Ulcerative colitis （UC）， which is characterized by a complex and multifactorial etiology， remains one of the challenging disorders in the international field of digestive system diseases. In recent years， rectal administration preparations have made rapid progress in UC therapeutic applications. This study systematically reviews the dosage forms， mechanisms of action， and clinical applications of rectally-administered preparations for the treatment of UC. It is found that suppositories are the most commonly used dosage forms for rectal administration. The newer suppositories have the advantages of high bioavailability and good stability. Enemas can retain the drug in the intestine as much as possible to achieve the effects of diluting intestinal toxins， cleansing the bowel， and reducing inflammation. Gels can achieve a drug-sustained-release effect and effectively improve intestinal mucosal damage. The mechanism of action of this type of preparation is mainly to inhibit inflammatory cell infiltration， regulate intestinal microbial homeostasis， and increase the expression of tight-junction proteins， so as to play anti-inflammatory， regulate the intestinal bacterial flora， repair the intestinal mucosa， and other efficacies. The diversity of rectal administration forms provides a wide range of choices for the clinical treatment of UC， such as Mesalazine suppositories， Lianshao enemas， and temperature- sensitive gels loaded with drugs for UC.

Objective To explore the mechanism by which She-Ti-Zhi-Qiu decoction alleviates allergic rhinitis (AR) through gut microbiota-mediated regulation of T helper cell 17(Th17)/regulatory T cells(Treg) balance and related cytokines. Methods Twenty-eight female SD rats were randomly divided into four groups: the Control group, Model group, STZQ group, and Probiotics group. Except for the Control group, all other groups were sensitized with ovalbumin (OVA) to establish AR models. The Control and Model groups received intragastric administration of normal saline, while the STZQ group was administered She-Ti-Zhi-Qiu Decoction, and Probiotics group received probiotics. After two weeks of continuous intragastric administration, nasal mucosa, serum, peripheral blood, and colon contents were collected. The inflammation of nasal mucosal tissue was assessed via HE staining. 16S rDNA sequencing was used to detect and analyze the structure and content of bacteria in colon contents. Flow cytometry was used to detect the relative proportions of Treg and Th17 cells in peripheral blood. ELISA was used to measure the levels of Th17- and Treg-related cytokines in serum. Results Compared with the Control group, the Model group showed an inflammatory response in nasal mucosal tissue, along with increased IL-17A and IL-17E levels and decreased IL-10 levels. The percentage of Th17 cells in peripheral blood increased, while the percentage of Treg cells decreased. Beneficial bacteria in the intestine were decreased, while pathogenic bacteria were increased. Compared with the Model group, the STZQ group showed lower serum IL-17A and IL-17E levels and higher IL-10 levels. The percentage of Th17 in peripheral blood decreased, while the percentage of Treg increased. There was an increase in beneficial bacteria in the intestine and a decrease in pathogenic bacteria. The changes in the microbiota were correlated with IL-17A, IL-17E, and IL-10 levels. Conclusion She-Ti-Zhi-Qiu decoction can ameliorate the inflammation of AR by regulating gut microbiota and Th17/Treg immune balance.
Animals ; T-Lymphocytes, Regulatory/drug effects* ; Th17 Cells/drug effects* ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/therapeutic use* ; Female ; Rhinitis, Allergic/microbiology* ; Rats ; Cytokines

Objective:To analyze the infiltration of immune cells in different molecular subtypes of endometrial cancer(EC)at the protein level and explore the correlation between immune infiltration and clinicopathological features.Methods:Clinical data from 75 mismatch repair-deficient(MMR-D)EC cases and 74 mismatch re-pair-proficient(MMR-P)EC cases with comparable differentiation levels,diagnosed at Sichuan Provincial People's Hospital between January 2013 and January 2021,were selected.Molecular classification of EC was con-ducted according to the ProMisE standard.Immunohistochemistry(IHC)staining and fluorescent multiplexed im-munohistochemistry(F-mIHC)techniques were used to quantify the distribution of CD8+T cells,regulatory T cells(Tregs),and macrophages.The clinicopathological features and immune infiltration characteristics of different subtypes were investigated.Results:Among 149 samples,75 were MMR-D,8 were POLE-mutated(POLEmut),13 were p53-mutated(p53abn),and 53 were p53 wild-type(p53wt).The infiltration characteristics of CD8+T cells,Tregs,and macrophages were no statistically significant differences correlated with age and pathological stage(P>0.05).Among the molecular subtypes of EC,MMR-D tumors demonstrated a significantly higher densi-ty of CD8+T cells and Tregs compared to MMR-P tumors(P<0.05).Further comparison across the four EC mo-lecular subtypes revealed that the MMR-D subtype,which had a favorable prognosis,displayed a significantly high density of CD8+T cells compared to the p53abn subtype and the p53wt subtype(P<0.05).Additionally,the Tregs density of the MMR-D tumors was significantly higher than that of the p53wt tumors,in both the tumor area(P<0.05)and the stroma area(P<0.05).The POLEmut type tumors,which had the best prognosis,showed a high infiltration of CD8+T cells and Tregs cells compared to the p53abn and p53wt types,although there was no signifi-cant statistical difference(P>0.05).The p53wt subtype,which had a moderate prognosis,exhibited low density of CD8+T cells(P<0.05)and Tregs(tumor area,P<0.01,stroma area,P<0.05)compared to MMR-D tumors.The p53abn subtype,which was associated with the worst prognosis,exhibited higher infiltration of M2-like macro-phages than the MMR-D subtype(P<0.05)and the p53wt subtype(P<0.05)in tumor region,and lower CD8+T cell density than the MMR-D subtype(P<0.05).No significant statistical difference was observed in the density of M1-like macrophages across the four molecular subtypes in either the tumor or stroma areae(P>0.05).Conclu-sions:There was no statistically significant relation found between infiltration characteristics of immune cells and clinicopathological features.The types and distribution of infiltrated immune cells were different across these EC molecular subtypes.This indicated that ECs with different molecular subtype exhibited different features of immune infiltration which is closely associated with patient prognosis.

Objective:To analyze the infiltration of immune cells in different molecular subtypes of endometrial cancer(EC)at the protein level and explore the correlation between immune infiltration and clinicopathological features.Methods:Clinical data from 75 mismatch repair-deficient(MMR-D)EC cases and 74 mismatch re-pair-proficient(MMR-P)EC cases with comparable differentiation levels,diagnosed at Sichuan Provincial People's Hospital between January 2013 and January 2021,were selected.Molecular classification of EC was con-ducted according to the ProMisE standard.Immunohistochemistry(IHC)staining and fluorescent multiplexed im-munohistochemistry(F-mIHC)techniques were used to quantify the distribution of CD8+T cells,regulatory T cells(Tregs),and macrophages.The clinicopathological features and immune infiltration characteristics of different subtypes were investigated.Results:Among 149 samples,75 were MMR-D,8 were POLE-mutated(POLEmut),13 were p53-mutated(p53abn),and 53 were p53 wild-type(p53wt).The infiltration characteristics of CD8+T cells,Tregs,and macrophages were no statistically significant differences correlated with age and pathological stage(P>0.05).Among the molecular subtypes of EC,MMR-D tumors demonstrated a significantly higher densi-ty of CD8+T cells and Tregs compared to MMR-P tumors(P<0.05).Further comparison across the four EC mo-lecular subtypes revealed that the MMR-D subtype,which had a favorable prognosis,displayed a significantly high density of CD8+T cells compared to the p53abn subtype and the p53wt subtype(P<0.05).Additionally,the Tregs density of the MMR-D tumors was significantly higher than that of the p53wt tumors,in both the tumor area(P<0.05)and the stroma area(P<0.05).The POLEmut type tumors,which had the best prognosis,showed a high infiltration of CD8+T cells and Tregs cells compared to the p53abn and p53wt types,although there was no signifi-cant statistical difference(P>0.05).The p53wt subtype,which had a moderate prognosis,exhibited low density of CD8+T cells(P<0.05)and Tregs(tumor area,P<0.01,stroma area,P<0.05)compared to MMR-D tumors.The p53abn subtype,which was associated with the worst prognosis,exhibited higher infiltration of M2-like macro-phages than the MMR-D subtype(P<0.05)and the p53wt subtype(P<0.05)in tumor region,and lower CD8+T cell density than the MMR-D subtype(P<0.05).No significant statistical difference was observed in the density of M1-like macrophages across the four molecular subtypes in either the tumor or stroma areae(P>0.05).Conclu-sions:There was no statistically significant relation found between infiltration characteristics of immune cells and clinicopathological features.The types and distribution of infiltrated immune cells were different across these EC molecular subtypes.This indicated that ECs with different molecular subtype exhibited different features of immune infiltration which is closely associated with patient prognosis.

Objective:To explore the predictive value of peripheral blood neutrophil to lymphocyte ratio (NLR) and serum trimethylamine oxide (TMAO) on in-hospital mortality events in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) upon admission.Methods:A retrospective collection of medical records of 103 AMICS patients admitted to the Shanxi Yingkang Life General Hospital from January 2018 to June 2023 was conducted. The patients were divided into a survival group ( n=78) and a death group ( n=25) based on whether they experienced in-hospital mortality events. Two groups of peripheral blood NLR, serum TMAO, baseline data, and other laboratory indicators were compared. A logistic regression model was used to analyze the risk factors for in-hospital mortality in AMICS patients and a prediction model was constructed. We established receiver operating characteristic (ROC) curves to evaluate the predictive efficacy of peripheral blood NLR, serum TMAO, peripheral blood NLR+ serum TMAO, and predictive model indicators for in-hospital mortality events in AMICS patients. Results:The peripheral blood NLR and serum TMAO levels in the death group were significantly higher than those in the survival group (all P<0.05). The age of the death group was higher than that of the survival group, and the proportion of hypertension, alanine aminotransferase, creatinine, random blood glucose, proportion of patients who did not receive emergency percutaneous coronary intervention (PCI) treatment, peak cardiac troponin I, B-type natriuretic peptide, Gensini score of coronary artery disease, and C-reactive protein were all higher than those of the survival group. Systolic blood pressure and platelet count were lower than those of the survival group, heart rate and erythrocyte sedimentation rate were faster than those of the survival group, and the pre hospital time was longer than that of the survival group. The differences were statistically significant (all P<0.05). The results of binary logistic regression analysis showed that after adjusting for confounding factors such as age, male proportion, body mass index, proportion of old myocardial infarction, proportion of hypertension, and proportion of PCI history, advanced age, long pre hospital time, failure to receive emergency PCI, elevated peripheral blood NLR, and elevated serum TMAO were independent risk factors for in-hospital mortality in AMICS patients ( P<0.05). The predictive model was obtained as 0.734×age+ 0.277×pre hospital time+ 2.263×failure to receive emergency PCI+ 0.549×peripheral blood NLR+ 0.608×serum TMAO-26.923. The ROC curve results showed that the area under the curve (AUC) values of peripheral blood NLR, serum TMAO, peripheral blood NLR+ serum TMAO, and predictive model indicators for predicting in-hospital mortality events in AMICS patients were 0.744, 0.781, 0.825, and 0.921, respectively. When the optimal cutoff value was taken, the sensitivities were 0.880, 0.520, 0.680, and 0.880, and the specificities were 0.526, 0.923, 0.872, and 0.821, respectively. Conclusions:Advanced age, long pre hospital duration, failure to undergo emergency PCI, elevated peripheral blood NLR, and elevated serum TMAO are independent risk factors for in-hospital mortality in AMICS patients. Peripheral blood NLR, serum TMAO, peripheral blood NLR+ serum TMAO, and prediction models all have certain predictive value for in-hospital mortality events in AMICS patients. Among them, the sensitivity and specificity of the prediction models are high, and the efficacy is good.

【Objective】 To analyze the disease burden of benign prostatic hyperplasia (BPH) in China, Japan and South Korea from 1990 to 2019, so as to provide scientific basis for rational allocation of health resources. 【Methods】 Data were obtained from the Global Burden of Disease Study 2019. The incidence, prevalence and years lived with disability(YLD)were used to analyze the burden, and the average annual percent change and annual percent change were calculated. 【Results】 The incidence, prevalence and YLD rate in China were much higher than those in Japan and South Korea. The crude incidence in China, Japan and South Korea increased by 2.56%, 1.49% and 3.59% per year from 1990 to 2019, the crude prevalence rate increased by 2.70%, 2.34% and 4.03%, and the crude YLD rate increased by 2.68%, 2.33% and 4.04%. After age standardization, the disease burden in China decreased with time, but the trend was not significant, and the standardized rate in Japan and Korea increased significantly with time. The disease burden of BPH increased with age, and those aged 60 to 84 years had the highest burden. In addition, the disease burden increased with the increase of socio-demographic index (SDI) in all three countries. 【Conclusion】 The disease burden of BPH was very heavy in China, Japan and South Korea, especially in China. Males aged 60 to 84 years were the high-risk group. Targeted intervention should be adopted for these population.

Primary intrahepatic stone （PIS）is one of the intractable diseases in hepatobiliary surgery and an important cause of death from benign biliary tract diseases, and it has a high prevalence in the Yangtze River basin and southeastern coastal areas of China. At present, the mechanism of PIS occurrence has not been fully elucidated, but the role of biliary flora in the formation of PIS has been recognized by more and more studies. This article reviews the research progress of biliary flora in the formation of PIS with a view to strengthening the clinical understanding of mechanism of PIS, increasing the attention to the detection of biliary flora, and providing a reference for the prevention and treatment of PIS and the improvement of prognosis.

Objective:To investigate the safety and effect of transcatheter arterial chemoembolization (TACE) combined with radiofrequency ablation (RFA) and sorafenib on large hepatocellular carcinoma (HCC) patients treatment.Methods:From Jan 2012 to Dec 2017, 36 patients (Male: 33, Female: 3, average age: 51.8) with large HCC lesions(5-7 cm) received TACE plus with RFA and sorafenib in the Third Affiliated Hospital of Sun Yat-sen University. Efficacy was evaluated after TACE. Each patient was received follow-up after RFA procedure. The occurrence rate of complications and overall survival (OS) were recorded. Log-rank univariate analysis was used to analyze the OS data.Results:The median TACE time was 4, and the RFA time was (1.7±0.7) . Mean duration time of sorafenib administration was (37.7±28.8) months. Adverse events of sorafenib: 26(72.2%) hand-foot skin reaction, 6(16.7%) hypertension, 22(61.1%) diarrhea, 17(47.2%) alopecia, 3(8.3%) oral ulcer and 1(2.8%) gastrointestinal hemorrhage. Median OS was 63.0 months, and 1-year, 3-year and 5-year survival rate was 100%, 72.7% and 52.6%. The cumulative survival rate of patients taking whole course of sorafenib ( n=21) was better than that of patients taking remedial ( n=15); the cumulative survival rate of patients with alpha fetal protein (AFP) <200 μg/L ( n=26) before treatment was better than ≥200 μg/L ( n=10); the cumulative survival rate of patients with good TACE response ( n=19) was better than that of patients with no response ( n=17), and the differences were statistically significant (all P<0.05). Conclusions:TACE plus with RFA and sorafenib are safe and effective for large HCC patients with 5-7 cm lesions and this treatment might improve OS. The whole-course sorafenib, lower base AFP value (<200 μg/L) and good TACE response were considered as the good factors for the combination therapy in large HCC patients.

Objective:To explore the protective effect of vitamin D in acute liver failure through a mouse model.Methods:Acute liver failure was induced by combining D-galactosamine (D-GalN) lipopolysaccharide (LPS) to observe the effect of long-term vitamin D deficiency on liver injury and inflammatory signals in a mouse model. Acute liver failure was induced by thioacetamide (TAA) to observe the effect of vitamin D deficiency on the survival rate, and further high-dose of vitamin D supplementation protective effect was determined in a mouse model. Liver function was evaluated by measuring serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and liver inflammation by hematoxylin-eosin staining. The expressions of tumor necrosis factor (TNF-α), interleukin (IL) -1β, NOD-like receptor family, pyrin domain containing 3 (NLRP-3), chemokines (CCL2, CXCL1 and CXCL2), etc. in liver tissues were detected by RT-qPCR. The quantitation of macrophages in liver tissue was detected by immunohistochemistry. The comparison between groups were performed by t-test. The survival curve was analyzed by log-rank (Mantel-Cox) test.Results:Long-term vitamin D deficiency had increased acute liver failure sensitivity in mice, which was manifested by increased blood cell extravasation, massive necrosis of parenchymal cells, up-regulation of TNF-α, IL-1β, and NLRP-3 mRNA expression ( P < 0.05), and increased macrophages quantitation ( P < 0.05) in liver tissues. At the same time, vitamin D deficiency had increased the mice mortality rate because of liver injury ( P < 0.01). On the contrary, pre-administration of high dose of vitamin D (100 IU/g) had significantly reduced liver injury, inhibited ALT and AST rise ( P < 0.01), alleviated liver necrosis, and down-regulated the mRNA expression of inflammatory factors in liver tissues ( P < 0.05). Conclusion:Mouse model shows that long-term vitamin D deficiency can aggravate drug-induced acute liver failure and reduce survival rates. Furthermore, high-dose of vitamin D has a certain hepatoprotective effect, which can significantly improve liver necrosis condition and inhibit inflammation. Therefore, adequate vitamin D can retain liver physiological balance to resist liver injury.

Natural bone is a mineralized biological material, which serves a supportive and protective framework for the body, stores minerals for metabolism, and produces blood cells nourishing the body. Normally, bone has an innate capacity to heal from damage. However, massive bone defects due to traumatic injury, tumor resection, or congenital diseases pose a great challenge to reconstructive surgery. Scaffold-based tissue engineering (TE) is a promising strategy for bone regenerative medicine, because biomaterial scaffolds show advanced mechanical properties and a good degradation profile, as well as the feasibility of controlled release of growth and differentiation factors or immobilizing them on the material surface. Additionally, the defined structure of biomaterial scaffolds, as a kind of mechanical cue, can influence cell behaviors, modulate local microenvironment and control key features at the molecular and cellular levels. Recently, nano/micro-assisted regenerative medicine becomes a promising application of TE for the reconstruction of bone defects. For this reason, it is necessary for us to have in-depth knowledge of the development of novel nano/micro-based biomaterial scaffolds. Thus, we herein review the hierarchical structure of bone, and the potential application of nano/micro technologies to guide the design of novel biomaterial structures for bone repair and regeneration.