Chaihu Guizhi Ganjiangtang was first recorded in the Treatise on Cold Damage （Shang Han Lun）. This prescription is composed of Bupleuri Radix， Scutellariae Radix， Cinnamomi Ramulus， Zingiberis Rhizoma， Trichosanthis Radix， Ostreae Concha， and Glycyrrhizae Radix et Rhizoma. It has the effects of soothing Lesser Yang， warming the spleen， and stimulating the generation of body fluid. It is mainly used to treat digestive tract diseases such as chronic cholecystitis （CC）， irritable bowel syndrome， and non-alcoholic fatty liver disease. Dyspepsia caused by CC presents a variety of gastrointestinal symptoms such as abdominal pain， poor appetite， postprandial fullness， aversion to greasy food， soft stool， and bitter mouth， being a type of biliary dyspepsia. In modern medicine， dyspepsia caused by CC is mainly managed by medical treatment and surgical treatment. Internal medicine mainly focuses on reducing inflammation， promoting the function of gallbladder， resolving stones， alleviating spasms， and relieving the pain for CC， demonstrating definite short-term efficacy but suffering from single effects， high recurrence rate， and poor compliance. Although surgical treatment can cure cholecystitis， it is accompanied by the increased incidence of adverse events such as abdominal pain， diarrhea， and dyspepsia. Modern clinical studies have confirmed that Chaihu Guizhi Ganjiangtang can significantly alleviate the symptoms such as abdominal pain and dyspepsia of CC patients. Pharmacological studies have found that Chaihu Guizhi Ganjiangtang mainly contains active ingredients such as Bupleuri Radix saponins， baicalin， cinnamaldehyde， gingerol， Trichosanthis Radix polysaccharide， Ostreae Concha polysaccharide， and Glycyrrhizae Radix et Rhizoma total flavonoids. Chaihu Guizhi Ganjiangtang can ameliorate the symptoms of dyspepsia caused by CC by inhibiting inflammatory responses， improving gallbladder contraction and gastrointestinal motility， regulating the bile acid-intestinal flora axis and the brain-gut axis， and modulating blood lipids through multiple targets. By reviewing the previous literature， this article summarizes the research progress in the treatment of dyspepsia caused by CC with Chaihu Guizhi Ganjiangtang and its main active ingredients as well as the pathogenesis of this disease and puts forward the shortcomings and improvement strategies for the current research. The review aims to provide a reference for the further research on Chaihu Guizhi Ganjiangtang in the treatment of dyspepsia caused by CC.

This paper systematically summarizes the practical experience of the 2025 Dingri earthquake emergency medical rescue in Tibet. It analyzes the requirements for earthquake medical rescue under conditions of high-altitude hypoxia, low temperature, and low air pressure. The paper provides a detailed discussion on the strategic layout of earthquake medical rescue at the national level, local government level, and through social participation. It covers the construction of rescue organizational systems, technical systems, material support systems, and information systems. The importance of building rescue teams is emphasized. In high-altitude and cold conditions, rapid response, scientific decision-making, and multi-party collaboration are identified as key elements to enhance rescue efficiency. By optimizing rescue organizational structures, strengthening the development of new equipment, and promoting telemedicine technologies, the precision and effectiveness of medical rescue can be significantly improved, providing important references for future similar disaster rescues.

BACKGROUND:Wogonin is a flavonoid extracted from the root of Scutellaria baicalensis.Previous studies have shown that baicalein has protective effects against cerebral ischemia-reperfusion injury,and can also reduce blood sugar and complications in diabetic mice,but its role and mechanism in diabetic cerebral infarction remain unclear. OBJECTIVE:To explore the effect of wogonin on nerve injury in rats with diabetic cerebral infarction and its mechanism. METHODS:Sprague-Dawley rats were randomly divided into six groups:control group,model group,low-dose wogonin group,medium-dose wogonin group,high-dose wogonin group,and high-dose wogonin+Ras homolog gene family member A(RhoA)activator group.Except for the control group,the other rats were established with diabetes and cerebral ischemia models using intraperitoneal injection of streptozotocin and middle cerebral artery occlusion.Low,medium-and high-dose wogonin groups were intragastrically given 10,20,40 mg/kg wogonin,respectively;high-dose wogonin+RhoA activator group was intragastrically given 40 mg/kg wogonin and intraperitoneally injected 10 mg/kg lysophosphatidic acid;control group and model group were given the same amount of normal saline once a day for 7 consecutive days.Rats in each group were evaluated for neurological deficits and their blood glucose levels were measured after the last dose.TTC staining was applied to detect the volume of cerebral infarction.Hematoxylin-eosin staining was applied to observe pathological changes in brain tissue.ELISA kit was applied to detect tumor necrosis factor-α,interleukin-6,malondialdehyde,and superoxide dismutase levels in brain tissue.Western blot was applied to detect the protein expression of RhoA and Rho-associated protein kinase(ROCK)2 in brain tissue. RESULTS AND CONCLUSION:Compared with the control group,the neuronal structure of rats in the model group was severely damaged,with cell necrosis and degeneration,the neurological deficit score,blood glucose level,and infarct volume were significantly elevated(P<0.05),the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue were significantly increased(P<0.05),and the superoxide dismutase level was decreased(P<0.05).Compared with the model group,the low-,medium-,and high-dose wogonin groups showed improved neuronal damage,reduced cell degeneration and necrosis,a significant reduction in neurological deficit score,blood glucose level,infarct volume,and the levels of tumor necrosis factor-α,interleukin-6,and malondialdehyde,and the protein expression of RhoA and ROCK2 in brain tissue,and an increase in the superoxide dismutase level(P<0.05).Compared with the high-dose wogonin group,the high-dose wogonin+RhoA activator group significantly weakened the improvement in the above indexes of rats with diabetic cerebral infarction(P<0.05).To conclude,wogonin can improve the blood glucose level in rats with diabetic cerebral infarction,reduce cerebral infarction and nerve injury,and its mechanism may be related to the inhibition of RhoA/ROCK signaling pathway.

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.

Objective:To explore the effects of neutrophil extracellular traps (NET) on the proliferation and migration of breast cancer cells and the related mechanisms.Methods:The peripheral blood neutrophils were separated using density gradient centrifugation, 100 nmol/L phorbol 12-myristate 13-acetate (PMA) was used to stimulate the formation of NET. Breast cancer cell line MDA-MB-231 was selected and treated with NET (NET group) or deoxyribonucleaseⅠ (DNase Ⅰ) digested NET (NET+DNase Ⅰ group),normal cultured MDA-MB-231 cells were used as the control group. In MDA-MB-231 cells of each group; cell proliferation ability was detected using CCK-8 assay; cell migration was detected by cell scratch assay and Transwell assay; real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the relative expressions of frizzled homolog 10 (FZD10), cyclin D1, E-cadherin and Vimentin immunofluorescence assay was performed to detect the formation of NET and the expressions of E-cadherin and Vimentin; Western blotting was used to detected the expression of FZD10-Wnt-β-catenin signaling pathway-related proteins.Results:Neutrophils were stimulated with PMA for 4 hours, and immunofluorescence assay results showed that NET exhibited fibrous reticular structure with high expression of citrullinated histone (citH3) and myeloperoxidase (MPO). The CCK-8 assay results showed that the absorbance values of cells in the control group, NET group and NET+DNase Ⅰ group were 1.25±0.06, 2.14±0.15 and 1.47±0.11, respectively, and the difference was statistically significant ( F = 80.60, P < 0.001). The results of scratch assay displayed that the percentage of wound closure in the control group, NET group and NET+DNase Ⅰ group were (36.2±1.3)%, (67.2±2.0)% and (46.3±3.2)%, respectively, and the difference was statistically significant ( F = 140.50, P < 0.001). Transwell assay indicated that the number of migrating cells in the control group, NET group and NET+DNase Ⅰ group were 317±18, 512±23 and 356±23, respectively, and the difference was statistically significant ( F = 75.39, P < 0.001). qRT-PCR assay revealed that the relative expressions of FZD10, cyclin D1 and Vimentin mRNA in the NET group were higher than those in the control group, while the relative expression of E-cadherin mRNA was lower than that in the control group, and the differences were statistically significant (all P < 0.001); the relative expressions of FZD10, cyclin D1 and Vimentin mRNA in the NET+DNase Ⅰ group were lower than those in the NET group, while the relative expression of E-cadherin mRNA was higher than that in the NET group, and the differences were statistically significant (all P < 0.001). Immunofluorescence assay indicated that the number of cells expressing Vimentin in the control group, NET group and NET+DNase Ⅰ group were 35±6, 86±13 and 51±6, respectively, and the difference was statistically significant ( F = 24.65, P = 0.001); the number of cells expressing E-cadherin were 31±4, 11±3 and 24±2, respectively, and the difference was statistically significant ( F = 38.36, P < 0.001). Western blotting results demonstrated that the relative expressions of FZD10, β-catenin and Vimentin proteins in the NET group were higher than those in the control group, while the relative expression of E-cadherin protein was lower than that in the control group; the relative expressions of FZD10, β-catenin and Vimentin proteins in the NET+DNase Ⅰ group were lower than those in the NET group, while the relative expression of E-cadherin protein was higher than that in the NET group. Conclusions:NET may promote the proliferation and migration of breast cancer cells by upregulating the expression of FZD10 and subsequently activating the Wnt-β-catenin signal pathway.

Objective:To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis. Methods:A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5′ and 3′ untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17). Results:The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ: C) and FⅫ antigen (FⅫ: Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c. 712_713insT (p.Cys238Leufs *73) in exon 8 and c. 1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p. Cys238Leufs*73 variant, while her older son was heterozygous for the p. Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p. Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein. Conclusion:The c. 712_713insT and c. 1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c. 712_713insT (NM_000505) was unreported previously.

BackgroundChildhood represents a critical stage for cognitive development. Accurate assessment of children's cognitive abilities and understanding their developmental characteristics are essential for promoting healthy growth. However， traditional cognitive assessment methods typically rely on manual administration， presenting limitations such as low efficiency and insufficient engagement. These methods struggle to meet the assessment needs of children and are difficult to scale up for large-scale applications. ObjectiveTo develop a digital cognitive assessment tool for children， so as to provide a more convenient approach for evaluating children's cognitive functions. MethodsBased on classic psychological paradigms （Stroop Task， N-back， digit span， spatial orientation， and face-name matching）， a digital cognitive assessment tool was developed. This tool includes five tasks including color matching， shape matching， greening the home， great collector， and face-name matching， designed to assess core cognitive functions such as inhibitory control， working memory， short-term memory， spatial orientation， and semantic processing， respectively. From August 2024 to March 2025， a total of 750 students aged 9–12 yeas old from a primary school in Chengdu were enrolled and assessed using the digital cognitive assessment tool. Three months later， 40 children were randomly selected for retesting using both the digital tool and its corresponding standardized psychological paradigms. Pearson correlation analysis was conducted to examine the correlation between the pre-test and retest scores of the digital cognitive assessment tool， as well as the correlation between the digital cognitive task scores and the corresponding psychological paradigm assessment results， in order to evaluate the reliability and validity of the digital cognitive assessment tool. Additionally， differences in scores across the cognitive tasks were compared among children of different age groups and genders. ResultsA total of 699 valid samples were included. The younger age group consisted of children aged 9–10 years old （n=460）， while the older age group comprised those aged 11–12 years old （n=239）. There were 356 boys （50.93%） and 343 girls （49.07%）. In the reliability analysis， the Pearson correlation coefficients between the pre-test and retest scores of each assessment task ranged from 0.732 to 0.970 （P<0.01）， indicating statistically significant results. In the validity analysis， the Pearson correlation coefficients between each task and its corresponding standard cognitive test ranged from 0.679 to 0.988 （P<0.01）. In the color-matching task， both the main effects of age and gender were statistically significant （F=31.071， 21.198， P<0.01）. In the shape-matching task， the main effects of age， gender， and their interaction were all statistically significant （F=20.933， 5.926， 4.318， P<0.05 or 0.01）. In the greening the home task， the main effect of age was significant （F=5.243， P=0.023）. In the great collector task， the main effect of age was significant （F=33.697， P<0.01）. In the face-name matching task， only the main effect of gender was significant （F=27.016， P<0.01）. Further analysis showed that within the female group， older group scored significantly higher than younger group in five tasks（P<0.05 or 0.01）. Within the male group， younger group scored lower than older group in both the color-matching and great collector tasks （P<0.05 or 0.01）. Within the younger group， boys scored significantly higher than girls in color-matching and shape-matching tasks （P<0.01）. In the older group， girls scored significantly higher than boys in face-name matching task （P<0.01）. ConclusionThe digital cognitive assessment tool developed in this study demonstrates good reliability and validity. The development of cognitive functions in children aged 9–12 years old showed significant differences in age and gender， with specific developmental trajectories across different cognitive dimensions. At younger ages， boys outperformed girls in inhibitory control and working memory tasks， though this advantage diminished with age. At older ages， girls exhibited superior performance in semantic processing compared with boys.

Objective: To investigate the impacts of remifentanil on the proliferation,apoptosis and Wnt/β-catenin pathway of breast cancer MDA-MB-231 cells. Methods: Different concentrations of remifentanil(0,0. 5,2. 5,5. 0,10. 0,20. 0,40. 0 μg/mL) were used to treat human normal breast MCF-10A cells and breast cancer MDAMB-231 cells to screen for experimental concentrations of remifentanil. MDA-MB-231 cells were divided into control group,remifentanil low(5. 0 μg/mL),medium(10. 0 μg/mL),and high(20. 0 μg/mL) concentration groups,and remifentanil + SKL2001(Wnt/β-catenin pathway agonist) group. MTT assay and colony formation assay were applied to detect cell proliferation ability. Flow cytometry was applied to detect cell apoptosis and cell cycle changes. Western blot was applied to detect protein expression related to cell proliferation,apoptosis,and the Wnt/β-catenin signaling pathway. Results: Remifentanil at concentrations of 5. 0,10. 0,and 20. 0 μg/mL could reduce the viability of MDA-MB-231 cells and had no prominent toxicity to MCF-10A cells. Compared with the control group,the optical density value of cell proliferation,colony formation number,proportion of S-phase cells,and the protein levels of cellular myelocytomatosis(c-Myc),Cyclin D1,B lymphoblastoma 2(Bcl-2),precursor of cysteine aspartate protease-3(pro-caspase-3) and β-catenin were lower in the low,medium,and high concentration remifentanil groups(P 0/G1 phase cells,apoptosis rate,early apoptosis rate,the protein levels of Bcl-2 associated X protein(Bax) and cleaved cysteine aspartate protease-3(Cleaved caspase-3),and glycogen synthase kinase-3β(GSK-3β) were higher( P ＜0. 05) ． SKL2001 could weaken the effects of remifentanil on the proliferation and apoptosis of MDA-MB-231 cells． Conclusion Remifentanil inhibits the proliferation of MDA-MB-231 cells，induces apoptosis and cell cycle arrest，and its mechanism may be related to the inhibition of Wnt / β-catenin signaling pathway activation．

OBJECTIVE: To analyze a Chinese pedigree with Hereditary coagulation factor Ⅻ (FⅫ) deficiency duo to variants of F12 gene and explore its molecular pathogenesis. METHODS: A patient who underwent laparoscopic cystectomy at the Department of Gynecology of the First Affiliated Hospital of Wenzhou Medical University in June 2012 was selected as the study subject. Coagulation factor indexes of the proband and her family members (5 individuals from three generations) were determined. All exons, flanking sequences, 5' and 3' untranslated regions of the F12 gene of the proband and her family members were analyzed by direct sequencing. Three bioinformatics software was used to analyze the conservation, pathogenicity and protein model of the variant. This study was approved by the Medical Ethics Committee of the Hospital (Ethics No. 2012-17). RESULTS: The activated partial thromboplastin time (APTT), FⅫ activity (FⅫ:C) and FⅫ antigen (FⅫ:Ag) of the proband was 180.0 s, 1.0% and 2.1%, respectively. DNA sequencing revealed that she has harbored compound heterozygous variants of the F12 gene, namely c.712_713insT (p.Cys238Leufs *73) in exon 8 and c.1561G>A (p.Glu521Lys) in exon 13. Her mother and younger son were heterozygous for the p.Cys238Leufs*73 variant, while her older son was heterozygous for the p.Glu521Lys variant. Bioinformatic analysis suggested that Cys238 is highly conserved and p.Cys238Leufs*73 is a pathogenic variant, which eventually resulted in a truncated protein. CONCLUSION The c.712_713insT and c.1561G>A compound heterozygous variants of the F12 gene probably underlay the decreased FⅫ level in this pedigree, among which c.712_713insT (NM_000505) was unreported previously.
Adult ; Female ; Humans ; Male ; Middle Aged ; Base Sequence ; China ; Factor XII/genetics* ; Heterozygote ; Mutation ; Pedigree ; Factor XII Deficiency/genetics* ; East Asian People

Objective To explore the expression of pepsinogen Ⅰ/Ⅱ(PG Ⅰ/PG Ⅱ),nucleosome assembly protein 1 like protein 1(NAP1L1),and SERPINB5 in the serum of gastric cancer patients and their correlation with prognosis.Methods From February 2019 to February 2022,200 gastric cancer patients admitted to Zhuozhou Hospital were served as the gastric cancer group and another 100 patients with benign gastric lesions who received the treatment at Zhuozhou Hospital during the same period were served as the benign group,with 200 healthy adults as the control group.Chemiluminescence and ELISA methods were used to detect the serum PG Ⅰ/PG Ⅱ,NAP1L1,and SERPINB5.ROC curve was used to explore the diagnostic value.Kaplan-Meier method was used to explore the survival curve.Moreover,multivariate Cox method was used to analyze the factors that affected the prognosis.Results Compared with the control group,the benign group and gastric cancer group had the lower serum PGⅠ/PG Ⅱ and higher serum NAP1L1 and SERPINB5,and the difference was statistically significant(P<0.05).Compared with the benign group,the gastric cancer group had the lower serum PG Ⅰ/PG Ⅱ and higher serum NAP1L1 and SERPINB5,and the difference was statistically significant(P<0.05).PG Ⅰ/PG Ⅱ,NAP1L1,and SERPINB5 were all influential factors in gastric carcinogenesis(P<0.05).The AUC values of serum PG Ⅰ/PG Ⅱ,NAP1L1,and SERPINB5 alone in the diagnosis of gastric cancer were 0.821,0.808,and 0.833,respectively.The AUC of the combination of the three was 0.916,indicating that their combined diagnostic value was superior(Z=3.142,3.896,3.114,P<0.05).During the 3-year follow-up period of gastric cancer patients,57 cases died,accounting for 28.50%(57/200),and 143 cases survived.Patients with the high expression of PG Ⅰ/PG Ⅱ had a higher 3-year overall survival rate after the surgery compared to those with low expression,and the difference was statistically significant(χ2=7.830,P<0.05);and patients with the low expression of NAP1L1 and SERPINB5 had a higher 3-year overall survival rate after the surgery compared to those with high expression,and the difference was statistically significant(χ2=8.612,13.321,P<0.05).The serum PG Ⅰ/PG Ⅱ levels in the death group were lower than those in the survival group,and the serum NAP1L1,SERPINB5 levels were higher in patients with preoperative lymph node metastasis and TNM stage Ⅲ-Ⅳ than those in the survival group,and the difference was statistically significant(P<0.05).Elevated level of PG Ⅰ/PG Ⅱ was a protective factor for the prognosis of gastric cancer patients,while preoperative lymph node metastasis,elevated levels of NAP1L1 and SERPINB5 were risk factors affecting the prognosis of gastric cancer patients(P<0.05).Conclusion Serum PG Ⅰ/PG Ⅱ levels are decreased and NAP1L1 and SERPINB5 levels are increased in gastric cancer patients,and NAP1L1 and SERPINB5 are risk factors affecting the prognosis of gastric cancer patients,while PG Ⅰ/PG Ⅱ is a protective factor.