OBJECTIVE To study the improvement effect and mechanism of Tripterygium wilfordii multiglucoside （TWM） on nephrotic syndrome in rats. METHODS The nephrotic syndrome model was established by intravenous injection of adriamycin via the tail vein. The modeling rats were randomly divided into the model group （distilled water）， prednisone group （10 mg/kg）， and TWM high- and low-dose groups （10 and 5 mg/kg， respectively）. Additionally， blank group （distilled water） without model induction was established. Each group consisted of 9 rats. Rats in each group were administered the corresponding drugs or distilled water by gavage， once a day， for 6 consecutive weeks. The histopathological morphology of kidney tissues in rats was observed； the levels of 24-hour urinary protein （24 h-UTP） and serum biochemical indicators [albumin （ALB）， blood urea nitrogen （BUN）， serum creatinine （SCr）， cholesterol （CHOL）， and triglyceride （TG）] in rats were determined； the levels of oxidative stress indicators [superoxide dismutase （SOD）， malondialdehyde （MDA）] in kidney tissue of rats were determined； expressions of hypoxia-inducible factor-1α （HIF-1α）/microRNA-155-5p （miR-155-5p）/nuclear factor erythriod 2- related factor 2 （Nrf2） signaling pathway-related mRNA and protein in the renal tissues of rats were detected. RESULTS Compared with the blank group， the rats in the model group exhibited disordered renal tissue structure， with a small amount of glomerular necrosis and edema of the renal tubular epithelial cells. 24 h-UTP， serum levels of SCr， BUN， CHOL and TG， MDA content， mRNA and protein expressions of HIF-1α and Keap1 as well as the expression of miR-155-5p in renal tissues were increased significantly （ P ＜0.05）. Serum level of ALB， SOD level in renal tissue as well as mRNA and protein expressions of Nrf2 were decreased significantly （ P ＜0.05）. Compared with the model group， TWM high-dose and low-dose groups exhibited significant improvements in renal injury， with notable reversals in the levels of the above quantitative indicators （ P ＜0.05）. CONCLUSIONS TWM can alleviate oxidative stress-induced damage and thereby improve nephrotic syndrome in rats by regulating the HIF-1α/miR-155-5p/Nrf2 signaling pathway.

Objective: To explore the impact of adverse childhood experiences (ACEs) on health risk behaviors (HRBs) among college students and the mediating role of psychological symptoms, so as to provide a basis for developing intervention strategies. Methods: From March to April 2023, a convenience cluster sample of 1 801 students from 12 universities in Nanning, Liuzhou, Guilin, Wuzhou of Guangxi completed an online survey. A self designed questionnaire, Adverse Childhood Experiences-International Questionnaire (ACE-IQ) and Symptom Checklist-90 (SCL-90) were used for evaluation tools. Binary Logistic regression, structural equation modeling (SEM) and Bootstrap methods were used to analyze the associations and mediating effects. Results: Overall, 71.2% of college students experienced at least one type of ACE, with emotional neglect (40.3%) and emotional abuse ( 25.2 %) having the highest detection rates. The top three HRBs were unhealthy diet (77.8%), physical inactivity (54.1%), and smoking/alcohol use (18.5%). Logistic regression showed that poor family functioning, abuse, and extra familial violence were each associated with an increased risk of smoking/alcohol use ( OR =1.14, 1.11, 1.18) and deliberate self harm ( OR =1.26, 1.19,1.30) (all P <0.05). Experience of abuse increased the risk of high risk sexual behavior and family dysfunction increaded the risk of physical inactivity, respectively ( OR = 1.07 , 1.04, both P <0.05). Mediation analysis revealed that anxiety ( β =0.20) and depression ( β = 0.09 ) partially mediated the pathway from poor family functioning to deliberate self harm; paranoia ( β =0.02) partially mediated the pathway from abuse to high risk sexual behavior; and obsessive-compulsive symptoms ( β =0.26) and depression ( β =0.10) partially mediated the pathway from extra familial violence to deliberate self harm (all P <0.05). Conclusion Psychological symptoms play a mediating role in the association between ACEs and HRBs, and mental health interventions may reduce the risk of HRBs among college students.

ObjectiveTo analyze the pharmacodynamic substance basis of Shangkeling Spray and its potential mechanisms in intervening knee osteoarthritis （KOA） using ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS）， network pharmacology， and molecular docking technology. MethodsUPLC-MS was used to identify the chemical components of Shangkeling Spray. Pharmacokinetic properties were employed to screen potential active ingredients. Network pharmacology methods were utilized to collect potential targets of these ingredients and the pathological gene set of KOA. An "active ingredient-disease" target network was constructed using databases such as STRING. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） functional enrichment analyses were performed using clusterProfiler. Libraries including NumPy were employed to calculate shortest path lengths to identify dominant pharmacodynamic links. Core gene clusters were identified using MCODE， validated through the Gene Expression Omnibus （GEO） database， and molecular docking was performed between key active ingredients and core targets. ResultsA total of 322 and 314 chemical components were identified under positive and negative ion modes， respectively， with 410 components in total after de-duplication， mainly including flavonoids， coumarins， terpenoids， organic acids， and alkaloids. Analysis of the "active ingredient-disease" network identified "development and regeneration"， "cell growth and death"， "immune system"， and "nervous system" as the dominant pharmacodynamic links of Shangkeling Spray in the treatment of KOA. Molecular docking showed that key active ingredients， such as bletillin A， formononetin， morin， oxymatrine， aconitine， gallic acid， curdione， apigenin， naringenin， and oleanolic acid， tightly bound to functional domains of 10 key targets including Jun proteins（JUN）， interleukin-6 （IL-6）， protein kinase B1 （Akt1）， Caspase-3， nuclear transcription factor-κB subunit p65（RELA）， nuclear factor-kappaB1（NF-κB1）， Cyclin D₁， mammalian target of rapamycin（mTOR）， tumor necrosis factor （TNF）， and Fos proto-oncogene protein （FOS）. These interactions synergistically regulated the phosphatidylinositol 3-kinase （PI3K）/Akt/mTOR-related signaling axis and nervous system-related pathways， mediating cartilage repair， reducing inflammation and pain， and improving KOA. ConclusionThis study preliminarily clarifies the pharmacodynamic substance basis of Shangkeling Spray and suggests that its main active ingredients may improve KOA by synergistically regulating the PI3K/Akt/mTOR-related pathways， providing a reference for subsequent exploration of its substance benchmark and mechanism of action.

Liumotang comes from the Yuan dynasty's Effective Prescription Handed Down for Generations of Physicians. It is composed of six medicinal materials： Arecae Semen， Aquilariae Lignum Resinatum， Aucklandiae Radix， Linderae Radix， Rhei Radix et Rhizoma， and Aurantii Fructus. It is a classical formula for treating abdominal pain due to Qi stagnation and constipation accompanied by heat. This study systematically collated the records of Liumotang in ancient medical books and modern clinical literature and conducted in-depth analysis and textual research on its formula source， main diseases， composition， dosage， medical books， container capacity， processing， preparation method， usage， drug basis， formula meaning， and other key information， so as to provide a powerful reference for the development and clinical application of compound preparations of the classical formula Liumotang. The results show that Liumotang was first seen in Effective Prescription Handed Down for Generations of Physicians， and many medical books of the past dynasties have imitated this. In terms of drug basis， the dried and mature seeds of the palm plant Areca catechu， resin-containing wood of the Daphneaceae plant Aquilaria sinensis， the dried roots of the Asteraceae plant woody Aucklandia lappa， the dried tuber root of the Lauraceae plant Lindera aggregata， the dried roots and rhizomes of the knotweed plant， R. palmatum， R.tangutikum， and R. officinale， and the dried and unripe fruits of the citrus genus C. aurantium and its cultivated varieties from the family Rutaceae were selected. In terms of dosage， through the textual research on bowls in the Ming and Qing dynasties， combined with the conversion of medicines and bowl capacity in the Qing dynasty， it was estimated that the dosage of each drug in the Yuan dynasty was 10.86 g. In the Ming and Qing dynasties， the dosage of drugs was mostly equal， but the dosage of drugs was somewhat different. In terms of processing， preparation method， and usage， in the medical books of the past dynasties， the processing of drugs has slightly changed， but raw drugs are used in all preparations. The preparation method and usage did not change much during the Yuan， Ming， and Qing dynasties， except for certain differences in dosage. In terms of syndrome， Liumotang was first used to treat abdominal pain due to Qi stagnation and constipation accompanied by heat. Medical books of the past dynasties often omit the symptoms of heat. In modern clinical practice， Liumotang is mainly used in the digestive system and urinary system diseases and is mostly used to treat constipation-predominant irritable bowel syndrome， biliary reflux gastritis， functional constipation， slow transit constipation， and other diseases， with no adverse reactions found yet. The above results provide a reliable scientific basis for the development and clinical treatment of Liumotang compound preparations.

Objective:To investigate clinical efficacy and safety of dupilumab in the treatment of moderate to severe atopic dermatitis (AD) complicated with asthma.Methods:A self-controlled study before and after treatment was conducted to retrospectively analyze 45 patients with moderate to severe atopic dermatitis combined with asthma who received dupilumab in the respiratory allergy clinic of North Theater Command General Hospital from January 2021 to May 2024, which age ≥12 years, including 27 males, 18 females. The treatment period was 4 to 12 months. All patients were treated with dupilumab combined with inhaled glucocorticoids and long-acting beta2-receptor agonists, as well as symptomatic drugs for atopic dermatitis. Analyze the clinical data of the patients before and after treatment, including lung function, asthma and AD-related assessment scales. Generalized estimation equation was used to analyze the simple effect of time on the repeated measurement data following non-normal distribution, and Wilcoxon signed rank test was used to compare the differences of each observation index before and after treatment.Results:Among 45 patients with moderate to severe atopic dermatitis complicated with asthma, after treatment with dupilumab, the FEV 1 increased from 2.39 (1.87, 2.83) L at baseline to 2.50 (1.84, 2.97) L 3 months after treatment ( Z=2.417, P=0.016), 2.60 (1.95, 3.14) L 6 months after treatment ( Z=2.896, P=0.004); the FEV 1pred% increased from 74.10% (67.70%, 78.75%) at baseline to 77.09% (68.40%, 80.24%) at 3 months after treatment ( Z=2.574, P=0.010), and 77.20% (71.10%, 80.72%) at 6 months after treatment ( Z=2.861, P=0.004). Meanwhile, there were statistically significant differences in the ACT and Mini-AQLQ scales at 3, 6, and 12 months after treatment compared with those before treatment (ACT score Z=3.170, 4.216, 5.723; Mini-AQLQ score Z=3.231, 4.133, 5.826; all P<0.05). The EASI scale decreased from baseline 25.90 (18.95, 33.45) to 6.20 (1.15, 8.35) at 4 months after treatment ( Z=5.842, P<0.05) and 4.90 (2.75, 8.35) at 6 months after treatment ( Z=5.841, P<0.05), 4.00 (3.15, 5.05) at 12 months after treatment ( Z=5.841, P<0.05); The scores of each scale of IGA, NRS and DLQI decreased significantly compared with the baseline after 4 months, 6 months and 12 months of treatment, and this trend became more obvious with the extension of treatment time. The differences were statistically significant (IGA score Z=6.247, 6.070, 5.946; NRS score Z=5.960, 5.893, 5.879; DLQI score Z=5.880, 5.850, 5.848; all P<0.05). During treatment, 1 patient had local adverse reactions at the injection site and 1 patient had conjunctivitis. Conclusion:Dupilumab may have a positive effect on improving the clinical efficacy of patients with moderate to severe atopic dermatitis complicated with asthma. During the 12-month observation period, this biological agent generally demonstrated good safety characteristics.

AIM To investigate the protective effects of verbascoside on D-galactose-induced liver injury in mice and its underlying mechanisms.METHODS C57BL/6J mice were randomly assigned to the normal group,the model group,the vitamin E group(100 mg/kg),and the low-dose and high-dose verbascoside groups(40,80 mg/kg),with 10 mice in each group.Simultaneous administration of medicine and subcutaneous injection of D-galactose(600 mg/kg)went on among the groups except the normal group for 8 weeks.Serum ALT,AST,ALP activities,along with TBil levels were measured using biochemical kits.Hepatic GSH,MDA concentrations,as well as SOD and GSH-Px activities were quantified.Liver pathological morphology was evaluated by HE staining,while hepatic fibrosis area was assessed using Sirius red staining.Western blot analysis determined hepatic expression of IL-6,IL-1β,TNF-ɑ,TLR4,NF-κB p65,IκBɑ and p-IKBɑ proteins.RESULTS Compared to the model group,the groups treated with vitamin E or verbascoside demonstrated significantly reduced body weight(P＜0.05,P＜0.01);increased hepatic index(P＜0.05,P＜0.01);decreased serum activities of ALT,AST and ALP alongsided reduced TBil levels(P＜0.05,P＜0.01);attenuated pathological damage of liver tissue and fibrosis severity;reduced hepatic MDA level(P＜0.05,P＜0.01);and elevated GSH level with enhanced SOD and GSH-Px activities(P＜0.05,P＜0.01).Furthermore,the high-dose verbascoside group showed significantly decreased hepatic expressions of IL-6,IL-1 β,TNF-ɑ,TLR4,NF-κB p65,and p-IKBɑ/IKBɑ proteins(P＜0.05,P＜0.01).CONCLUSION Verbascoside improves D-galactose-induced liver injury through its antioxidant activity,anti-inflammatory effects,and suppression of the TLR4/NF-κB signaling pathway.

Objective:To compare the differences in specimen results between the intelligent robotic phlebotomy group and the manual venipuncture group, and to evaluate the clinical applicability of the autonomous blood collection system.Methods:From January 20 to October 28, 2022, 154 volunteers at Zhongshan Hospital, Fudan University underwent paired blood collections (robotic and manual) within 5 minutes. The collected samples were analyzed for: hemolysis index (HI), alanine transaminase (ALT), aspartate transaminase (AST), L-γ-glutamyltransferase (γ-GT), lactate dehydrogenase (LDH), urea nitrogen (UREA), creatinine (CRE), uric acid (UA), glucose (GLU), total cholesterol (TC), triglyceride (TG), natrium (Na), kalium (K), chlorine (Cl), creatine kinase (CK), CK-MB, CK-MM, and neuron-specific enolase (NSE). Statistical analyses used t-tests and Wilcoxon signed-rank tests.Results:The results of two different blood collection methods revealed that the HI values of 154 specimens in the intelligent robot blood collection group were all less than 20SI, while 7 specimens (4.54%) in the manual blood collection group had HI values exceeding 20SI; In the comparison of 17 biochemical and immunological markers, there were statistically significant differences between groups in 8 items including γ-GT[20.00(15.00, 37.75)U/L vs. 19.00 (14.00, 36.25)U/L, Z=2.497, P<0.05], LDH[165.5 (147.0, 183.0)U/L vs. 173.0 (155.0, 193.0)U/L, Z=8.629, P<0.05], TC[(5.002±0.856)mmol/L vs.(5.031±0.870) mmol/L, t=-3.006, P<0.05], K[4.1 (4.0, 4.3)mmol/L vs. 4.3 (4.1, 4.4)mmol/L, Z=5.592, P<0.05], CK[97.00 (73.00, 133.00)U/L vs. 99.00 (74.75, 136.25)U/L, Z=3.490, P<0.05], CK-MB[13 (11, 15)U/L vs. 14 (12, 16)U/L, Z=6.581, P<0.05], CK-MM[84.00 (60.00, 119.00)U/L vs. 83.50 (58.75, 118.00)U/L, Z=3.790, P<0.05], and NSE[10.600 (9.500, 11.700)ng/ml vs. 11.950 (10.475, 13.725)ng/ml, Z=8.151, P<0.05]. Conclusions:In the collection of serum samples, intelligent blood collection robots can achieve standardization and normalization of specimen collection volume and mixing in the pre-analysis stage. The hemolysis related indicators of the collected specimens are lower than those of the manual collection group, and can be used for the collection of clinical serological specimens.

OBJECTIVE To investigate the effects of Tripterygium wilfordii multiglycoside （TWM） on renal injury in diabetic nephropathy （DN） rats through tumor protein p53/microRNA-214 （miR-214）/UNC-51-like kinase 1 （ULK1） axis. METHODS Male SD rats were randomly divided into normal group （n＝6） and modeling group （n＝28）； the modeling group was fed with high fat and high glucose plus intraperitoneal injection of streptozotocin to establish DN model. The modeled rats were randomly divided into model group， valsartan group [8.33 mg/（kg·d）] and TWM group[6.25 mg/（kg·d）]， with 8 rats in each group. Rats in each group were gavaged with the corresponding medication or normal saline， once a day， for 6 consecutive weeks. After the last medication， liver and renal function indexes [24 h urinary total protein （24 h-UTP）， blood urea nitrogen （BUN）， serum creatinine （SCr）， albumin （ALB）， alanine transaminase （ALT）]， blood lipid indexes （triglycerides， total cholesterol） and blood glucose index （fasting blood glucose） in urine/blood sample of rats were detected in each group. Renal pathologic change was observed， protein and mRNA expressions of p53， ULK1， Beclin-1 and microtubule-associated protein 1 light chain 3 （LC3）， and expression of miR-214 in renal tissue were also determined. RESULTS Compared with the normal group， the renal tubular epithelium of rats in the model group showed obvious edema， cell swelling， accompanied by lymphocyte infiltration； the levels of 24h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 in rats in the model group and administration groups were significantly increased or up-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1， Beclin-1 protein and mRNA were significantly decreased or down-regulated （P＜0.01）. Compared with the model group， the histopathological damage of the kidney in rats was improved in administration groups； the levels of 24 h-UTP， BUN， SCr， ALT and glycolipid indexes， the expressions of p53 protein and mRNA， as well as the expression of miR-214 were all significantly decreased or down-regulated， while ALB level， LC3-Ⅱ/LC3-Ⅰ， the expressions of LC3 mRNA， the expressions of ULK1 and Beclin-1 protein and mRNA were significantly increased or up-regulated （P＜0.01）. CONCLUSIONS TG can alleviate renal damage in DN rats， and improve their liver and renal function， as well as glucose and lipid levels. These effects may be related to the regulation of the p53/miR-214/ULK1 axis and the restoration of cellular autophagy.

ObjectiveA multiplex amplification system was constructed based on the capillary electrophoresis platform for simultaneous detection of saliva, semen, and vaginal secretions using tissue-specific RNA markers. The aim of this study is to identify the tissue origin of suspicious body fluid stains found at crime scenes and determine whether the body fluid stains at the crime scene are one or several types among saliva, semen, and vaginal secretions. MethodsThirty saliva samples, forty semen samples, and forty vaginal secretion samples (half from 2015 and half from 2024) were collected from healthy adult volunteers. Through primer designing, system formulation, and PCR condition optimization, a multiplex fluorescent amplification system was constructed. The specificity, sensitivity, and detection ability for mixed samples of this system were investigated, and it was tested using real crime scene materials. In the primer design stage, to reduce the requirements for RNA template quality, the amplification products were set within 80-300 bp. In the system formulation stage, dominant and subordinate primers were mainly considered. By reducing the concentration of dominant primers and increasing that of subordinate primers, a capillary electrophoresis spectrum with an appropriate peak height ratio was finally obtained. Additionally, gradient experiments were designed to adjust the concentrations of PCR reagents and PCR amplification conditions, and multiple versions of DNA amplification enzymes were optimized to achieve the best experimental results. ResultsThrough statistical analysis, there was no significant difference in the capillary electrophoresis of the 3 types of body fluid samples from the two years (2015 and 2024), demonstrating that the sample preservation method in this study can preserve samples for a relatively long time. The composite amplification system constructed in this study exhibited high specificity for all 3 types of body fluid, with no cross-reactions between the markers of each type of body fluid. The minimum detection thresholds for the 3 types of body fluid reached 0.002 9, 0.001 5, and 0.42 mg/L, respectively. This system also had a high degree of discrimination for mixed samples, especially for semen-saliva mixtures, where each body fluid marker could still be successfully detected when the concentration ratio of semen to saliva was 100:1. Meanwhile, in the two actual cases presented in this article, the application of this composite amplification system performed outstandingly. ConclusionThe composite amplification detection system constructed in this study can achieve the correct screening of saliva, semen, and vaginal secretions, overcoming the problems such as low specificity and sensitivity of marker tests and unbalanced RFU values of each marker in previous studies. The specificity and sensitivity meet the practical work requirements, and the operation is simple. It provides an analytical and identification method for body fluid stains in actual case and is applicable to the identification of the tissue origin of biological evidence at crime scenes involving sexual assault, indecent assault, and other criminal acts. In the future, more types of body fluid markers will be screened to expand the types of body fluids detected by the system, and body fluid-specific cSNP and cInDel genetic markers will be introduced to infer the sources (individuals and types) of mixed and complex stains more accurately.

OBJECTIVE: To propose a machine learning-based method for predicting the trajectories during manual acupuncture manipulation (MAM), aiming to improve the precision and consistency of acupuncture practitioner' operation and provide the real-time suggestions on MAM error correction. METHODS: Computer vision technology was used to analyze the hand micromotion when holding needle during acupuncture, and provide a three-dimensional coordinate description method of the index finger joints of the holding hand. Focusing on the 4 typical motions of MAM, a machine learning-based MAM trajectory predictive model was designed. By integrating the changes of phalangeal joint angle and hand skeletal information of acupuncture practitioner, the motion trajectory of the index finger joint was predicted accurately. Besides, the roles of machine learning-based MAM trajectory predictive model in the skill transmission of acupuncture manipulation were verified by stratified randomized controlled trial. RESULTS: The performance of MAM trajectory predictive model, based on the long short-term memory network (LSTM), obtained the highest stability and precision, up to 98%. The learning effect was improved when the model applied to the skill transmission of acupuncture manipulation. CONCLUSION The machine learning-based MAM predictive model provides acupuncture practitioner with precise action prediction and feedback. It is valuable and significant for the inheritance and error correction of manual operation of acupuncture.
Humans ; Acupuncture Therapy/instrumentation* ; Machine Learning ; Adult ; Male ; Female