Renal fibrosis is a critical factor in progression of chronic kidney disease to end-stage renal disease.Underlying mechanisms driving renal fibrosis remain unclear.Lymphocytes play a pivotal and dual role in initiation and progression of renal fibro-sis.Through secretion of cytokines and chemokines,as well as direct cell-cell interactions,lymphocytes can exert profibrotic effects while also demonstrating antifibrotic potential under certain conditions.This review aims to summarize current research advances regarding interplay between lymphocytes and renal fibrosis and to explore their potential applications in antifibrotic therapies.

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

Renal fibrosis is a critical factor in progression of chronic kidney disease to end-stage renal disease.Underlying mechanisms driving renal fibrosis remain unclear.Lymphocytes play a pivotal and dual role in initiation and progression of renal fibro-sis.Through secretion of cytokines and chemokines,as well as direct cell-cell interactions,lymphocytes can exert profibrotic effects while also demonstrating antifibrotic potential under certain conditions.This review aims to summarize current research advances regarding interplay between lymphocytes and renal fibrosis and to explore their potential applications in antifibrotic therapies.

Objective:Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) occurring at multiple sites during the same period of time is extremely rare, and the aim of this study was to investigate the clinicopathologic features of SMMN-FGT and its relationship with prognosis.Methods:We retrospectively analyzed the clinicopathological features and follow-up records of 25 cases of SMMN-FGT diagnosed from January 2012 to October 2022 in the case database of Obstetrics and Gynecology Hospital of Fudan University.Results:The median age at onset was 46 years old, respectively. Clinical manifestations included irregular vaginal bleeding or drainage, pelvic pain, and ovarian cysts, etc. Germline genetic test confirmed Peutz-Jeghers syndrome (P-J syndrome) in two patients. All patients underwent surgery, and 13 patients had postoperative adjuvant radiotherapy and/or chemotherapy. The most frequent site of lesion was the cervix (21 cases), with 11, 10 and 16 cases occurring in the endometrium, fallopian tubes and ovaries, respectively. Six cases involved three sites simultaneously, and only one case had all four sites involved at the same time. Among the 9 cases with P53 mutation phenotype, 6 cases had gastric-type mucinous adenocarcinoma, 2 cases had lobular endocervical glandular hyperplasia, and 1 case had mucinous adenocarcinoma, whereas all the minimally deviated adenocarcinomas had wild phenotype of P53. The median follow-up time was 59 months, during which 3 cases died and 6 cases developed local recurrence or distant metastasis. According to our analysis, postoperative recurrence or metastasis was correlated with the FIGO stage of the disease, the number of lesion sites and the severe degree of the uterine lesions ( P＜0.05). Conclusions:SMMN-FGT has a relatively good clinical prognosis, and even advanced patients can benefit from surgery and adjuvant therapy. In young patients, the ovaries may be preserved if no evidence of lesions are seen after adequate evaluation. In SMMN-FGT, gastric-type mucinous adenocarcinoma occurring in the cervix may have a better prognosis than gastric-type mucinous adenocarcinoma of the cervix alone, so the accurate diagnosis of SMMN-FGT is critical for clinical management.

Objective To investigate the mechanism of enhancer of zeste homolog 2(EZH2),a histone methyltransferase,in regula-ting the biological behavior of ovarian cancer(OC)and provide the experimental support for finding new therapeutic targets in the treat-ment of OC.Methods The small interfered RNAs(siRNAs)of EZH2 were used to knock down EZH2 in different OC cell lines,and the interfering efficiency of siEZH2 mRNAs and protein were evaluated by qRT-PCR and Western blot.The cell proliferation,migra-tion,invasion ability and apoptosis of OC cells before and after EZH2 interference were evaluated by the CCK-8,wound healing,Tran-swell and flow cytometry.The expression levels of early growth response 1(EGR1)and H3K27me3 proteins after EZH2 interference were determined by Western blot.Meanwhile,the mechanism of EZH2 regulating the biological behavior of OC cells was explored.Re-sults The expression levels of EZH2 mRNA in OC cells transfected with siEZH2 were significantly lower than that in the negative con-trol group(P＜0.05)and the expression levels of EZH2 protein in A2780 cells were also significantly downregulated(P＜0.05).The results of Western blot showed that the expression levels of EGR1 and H3K27me3 proteins were reduced to varying degrees.After trans-fection with siEZH2-1,the proliferation ability of A2780 cells in the transfected group was significantly lower than that in the negative control group(P＜0.05).The results of the cell scratch test and Transwell test showed that the migration and invasion ability of OC cells transfected with siEZH2-1 were significantly weakened(P＜0.05).The results of flow cytometry showed that the apoptosis of OC cells transfected with siEZH2-1 was significantly enhanced(P＜0.05).Conclusion EZH2 is highly expressed in OC cells and can promote the proliferation,migration,invasion and anti-apoptosis of A2780 cells.However,EZH2 affects the biological behavior of ovar-ian cancer not by regulating the expression of EGR1 through its H3K27me3 transferase activity.

Objective:Synchronous mucinous metaplasia and neoplasia of the female genital tract (SMMN-FGT) occurring at multiple sites during the same period of time is extremely rare, and the aim of this study was to investigate the clinicopathologic features of SMMN-FGT and its relationship with prognosis.Methods:We retrospectively analyzed the clinicopathological features and follow-up records of 25 cases of SMMN-FGT diagnosed from January 2012 to October 2022 in the case database of Obstetrics and Gynecology Hospital of Fudan University.Results:The median age at onset was 46 years old, respectively. Clinical manifestations included irregular vaginal bleeding or drainage, pelvic pain, and ovarian cysts, etc. Germline genetic test confirmed Peutz-Jeghers syndrome (P-J syndrome) in two patients. All patients underwent surgery, and 13 patients had postoperative adjuvant radiotherapy and/or chemotherapy. The most frequent site of lesion was the cervix (21 cases), with 11, 10 and 16 cases occurring in the endometrium, fallopian tubes and ovaries, respectively. Six cases involved three sites simultaneously, and only one case had all four sites involved at the same time. Among the 9 cases with P53 mutation phenotype, 6 cases had gastric-type mucinous adenocarcinoma, 2 cases had lobular endocervical glandular hyperplasia, and 1 case had mucinous adenocarcinoma, whereas all the minimally deviated adenocarcinomas had wild phenotype of P53. The median follow-up time was 59 months, during which 3 cases died and 6 cases developed local recurrence or distant metastasis. According to our analysis, postoperative recurrence or metastasis was correlated with the FIGO stage of the disease, the number of lesion sites and the severe degree of the uterine lesions ( P＜0.05). Conclusions:SMMN-FGT has a relatively good clinical prognosis, and even advanced patients can benefit from surgery and adjuvant therapy. In young patients, the ovaries may be preserved if no evidence of lesions are seen after adequate evaluation. In SMMN-FGT, gastric-type mucinous adenocarcinoma occurring in the cervix may have a better prognosis than gastric-type mucinous adenocarcinoma of the cervix alone, so the accurate diagnosis of SMMN-FGT is critical for clinical management.

Objective:To observe the anti-inflammatory and glycometabolic effects of glutathione(GSH)on macrophages in collagen induced arthritis(CIA)mice.Methods:①CIA model establishment and groups:A total of 14 female DBA/1J mice were ran-domly divided into:CIA+PBS group and CIA+GSH group.The mice were sacrificed on the 50th day,collecting serum and isolating bone marrow derived macrophages(BMDM),which were marked as BMDM1.②Trained immunity model establishment and groups:BMDM were isolated from normal DBA/1J mice,and were pretreated with histone H3K27 demethylases inhibitor(GSKJ1)or PBS for 2 h.Then,serum from CIA model mice in vivo was incubated for 24 h,and the samples were grouped as follows:(CIA+GSH)+PBS group,(CIA+GSH)+GSKJ1 group,(CIA+PBS)+PBS group,(CIA+PBS)+GSKJ1 group.Lipopolysaccharide(LPS)was adopted to stimulated cells on the 6th day,which were marked as BMDM2.③RNA sequencing was used to detect differentially expressed genes(DEGs)and their function in BMDM1 and BMDM2.q-PCR was adopted to estimate the mRNA levels of PFK and Idh3g.The culture supernatants were used to measure the protein levels of TNF-α and IL-6 by ELISA.Results:①Compared with CIA+PBS group,the mice in CIA+GSH group showed lighter of joint swelling(P<0.05),less arthritis index(P<0.05),HE staining suggested less inflam-matory cell infiltration,Safranin O-fast green staining showed more chondrocytes,TRAP staining indicated reduced osteoclasts.②In BMDM1,GO analysis showed that DEGs were mainly involved in glutathione derivative metabolic process,IL-6 production,inflammatory response,innate immune response,regulation of primary metabolic process and glycolipid binding,compared with CIA+GSH and CIA+PBS group.In CIA+GSH group,the mRNA level of PFK was significantly decreased(P<0.05),while Idh3g was also significantly up-regulated(P<0.05),and the expression of TNF-α,IL-6 were both reduced(P<0.05)compared with CIA+PBS group.③In BMDM2,GO analysis showed that DEGs were also involved in inflammatory response,activation of innate immune response,regulation of tumor necrosis factor production,positive regulation of IL-6 production,regulation of glycolytic process and 1,3-β-D-glucan binding between CIA+GSH and CIA+PBS group.Furthermore,in(CIA+GSH)+PBS group,PFK was decreased(P<0.05),Idh3g was up-regulated(P<0.05),and IL-6 was also significantly down-regulated(P<0.05)compared with(CIA+PBS)+PBS group.However,there was no significant difference in the expression of Idh3g and PFK,moreover,TNF-α and IL-6 were significantly up-regulated compared with(CIA+GSH)+GSKJ1 group and(CIA+GSH)+PBS group.Conclusion:GSH can regulate glycometabolism and inflammatory response of macrophages via demethylation of histone H3K27,and it can also alleviate CIA in mice.

Objective:To explore the clinical and genetic characteristics of patients with Ehlers-Danlos syndrome (EDS) and gastrointestinal involvement.Methods:We retrospectively collected the clinical data of patients with EDS and gastrointestinal involvement from the electronic medical records at Peking Union Medical College Hospital (PUMCH) from January 2003 to September 2023. Additionally, we conducted a systematic review by searching cases with EDS and gastrointestinal involvement in PubMed, Embase, Web of Science, and the Cochrane Library databases from January 2000 to September 2023.Results:Ninety-four patients with EDS and gastrointestinal involvement were retrieved, including five patients from PUMCH and 89 patients from 80 published articles. The average age of patients was (29±14) years. The most common manifestation of gastrointestinal involvement was gastrointestinal perforation ( n=46, 48.9%), followed by functional gastrointestinal symptoms ( n=33, 35.1%), and digestive arterial disorders ( n=10, 10.6%). The most common clinical subtype was vascular-EDS (vEDS) ( n=50, 53.2%) followed by hypermobile-EDS (hEDS) ( n=20, 21.3%). The most frequent genetic mutation occurred in the COL3A1 gene ( n=30, 31.9%). Among patients with vEDS, gastrointestinal manifestations included gastrointestinal perforation ( n=33, 66.0%), arterial lesions ( n=9, 18.0%), and functional gastrointestinal symptoms ( n=7, 14.0%). Among patients with hEDS, gastrointestinal manifestations included functional gastrointestinal symptoms ( n=18, 90.0%), visceral prolapse ( n=3, 15.0%) and intestinal volvulus ( n=1, 5.0%). Conclusions:The most common subtypes of gastrointestinal involvement in EDS were vEDS and hEDS. Patients with hEDS mainly presented with functional gastrointestinal symptoms, whereas those with vEDS primarily showed gastrointestinal perforation and digestive arterial disorders.

Cerebral infarction, with high incidence, high mortality, high disability and high recurrence rates, can impose a serious burden on families and society. After cerebral infarction occurrence, neurons, as the fundamental structures of the central nervous system, are unable to renew or multiply after death; hence, full recovery from neurological impairments following cerebral infarction is challenging. With stem cell and genetic recombination advancements, cellular replacement therapy after cerebral infarction progresses, which helps clinical transformation and application. In this paper, the basic researches of cellular replacement therapy after cerebral infarction are reviewed from 3 aspects: endogenous nerve regeneration, exogenous stem cell transplantation, and in situ somatic cell trans-differentiation into neurons, in order to provide references for cerebral infarction treatment

Pregnancy ; Female ; Humans ; Placenta ; Nuclear Transfer Techniques ; Embryo, Mammalian ; Cell Nucleus