Objective To explore prescription medication rules and potential mechanism of traditional Chinese medicine(TCM)in the treatment of alcoholic liver disease(ALD)based on the technology of data mining and network pharmacology.Methods The prescriptions related to the treatment of ALD were retrieved in Chinese National Knowledge Infrastructure,Wanfang,Chinese Biomedical Literature and VIP databases.After the data were collated according to the filter criteria,IBM SPSS Statistics 27.0 and IBM SPSS Modeler 18 software were used to analyze the prescription rules and association rules.Then,the medication rules of TCM in the treatment of ALD were summarized,and the core drug combinations were obtained.Active ingredients in the core drug combinations for ALD and their targets were screened by network pharmacology.GO and KEGG analysis were performed on the main targets,and molecular docking technique was used to verify the binding ability of active ingredients to main targets.Results A total of 143 prescription for ALD were screened,involving 222 Chinese medicine,among which 28 high-frequency Chinese medicine were used with a frequency≥25 times.Eight core drug combinations were obtained by associations rule analysis.It has been found that there are 215 intersection targets between"Poria-Atractylodis macrocephalae Rhizoma-Hearba Artemisiae Scopariae"and ALD,including six core targets of AKT1,TNF,VEGFA,IL-1β,SRC,EGFR.One hundred and sixty-eight of signaling pathways are involved,including cancer pathways,PI3K/AKT signaling pathways,chemical carcinogenesis-reactive oxygen species,lipid and atherosclerosis,etc.Molecular docking results showed that the main active components including cerevisterol,genkwanin and demethoxycapillarisin had good binding ability to AKT1.Conclusion The main active ingredients in"Poria-Atractylodis macrocephalae Rhizoma-Hearba Artemisiae Scopariae"can participate in the regulation of key signaling pathways such as PI3K/AKT by acting on key target proteins(AKT1,TNF,and VEGFA).Subsequently,they play a role in inhibiting inflammatory response and apoptosis,slowing down liver fibrosis,and promoting hepatocyte repair.This study provides data support and theoretical guidance for the study of TCM in the treatment of ALD.

Objective:To explore the influence and its mechanism of allogeneic dermal papilla cells (DPCs) on the wound healing of full-thickness skin defects in mice.Methods:This study was an experimental study. DPCs were isolated from the whisker follicles of five 6-week-old male C57BL/6J mice by combining microdissection with collagenase digestion and were successfully identified. Eighteen 8-week-old male C57BL/6J mice were divided into phosphate buffer solution (PBS) group and DPC group according to the random number table, with 9 mice in each group, and the full-thickness skin defect wound model was created on the back of all mice. On day 2, 4, and 6 after injury, the mice in DPC group were administered 100 μL of cell suspension containing 1×10 6 DPCs of the 4 th passage by subcutaneous injection around the wound, and the mice in PBS group was administered an equal volume of PBS. On day 3, 7, 10, and 14 after injury, the wound healing and hair growth of mice in two groups were observed, and the residual wound area was measured, and the hair coverage area on the wound of mice in two groups was measured on day 14 after injury. On day 14 after injury, the wound tissue samples of mice in two groups were collected. Hematoxylin-eosin staining was performed to observe the condition of newborn hair follicles and the number was counted, Masson staining was performed to observe the collagen deposition in the dermis and the collagen deposition area was measured, the immunofluorescence method was used to detect the protein expressions of Wnt/β-catenin signaling pathway related molecules β-catenin and lymphoid enhancer binding factor 1 (Lef1), and Western blotting and real-time fluorescence quantitative reverse transcription polymerase chain reaction were used to detect the protein and mRNA expressions of β-catenin and Lef1, respectively. The number of samples in each experiment was 3. Results:Compared with those in PBS group, the mice in DPC group had accelerated wound re-epithelialization at each time point after injury, and more hair growth on day 10 and 14 after injury. On day 7, 10, and 14 after injury, the residual wound areas of mice in DPC group were (13.92±2.90), (3.69±1.78), and (1.09±0.14) mm 2, respectively, which were significantly smaller than (26.19±2.06), (10.84±3.59), and (6.75±2.11) mm 2 in PBS group, respectively (with t values of 5.85, 3.09, and 4.63, respectively, P values all <0.05). On day 14 after injury, the hair coverage area on the wound of mice in DPC group was (62±7) mm 2, which was significantly larger than (35±6) mm 2 in PBS group ( t=2.89, P<0.05). On day 14 after injury, compared with those in PBS group, the number of newborn hair follicles in the wound tissue of mice in DPC group was significantly increased ( t=5.43, P<0.05), and the dermal collagen deposition area was significantly reduced ( t=3.56, P<0.05). On day 14 after injury, both the immunofluorescence method and the Western blotting detection showed that the protein expressions of β-catenin (with t values of 5.49 and 4.25, respectively, P values all <0.05) and Lef1 (with t values of 7.50 and 11.54, respectively, P values all <0.05) in the wound tissue of mice in DPC group were significantly higher than those in PBS group; the mRNA expressions of β-catenin and Lef1 in the wound tissue of mice in DPC group were significantly higher than those in PBS group (with t values of 7.68 and 9.67, respectively, P<0.05). Conclusions:DPCs can accelerate the re-epithelialization of full-thickness skin defect wounds in mice by activating Wnt/β-catenin signaling pathway and promote hair follicle regeneration during the process of wound healing.

Objective: To investigate the pathological changes and conduct viral gene analysis of OPA and MVD co-occurrence in Inner Mongolia, China. Methods: Using gross pathology, histopathology, immunohistochemistry, ultrastructural pathology, PCR, and sequence analysis, we investigated the concurrent infection of JSRV and MVV in 319 Dorper rams slaughtered in a private slaughterhouse in Inner Mongolia, in 2022. Results: Of the 319 rams included, 3 showed concurrent JSRV and MVV infection. Gross lung pathology showed diffuse enlargement, consolidation, and greyish-white miliary nodules on the lung surface; the trachea was filled with a white foamy fluid; hilar and mediastinal lymph nodes were significantly enlarged. Histopathology results revealed typical OPA and MVD lesions in the lung tissue. Immunohistochemical results were positive for JSRV envelope protein (Env) in the tumor cells and MVV CA in alveolar macrophages. Transmission electron microscopy showed several virions and autophagosomes in the lung tissue, severely damaged mitochondria, and the induced mitophagy. Nucleotide sequences obtained for JSRV env and MVV gag showed the highest homology with the Inner Mongolian strains of JSRV env (JQ837489) and MVV gag (MW248464). Conclusions and Relevance: Our study confirmed that OPA and MVD co-occurrence and identified the pathological changes in Inner Mongolia, China, thereby providing references for the identification of concurrent JSRV and MVV infections.

Objective:To explore the short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction.Methods:The cohort of this prospective cohort study comprised 45 patients (nine men and 36 women) with radiation-induced enteritis complicated by intestinal obstruction admitted to Shanghai Tenth People's Hospital Affiliated to Tongji University from January 2022 to October 2022. The median age was 53 (42–65) years. Thirty-five of the patients had gynecological tumors and 10 colorectal malignancies. The patients were randomly allocated to a fecal microbiota transplantation group of 20 patients who underwent fecal microbiota transplantation starting 2 weeks before surgery for 6 days, in addition to receiving conventional perioperative treatment, and a conventional treatment group of 25 patients who only received nutritional support during the perioperative period. There were no significant differences in baseline characteristics (sex, age, preoperative nutritional indices, and surgical procedure) between the two groups (all P>0.05). Postoperative recovery (time to passing flatus or a bowel movement, length of stay) and complications were compared between the two groups. Postoperative complications within 30 days after surgery classified in accordance with the international Clavien–Dindo classification of surgical complications (I–V) were statistically analyzed. Improvement in gastrointestinal symptoms, namely abdominal pain, distension, diarrhea, and rectal bleeding) and gastrointestinal quality of life scores (which include 36 problems rated 0–144 points related to physical, psychological, social activities and family life; the lower the score, the more severe the symptoms) were compared between the two groups. Nutritional recovery was assessed by body mass, body mass index, total protein, albumin, prealbumin, and hemoglobin. Results:Compared with the conventional treatment group, the postoperative hospital stay was shorter in the fecal microbiota transplantation group (8.0±4.3 days vs. 11.2±5.4 days, t=2.157, P=0.037) and the time to passage of flatus or having a bowel movement was earlier (2.2±3.2 days vs. 3.9±2.3 days, t=2.072, P=0.044). There were 26 postoperative complications in the fecal microbiota transplantation group and 59 in the conventional treatment group. There were 20 and 36 Grade I to II complications and no and three Grade III to V complications in the transplantation and conventional treatment group, respectively. The overall grade of complication did not differ significantly between the two groups ( P=0.544). However, the incidence of postoperative intestinal inflammatory obstruction was lower in the fecal microbiota transplantation than the conventional treatment group (10.0% [2/20] vs. 40.0% [10/25], P=0.040). One patient in the conventional treatment group died. This patient had complete intestinal obstruction complicated by severe malnutrition preoperatively, and an intestinal fistula complicated by abdominal infection postoperatively, and died despite active treatment. Nineteen and 23 patients in the transplantation and conventional treatment group, respectively, attended for follow-up 1 month after surgery; 19 and 21, respectively, attended for follow-up 3 months after surgery, and 17 and 20, respectively, attended for follow-up 6 months after surgery. There were no significant differences between the two groups in abdominal pain or rectal bleeding 1, 3, or 6 months after surgery (all P>0.05). One month after surgery, the incidence of abdominal distension and diarrhea was lower in the fecal microbiota transplantation than in the conventional treatment group (3/19 vs. 48.0% [11/23], P=0.048; 3/19 vs. 52.2% [12/23], P=0.023). However, at the 3 and 6 month follow-ups the incidence of abdominal distension and diarrhea had gradually decreased in both groups and the differences between the groups were not statistically significant ( P>0.05 for all). Scores for gastrointestinal quality of life improved significantly in both treatment groups compared with preoperative values ( F=71.250, P<0.001; F=79.130, P<0.001, respectively). Scores for gastrointestinal quality of life were higher in the fecal microbiota transplantation than the conventional treatment group at all follow-up time points ( P<0.05). One-way ANOVA showed that body mass, body mass index, and total protein, albumin and hemoglobin concentrations improved in both groups compared with preoperative values (all P<0.05). Prealbumin concentration improved significantly in the transplantation ( F=5.514, P=0.002), but not in the conventional, group ( F=1.535, P=0.211). The improvements in body mass, body mass index, total protein, and albumin were better in the fecal microbiota transplantation than conventional treatment group at 3 and 6 months of follow-up (all P<0.05). Conclusion:Perioperative fecal microbiota transplantation combined with nutritional support is effective in improving early postoperative nutritional status and quality of life in patients with radiation-induced enteritis complicated by intestinal obstruction.

Objective:To explore the short-term efficacy of perioperative fecal microbiota transplantation combined with nutritional support in patients with radiation-induced enteritis complicated by intestinal obstruction.Methods:The cohort of this prospective cohort study comprised 45 patients (nine men and 36 women) with radiation-induced enteritis complicated by intestinal obstruction admitted to Shanghai Tenth People's Hospital Affiliated to Tongji University from January 2022 to October 2022. The median age was 53 (42–65) years. Thirty-five of the patients had gynecological tumors and 10 colorectal malignancies. The patients were randomly allocated to a fecal microbiota transplantation group of 20 patients who underwent fecal microbiota transplantation starting 2 weeks before surgery for 6 days, in addition to receiving conventional perioperative treatment, and a conventional treatment group of 25 patients who only received nutritional support during the perioperative period. There were no significant differences in baseline characteristics (sex, age, preoperative nutritional indices, and surgical procedure) between the two groups (all P>0.05). Postoperative recovery (time to passing flatus or a bowel movement, length of stay) and complications were compared between the two groups. Postoperative complications within 30 days after surgery classified in accordance with the international Clavien–Dindo classification of surgical complications (I–V) were statistically analyzed. Improvement in gastrointestinal symptoms, namely abdominal pain, distension, diarrhea, and rectal bleeding) and gastrointestinal quality of life scores (which include 36 problems rated 0–144 points related to physical, psychological, social activities and family life; the lower the score, the more severe the symptoms) were compared between the two groups. Nutritional recovery was assessed by body mass, body mass index, total protein, albumin, prealbumin, and hemoglobin. Results:Compared with the conventional treatment group, the postoperative hospital stay was shorter in the fecal microbiota transplantation group (8.0±4.3 days vs. 11.2±5.4 days, t=2.157, P=0.037) and the time to passage of flatus or having a bowel movement was earlier (2.2±3.2 days vs. 3.9±2.3 days, t=2.072, P=0.044). There were 26 postoperative complications in the fecal microbiota transplantation group and 59 in the conventional treatment group. There were 20 and 36 Grade I to II complications and no and three Grade III to V complications in the transplantation and conventional treatment group, respectively. The overall grade of complication did not differ significantly between the two groups ( P=0.544). However, the incidence of postoperative intestinal inflammatory obstruction was lower in the fecal microbiota transplantation than the conventional treatment group (10.0% [2/20] vs. 40.0% [10/25], P=0.040). One patient in the conventional treatment group died. This patient had complete intestinal obstruction complicated by severe malnutrition preoperatively, and an intestinal fistula complicated by abdominal infection postoperatively, and died despite active treatment. Nineteen and 23 patients in the transplantation and conventional treatment group, respectively, attended for follow-up 1 month after surgery; 19 and 21, respectively, attended for follow-up 3 months after surgery, and 17 and 20, respectively, attended for follow-up 6 months after surgery. There were no significant differences between the two groups in abdominal pain or rectal bleeding 1, 3, or 6 months after surgery (all P>0.05). One month after surgery, the incidence of abdominal distension and diarrhea was lower in the fecal microbiota transplantation than in the conventional treatment group (3/19 vs. 48.0% [11/23], P=0.048; 3/19 vs. 52.2% [12/23], P=0.023). However, at the 3 and 6 month follow-ups the incidence of abdominal distension and diarrhea had gradually decreased in both groups and the differences between the groups were not statistically significant ( P>0.05 for all). Scores for gastrointestinal quality of life improved significantly in both treatment groups compared with preoperative values ( F=71.250, P<0.001; F=79.130, P<0.001, respectively). Scores for gastrointestinal quality of life were higher in the fecal microbiota transplantation than the conventional treatment group at all follow-up time points ( P<0.05). One-way ANOVA showed that body mass, body mass index, and total protein, albumin and hemoglobin concentrations improved in both groups compared with preoperative values (all P<0.05). Prealbumin concentration improved significantly in the transplantation ( F=5.514, P=0.002), but not in the conventional, group ( F=1.535, P=0.211). The improvements in body mass, body mass index, total protein, and albumin were better in the fecal microbiota transplantation than conventional treatment group at 3 and 6 months of follow-up (all P<0.05). Conclusion:Perioperative fecal microbiota transplantation combined with nutritional support is effective in improving early postoperative nutritional status and quality of life in patients with radiation-induced enteritis complicated by intestinal obstruction.

OBJECTIVE To systematically review the efficacy and safety of kidney -tonifying Chinese patent medicine combined with phosphodiesterase type 5（PDE5）inhibitors in the treatment of erectile dysfunction （ED），and to provide evidence - based reference for clinical medication . METHODS Retrieved from PubMed ，Embase，Cochrane Library ，Web of Science ，VIP， China Biomedical Literature Database ，CNKI and Wanfang database ，randomized controlled trials （RCTs）of kidney -tonifying Chinese patent medicine combined with PDE 5 inhibitors（trial group ）versus PDE 5 inhibitors or kidney -tonifying Chinese patent medicine alone （control group ）were collected . The search period was from the establishment of the database to February 15，2022. After literature screening and data extraction ，the risk of bias assessment tool recommended in Cochrane System Reviewer ’s Handbook 6.1.0 was used to evaluate the quality of the included literature ；Stata 16.0 software was used for network meta -analysis； and the funnel plot was used for publication bias analysis . RESULTS A total of 23 RCTs were included ，with a total of 2 417 patients， involving 8 kinds of Chinese patent medicines ， including Congrong yishen granule ，Canrong zhutian capsule ， Compound xuanju capsule ， Huanshao capsule ， Shanhaidan granule， Shengjing capsule ， Shisanwei ziyin zhuangyang capsule，Shugan yiyang capsule . The results of network meta analysis showed that in terms of total effective rate ，Compound xuanju capsule combined with PDE 5 inhibitor，Shengjing capsule combined with PDE 5 inhibitor，Shugan yiyang capsule combined with PDE 5 inhibitor had higher total effective rate ；in terms of international index of erectile function 5，the scores of Compound xuanju capsule combined with PDE 5 inhibitor，Congrong yishen granule combined with PDE 5 inhibitor，and Canrong zhutian capsule combined with PDE 5 inhibitor were higher ；in terms of safety ，the incidence of adverse drug reactions caused by Huanshao capsule ，Shanhaidan granule and Shugan yiyang capsule were lower . CONCLUSIONS Kidney-tonifying Chinese patent medicine combined with PDE 5 inhibitor can improve the erectile function of ED patients and reduce the occurrence of adverse drug reactions . In terms of efficacy and safety ，Compound xuanju capsule combined with PDE 5 inhibitor is the best .

Metabolic-associated fatty liver disease (MAFLD), which is previously known as non-alcoholic fatty liver disease (NAFLD), represents a major health concern worldwide with limited therapy. Here, we provide evidence that ferroptosis, a novel form of regulated cell death characterized by iron-driven lipid peroxidation, was comprehensively activated in liver tissues from MAFLD patients. The canonical-GPX4 (cGPX4), which is the most important negative controller of ferroptosis, is downregulated at protein but not mRNA level. Interestingly, a non-canonical GPX4 transcript-variant is induced (inducible-GPX4, iGPX4) in MAFLD condition. The high fat-fructose/sucrose diet (HFFD) and methionine/choline-deficient diet (MCD)-induced MAFLD pathologies, including hepatocellular ballooning, steatohepatitis and fibrosis, were attenuated and aggravated, respectively, in cGPX4-and iGPX4-knockin mice. cGPX4 and iGPX4 isoforms also displayed opposing effects on oxidative stress and ferroptosis in hepatocytes. Knockdown of iGPX4 by siRNA alleviated lipid stress, ferroptosis and cell injury. Mechanistically, the triggered iGPX4 interacts with cGPX4 to facilitate the transformation of cGPX4 from enzymatic-active monomer to enzymatic-inactive oligomers upon lipid stress, and thus promotes ferroptosis. Co-immunoprecipitation and nano LC-MS/MS analyses confirmed the interaction between iGPX4 and cGPX4. Our results reveal a detrimental role of non-canonical GPX4 isoform in ferroptosis, and indicate selectively targeting iGPX4 may be a promising therapeutic strategy for MAFLD.

Tongue diagnosis is one of the diagnostic methods of Traditional Chinese Medicine (TCM), but its development has always been restricted by the lack of objective quantitative indicators. With the rapid development of computer technology and the advent of the algorithm era, the modernization of TCM tongue diagnosis has gradually become a hot research spot. This paper annalyses the literature and related patents of the modernization of tongue diagnosis and summarizes the R&D progress and application of tongue diagnosis as well as related instruments. It is found that domestic and foreign scholars focus on tongue diagnosis related research and attach importance to the formulation of relevant international standards. Tongue collection and analysis technology continues to develop; tongue diagnostic instruments are also gradually enriched. At present, their applications are extended to family self-use, but they are still mainly used in teaching, scientific research and other fields, involving the clinical efficacy evaluation of TCM, clinical case classification and health management, and there is still much room for development. In the future, we should strengthen the communication between multi-regional research centers, promote the communication among talents in different fields, constantly make up for the deficiencies and promote the development of tongue diagnosis research.

Objective:To define more information for familial hematuria by genetic screening in a pedigree with familial hematuria.Methods:This was a 4 generation pedigree included 20 family members. The clinical data and laboratory manifestations of the family members were reviewed and collected from medical records. Meanwhile, the peripheral blood samples of 11 family members of the pedigree were collected, and then DNA samples were extracted by salting out method for genetic analysis. For genetic analysis, firstly, three family members including the proband were selected for whole exome sequencing, and the genetic variations were screened according to the sequence variation interpretation guidelines from the American College of Medical Genetics and Genomics (ACMG) for diagnostic sequence interpretation. Then PCR and Sanger sequencing were used to verify the identified pathogenic variants in all family members in the pedigree.Results:In the pedigree, 6 female members had persistent hematuria. Among them, 2 died due to end-stage renal disease, 2 died due to non-renal diseases, and 2 maintained stable renal function. One of the two members with stable renal function was diagnosed as IgA nephropathy by renal biopsy. Moreover, diffuse basement membrane lesions were identified in her renal biopsy sample after the electron microscope examination, which resulted in the suspected diagnosis of Alport syndrome. Genetic testing in this pedigree revealed two novel mutations in COL4A4 gene (NM_000092), c.G446T:p.G149V in exon 7 and c.G1249A:p.G417R in exon 20. Conclusion:Two novel mutations of COL4A4 gene (c.G446T:p.G149V in exon 7 and c.G1249A:p.G417R in exon 20) in a hematuria pedigree are related with phenotype of familial hematuria.

Background: Maedi/Visna virus (MVV) is a contagious viral pathogen that causes considerable economic losses to the sheep industry worldwide. Objectives: In China, MVV has been detected in several regions, but its molecular characteristics and genetic variations were not thoroughly investigated. Methods: Therefore, in this study, we conducted next-generation sequencing on an MVV strain obtained from northwest China to reveal its genetic evolution via phylogenetic analysis. Results: A MVV strain obtained from Inner Mongolia (NM) of China was identified. Sequence analysis indicated that its whole-genome length is 9193 bp. Homology comparison of nucleotides between the NM strain and reference strains showed that the sequence homology of gag and env were 77.1%–86.8% and 67.7%–75.5%, respectively. Phylogenetic analysis revealed that the NM strain was closely related to the reference strains isolated from America, which belong to the A2 type. Notably, there were 5 amino acid insertions in variable region 4 and a highly variable motif at the C-terminal of the surface glycoprotein (SU5). Conclusions The present study is the first to show the whole-genome sequence of an MVV obtained from China. The detailed analyses provide essential information for understanding the genetic characteristics of MVV, and the results enrich the MVV library.