BACKGROUND: Arsenic trioxide (ATO) is indicated as a broad-spectrum medicine for a variety of diseases, including cancer and cardiac disease. While the role of ATO in hepatic ischemia/reperfusion injury (HIRI) has not been reported. Thus, the purpose of this study was to identify the effects of ATO on HIRI. METHODS: In the present study, we established a 70% hepatic warm I/R injury and partial hepatectomy (30% resection) animal models in vivo and hepatocytes anoxia/reoxygenation (A/R) models in vitro with ATO pretreatment and further assessed liver function by histopathologic changes, enzyme-linked immunosorbent assay, cell counting kit-8, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assay. Small interfering RNA (siRNA) for extracellular signal-regulated kinase (ERK) 1/2 was transfected to evaluate the role of ERK1/2 pathway during HIRI, followed by ATO pretreatment. The dynamic process of autophagic flux and numbers of autophagosomes were detected by green fluorescent protein-monomeric red fluorescent protein-LC3 (GFP-mRFP-LC3) staining and transmission electron microscopy. RESULTS: A low dose of ATO (0.75 μmol/L in vitro and 1 mg/kg in vivo ) significantly reduced tissue necrosis, inflammatory infiltration, and hepatocyte apoptosis during the process of hepatic I/R. Meanwhile, ATO obviously promoted the ability of cell proliferation and liver regeneration. Mechanistically, in vitro  studies have shown that nontoxic concentrations of ATO can activate both ERK and phosphoinositide 3-kinase-serine/threonine kinase (PI3K-AKT) pathways and further induce autophagy. The hepatoprotective mechanism of ATO, at least in part, relies on the effects of ATO on the activation of autophagy, which is ERK-dependent. CONCLUSION Low, non-toxic doses of ATO can activate ERK/PI3K-AKT pathways and induce ERK-dependent autophagy in hepatocytes, protecting liver against I/R injury and accelerating hepatocyte regeneration after partial hepatectomy.
Animals ; Arsenic Trioxide ; Autophagy/physiology* ; Reperfusion Injury/prevention & control* ; Mice ; Male ; Proto-Oncogene Proteins c-akt/physiology* ; Arsenicals/therapeutic use* ; Oxides/therapeutic use* ; Liver/metabolism* ; Extracellular Signal-Regulated MAP Kinases/metabolism* ; Mice, Inbred C57BL

AIM To investigate the protective effects of the aqueous extract of Bulbophyllum kwangtungense Schltr.on D-galactose(D-gal),an oxidative stress-induced liver damage in rats.METHODS 60 Male SD rats were randomly divided into the normal control group,the model group,the resveratrol group(20 mg/kg),and low-dose,medium-dose,and high-dose B.kwangtungense aqueous extract groups(750,1 500 and 3 000 mg/kg).Except for those of the normal control group,the rats of the other groups were subcutaneously injected with D-gal(200 mg/kg)in the back of neck to establish a liver damage model.Simultaneously,each group underwent the corresponding drug administration by gavage(10 mL/kg)once daily for 42 days.After the treatment period,the rats had their peripheral blood and liver tissues collected for the calculation of the liver index;their serum AST and ALT activities,hepatic SOD and GSH-Px activities,and MDA levels measured;their hepatic pathological changes observed using HE staining;their hepatic mRNA expressions of Nrf2,NQO-1 and HO-1 detected by RT-qPCR;and their hepatic protein expressions of Nrf2,NQO-1,HO-1,Bax,Bcl-2 and cleaved Caspase-3 measured by Western blot.RESULTS Compared with the model group,the groups intervened with medium-dose or high-dose B.kwangtungense aqueous extract showed increased liver index level(P＜0.01);decreased serum AST and ALT activities(P＜0.01);increased hepatic SOD and GSH-Px activities(P＜0.05,P＜0.01);reduced MDA levels(P＜0.01);alleviated pathological liver damage and increased hepatic mRNA and protein expressions of Nrf2,NQO-1 and HO-1(P＜0.05,P＜0.01);and reduced protein expressions of cleaved Caspase-3 and the Bax/Bcl-2 ratio as well(P＜0.05,P＜0.01).CONCLUSION The aqueous extract of B.kwangtungense is protective of rats with D-gal-induced liver injury,and the underlying mechanism may associate with the inhibition of oxidative stress and the suppression of hepatocellular apoptosis mediated by the activation of the Nrf2/HO-1/NQO-1 signaling pathway.

Objective To investigate the effect of local histopathological changes of thyroid nodules after ultrasound-guided fine needle aspiration biopsy(US-FNBA)on laparoscopic thyroid surgery.Methods The clinical data of 120 patients with thyroid malignant tumors admitted to Xiaogan Hospital of Wuhan University of Science and Technology from January 2020 to December 2022 were retrospectively analyzed,and according to whether received US-FNAB before surgery they were divided into the observation group(with US-FNAB)and the control group(without US-FNAB),with 60 cases in each group.The operation time,change of parathyroid hormone(ΔPTH)before and after surgery,change of serum Ca2+concentration(serum ΔCa2+)before and after surgery,drainage volume 24 hours after surgery and incidence of complications were compared between the two groups.According to fine needle aspiration-to-surgery(FTS),the patients in the observation group were further divided into the group A(FTS≤3 days)and the group B(FTS>3 days),and the effect of US-FNAB on laparoscopic thyroid surgery was explored combined with the pathological changes of the thyroid puncture capsule of the two groups.Results The operation time of the observation group was longer than that of the control group(P<0.05),and there was no significant difference in the drainage volume 24 hours after surgery,ΔPTH,serum ΔCa2+,or proportions of facial or limb numbness,hypoparathyroidism,recurrent laryngeal nerve integrity,and hypocalcemia between the two groups(P>0.05).There was no significant difference in the operation time,ΔPTH,serum ΔCa2+,drainage volume 24 hours after surgery,hypocalcemia,recurrent laryngeal nerve integrity or hypothyroidism between the group A and group B(P>0.05).The proportion of patients with facial or limb numbness after surgery in the group A was significantly lower than that in the group B(P<0.05).Conclusion Preoperative US-FNAB for thyroid nodules may prolong the operation time in patients undergoing laparoscopic thyroid surgery,and surgical treatment in early aspiration can help decrease this effect and reduce the incidences of postoperative hypocalcemia and hypothyroidism.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective:To investigate the correlation between the expression level of glypican-6 (GPC6) in gliomas and the prognosis of patients, as well as the effect of GPC6 on the proliferation of glioma cells in vitro.Methods:The transcriptome sequencing (RNA-seq) data of GPC6 gene and clinical data of glioma patients were downloaded from The Cancer Genome Atlas (TCGA) database. A total of 667 patients were enrolled, and the median FPKM value of GPC6 RNA-seq was used to distinguish the low and high expression of GPC6 gene. Kaplan-Meier method was used to analyze the overall survival (OS) of GPC6 high and low expression groups in 664 patients with survival data, and log-rank test was used for inter group comparison. The postoperative tumor tissue chips were retrospectively collected from glioma patients who underwent surgery from February 2008 to October 2011, immunohistochemistry (IHC) was used to detect the expression of GPC6 protein in 147 samples, and semi-quantitative scoring ≥ 4 points or not was used to distinguish the high and low expression of GPC6 protein based on the proportion of positive cells and staining intensity. The distributions of patients with high and low expression of GPC6 protein in tumor tissues were compared between different clinical pathological features in 147 patients, and Kaplan-Meier method was used to analyze the overall survival and disease-free survival (DFS) of patients in the GPC6 protein high and low expression groups; the risk factors that affect poor OS and DFS in patients were analyzed using univariate and multivariate Cox proportional hazards models. The human glioma U251 cells were infected with lentivirus packaged with GPC6 small interfering RNA and lentivirus packaged with unrelated control sequences, namely ShGPC6 group and ShCtrl group, respectively; green fluorescent cells were counted daily and the cell proliferation fold was calculated for 5 days, and the cell proliferation curve was plotted.Results:In TCGA database, the median FPKM value of 667 glioma patients was 225.66. The median FPKM value of GPC6 gene in 515 World Health Organization (WHO) classification low-grade glioma patients was lower than that in 152 high-grade glioma patients (201.10 vs. 347.92), and the difference was statistically significant ( Z = 5.36, P < 0.001); the OS of patients in GPC6 low expression group (332 cases) was better than that in GPC6 high expression group (332 cases), and the difference was statistically significant ( P < 0.001). IHC staining of the tissue chip showed that GPC6 protein was mainly expressed in the cytoplasm and nucleus of glioma cells; high expression of GPC6 protein accounted for 31.3% (46/147) of patients. Among patients who died, relapsed, had high grading, had survival time ≤ 84 months, and had positive epidermal growth factor receptor, the proportion of patients with GPC6 protein high expression was relatively higher, and the differences were statistically significant (all P < 0.05). There were no statistically significant differences in the proportions of GPC6 protein high expression patients among patients with different genders, age ≤ 43 years old, Ki-67 positivity, and programmed death receptor ligand 1 positivity (all P > 0.05); compared to the GPC6 low expression group (101 cases), the GPC6 protein high expression group (46 cases) had worse overall survival (median OS time: 57.0 months vs. not reached) and DFS (median DFS time: 33.0 months vs. not reached), and the differences were statistically significant (both P < 0.001). Multivariate Cox regression analysis showed that high expression of GPC6 protein (high expression vs. low expression, HR = 1.86, 95% CI: 1.04-3.31, P = 0.036) was the independent risk factor for poor OS in glioma patients, but the expression level of GPC6 protein was not the independent influencing factor for DFS (high expression vs. low expression, HR = 1.55, 95% CI: 0.95-2.53, P = 0.077). After infecting U251 cells with recombinant lentivirus for 3 days, reverse transcription polymerase chain reaction detection showed that the relative expression level of GPC6 mRNA in the ShGPC6 group was lower than that in the ShCtrl group, and the difference was statistically significant ( P < 0.001), the knockdown efficiency of GPC6 reached 79.32%; under the fluorescence microscope, the number and intensity of fluorescence positive U251 cells in the ShCtrl group increased day by day after infection with recombinant lentivirus, while there was no significant change in the ShGPC6 group; starting from the second day, the proliferation rate of U251 cells in the ShCtrl group was higher than that in the ShGPC6 group, and the differences were statistically significant (all P < 0.01). Conclusions:High GPC6 expression level may associate with the high risk of death in glioma patients, and high GPC6 expression may promote the proliferation of glioma cells.

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Primary ciliary dyskinesia (PCD) is a clinically rare, genetically and phenotypically heterogeneous condition characterized by chronic respiratory tract infections, male infertility, tympanitis, and laterality abnormalities. PCD is typically resulted from variants in genes encoding assembly or structural proteins that are indispensable for the movement of motile cilia. Here, we identified a novel nonsense mutation, c.466G>T, in cilia- and flagella-associated protein 300 ( CFAP300 ) resulting in a stop codon (p.Glu156*) through whole-exome sequencing (WES). The proband had a PCD phenotype with laterality defects and immotile sperm flagella displaying a combined loss of the inner dynein arm (IDA) and outer dynein arm (ODA). Bioinformatic programs predicted that the mutation is deleterious. Successful pregnancy was achieved through intracytoplasmic sperm injection (ICSI). Our results expand the spectrum of CFAP300 variants in PCD and provide reproductive guidance for infertile couples suffering from PCD caused by them.
Adult ; Female ; Humans ; Male ; Pregnancy ; China ; Ciliary Motility Disorders/genetics* ; Codon, Nonsense ; East Asian People/genetics* ; Exome Sequencing ; Homozygote ; Infertility, Male/genetics* ; Kartagener Syndrome/genetics* ; Pedigree ; Sperm Injections, Intracytoplasmic ; Cytoskeletal Proteins/genetics*

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.