OBJECTIVE To explore the mechanism by which Qingre antai decoction improves pregnancy outcomes of threatened abortion rats with blood heat syndrome. METHODS The pregnant rats were randomly divided into normal group， model group， dydrogesterone group （0.002 g/kg）， and Qingre antai decoction group （44.1 g/kg）， with 13 rats in each group. Except for normal group， other groups were given warming-yang Chinese medicine and corresponding drugs intragastrically， once a day， for 12 consecutive days. On the 13th day of pregnancy， a single intragastric administration of mifepristone （5 mg/kg） was performed to establish a model of threatened abortion with blood heat syndrome. On the 14th day of pregnancy， the abortion rate and uterine coefficient were calculated； the pathological morphology of pregnant uterine was observed； the serum levels of 3，5，3′-triiodothyronine （T3）， thyroid hormone （T4）， thyroid stimulating hormone （TSH）， as well as the levels of vascular endothelial growth factor （VEGF） and nitric oxide （NO） in the pregnant uterus were all determined； the expressions of mRNA and protein related to Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） and phosphatidylinositol 3-kinase （PI3K）/protein kinase B （AKT） pathways were detected. RESULTS Compared with normal group， the model group exhibited endometrial tissue damage， a reduced number of decidual cells， and a significant presence of blood stasis within the uterus； abortion rate， the serum levels of T3， T4 and TSH， the mRNA expressions of JAK2， STAT3 and suppressor of cytokine signaling 3 （SOCS3） as well as protein expressions of p-JAK2， p-STAT3 and SOCS3 in the pregnant uterus were increased significantly （ P ＜0.05）； uterine coefficient， the levels of VEGF and NO in pregnant uterus， mRNA expressions of VEGFR2， PI3K， AKT and endothelial nitric oxide synthase（eNOS）， protein expressions of VEGFR2， PI3K and eNOS as well as phosphorylation level of AKT in the pregnant uterus were significantly reduced （ P ＜0.05）. Compared with model group， the endometrial tissue damage and congestion in the Qingre antai decoction group were significantly improved， and the levels of the aforementioned quantitative indicators were significantly reversed （ P ＜0.05）. CONCLUSIONS Qingre antai decoction can improve the pregnancy outcomes in rats with threatened abortion of blood heat syndrome， the mechanism of which may be associated with inhibiting JAK2/STAT3 pathway and activating PI3K/AKT pathway.

This paper summarizes Professor WANG Yaoxian's experience in treating diabetic kidney disease （DKD） from the perspective of spleen and stomach based on the "internal heat leading to concretions" theory. It is considered that internal heat leading to concretions constitutes the core pathogenesis of DKD， with the spleen and stomach serving as the source of internal heat； therefore， treatment should be based on regulating the spleen and stomach. In the early stage of DKD， dysfunction of the spleen and stomach leads to the initial generation of internal heat. Common syndrome patterns include gastrointestinal heat accumulation and constrained heat in the liver and stomach， for which modified Gegen Qinlian Decoction （葛根芩连汤） can be used to clear heat bind while modified Dachaihu Decoction （大柴胡汤） is used to clear stomach and soothe liver， respectively. In the middle stage of DKD， weakness of the spleen and stomach results in the initial formation of concretions and conglomerations. Common patterns include spleen deficiency with prevalence of dampness and deficiency of both the spleen and kidney. Treatment emphasizes strengthening the spleen and resolving dampness， raising yang and boosting the stomach with modified Shengyang Yiwei Decoction （升阳益胃汤）， or supplementing spleen and boosting kidney， dissipating bind and dispe-ring concretions with modified Shenqi Dihuang Decoction （参芪地黄汤）， respectively. In the late stage of DKD， it is characterized by spleen and stomach depletion， and rampant accumulation of turbidity and toxin， and the common syndrome patterns are damp-turbidity obstruction in the middle jiao （焦） and spleen-kidney yang deficiency. Treatment aims to remove turbidity and harmonize the stomach， or to warm the kidney and strengthen the spleen while elimina-ting turbidity， using modified Dahuang Gancao Decoction（大黄甘草汤） and Jupi Zhuru Decoction （橘皮竹茹汤） or modified Baoyuan Decoction （保元汤） and Lizhong Decoction （理中汤）， respectively. In clinical practice， appropriate formulas and medications are flexibly selected according to specific syndromes.

In recent years, with continuous advancements in molecular biology and gene testing technologies, the diagnosis and treatment of colorectal cancer have been rapidly transitioning toward precision medicine. The application of molecular classification, target detection, and liquid biopsy technologies has driven ongoing updates to clinical guidelines. Multidisciplinary team colla-boration, innovations in precision surgical techniques, and the widespread adoption of neoadjuvant combination therapies have collectively promoted more individualized and scientific management of colorectal cancer. Looking ahead,the authors believe that as multi-omics biomarkers, organoid models, and artificial intelligence are increasingly integrated into clinical practice, precision diagnosis and treatment of colorectal cancer will deepen further, offering patients more efficient and personalized therapeutic options.

Objective:To analyze the clinical characteristics of locally advanced rectal cancer patients with pathological complete response (pCR) after neoadjuvant chemoradiotherapy combined with immunotherapy.Methods:The retrospective cohort study was conducted. The clinicopatholo-gical data of 46 patients with locally advanced rectal cancer who were admitted to 6 medical centers, including Beijing Friendship Hospital of Capital Medical University et al, from June 2021 to November 2022 were collected. There were 29 males and 17 females, aged (61±4)years. Patients received neoadjuvant chemoradiotherapy combined with immune checkpoint inhibitor therapy, and under-went radical total mesorectal excision during 6-12 weeks after radiotherapy. Observation indicators: (1) comparison of clinical characteristics between pCR and non-pCR patients;(2) postoperative complications and adverse reactions of pCR and non-pCR patients. Comparison of measurement data with normal distribution between groups was conducted using the t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data between groups was conducted using the Mann-Whitney U test. Results:(1) Comparison of clinical characteristics between pCR and non-pCR patients. Before neoadjuvant therapy, there were 14 cases aged ≥50 years and 6 cases aged <50 years in pCR patients, versus 25 cases and 1 case in non-pCR patients, showing a significant difference between the two groups ( P<0.05). After neoadjuvant therapy, cases in clinical stage T0, T1, T2, T3, T4 were 11, 1, 5, 3, 0 for pCR patients versus 7, 4, 2, 11, 2 for non-pCR patients, cases of tumor regression grade 1, 2, 3, 4 were 11, 8, 1, 0 for pCR patients versus 7, 14, 4, 1 for non-pCR patients, cases in low-risk, medium-risk, high-risk of neoadjuvant rectal scoring and grading were 20, 0, 0 for pCR patients versus 4, 18, 4 for non-pCR patients, respectively, showing significant differences in above indicators between the two groups ( Z=-2.256, -2.104, -5.458, P<0.05). (2) Postoperative complications and adverse reactions of pCR and non-pCR patients. Postoperative complications occurred in 2 cases of pCR patients and 5 cases of non-pCR patients, postoperative adverse reactions occurred in 11 cases of pCR patients and 10 cases of non-pCR patients, showing no significant difference between the two groups ( P>0.05). Conclusion:Compared with locally advanced rectal cancer patients aged ≥50 years, those aged <50 years have significant benefits from neoadjuvant chemoradiotherapy combined with immunotherapy. Clinical T staging and magnetic resonance imaging-detected tumor regression grade after neoadjuvant therapy have predictive value for patients with pCR .

Objective To explore the effect of diet therapy on alcohol-induced chronic liver injury in rats and its relationship with TLR4 pathway.Methods According to Pueraria:Poria:Amomum villosum:Pericarpium Citri Reticulatae:Codonopsis:Zingiberis Rhizoma=15∶15∶10∶10∶10∶6,the water extract of the therapeutic prescription was prepared.A total of 78 female SD rats were randomly divided into 6 groups:normal group(n=12),model group(n=18),Hugan tablet group(0.35 g·kg-1,n=12),low-,medium-and high-dose Shiliaofang groups(2,6,18 g·kg-1,n=12).Except for the normal group,the rats in each group were induced alcoholic liver disease(ALD)by gradient alcohol gavage.After 10 weeks of intervention,the changes of body weight and water intake of rats were observed.The whole blood routine,serum alanine aminotransferase(ALT),aspartate aminotransferase(AST),triglyceride(TG),total cholesterol(TC)and liver malondialdehyde(MDA)were measured.The levels of serum alcohol dehydrogenase(ADH),aldehyde dehydrogenase(ALDH),lipopolysaccharide(LPS),D-lactic acid(D-LA),tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and interleukin-10(IL-10)were detected by enzyme-linked immunosorbent assay.HE staining was used to observe the pathological changes of liver and ileum.Oil red staining was used to observe liver fat deposition.Immunohistochemistry was used to detect the expression of ileal tight junction component occludin.Western blot was used to detect the expression of TLR4,MyD88 and NF-κB p65 protein in liver.Results Compared with the model group,the levels of WBC,LYC,TC,ALT,AST,LPS,D-LA,TNF-α and IL-6 in each diet group decreased,IL-10 increased,liver inflammatory cell infiltration and red lipid droplets decreased,intestinal villi were intact and densely arranged,the expression of occludin protein in ileum increased,and the expression of TLR4,MyD88 and NF-κB p65 protein in liver decreased.Conclusion The self-made dietotherapy prescription has a significant protective effect on chronic liver injury induced by alcohol in rats,which may be related to its down-regulation of TLR4-MyD88-NF-κB p65 protein expression and up-regulation of ileal occludin protein expression,improvement of intestinal mucosal barrier function,reduction of endotoxin entry into the liver,activation of TLR4/MyD88/NF-κB pathway,thereby reducing the second hit to the liver.This diet can be developed as a potential anti-alcoholic liver injury drug.

This study was aimed at investigating the infection status of orf virus(ORFV)and the genetic evolution characteristics of epidemic ORFV isolates from Anhui province.A total of 303 clinical samples collected from major meat sheep breeding cities in An-hui during 2021-2023 were subjected to ORFV detection with fluorescence quantitative PCR(qPCR).The full-length B2L and F1L genes of ORFV in the positive samples were amplified through conventional PCR and sequenced.Genetic evolution analysis of the B2L and F1L genes was conducted after sequencing.The qPCR results indicated a total ORFV positivity rate in the clinical samples of 48.8%(148/303).Multiple sequence comparisons indicated that the B2L genes of 56 sample isolates shared 96.7%-100.0%DNA and 97.4%-100.0%amino acid sequence identity.Moreover,the F2L genes of 56 sample isolates shared 95.1%-100.0%DNA and 95.0%-100.0%amino acid sequence identity.The genetic evolution tree constructed with the B2L gene DNA sequences indicated sample iso-lates and 21 reference strains located in subgroup 1,and 26 sheep-derived sample isolates and 17 reference strains located in sub-group 2.Among them,the goat-derived sample isolate FY-TYA was located in the same sub-branch as the human-derived reference strain Gansu,whereas the goat-derived sample isolate FY-XQC was located in the same sub-branch as the reference strains China Vaccine and OV-HLJ-04.The genetic evolution tree constructed with the F1L gene DNA sequences showed,the goat sample isolates FY-XQA and FY-XQC were located in the same sub-branch as the sheep-derived reference strain Xinjiang.ORFV infection was rela-tively widespread in the major meat sheep breeding areas of Anhui province,and the DNA and amino acid sequences of the B2L and F1L genes of current circulating ORFV isolates showed different degrees of genetic variation,among which F1L gene had a high de-gree of variation.Furthermore,some goat-derived sample isolates were closely related to human,vaccine,and sheep-derived refer-ence strains.These results may serve as a reference for the prevention and control of ORFV infection in Anhui province.

Objective:To investigate the effects of two anastomosis methods on perioperative and pathological outcomes during totally laparoscopic right hemicolectomy (TLRH).Methods:In a national multicenter snapshot study, 1,854 patients who underwent laparoscopic right hemicolectomy were enrolled from 52 tertiary hospitals across China. The post-hoc analysis based on this study compared the data of 303 patients who underwent TLRH. Patients were divided into the antiperistaltic group (33 cases) and the isoperistaltic group (270 cases) according to type of anastomosis. Due to the significant difference in sample size between the two groups, propensity score matching (PSM) was performed to eliminate the influence of baseline characteristic discrepancies. The matching was based on the following known confounding factors: age, gender, body mass index (BMI), history of abdominal surgery, and history of diabetes, with a caliper value of 0.2. Perioperative and pathological outcomes were compared between the two groups.Results:After PSM, 33 patients were included in the antiperistaltic group and 65 patients in the isoperistaltic group. There were no statistically significant differences in baseline data between the two groups (all P>0.05). No significant differences were observed between the two groups in terms of operation time, blood loss, time to first defecation, time to first oral intake, or the incidence and grading of complications either (all P>0.05). However, length of postoperative hospital stay in the isoperistaltic group was significantly shorter than that in the antiperistaltic group, however (7.0 [6.0, 9.0] days vs. 8.0 [7.0, 10.5] days, P=0.049). In terms of pathological outcomes, there were also no statistically significant differences between the two groups in the number of harvested lymph nodes or the number of positive lymph nodes (all P>0.05). Conclusions:The two digestive tract reconstruction modalities, antiperistaltic and isoperistaltic anastomosis, have comparable perioperative safety and efficacy in TLRH. The isoperistaltic group had better outcomes in terms of postoperative hospital stay.

Objective:Exploring the association between Life's Crucial 9 (LC9) and the risk of thyroid dysfunction (TD), as well as its potential predictive capacity.Methods:A total of 247 600 TD-free participants from the UK Biobank were enrolled in the study. The LC9 score was divided into three CVH groups: low (0-), medium (50-), and high (80-100). Cox proportional hazards regression models were used to calculate the HRs and 95% CIs of the risk of TD with LC9 CVH status. Calculate Harrell's concordance index ( C-index), net reclassification improvement (NRI), and integrated discrimination improvement (IDI) to evaluate the predictive ability of the LC9 score and Life's Essential 8 (LE8) score. Results:During a median follow-up of 12.3 years, 5 515, 911, and 4 869 new cases of TD, hyperthyroidism, and hypothyroidism were documented, respectively. Participants with a high LE8 CVH group had 57.00% ( HR=0.43, 95% CI: 0.38-0.49), 55.00% ( HR=0.45, 95% CI: 0.34-0.60), and 58.00% ( HR=0.42, 95% CI: 0.37-0.47) lower risk of TD, hyperthyroidism, and hypothyroidism, respectively, than those with low CVH group. Compared with the LE8 score, the improvement in C-index for the LC9 score predicted TD risk was 0.004 (95% CI: 0.001-0.007), the NRI was 0.101 (95% CI: 0.021-0.103), and the IDI was 0.001 (95% CI: 0.000-0.001). Conclusions:The better CVH status, defined by LC9, was associated with a lower risk of TD. Compared to the LE8 score, the LC9 score demonstrated a significant enhancement in both risk discrimination and reclassification capability for TD risk.

Objective To investigate the mechanism of Shugan Zhixie Prescription in treating irritable bowel syndrome with diarrhea(IBS-D)using network pharmacology;To validate the findings through in vivo experiments.Methods Active components and potential targets of Shugan Zhixie Prescription were identified via the TCMSP database.Disease targets for IBS-D were retrieved from GeneCards,DisGeNET and OMIM databases.The intersection of drugs and disease targets was taken,and the protein interaction network was constructed by using STRING database.GO and KEGG pathways were enriched to identify the key signaling pathways of Shugan Zhixie Prescription in the treatment of IBS-D.The rat model of liver depression and spleen deficiency type IBS-D was established by the method of abnormal hunger and satiety,restraint pinch stress and intestinal perfusion of acetic acid.The rats were intervened with low-,medium-and high-dosage of Shugan Zhixie Prescription respectively for 14 days.Serum contents of diamine oxidase(DAO),interleukin(IL)-8,and IL-18 were measured by ELISA.Protein expressions and mRNA expressions of relevant targets in colonic tissue were detected using Western blot and RT-qPCR.Results A total of 26 active components and 553 targets of Shugan Zhixie Prescription were obtained,and 1 930 targets of IBS-D disease were obtained,with 184 drug-disease intersection targets.The possible mechanism was related to NF-κB,AGE-RAGE,Th17 cell differentiation and other signaling pathways.Animal experiments demonstrated that Shugan Zhixie Prescription could significantly reduce defecation frequency,fecal water content,and inflammatory cytokine levels in model rats.It markedly decreased TLR4 and NF-κB protein expressions(P<0.01),while increased AQP3,AQP8 and Occludin protein expressions in colonic tissue(P<0.01,P<0.05).Conclusion Shugan Zhixie Prescription exerts therapeutic effects on IBS-D through multiple pathways and targets,and the mechanism may be related to inhibiting TLR4/NF-κB signaling pathway and promoting intestinal barrier repair.

Objective:To investigate the relationship between the BCL2 family protein BIM and ibrutinib resistance in chronic lymphocytic leukemia (CLL) and to analyze its regulatory mechanisms on apoptosis and autophagy.Methods:RNA sequencing (RNA-seq) was used to examine changes in the expression of BCL2 family proteins in samples from patients with CLL, MEC1 cell lines, and ibrutinib-resistant cell lines (MR). Western blot was used to analyze changes in BIM protein expression during apoptosis in MR. shRNA knockdown was used to assess the effects of BIM on cell proliferation and apoptosis. RNA-seq and the autophagy inhibitor chloroquine treatment were used to study autophagy-related changes in MR.Results:BIM expression was significantly downregulated before and after drug resistance in CLL primary cells and MEC1 cell lines ( P<0.0001). Knockdown of BIM in CLL cells inhibited ibrutinib-induced apoptosis and promoted cell proliferation ( P<0.05 for both). In addition, protective autophagy was increased in MR and apoptosis was increased after administration of chloroquine and small interfering RNA. The increased expression of LC3-Ⅱ protein in BIM-knockdown cell lines ( P<0.01) suggested that reduction of BIM may mediate autophagy activation. Conclusion:Downregulation of BIM may be a key factor in promoting ibrutinib resistance in CLL by activating protective autophagy. These findings provided a potential target for improving CLL treatment.