Based on the literature study,the thoughts and possible therapeutic mechanism in treating male infertility from the perspective of spleen and kidney by regulating intestinal flora were explored.Disturbance of intestinal flora is one of the important factors leading to the development of male infertility,and the spleen and kidney have certain similarities to intestinal flora in the physiological function and pathological changes.Moreover,tonifying the kidney and strengthening the spleen can regulate the intestinal flora by fostering the growth of beneficial bacteria,inhibiting the reproduction of pathogenic bacteria,and protecting the barrier of the intestinal mucosa.Therefore,the possible therapeutic mechanisms in treating male infertility with the prescriptions for tonifying the kidney and strengthening the spleen to regulate intestinal flora are as follows:inhibiting the expression of inflammatory factors to reduce the inflammatory reaction of testicular tissues;improving the antioxidant capacity to alleviate the damage of spermatozoa caused by oxidative stress,and improving the bad mood to alleviate the impact of psychological stress on the reproductive system.The exploration of the thoughts for treating male infertility from the perspective of spleen and kidney by regulating intestinal flora may provide a new entry point for modern Chinese medicine clinical treatment of male infertility.

Objective:To explore the mechanism of hypertension inducing erectile dysfunction(ED)using transcriptomics and network pharmacology.Methods:We randomly divided 12 male rats with spontaneous hypertension(SHT)into an L-arginine(LA)group(n=6)and an SHT model control(MC)group(n=6),took another 6 Wistar Kyoto male rats as normal controls(NC),and treated the animals in the LA group by intraperitoneal injection of LA at 400 mg/kg and those in the latter two groups with physio-logical saline,once a day,all for 7 days.Then we observed the blood pressure and penile erection of the rats,and determined the ex-pressions of the cGMP/PKG signaling pathway-related proteins and mRNAs in different groups using ELISA,Western blot and RT-qPCR.Results:Transcriptomics combined with network pharmacology showed that the cGMP/PKG signaling pathway played a key role in hypertension-induced ED.In vivo animal experiments revealed a significantly lower frequency of penile erections in the MC than in the NC group(1.33±0.52 vs 2.67±0.51,P＜0.05).The protein expressions of eNOS,PKG and sGC were markedly de-creased in the model controls compared with those the normal controls(P＜0.05),but remarkably upregulated in the LA group com-pared with those in the MC group(P＜0.05).Conclusion:Hypertension decreases the expressions of eNOS,NO,sGC,cGMP and PKG proteins and the level of testosterone by inhibiting the cGMP/PKG signaling pathway,which consequently suppresses the relaxa-tion of the penile vascular smooth muscle and reduces erectile function.

Epigenomic imbalance drives abnormal transcriptional processes,promoting the onset and progression of cancer.Although defective gene regulation generally affects carcinogenesis and tumor suppression networks,tumor immunogenicity and immune cells involved in antitumor responses may also be affected by epigenomic changes,which may have significant implications for the development and application of epigenetic therapy,cancer immunotherapy,and their combinations.Herein,we focus on the impact of epigenetic regulation on tumor immune cell function and the role of key abnormal epigenetic processes,DNA methylation,histone post-translational modification,and chromatin structure in tumor immunogenicity,and introduce these epigenetic research methods.We emphasize the value of small-molecule inhibitors of epigenetic modulators in enhancing antitumor immune responses and discuss the challenges of developing treatment plans that combine epigenetic therapy and immuno-therapy through the complex interaction between cancer epigenetics and cancer immunology.

N ⁶-methyladenosine (m⁶A) modification is critical for mRNA splicing, nuclear export, stability and translation. Fat mass and obesity-associated protein (FTO), the first identified m⁶A demethylase, is critical for cancer progression. Herein, we developed small-molecule inhibitors of FTO by virtual screening, structural optimization, and bioassay. As a result, two FTO inhibitors namely 18077 and 18097 were identified, which can selectively inhibit demethylase activity of FTO. Specifically, 18097 bound to the active site of FTO and then inhibited cell cycle process and migration of cancer cells. In addition, 18097 reprogrammed the epi-transcriptome of breast cancer cells, particularly for genes related to P53 pathway. 18097 increased the abundance of m⁶A modification of suppressor of cytokine signaling 1 (SOCS1) mRNA, which recruited IGF2BP1 to increase mRNA stability of SOCS1 and subsequently activated the P53 signaling pathway. Further, 18097 suppressed cellular lipogenesis via downregulation of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), and C/EBPβ. Animal studies confirmed that 18097 can significantly suppress in vivo growth and lung colonization of breast cancer cells. Collectively, we identified that FTO can work as a potential drug target and the small-molecule inhibitor 18097 can serve as a potential agent against breast cancer.

Objective:To explore the effect of pectin on improving intestinal barrier injury in elderly stroke patients.Methods:A total of 60 elderly stroke patients who received enteral nutrition in Department of Critical Care Medicine of Taizhou People's Hospital from November 2020 to October 2021 were included. The control group included 30 cases, using conventional enteral nutrition solution. The other 30 cases were in the study group, and pectin was added on the basis of routine enteral nutrition solution. The levels of serum diamine oxidase (DAO) and D-lactic acid (D-LA) were measured on the first and 7th days of enteral nutrition to evaluate the intestinal barrier function of elderly stroke patients. The levels of interleukin-6 (IL-6), procalcitonin (PCT) and high-sensitivity C-reactive protein (CRP) were measured to evaluate the inflammatory response level of elderly stroke patients. The clinical prognosis of the two groups was compared.Results:Compared with the control group, the values of DAO [(4.05±1.56)ng/mL] and D-LA [(6.11±2.20) μmol/L] in the study group were significantly lower than those in the control group on the 7th day (all P < 0.05). Also the levels of IL-6 [(15.43±12.53) ng/mL], PCT [(0.82±0.98) ng/mL] and CRP [(6.94±6.60) mg/L] in the study group were lower than those in the control group, and the difference between the two groups was statistically significant (all P < 0.05). Compared with the control group, the length of ICU stay and total length of hospital stay in the study group were shorter than those in the control group ( P<0.05), but there was no significant difference in the incidence of stroke-related pneumonia (16.7% vs. 30.0%) and 30-day mortality (16.7% vs. 20.0%) between the two groups ( P>0.05). Conclusions:The enteral nutrition with pectin supplementation can improve intestinal barrier function and reduce inflammatory response in elderly stroke patients.

Objective::To detect the expression levels of peripheral blood Treg/Th17 cells and related cytokines in patients with Hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) with different traditional Chinese medicine (TCM) syndrome " Yanghuang-Yinyanghuang-Yinhuang" , in order to explore the cellular immunological characteristics of different TCM syndromes of liver failure. Method::The 32 cases of patients with HBV-ACLF in early, middle and late stages in line with the " Yanghuang-Yinyanghuang-Yinhuang" TCM syndrome grouping were selected. Flow cytometry was used to detect the frequency expression of Treg/Th17 cells in peripheral blood. The expression levels of interleukin-10(IL-10), transforming growth factor-β(TGF-β), interleukin-17A(IL-17A), tumor necrosis factor-α(TNF-α) and interleukin-23(IL-23) were detected by cytometric bead array (CBA). The expressions of transcription factor forkhead box P3(FoxP3) and retinoid-related orphan nuclear receptor-γt(ROR-γt) mRNA were detected by Real-time PCR. The SPSS 20.0 software was applied in data statistics and processing to analyze the expression characteristics of Treg/Th17 cells and related cytokines in patients with different TCM syndrome types of HBV-ACLF. Result::The patients with HBV-ACLF Yanghuang syndrome were mainly distributed in the early stage of liver failure, those with Yinyanghuang syndrome were mainly distributed in the middle stage, and those with Yinhuang syndrome were distributed in the late stage. From Yanghuang syndrome, Yinyanghuang syndrome to Yinhuang syndrome, the frequency of Treg and Th17 cells gradually increased, and the differences among the groups were statistically significant (P<0.05). From Yanghuang syndrome, Yinyanghuang syndrome to Yinhuang syndrome, Treg cytokines IL-10, TGF-β gradually increased, and the differences among the groups were statistically significant (P<0.05). Th17 cytokines IL-17A, TNF-α, IL-23 gradually increased, of which IL-17A were differences between Yanghuang syndrome and the Yinyanghuang syndrome, as well as Yanghuang syndrome and Yinhuang syndrome (P<0.05). From Yanghuang syndrome, Yinyanghuang syndrome to Yinhuang syndrome, the expression of FoxP3 was gradually decreased, while that of ROR-γt was gradually increased, and the differences among the groups were statistically significant (P<0.01). Conclusion::There is a certain correlation between the different course of early, middle and late stages of HBV-ACLF and the distribution of TCM syndromes. The frequency of Treg and Th17 cells and the correlation of IL-17A, TGF-β and IL-10 with TCM syndrome differentiation are related, suggesting that Treg and Th17 cells have a certain reference value for the diagnosis of patients with HBV-ACLF and the syndrome differentiation of TCM syndromes.