This article systematically explores the traditional Chinese medicine （TCM） pathogenesis evolution and metastatic mechanisms of advanced gastric cancer from the perspective of "phlegm-toxin flowing infusion". Based on this theory， it is proposed that advanced gastric cancer presents a pathogenesis evolution characterized by healthy qi depletion， phlegm-toxin flowing infusion， and collateral damage with blood stasis. Healthy qi depletion is the root of the disease， in which spleen and kidney insufficiency leads to weakened healthy qi and inability to resist pathogenic factors. Phlegm-toxin flowing infusion is the core pathogenesis， where phlegm-dampness and cancer toxin intertwine and migrate to other organs along with qi movement. Collateral damage with blood stasis constitutes the final pathological stage of metastasis， where phlegm-toxin obstruction damages the collaterals， and congealed qi and blood form accumulations. On this basis， the meridian pathways and metastasis mechanisms of advanced gastric cancer spreading to multiple sites such as the liver， peritoneum， lungs， bones， brain， ovary， and lymph nodes are further analyzed， providing references for clinical management and research of this disease.

ObjectiveTo analyze the distribution of traditional Chinese medicine （TCM） syndrome elements in patients with immune-related adverse events （irAEs） associated with malignant tumor immunotherapy and to explore the influencing factors for the occurrence of irAEs. MethodsClinical data were retrospectively collected from malignant tumor patients treated with programmed death-1 （PD-1） inhibitors， including demographic information， tumor history， duration of immunotherapy， occurrence of irAEs， types and grades of irAEs （G1-G5）， and TCM four-diagnostic information. Patients were divided into irAEs group and the non-irAEs group based on the occurrence of irAEs. Propensity score matching （PSM） at a 1∶2 ratio was performed to balance baseline characteristics between groups. Syndrome elements before treatment and cumulative contributions of syndrome elements before and after irAEs onset were evaluated using the "Syndrome Elements Differentiation Scale". Logistic regression analysis was conducted to identify factors associated with the occurrence of irAEs. The use of glucocorticoids in the irAEs group was also analyzed. ResultsAfter 1∶2 matching， 59 patients were included in the irAEs group and 118 were in the non-irAEs group. No statistically significant differences were found between groups in terms of age， gender， primary tumor site， pathological type， or tumor stage （P＞0.05）. Patients in the non-irAEs group were more likely to have received targeted therapy， while the irAEs group had a longer duration of immunotherapy and a higher rate of positive programmed death-ligand 1 （PD-L1） expression （P＜0.05）. In total， 72 irAEs events occurred among 59 patients， with an overall incidence rate of 19.4% （59/304） and a grade 3~5 incidence rate of 6.8% （4/59）， mainly presenting as cardiotoxicity， nephrotoxicity， and pneumotoxicity.Before immunotherapy， the top three syndrome elements in the irAEs group were spleen （71.2%， 42/59）， kidney （42.4%， 25/59）， and lung （39.0%， 23/59）. For the pathogenic nature elements， yin deficiency （52.5%， 31/59）， phlegm （40.7%， 24/59）， and dampness （35.6%， 21/59） ranked highest. Compared to the non-irAEs group， the distribution of spleen， kidney， liver， yin deficiency， and qi deficiency elements showed significant differences in the irAEs group （P＜0.05）. After the occurrence of irAEs， the cumulative contributions of spleen， lung， stomach， heart， yin deficiency， qi deficiency， and yang hyperactivity elements increased significantly （P＜0.05）. Multivariate Logistic regression analysis indicated that duration of immunotherapy， spleen syndrome element， kidney syndrome element， liver syndrome element， yin deficiency element， and qi deficiency element were independent risk factors for irAEs （P＜0.05 or P＜0.01）. Among the irAEs patients， 15 received glucocorticoid combined with TCM treatment， while 6 received glucocorticoid therapy alone. Patients receiving combined treatment required lower doses and shorter courses of glucocorticoids compared to those treated with glucocorticoids alone （P＜0.05）. ConclusionIn malignant tumor patients， spleen， kidney， lung， yin deficiency， phlegm， dampness， and qi deficiency are the predominant syndrome elements before and after the occurrence of irAEs. However， elements such as heat and qi stagnation significantly increase after irAEs onset. Duration of immunotherapy， spleen， kidney， liver syndrome elements， yin deficiency， and qi deficiency are independent risk factors for the development of irAEs.

Objective To explore the value of high-frequency ultrasound in the detection of metastatic hepatocellular carcinoma and displaying lesion characteristics. Methods A total of 38 paitients with hepatocellular carcinoma satellite lesions within 40 mm of subcutaneous tissue were underwent low-frequency (1-5 MHz) and high-frequency (6-9 MHz) ultrasound. Detection rates and ultrasonic features were compared. Results High-frequency grayscale ultrasound had a higher detection rate (71.1% vs. 36.8%, P＜0.001). Subgroup analysis showed higher detection rates with chemotherapy history (88.9% vs. 33.3%, P＝0.002), fatty liver (71.9% vs 31.3%, P＜0.001) or superficial lesion (within 20 mm, 76.5% vs 41.2%, P＝0.031). High-frequency ultrasound also showed clearer margins (P＝0.004) and more arterial-phase rim enhancement (P＝0.007). Conclusions 6-9 MHz ultrasound detects metastatic hepatocellular carcinoma, especially superficial lesions, more effectively than 1-5 MHz ultrasound and better visualizes characteristics.

ObjectiveTo investigate the association between the maintenance treatment of modified Yiqi Huoxue Jiedu Formula （益气活血解毒方） or poly ADP ribose polymerase （PARP） inhibitors and the recurrence and metastasis of advanced ovarian cancer. MethodsA case-control study design was employed， dividing patients with advanced ovarian cancer into two groups based on the occurrence of recurrence and metastasis following first-line maintenance treatment. Patients with recurrence and metastasis comprised the case group， while those without recurrence and metastasis served as the control group. The previous first-line maintenance treatment method was set as the exposure factor in the study （with the use of modified Yiqi Huoxue Jiedu Formula defined as exposed and PARP inhibitors defined as unexposed）. Basic information was collected for both groups， including the achievement of satisfactory R0 surgery， age， stage， neoadjuvant chemotherapy， lymph node metastasis， germline BRCA1/2 mutations， homologous recombination deficiency positivity， first-line maintenance treatment method （modified Yiqi Huoxue Jiedu Formula or PARP inhibitors）， and CA125 levels after the last chemotherapy. The baseline data of the two groups were assessed for differences. If there exists difference， a 1∶1 nearest neighbor matching method was used for propensity score matching. Univariate and multivariate logistic regression analyses were employed to evaluate the association between the modified Yiqi Huoxue Jiedu Formula or PARP inhibitors and the recurrence and metastasis of ovarian cancer. ResultsA total of 201 patients with advanced ovarian cancer were included， with 97 in the case group and 104 in the control group. Both groups showed statistically significant differences in R0 surgery， stage， neoadjuvant chemotherapy， and CA125 levels after the last chemotherapy （P＜0.05）， indicating baseline imbalance. After propensity score matching， there were 71 patients in both the case and control groups， achieving baseline balance （P＞0.05）. Univariate logistic regression analysis indicated that the achievement of satisfactory R0 surgery （P = 0.006）， disease stage （P = 0.001）， the use of neoadjuvant chemotherapy （P = 0.024）， treatment modality （P = 0.006）， and CA125 levels after the last chemotherapy （P = 0.013） were associated with the recurrence and metastasis of ovarian cancer. Multivariate logistic regression analysis revealed that disease stage was an independent influencing factor for the recurrence and metastasis of ovarian cancer （P = 0.030）， whereas the P-value for the correlation between first-line maintenance treatment and ovarian cancer was 0.188. ConclusionFirst-line maintenance treatment of ovarian cancer patients with the use of modified Yiqi Huoxue Jiedu Formula or PARP inhibitors does not correlate with the recurrence and metastasis of ovarian cancer.

A scientific and efficient comprehensive operation system for the transformation of clinical research achievements is an important guarantee to fully release the capability of public hospitals of the achievement transformation. A public hospital, focusing on the bottleneck problems faced in the process of transforming scientific and technological achievements, began to explore the construction of a comprehensive operation system for the transformation of clinical research achievements and implemented it throughout the hospital from October 2023. By improving the organizational structure and setting up full-time management positions; formulating supporting policies and perfecting the incentive mechanism; drawing a systematic portrait and creating a standard pathway; expanding the transformation platform and promoting coordinated development; innovating management services and strengthening digital empowerment; and highlighting publicity and education to enhance the capability of transformation, the hospital has effectively promoted the transformation of clinical research achievements. This practice can provide a reference for other hospitals to improve the management of clinical research achievements transformation and promote high-quality hospital development.

Objective:To explore the role of P2Y1Receptor(P2Y1R)-activated astrocytes in delayed encephalopathy after acute carbon monoxide poisoning(DEACMP).Methods:SD rats were randomly divided into Control,DEACMP,DEACMP+DMSO,and DEACMP+MRS2179 groups.The latter three groups were exposed to static CO inhalation to establish the DEACMP model,while the Control group inhaled air.The rats in DEACMP+MRS2179 group were injec-ted with 3 μl of P2Y1R antagonist MRS2179 with concentration of 1 mmol/L via lateral ventricle,while the DEACMP+DMSO group an equal volume of DMSO.At 14 and 21 day after DEACMP model establishment,the spatial learning and memory ability of rats were observed by Morris water maze,the injury of pyramidal cells in the CA1 area of the hippo-campus was observed by HE staining.The protein levels of glial fibrillary acidic protein(GFAP)and P2Y1receptor(P2Y1R)in the hippocampal tissues of rats were detected by immunohistochemistry and Western blot.The expressions of interleukin-1β(IL-1β),interleukin-6(IL-6)and tumor necrosis factor-α(TNF-α)in the hippocampal tissues of rats were detected by ELISA.Results:In comparison with the Control group,the escape latency was found to be signifi-cantly prolonged in the DEACMP group and the DEACMP+DMSO group.Furthermore,the expression levels of GFAP,P2Y1R,IL-1β,IL-6,and TNF-α were significantly increased in the pyramidal cells of the CA1 region of the hippocam-pal tissue(P<0.05).In contrast,the escape latency was significantly reduced and the expression levels of GFAP,P2Y1R,IL-1β,IL-6,and TNF-α were significantly decreased in the DEACMP+MRS2179 group when compared with the DEACMP+DMSO group(P<0.05).Conclusion:P2Y1R activates astrocytes to release inflammatory factors lead-ing to the onset of cognitive impairment in DEACMP,and inhibition of P2Y1R reduces the expression of inflammatory factors and thus improves cognitive function in DEACMP.

Objective To analyze the physical activity and health-related policies and guidelines for type 2 diabetes mellitus(T2DM)issued by international organizations and countries,including World Health Organization(WHO),Euro-pean Union,the United States,Canada,Australia and China.Methods A content analysis and a comparative study were conducted to examine physical activity-related policies and guidelines at international and national levels.Results International organizations and countries all recognized physical activity as a key measure for preventing and controlling T2DM and improving population health.WHO established clear global targets and monitoring indica-tors.The United States,Canada and Australia closely integrated community interventions,healthcare incentives and structured exercise programs,while China combined national fitness initiatives with public health services.International T2DM-related exercise guidelines recommended>150 minutes of moderate-intensity aerobic exer-cise per week combined with resistance training.Conclusion At both international and national levels,T2DM-related physical activity and health policies aim to increase participation in physical activity,improve population health,and effectively reduce the incidence and mortality of chronic diseases such as T2DM.Guidelines emphasize a multidisciplinary collaboration model to enhance practi-cal applicability,implementation effectiveness and the sustainability of health-related physical activity.Future de-velopment priorities will include establishing personalized physical activity programs for T2DM based on indi-vidual needs,and building an integrated health-related service system that combines physical activity,community health,chronic disease management and digital technologies.

DiGeorge(DGS)syndrome is an autosomal dominant disorder caused by 22q11.2 microdeletions,most patients developed the disease in childhood.22q11.2 deletion syndrome,and the mutation types are dominated by haploid deletion of this gene.We report a young patient with hypoparathyroidism(parathyroidism)induced by DGS syndrome combined with hypocalcemic heart failure.Genetic testing revealed pathogenic copy number variants associated with the clinical phenotype of the subject.About 2 674 kb of deletion variation was detected at q11.21 position on chromosome 22,which contained the TBX1 gene and was a pathogenic mutation.This paper discusses the clinical features,pathogenesis and current treatment of DGS,and emphasizes the importance of early screening,early diagnosis and treatment,and regular follow-up of heart failure,aiming to enhance the awareness of clinicians and geneticists on DGS syndrome.

AIM:Study on the bioequivalence of rivaroxaban tablets from two different manufactur-ers in healthy subjects under fasting and postpran-dial conditions.METHODS:Adopting a single cen-ter,randomized,open,fasting and postprandial,four cycle,fully repeated crossover trial design.28 healthy male and female subjects were given oral administration of either the test or reference for-mulation(10 mg)on an empty stomach or in a post-prandial state,with a cleaning period of 7 days be-tween cycles.The concentration of rivaroxaban in the plasma(heparin sodium)of the subjects was measured using liquid chromatography tandem mass spectrometry(LC-MS/MS),and pharmacoki-netic(PK)parameters were calculated using Phoe-nix WinNonlin 7.0 software to evaluate the bio-equivalence of the test and reference formulations.RESULTS:Fasting group:After oral administration of the investigational drug,the Cmax of the test formula-tion and reference formulation were(200.96±68.99)ng/mL and(196.96±50.97)ng/mL,respec-tively,and the AUC0-t were(1 439.93±493.94)h·ng·mL-1 and(1 395.90±411.49)h·ng·mL-1,respectively,the AUC0-∞ were(1 506.56±511.47)h·ng·mL-1 and(1 451.94±417.89)h·ng·mL-1,respectively,the 90％confidence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 91.87％-103.37％,95.00％-105.07％,95.33％-105.57％,respectively,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t,AUC0-∞were 0.88-1.73,0.74-1.45 and 0.72-1.41,respectively.Post-prandial group:After oral administration of the ex-perimental drug,the Cmax of the test and reference formulations were(241.23±54.44)ng/mL and(226.54±48.04)ng/mL,respectively,and the AUC0-t were(1 383.26±437.05)h·ng·mL-1 and(1 333.54±372.53)h·ng·mL-1,respectively,the AUC0-∞ were(1 404.01±439.89)h·ng·mL-1 and(1 352.31±374.45)h·ng·mL-1,respectively,the 90％confi-dence intervals for the geometric mean ratios of Cmax,AUC0-t,and AUC0-∞ were 100.92％-110.50％,98.30％-108.31％,and 98.46％-108.39％,respective-ly,the 90％CI of the intra-individual standard devia-tion ratio(SWT/SWR)for Cmax,AUC0-t and AUC0-∞ were 0.63-1.29,0.78-1.61 and 0.79-1.61,respectively.CONCLUSION:Bioequivalence of the two prepara-tions in fasting and postprandial state in healthy subjects.

Objective:To investigate the surgical effect of total parathyroidectomy combined with calf subcutaneous autotransplantation in the treatment of secondary hyperparathyroidism.Method:From Dec 2018 to Dec 2022,31 patients with secondary hyperparathyroidism who underwent total parathyroidectomy combined with calf subcutaneous autotransplantation in our hospital were selected to analyze the therapeutic effect.Results:All 31 operations were successfully completed.A total of 120 parathyroid glands were removed,including 27 cases(87.10%)with 4 parathyroid glands and 4 cases(12.90%)with 3 parathyroid glands.The average length of hospitalization was(15.82±8.74)days.Compared with preoperative parathyroid hormone,the value of parathyroid hormone decreased by more than 50%after 20 min of total parathyroidectomy.The levels of serum calcium,phosphorus,iPTH and calcium-phosphorus product at each time point after operation were significantly lower than those before operation(P＜0.01).The symptoms of joint pain was significantly improved in all patients after operation.During the postoperative follow-up of 31 patients,1 patient was confirmed to have graft recurrence at 6 months after operation,which was surgically removed.Conclusion:Total parathyroidectomy combined with calf subcutaneous autotransplantation can effectively treat secondary hyperparathyroidism and significantly improve the quality of life.