: 78.3%; AUC: 79.3%). CONCLUSION Novel SNP sites associated with DR were identified in the DR pedigree. Inclusion of rs146694895 and rs201407189 significantly enhanced the performance of the ML-based DR prediction model.
Diabetic Retinopathy/diagnosis* ; Humans ; Machine Learning ; Male ; Female ; Polymorphism, Single Nucleotide ; Middle Aged ; Exome Sequencing ; Aged ; Adult ; Pedigree ; Diabetes Mellitus, Type 2/complications* ; Genetic Predisposition to Disease ; Mutation

Objective:Investigating the migration pattern of microorganisms in the oil-water phase during the prep-aration of sterile test solutions for drugs by extraction method,providing reference for the pre-treatment of oil-based matrix test samples.Methods:Inoculate 6 strains of test bacteria separately into sterile isopropyl tetradecanoate,simulate the sample preparation process of extraction method,and detect the growth status of microorganisms in oil-water phase;Detect the recovery ratio of each test bacterium in the aqueous phase using the extraction method.Select semi-solid oily matrix samples and prepare the test solution using extraction method.Establish a sterility test method according to Part 1101 of the 2020 edition of the Chinese Pharmacopoeia.Results:After extraction,the recovery ratio of each test bacteria in the water phase is in the range of 0.64-0.89.After the oily matrix sample is extracted,the water phase is taken for microbial test,which effectively solves the problems of filter membrane blockage and difficult antibacterial removal,and is beneficial to the subsequent microbial inspection.Conclusion:The extraction method can improve the accuracy and sensitivity of microbial detection in the prepara-tion of test solutions for oily matrix samples.The applicability test of the established sterile inspection method meets the requirements of the Chinese Pharmacopoeia.

Glyceryl phenylbutyrate(GPB)serves as a long-term management medication for Ornithine transcarbamylase deficiency(OTCD),effectively controlling hyperammonemia,but there is a lack of experience in using this medicine in China.This article retrospectively analyzes the case of a child diagnosed with OTCD at Shanghai Children's Medical Center,Shanghai Jiao Tong University School of Medicine,including a review of related literature.After diagnosis,the patient was treated with GPB,followed by efficacy follow-up and pharmacological monitoring.The 6-year and 6-month-old male patient exhibited poor speech development,disobedience,temper tantrums,and aggressive behavior.Blood ammonia levels peaked at 327 μmol/L;urine organic acid analysis indicated elevated uracil levels;cranial MRI showed extensive abnormal signals in both cerebral hemispheres.Genetic testing revealed de novo mutation in the OTC gene(c.241T＞C,p.S81P).Blood ammonia levels were approximately 43,80,and 56 μmol/L at 1,2,and 3 months after starting GPB treatment,respectively.During treatment,blood ammonia was well-controlled without drug-related adverse effects.The patient showed improvement in developmental delays,obedience,temperament,and absence of aggressive behavior.

Objective To investigate the effects of hederagenin (HDG) on proliferation, migration, invasion and apoptosis of glioblastoma (GBM) cells and involved mechanism.Methods Human GBM cell lines U87, U251 and human brain glial cell line (HEB) were selected as the study subjects, and HDG 0μmol/L (or 0 mg/kg) was used as the control group.MTT, EdU staining and cell plate cloning were used to detect the effect of HDG on the proliferation of GBM cells.Trypan blue staining was used to detect GBM cell death affected by HDG.The effects of HDG on migration and invasion of GBM cells were detected by cell scratch and Transwell assay.To analyze the effects of HDG on apoptosis of GBM cells, apoptosis-related proteins Bcl-2, Bax, p53 and cleaved caspase-3 were detected by Western blot.Mitochondrial potential change was detected by JC-10 staining, and apoptotic cell count was displayed by Annexin V-FITC staining.The effect of HDG on tumor bearing in GBM was analyzed by xeno-transplantation in BALB/C mice.Results Compared with the control group (HDG0 μmol/L), HDG significantly inhibited the proliferation, migration and invasion of U87 and U251 cells, and they were dependent on the use dose of HDG.Trypan blue staining showed that HDG obviously increased death number of GBM cells.The mitochondrial potential of GBM cells was remarkedly decreased, the number of apoptotic GBM cells obviously increased, the ex-pressions of apoptosis-related proteins p53, Bax, cleaved-caspase3 were up-regulated and Bcl-2 was down-regulated by HDG in U87 and U251 cells.HDG significantly inhibited the size of subcutaneous GBM, the Ki67 positive rate of GBM cells and caused a large number of GBM cells to die in BALB/C mice.HDG had no obvious toxic effect on human HEB cells and the liver of tumor-bearing mice.Conclusion HDG can significantly inhibit the prolifera-tion, migration and invasion of GBM cells and induce the apoptosis of them.The mechanism of HDG induced apop-tosis of GBM cells may be through mitochondrial damage and regulation of p53 and Bcl-2/Bax expression.