ObjectiveTo characterize the quality differences among different germplasm and introduced varieties of Bupleurum scorzonerifolium roots（BSR）， and explore the underlying molecular mechanisms， providing a basis for high-quality production and quality control. MethodsWild BSR from Yulin（YLW） served as the quality reference， we conducted comparative analysis among YLW， locally domesticated wild germplasm in Yulin（YLC3）， Daqing germplasm introduced and cultivated in Yulin（YLDQC3）， and locally cultivated germplasm in Daqing（DQC3）. A combination of traditional pharmacognostic methods and modern multi-omics analyses was employed， including macroscopic traits（appearance， odor）， microscopic features（proportions of cork， phloem， xylem）， cell wall component contents（hemicellulose， cellulose， lignin）， carbohydrate contents（starch， water-soluble polysaccharides）， marker compound contents（ethanol-soluble extracts， total saponins， liposoluble extracts， and saikosaponins A， B₂， C， D）， metabolomics， and transcriptomics， in order to systematically characterize quality differences and investigate molecular mechanisms among these samples. ResultsMacroscopically， Yulin-produced BSR（YLW， YLC3， YLDQC3） exhibited significantly greater weight， length， and upper and middle diameters than Daqing-produced BSR（DQC3）. Odor-wise， YLW and YLC3 had a a fragrance taste， YLDQC3 had a rancid oil odor， and DQC3 had a sweet and fragrant taste. Microscopically， Yulin germplasm（YLW， YLC3） and Daqing germplasm（YLDQC3， DQC3） shared similar structural features， respectively. However， Yulin germplasm showed significantly higher proportions of cork and phloem， as well as stronger xylem vessel staining intensity compared to Daqing germplasm. Regarding various component contents， Yulin germplasm contained significantly higher levels of ethanol-soluble extracts， total saponins， and saikosaponins A， B₂， C， D， while Daqing germplasm had significantly higher levels of hemicellulose， starch， and liposoluble extracts. After introduction to Yulin， the Daqing germplasm（YLDQC3） showed increased starch， water-soluble polysaccharides and liposoluble extracts contents， decreased cell wall component content， but no significant difference in other component contents. Metabolomics revealed that saponins and terpenes accumulated significantly in Yulin germplasm， while alcohols and aldehydes accumulated predominantly in Daqing germplasm. Transcriptomics indicated similar gene expression patterns within the same germplasm but specificity between different germplasms. Integrative metabolomic-transcriptomic analysis identified 145 potential key genes associated with the saikosaponin biosynthesis pathway， including one acetyl-coenzyme A（CoA） acetyltransferase gene（ACAT）， one 3-hydroxy-3-methylglutaryl-coenzyme A synthase gene（HMGS）， two hydroxymethylglutaryl-CoA（HMG-CoA） reductase genes（HMG）， one phosphomevalonate kinase gene（PMK）， one 1-deoxy-D-xylose-5-phosphate synthase gene（CLA）， one hydroxymethylbuten-1-aldol synthase gene（HDR）， two farnesyl pyrophosphate synthase genes（FPPS）， one squalene synthase gene（SQS）， one β-amyrin synthase gene（BAS）， 102 cytochrome P450（CYP450） gene family members， and 32 uridine diphosphate-glucuronosyltransferase（UGT） gene family members. ConclusionAmong the three cultivated types， YLC3 most closely resembles YLW in appearance， microscopic features， contents of major bioactive constituents， metabolomic and transcriptomic profiles. Yulin germplasm exhibits superior saponin synthesis capability compared to Daqing germplasm， and Yulin region is more suitable for the growth of B. scorzonerifolium. Based on these findings， it is recommended that artificial cultivation in northern Shaanxi and similar regions utilize the local Yulin germplasm source cultivated for at least three years.

Objective:To explore the clinical characteristics and genetic variant in a premature infant with Netherton syndrome (NS).Methods:A neonate with NS caused by variants of SPINK5 gene diagnosed at the Children′s Hospital Affiliated to Zhejiang University School of Medicine in March 2020 was selected as the study subject. Clinical data and family history were collected. Peripheral blood samples (2 mL each) were obtained from the child and her parents for whole-exome sequencing (WES). Candidate variants were subjected to pathogenicity classification and deleteriousness evaluation. This study has been approved by the Medical Ethics Committee of the Hospital (Ethics No. 2024-IRB-0251-P-01). Results:The infant was born prematurely at 35 + 3 weeks due to "premature rupture of membranes for 4 hours" and exhibited generalized skin peeling, with meconium-stained amniotic fluid resembling bean curd residue. The condition improved with supportive treatments such as anti-infection and moisturizing therapy, though periodic hair loss had persisted. No similar case was reported by family history. WES has revealed a heterozygous c. 1130delG (p.G377Efs*127) variant in exon 14 of the SPINK5 gene, which was inherited from her mother, and deletion of exons 1 ~ 33 of the SPINK5 gene, which was inherited from her father. Conclusion:This case of NS presented with intrauterine onset in a preterm infant, which has not been previously reported. The identification of c. 1130delG (p.G377Efs*127) variant has expanded the mutation spectrum of the SPINK5 gene.

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:This study aimed to investigate the regulatory role and mechanism of myosin heavy chain 9 (MYH9) in the invasion of Zika virus (ZIKV) into human glioma cells (U251).Methods:Utilizing CRISPR/Cas9 technology, MYH9-knockout U251 cells (U251-MYH9 KD) were constructed. Following ZIKV infection, the protein expression levels, RNA load, and viral titer of ZIKV were detected through western blot (WB), Real-time fluorescence quantitative polymerase chain reaction (qPCR), and plaque formation assays, respectively. The infection efficiency of ZIKV in U251 cells treated with the MYH9 inhibitor blebbistatin was assessed. The binding and internalization efficiency of ZIKV were measured in U251-MYH9 KD cells. The interaction between MYH9 and the ZIKV envelope protein (E) was studied using co-immunoprecipitation (Co-IP). The effects of soluble MYH9 recombinant protein and anti-human MYH9 antibodies on ZIKV infection were evaluated by qPCR and plaque formation assays. Results:It was found that knockout or inhibition of MYH9 significantly suppressed ZIKV infection in U251 cells. MYH9 knockout notably inhibited the binding and internalization of ZIKV in U251 cells. MYH9 interacted with the ZIKV E protein, and both MYH9 recombinant protein and anti-human MYH9 antibodies, by blocking the binding of ZIKV E protein to cell surface MYH9, inhibited ZIKV infection in U251 cells in a dose-dependent manner.Conclusions:MYH9 facilitates ZIKV invasion into U251 cells through interaction with the ZIKV E protein.

Objective To explore the effect of repetitive transcranial magnetic stimulation(rTMS)on the sleep disorder and examination results of recruits.Methods At a training base,the Pittsburgh Sleep Quality Index(PSQI)was used to screen the recruits with sleep disorders(total score of PSQI>7).The recruits were randomly assigned to rTMS group or sham rTMS group.Both groups received cognitive and behavioral intervention therapy,including sleep health education and relaxation training.Moreover,the rTMS group was treated with rTMS at the right posterior parietal lobe by continuous theta burst stimulation(cTBS)twice a day at an interval of at least 50 min for 5 consecutive days as a course of treatment with an interval of 2 days for a total of 2 courses of treatment.The coil position and stimulus intensity of sham rTMS group were consistent with the rTMS group,but the head of subjects was perpendicular to the coil plane and there was no effective stimulation.Before and after treatment,PSQI,self-rating depression scale,generalized anxiety disorder-7 and health questionnaire-15 were used to evaluate the sleep,mood and physical state of the recruits.The training result was assessed one month after treatment.The total effective rate of PSQI improvement and examination results were compared between the two groups.The independent influencing factors of excellent examination result were analyzed.Results Among 351 recruits,83 with sleep disorders completed treatment and follow-up.There were 40 patients in the rTMS group and 43 patients in the sham rTMS group.There was no significant difference between the two groups at baseline.After treatment,the total effective rate of PSQI improvement in the rTMS group was higher than that in the sham rTMS group(77.50%vs 53.49%,P=0.022).The average examination score and excellent rate of the rTMS group were higher than those of the sham rTMS group(91.58±3.19 vs 89.47±4.67,P=0.020;85%vs 65.12%,P=0.037).Logistic regression analysis showed that the treatment mode(rTMS group)was the independent influencing factor of excellent examination results(P=0.032).Conclusion rTMS can effectively and safely improve the sleep disorders and examination results of recruits.rTMS may play a positive role in improving the learning and training effect of recruits,which needs to be further proved.

Objective To study the traditional Chinese medicine(TCM)syndromes of patients with chronic heart failure(CHF)combined with diuretic resistance by using the Wenyang Huayin Yangxin Prescription,and to observe its therapeutic efficacy.Methods A total of 68 CHF patients complicated with diuretic resistance and who had Yangqi deficiency and presenting blood stasis syndrome combined with Tanyin were randomly assigned to a control group and an observation group.The control group was given intravenous furosemide(≥ 80 mg/d)via infusion pump in addition to standard Western medical treatment,while the observation group was given intravenous furosemide(＜80 mg/d)via infusion pump along with the Wenyang Huayin Yangxin Prescription(30 g Astragalus,15 g Poria,15 g Baizhu,15 g Chuanxiong,10 g Danfu tablet,10 g Cassia,10 g Alisma,and 10 g Zhimu).The quantitative index of diuretic resistance was used as the primary outcome measure.In addition,the differences between the two groups in TCM syndromes,cardiac function-related indicators,incidence of endpoint events,and readmission rate were compared.Results After 2 weeks of treatment,the filtration sodium excretion fraction(FENa)in the observation group was(0.18±0.04)％,while that of the control group was(0.16±0.03)％,showing a statistically significant difference(P=0.037).The 24-hour urine volume and urine Na+/K+ratio in the observation group increased significantly from baseline levels and were higher than those in the control group(P＜0.05).The differences in the changes of 24-hour urine volume,urine sodium,FENa,and urine Na+/K+ratio between the two groups were statistically significant(P＜0.05).The TCM syndrome scores decreased in both groups after 2 weeks of treatment,with the observation group showing a significantly greater reduction compared with the control group(P＜0.001).The differences in the changes of TCM syndrome scores between the two groups were statistically significant(P＜0.001).After 2 weeks of treatment,the observation group showed significant improvements in palpitations,shortness of breath,facial and limb edema,spontaneous sweating,chest tightness(pain),asthma,and oliguria compared with the baseline data(P＜0.05),while the control group showed improvements only in facial and limb edema,asthma,and oliguria(P＜0.05).Except for the asthma syndrome after 2 weeks of treatment,the observation group showed better outcomes in spontaneous sweating,chest tightness(pain),asthma,and oliguria at various time points after treatment compared with the control group(P＜0.05).After 2 weeks of treatment,the observation group had significantly better cardiac output(CO)and stroke volume(SV)compared with those of the control group(P＜0.05).The differences in the changes in N-terminal pro-brain natriuretic peptide(NT-proBNP),left ventricular ejection fraction(LVEF),SV,and CO between the two groups were statistically significant(P＜0.05).After 24 weeks of follow-up,no significant differences in the incidence of end-point events or readmission rates between the two groups were observed.Conclusion The Wenyang Huayin Yangxin Prescription,combined with low-dose intravenous furosemide administered through an infusion pump,can improve the TCM syndromes of patients with Yangqi deficiency and blood stasis syndrome combined with Tanyin in addition to CHF complicated by diuretic resistance.This treatment improves the patients'heart function and diuretic resistance,reduces the intravenous dosage of diuretic,and enhances clinical efficacy.This approach should be more widely applied in clinical settings.

Objective To observe the clinical efficacy of toripalimab combined with bronchial ar-terial chemoembolization(BACE)and intensity-modulated radiotherapy(IMRT)in advanced lung cancer.Methods A prospective single-arm trial was conducted in 104 patients with programmed death-ligand 1(PD-L1)-positive,driver gene-negative non-small cell lung cancer(NSCLC)in stages of Ⅲ B to Ⅳ admitted to the First People's Hospital of Guangyuan City of Sichuan Province.All patients received toripalimab combined with BACE and IMRT.Clinical efficacy,symptom improve-ment time,tumor biomarker levels[carcinoembryonic antigen(CEA),carbohydrate antigen 199(CA199),cytokeratin 19 fragment(CYFRA21-1),neuron-specific enolase(NSE)],T-lymphocyte subsets(CD3+,CD4+,CD4+/CD8+),survival outcomes,and adverse events were analyzed.Results Among 102 patients,the objective response rate(ORR)was 75.49％,disease control rate(DCR)was 90.20％,survival rate was 68.63％,and 12-month progression-free survival rate was 62.75％.The overall incidence of adverse events of any grade was 72.55％.Post-BACE,post-IMRT,and post-toripalimab treatment levels of CEA,CYFRA21-1,CA199,and NSE were significantly lower than baseline data(P＜0.05),with the lowest levels observed after toripalimab treatment compared to post-BACE and post-IMRT(P＜0.05).CD3+,CD4+,and CD4+/CD8+decreased after BACE,IMRT and toripalimab therapy,but they were increased following toripalimab therapy compared with the other two therapies(P＜0.05).Conclusion Toripalimab combined with BACE and IMRT demonstrates significant clinical efficacy and acceptable tolerability in PD-L1-positive,driver gene-negative NSCLC in stages of ⅢB to Ⅳ,serving as a preferred consolidation regimen after unresect-able chemoradiotherapy.

Rhabdomyolysis is a clinical syndrome characterized by damage to the integrity of skel-etal muscle cell membranes,massive release of intracellular contents(such as myoglobin,creatine ki-nase,and electrolytes)into the bloodstream,thereby triggering systemic pathophysiological responses.Its most common and severe complication is acute kidney injury,primarily resulting from the combined effects of myoglobin deposition in renal tubules and renal ischemia.Due to lack of specific early clini-cal manifestations,patients are often misdiagnosed or experience delayed treatment,which can lead to exacerbation of the condition and even life-threatening consequences.This article reports a case of a patient who presented with unexplained rhabdomyolysis at onset and subsequently developed acute kid-ney injury during the course of the disease.A systematic analysis and discussion of the potential etiolo-gy are conducted based on the patient's clinical features and laboratory test results.

Objective To investigate the predictive value of atherosclerotic index of plasma(AIP)for the risk of coronary heart disease(CHD)in patients with nonalcoholic fatty liver disease(NAFLD).Methods A retrospective analysis was conducted in 299 patients with NAFLD.Based on presence or absence of CHD,the patients were divided into NAFLD with CHD group(n=177)and NAFLD group(n=122).Clinical data were collected from both groups,and AIP was calculat-ed.Multivariate Logistic regression analysis was performed to explore the independent risk factors for CHD in patients with NAFLD.Receiver operating characteristic(ROC)curves were plotted to evalu-ate the predictive value of AIP for the risk of CHD in patients with NAFLD.Results The NAFLD with CHD group had a higher proportion of males,smokers,and higher levels of alanine aminotrans-ferase(ALT),aspartate aminotransferase(AST),fasting plasma glucose(FPG),triglycerides(TG),low-density lipoprotein cholesterol(LDL-C),γ-glutamyltransferase(GGT),uric acid(UA),and AIP than the NAFLD group.The NAFLD with CHD group also had lower levels of high-density lipoprotein cholesterol(HDL-C)than the NAFLD group(P＜0.05).Multivariate Logistic regression analysis revealed that males(OR=2.548,95％CI,1.402 to 4.632,P=0.002),high levels of AST(OR=1.038,95％CI,1.002 to 1.077,P=0.041),high levels of LDL-C(OR=1.811,95％CI,1.242 to 2.640,P=0.002),and high AIP(OR=16.117,95％CI,1.874 to 138.609,P=0.011)were independent risk factors for CHD in patients with NAFLD(P＜0.05).ROC curve analysis showed that AIP had an area under the curve of 0.746(95％CI,0.688 to 0.804)for pre-dicting CHD in patients with NAFLD,with a sensitivity of 76.3％and a specificity of 73.0％.Conclusion AIP is an independent influencing factor for CHD in patients with NAFLD and has certain predictive value for the risk of CHD in these patients.

Objective To evaluate the effect of Kaixin San(KXS)combined with fluoxetine on hippocampal neural stem cells in mice with chronic stress stress and depression.Methods A mouse model of depression was constructed using the method of chronic unpredictable stress stress,and the highest dose of KXS water extract and fluoxetine for clinical application was given for 28 days,and behavioral tests were carried out.Nissl staining was used to detect the pathological status of hippocampal tissues in mice.The expression of TUNEL and Nestin in mouse hippocampus was determined by immunofluorescence.Western blotting was used to detect the expressions of apoptotic proteins cleaved caspase-3 and caspase-3,pyroptosis proteins GSDMD and cleaved caspase-1,as well as the expression of neural stem cell marker Nestin in the hippocampus,and the expression of Wnt/β-catenin signaling pathway-related proteins in the hippocampus.Results The combination of KXS extract and fluoxetine can significantly improve the depression-like behavior of model mice,and the effect is better than fluoxetine alone.The combination inhibited the activation of apoptosis and pyroptosis signaling pathways in the hippocampus when used alone with high-dose fluoxetine,significantly upregulated the expression of Nestin,and regulated the expression of Wnt/β-catenin signaling pathway protein.Conclusion The combination of KXS and high-dose fluoxetine can improve apoptosis and pyroptosis in the hippocampus of stress stress and depression model mice,and upregulate the expression of neural stem cell marker Nestin by regulating the Wnt/β-catenin signaling pathway,which may be a key link to improve the antidepressant effect of the combination drug.