OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

OBJECTIVE To explore the mechanism of the active ingredient compatibility（quercetin， quercitrin and kaempferol at a mass ratio of 2∶9∶3）of Dimocarpus longan Lour. leaves（abbreviated as CDL） on ameliorating glucose and lipid metabolism disorders in type 2 diabetes mellitus （T2DM） rats. METHODS SD rats were randomly divided into blank control group， model group， metformin hydrochloride group （100 mg/kg）， and CDL high-， medium- and low-dose groups （280， 140， 75 mg/kg）， with 10 rats in each group. Rats in the blank control group were fed with standard chow， while rats in the other groups were given high-sugar and high-fat diet combined with intraperitoneal injection of streptozotocin to establish the T2DM rat model. After successful modeling， rats in each administration group were given corresponding drug solution， and rats in the blank control group and model group were intragastrically administered with equal volume of pure water， once a day， for consecutive 4 weeks. Fasting blood glucose （FBG） was detected at fixed time every week. The curves of oral glucose tolerance test （OGTT） and intraperitoneal insulin tolerance test （IPITT） were plotted， and the area under curve （AUC） was calculated. The pancreatic islet function indexes [fasting insulin （FINS）， homeostasis model assessment of insulin resistance （HOMA-IR）， insulin sensitivity index （ISI）]，blood lipid indexes [total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C）， high-density lipoprotein cholesterol （HDL-C）] and hepatic glycogen content were determined. The pathological morphological changes of liver and pancreatic tissues were observed. The protein and mRNA expression levels of molecules related to phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway in liver tissues were detected. RESULTS Compared with the blank control group， the FBG， AUC of IPITT curve， AUC of OGTT curve， HOMA-IR， the levels of FINS， TC， TG and LDL-C， as well as the protein and mRNA expression of phosphatase and tensin homolog， forkhead box protein O1 and glycogen synthase kinase-3β in liver tissues were significantly increased in the model group （ P ＜0.05）. ISI， the levels of HDL-C and hepatic glycogen content， along with the protein and mRNA expression of PI3K， insulin receptor substrate-1， Akt and protein expression of phosphorylated Akt in liver tissues were markedly decreased （ P ＜0.05）. In model group rats， the arrangement of hepatocytes was irregular， the overall structure of pancreatic lobules was disordered， and a large number of inflammatory cell infiltration was observed. Compared with the model group， most of the above quantitative indexes were significantly reversed in the CDL high-dose group （ P ＜0.05）， and the pathological lesions of liver and pancreas were obviously alleviated. CONCLUSIONS CDL can regulate glucose and lipid metabolism disorders， elevate insulin sensitivity and relieve insulin resistance in T2DM rats. Its mechanism may be related to the activation of the PI3K/Akt signaling pathway.

OBJECTIVE To systematically review the key regulatory requirements for pharmacy compounding drug products in the United States， and to provide references for improving the management framework of pharmacy compounding drug products in China， thereby ensuring the safety and accessibility of medication use. METHODS A literature revi ew was conducted to summarize the regulatory requirements and practical characteristics of pharmacy compounding drug products under Section 503A of the United States Federal Food， Drug， and Cosmetic Act . Based on regulatory experience of the United States， current status and existing deficiencies in pharmacy compounding drug products in China were analyzed， and targeted recommendations were proposed. RESULTS &CONCLUSIONS The United States has established a systematic regulatory framework for pharmacy compounding drug products under Section 503A， covering prescription management， active pharmaceutical ingredient management， list management of withdrawn or removed drugs and drugs that present demonstrable difficulties for compounding， recordkeeping management， interstate distribution and so on. Through standardized regulation of the entire compounding process and collaborative governance with expert advisory committees， this framework effectively balances individualized medication needs with drug quality and safety. In contrast， pharmacy compounding drug products in China remain largely confined to traditional Chinese medicine and face several challenges， including the lack of legal and regulatory support， inadequate quality control， lagging development of industry standards， and shortages of specialized personnel. It is recommended that China should establish a tiered regulatory system， develop comprehensive technical standards， build a localized regulatory framework， promote technological innovation， and strengthen professional talent cultivation to better balance the legitimate rights and interests of public medication use with drug safety and efficacy， thereby enhancing public health.

Digital intelligence technology is a comprehensive technical system with data as the key element and artificial intelligence as the core driving force. It provides innovative methodological support for addressing core bottlenecks in rare disease etiology research, including sample scarcity, high-dimensional datacomplexity, intricate pathogenic mechanisms, and challenges in causal validation. This paper systematically reviews the application pathways and current implementation of digital intelligence across four major stages of rare disease research, including etiological clue mining, causal inference, mechanism analysis, and clinical translation. Furthermore, it summarizes the technical strengths, existing limitations, and developmental challenges, aiming to inform optimization of the research paradigm and promote the sustainable advancement of rare disease research.

Objective:To investigate the effects and mechanism of Shenshuaikang Enema on hypoxia/reoxygenation (H/R) NRK-52E cells; To provide references for Shenshuaikang Enema to treat AKI.Methods:The H/R-induced NRK-52E cell model was established, and control group, model group, drug-containing serum group, drug-containing blood group +p53 agonist group, p53 agonist group, p53 inhibitor group were set up. Cell viability was detected by CCK8. The cell cycle distribution in each group was analyzed using flow cytometry, while cell senescence was assessed via β-galactosidase staining. The levels of IL-6, IL-1β, and TNF-α in the cell supernatant were evaluated using ELISA. Western Blot analyses were conducted to measure the protein expressions of p53, phosphorylated p53 (p-p53), and p21.Results:Compared with model group, NRK-52E cell vitality significantly increased in the drug-containing serum group and p53 inhibitor group ( P<0.01, P<0.05), S phase and G2/M phase percentage was significantly reduced ( P<0.01), β-galactoase staining decreased ( P<0.01), the levels of IL-1β, IL-6 and TNF-α decreased ( P<0.05, P<0.01), the protein expressions of p-p53 and p21 decreased ( P<0.01). Compared with the drug-containing serum group, NRK-52E cell vitality significantly decreased in the drug-containing serum+p53 agonist group and p53 agonist group ( P<0.01), S phase and G2/M phase percentage was significantly increased ( P<0.01), β-galactoase staining increased ( P<0.01), the levels of IL-1β, IL-6 and TNF-α increased ( P<0.01), the protein expressions of p-p53 and p21 increased ( P<0.01 or P<0.05). Conclusion:The drug-containing serum of Shenshuaikang Enema may promote cell proliferation, improve cell cycle arrest, inhibit pro-inflammatory and senescence related secretory phenotypes, and inhibit cell senescence by inhibiting p53/p21 signaling pathway, so as to promote H/ R-induced NRK-52E cell damage repair.

Objective To investigate the effect of Shugan Lipi Prescription on patients with diarrhea-predominant irritable bowel syndrome(IBS-D)of liver stagnation and spleen deficiency type from the perspective of bile acid-intestinal flora axis imbalance.Methods From May 2022 to May 2023,a total of 122 patients with IBS-D of liver stagnation and spleen deficiency type admitted to the Xi'an No.9 Hospital were enrolled into the investigation.The patients were randomly divided into the control group and the observation group by random number table method,with 61 patients in each group.The control group was given conventional western medicine treatment with oral administration of Dicetel plus Compound Diphenoxylate Tablets and Bifidobacterium Quadruple Viable Tablets,and the observation group was treated with Shugan Lipi Prescription on the basis of treatment for the control group.One course of treatment covered seven days,and both groups were treated for four courses in total.The changes of Irritable Bowel Syndrome Symptom Severity Scale(IBS-SSS)score,levels of serum bile acid and the fecal levels of intestinal flora such as Bifidobacterium,Lactobacillus,and Enterococcus in the two groups of patients before and after treatment were observed.Moreover,the clinical efficacy and the incidence of adverse reactions during the treatment of the two groups were compared.Results(1)After four courses of treatment,the total effective rate of the observation group was 96.72%(59/61)and that of the control group was 83.61%(51/61),and the intergroup comparison(tested by chi-square test)showed that the efficacy of the observation group was significantly superior to that of the control group(P<0.05).(2)After treatment,the scores of IBS-SSS items such as abdominal pain,abdominal pain duration,abdominal distension,defecation satisfaction and life interference in the two groups were all decreased when compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(3)After treatment,the levels of serum taurodeoxycholic acid(TDCA),taurocholic acid(TCA)and taurolithocholic acid(TLCA)in the two groups were decreased when compared with those before treatment(P<0.05),and the decrease in the observation group was significantly superior to that in the control group(P<0.01).(4)After treatment,the fecal level of Enterococcus,a kind of pathogenic bacterium,in both groups was decreased when compared with that before treatment(P<0.05),and the fecal levels of probiotics of Bifidobacterium and Lactobacillus in both groups were increased when compared with those before treatment(P<0.05).The effects on the decrease of fecal Enterococcus level and on the increase of fecal Bifidobacterium and Lactobacillus levels in the observation group were significantly superior to those in the control group(P<0.05 or P<0.01).(5)The incidence of adverse reactions in the observation group was 8.20%(5/61)and that in the control group was 6.55%(4/61),and the intergroup comparison showed that the difference was not statistically significant(P>0.05).Conclusion Shugan Lipi Prescription exerts certain therapeutic effect for IBS-D patients of liver stagnation and spleen deficiency type,and is with higher safety.Its therapeutic mechanism may be related to the restoration of the function of bile acid-intestinal flora axis.

This article introduced clinical experience in treating narcolepsy from the perspective of Shaoyin disease.Narcolepsy is a sleep disorder characterized by excessive daytime sleepiness,cataplexy and nocturnal sleep disturbances.The outline syndrome of Shaoyin disease with"constant desire to sleep"is highly similar to the manifestations of narcolepsy.Additionally,the core pathogenesis of narcolepsy involves Shaoyin heart-kidney yang deficiency,and the time when Shaoyin disease is about to be resolved coincides with the change time of narcolepsy.Based on the above,narcolepsy can be treated from Shaoyin disease.Mahuang Fuzi Gancao Decoction or Mahuang Xixin Fuzi Decoction can be selected to treat the disease.When treating clinical cases,it is necessary to adhere to the standards of original prescriptions:first,comply with the compatibility and dosage of the original prescriptions;second,Ephedrae Herba,Aconiti Lateralis Radix Praeparata and Asari Radix et Rhizoma need to be decocted first without the lid and remove the foam;the third is to take medicine after breakfast and lunch to avoid affecting sleep at night.

Objective:To investigate the clinicopathological and genetic characteristics of monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL).Methods:The forty-two MEITL cases diagnosed in the Department of Pathology, Ruijin Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China from 2016 to 2022 was retrospectively analyzed. Clinical data were collected, and follow-up was performed. Morphological characteristics were observed. Immunohistochemistry, Epstein-Barr virus (EBV) in situ hybridization, clonal rearrangement analysis of T-cell receptor (TCR) genes, and targeted next-generation sequencing (NGS) were performed.Results:Among the 42 patients (male/female ratio of 2.8∶1.0), the age range was 32-77 years with a median age of 59.5 (52.0-65.0) years. Grossly, the tumors were presented as ulcerative or exophytic lesions, with a maximum diameter of 2-18 cm. There were 34 cases with a single lesion and 8 cases with more than 1 lesion. The tumor cells in all 42 cases were relatively monotonous in histology and small or medium in size. They had round or oval nuclei, moderately pale or clear cytoplasm, evenly distributed nuclear chromatin, inconspicuous nucleoli, and frequent mitotic figures. In one of the cases, there were moderately large cells, vacuolated nuclei, and clear nucleoli. Lymphoepithelial lesions were observed in 36 (85.7%) of the 42 cases, tumor necrosis in 4 (9.5%) cases, scattered eosinophils and/or plasma cell infiltration in the background in 9 (21.4%) cases, and a "starry sky" phenomenon in 1 (2.4%) case. The tumor cells in all cases exhibited high expression of CD3, CD2, CD7, CD8, CD56, TIA1, Granzyme B, and Perforin, while some also expressed CD4 (5/41, 12.2%), CD5 (3/41, 7.3%), CD20 (4/41, 11.9%), CD79α (2/37, 5.4%), and CD30 (1/34, 2.9%). The Ki-67 proliferation index ranged from 40% to 90%. EBER in situ hybridization tests were negative in all cases. TCR gene clonal rearrangement was detected in 96.4% (27/28) of the tested cases. Targeted NGS revealed commonly mutated genes including SETD2, STAT5B, JAK3, TP53, and CREBBP. The primary treatment was chemotherapy, with 2 cases undergoing autologous hematopoietic stem cell transplantation. Follow-up information was obtained for 29 cases, with a follow-up period of 1-73 months. The mortality was 93.1% (27/29).Conclusions:MEITL is a rare and highly aggressive peripheral T-cell lymphoma. Its clinical manifestations are diverse, and diagnosis primarily relies on a comprehensive assessment of pathological morphology, immunohistochemical profiles, and EBV infection status, supplemented by genetic testing if necessary. At present, there is no effective treatment, and its overall prognosis is poor.

Pathological interaction between CD4 + T cells and B cells is one of the important mechanisms of systemic autoimmune diseases. Follicular helper T cells (Tfh) and peripheral helper T cells (Tph) are key cells for assisting B cells. Tph cell is a newly discovered helper T cell subset, and their phenotype is PD-1 highCXCR5 -CD4 +. Tph cell and Tfh cell have certain differences in phenotype, function, and site of action. It interacts with B cells, promoting the differentiation of B cells into plasma cells and the production of autoantibodies, as well as promoting the formation of ELS to maintain local inflammation and antibody responses. Tph cells have recently been reported in various autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus, Sjogren′s syndrome, and IgG4-related diseases. This review summarizes the progress in peripheral immune response of Tph cells in different systemic autoimmune diseases, aiming to explore the new mechanism of autoantibody production and help to develop new diagnostic and therapeutic targets in the future.

Objective:To examine the prevalence of malnutrition and evaluate the impact of nutritional support on clinical outcomes in elderly patients diagnosed with gastric and colorectal cancer.Methods:A retrospective cohort study was conducted, analyzing elderly patients with gastrointestinal tumors who underwent surgical treatment in the general surgery department from January 2019 to June 2020.The Global Leadership Initiative on Malnutrition(GLIM)criteria were utilized to diagnose malnutrition, and the effects of malnutrition and nutritional support on clinical prognosis were investigated.Results:A total of 426 elderly hospitalized patients with gastric and colorectal tumors who underwent surgical treatment were included in this study.This cohort comprised 199 cases of gastric cancer and 227 cases of colorectal cancer, with ages ranging from 65 to 91 years(mean age: 72.05±5.99).According to the GLIM criteria, 43.7%(186/426)of the patients were diagnosed with malnutrition, of which 25.6%(109/426)were moderately malnourished and 18.1%(77/426)were severely malnourished.Among the gastric cancer patients, 73.4%(146/199)were identified as having nutritional risk, with 48.7%(97/199)being malnourished and 22.6%(45/199)experiencing severe malnutrition.In the colorectal cancer group, 63.9%(145/227)were at nutritional risk, 39.2%(89/227)were malnourished, and 14.1%(32/227)had severe malnutrition.Additionally, 60.3%(257/426)of the patients received nutritional support therapy: 25.4%(108/426)received parenteral nutrition(PN), 11.3%(48/426)received enteral nutrition(EN), 23.7%(101/426)received a combination of EN and PN, while 39.7%(169/426)did not receive any nutritional support.Regardless of the presence or degree of malnutrition, patients who received nutritional support had significantly shorter total hospital stays compared to those who did not receive nutritional support, and this difference was statistically significant( t=5.58, 3.69, 2.21, 3.03, all P<0.05). Conclusions:Providing nutritional support to malnourished patients can reduce the length of hospital stay and improve clinical outcomes.