OBJECTIVES: To investigate the neuroprotective effects of electroacupuncture (EA) preconditioning against cerebral ischemia-reperfusion injury (CIRI) mediated by gut microbiota modulation, Nrf2/HO-1 pathway activation, and ferroptosis suppression. METHODS: Adult male SD rats were divided into sham operation group, CIRI model group, and EA preconditioning group. In the latter two groups, rat models of CIRI were established by middle cerebral artery occlusion (MCAO), and in EA preconditioning group, EA was applied at Baihui (DU20) and Zusanli (ST36) for 3 days before modeling. Neurological deficits, cerebral infarction, and hippocampal pathology of the rats were evaluated using behavioral tests, TTC staining, and Nissl and HE staining, and the oxidative stress markers (MDA, ROS, and SOD), apoptosis/ferroptosis-related proteins (Bax, Bcl-2, GPX4, and SLC7A11), and changes in gut microbiota were analyzed. RESULTS: EA preconditioning significantly reduced neurological deficits, decreased infarct volume, promoted hippocampal neuronal survival, and improved structural integrity of the hippocampal neurons in MCAO rats. EA preconditioning also significantly lowered MDA and ROS and increased SOD levels, upregulated Bcl-2, GPX4, and SLC7A11 expressions, and downregulated Bax expression in the hippocampal tissue of the rats, causing also activation of Nrf2/HO-1 signaling and improvement of gut microbiota composition. CONCLUSIONS EA preconditioning alleviates CIRI in rats by suppressing ferroptosis and apoptosis, enhancing antioxidant defenses via activating Nrf2/HO-1 signaling, and regulating the gut-brain axis.
Animals ; Electroacupuncture ; NF-E2-Related Factor 2/metabolism* ; Rats, Sprague-Dawley ; Signal Transduction ; Reperfusion Injury/therapy* ; Ferroptosis ; Male ; Rats ; Brain Ischemia ; Gastrointestinal Microbiome ; Heme Oxygenase (Decyclizing)/metabolism* ; Brain/metabolism* ; Oxidative Stress ; Heme Oxygenase-1/metabolism* ; Apoptosis

Village doctors and township hospitals are important parts of the rural three-level medical and health system.Promoting the medical cooperation under the perspective of hierarchical diagnosis and treatment is of great significance to ensuring the health of rural residents and promoting the development of rural primary medical treatment.However,the medical cooperation between village doctors and township hospitals needs to be clarified;the two-way referral mechanism needs to be improved;medical human resources need to be integrated;and the construction of medical information platform needs to be promoted.Therefore,it is necessary to accelerate the clarification of medical cooperation relationship,establish and improve the two-way referral mechanism,promote the integration of medical human resources,and strengthen the construction of medical information platform,so as to improve the effective cooperation between the village doctors and county hospitals,and to promote the rural primary medical service level.

Objectives:To investigate the clinical and cardiopulmonary functional characteristics of cardiopulmonary-phenotype idiopathic pulmonary arterial hypertension(IPAH)patients in comparison with classical IPAH patients and pulmonary hypertension patients associated with chronic lung disease(CLD-PH).Methods:In this retrospective study,data were collected from 30 patients with classical IPAH,20 cardiopulmonary phenotype IPAH patients,and 20 patients with CLD-PH,who were hospitalized in the Department of Respiratory and Critical Care Medicine at Beijing Chaoyang Hospital from November 2017 to February 2025.Pulmonary hypertension was diagnosed via right heart catheterization and all patients underwent pulmonary function tests,chest computed tomography(CT),echocardiography,and patients were followed up to 5 years.Results:Compared to classical IPAH patients,both cardiopulmonary phenotype IPAH patients and CLD-PH patients exhibited later onset age,higher proportions of World Health Organization(WHO)functional class Ⅲ-Ⅳ,males,and smokers(all P<0.05).The cardiopulmonary-phenotype IPAH patients also had higher rates of coronary artery disease and diabetes compared to classical IPAH patients(all P<0.05).Physiologically,the cardiopulmonary-phenotype IPAH patients showed reduced diffusing capacity for carbon monoxide(DLCO)and partial pressure of oxygen(PaO2),along with higher rates of emphysema and pulmonary fibrosis compared to classical IPAH(all P<0.05).In contrast,CLD-PH patients had lower mean pulmonary arterial pressure(mPAP),pulmonary vascular resistance(PVR),and pulmonary artery wedge pressure(PAWP),as well as reduced forced expiratory volume in the first second(FEV1%predicted),FEV1/forced vital capacity(FVC)ratio,and DLCO.However,CLD-PH patients demonstrated higher tricuspid annular plane systolic excursion(TAPSE),peak systolic velocity of the tricuspid annulus(S`),and partial pressure of carbon dioxide(PaCO2),along with increased rates of emphysema and pulmonary fibrosis(all P<0.05).Compared with LCD-PH,cardiopulmonary-phenotype IPAH patients had higher mPAP,PVR,FEV1%predicted,FEV1/FVC ratio,PAWP,and systolic pulmonary artery pressure,but lower DLCO,cardiac output,TAPSE,S′,and PaCO2(all P<0.05).No statistical difference was observed in PaO2 between these two groups.All cardiopulmonary-phenotype IPAH patients and classical IPAH patients received targeted medications,55%of CLD-PH patients did not receive targeted therapy,45%received monotherapy only(compared with cardiopulmonary-phenotype IPAH patients and classical IPAH groups,P<0.05).The 1,2,and 5-year survival rates were 79.2%,62.2%,and 46.7%,respectively in patients with cardiopulmonary-phenotype IPAH,100%,94.4%,and 94.4%,respectively in classic IPAH patients,and 92.9%,77.4%and 77.4%,respectively in patients with CLD-PH.Survival rates for cardiopulmonary-phenotype IPAH patients were significantly lower than those of classical IPAH and CLD-PH patients(log-rank P=0.008).Conclusions:IPAH cardiopulmonary phenotype patients are older,predominantly male,and often have a smoking history(median 30 pack-years).They exhibit severe hypoxemia,markedly reduced DLCOc,preserved spirometry,and severe pulmonary hypertension and lower survival rate.

Village doctors and township hospitals are important parts of the rural three-level medical and health system.Promoting the medical cooperation under the perspective of hierarchical diagnosis and treatment is of great significance to ensuring the health of rural residents and promoting the development of rural primary medical treatment.However,the medical cooperation between village doctors and township hospitals needs to be clarified;the two-way referral mechanism needs to be improved;medical human resources need to be integrated;and the construction of medical information platform needs to be promoted.Therefore,it is necessary to accelerate the clarification of medical cooperation relationship,establish and improve the two-way referral mechanism,promote the integration of medical human resources,and strengthen the construction of medical information platform,so as to improve the effective cooperation between the village doctors and county hospitals,and to promote the rural primary medical service level.

Objectives:To investigate the clinical and cardiopulmonary functional characteristics of cardiopulmonary-phenotype idiopathic pulmonary arterial hypertension(IPAH)patients in comparison with classical IPAH patients and pulmonary hypertension patients associated with chronic lung disease(CLD-PH).Methods:In this retrospective study,data were collected from 30 patients with classical IPAH,20 cardiopulmonary phenotype IPAH patients,and 20 patients with CLD-PH,who were hospitalized in the Department of Respiratory and Critical Care Medicine at Beijing Chaoyang Hospital from November 2017 to February 2025.Pulmonary hypertension was diagnosed via right heart catheterization and all patients underwent pulmonary function tests,chest computed tomography(CT),echocardiography,and patients were followed up to 5 years.Results:Compared to classical IPAH patients,both cardiopulmonary phenotype IPAH patients and CLD-PH patients exhibited later onset age,higher proportions of World Health Organization(WHO)functional class Ⅲ-Ⅳ,males,and smokers(all P<0.05).The cardiopulmonary-phenotype IPAH patients also had higher rates of coronary artery disease and diabetes compared to classical IPAH patients(all P<0.05).Physiologically,the cardiopulmonary-phenotype IPAH patients showed reduced diffusing capacity for carbon monoxide(DLCO)and partial pressure of oxygen(PaO2),along with higher rates of emphysema and pulmonary fibrosis compared to classical IPAH(all P<0.05).In contrast,CLD-PH patients had lower mean pulmonary arterial pressure(mPAP),pulmonary vascular resistance(PVR),and pulmonary artery wedge pressure(PAWP),as well as reduced forced expiratory volume in the first second(FEV1%predicted),FEV1/forced vital capacity(FVC)ratio,and DLCO.However,CLD-PH patients demonstrated higher tricuspid annular plane systolic excursion(TAPSE),peak systolic velocity of the tricuspid annulus(S`),and partial pressure of carbon dioxide(PaCO2),along with increased rates of emphysema and pulmonary fibrosis(all P<0.05).Compared with LCD-PH,cardiopulmonary-phenotype IPAH patients had higher mPAP,PVR,FEV1%predicted,FEV1/FVC ratio,PAWP,and systolic pulmonary artery pressure,but lower DLCO,cardiac output,TAPSE,S′,and PaCO2(all P<0.05).No statistical difference was observed in PaO2 between these two groups.All cardiopulmonary-phenotype IPAH patients and classical IPAH patients received targeted medications,55%of CLD-PH patients did not receive targeted therapy,45%received monotherapy only(compared with cardiopulmonary-phenotype IPAH patients and classical IPAH groups,P<0.05).The 1,2,and 5-year survival rates were 79.2%,62.2%,and 46.7%,respectively in patients with cardiopulmonary-phenotype IPAH,100%,94.4%,and 94.4%,respectively in classic IPAH patients,and 92.9%,77.4%and 77.4%,respectively in patients with CLD-PH.Survival rates for cardiopulmonary-phenotype IPAH patients were significantly lower than those of classical IPAH and CLD-PH patients(log-rank P=0.008).Conclusions:IPAH cardiopulmonary phenotype patients are older,predominantly male,and often have a smoking history(median 30 pack-years).They exhibit severe hypoxemia,markedly reduced DLCOc,preserved spirometry,and severe pulmonary hypertension and lower survival rate.

Objective To study the effect of sex-determining region Y-frame protein 3(SOX3)on proliferation and estradiol secretion in human ovarian granulosa cells(KGN cell line).Methods The gene sequence of human SOX3(NM_005634.3)was searched in Gene-Bank,an NCBI database,and the target gene SOX3 was amplified by PCR,which was cloned into lentiviral vector pLV-EF1a-GFP-2A-Puro to obtain the overexpression lentiviral re-combinant plasmid pLV-EF1a-GFP-2A-Puro-SOX3;the correctly sequenced overexpressed lentiviral recombinant plasmid as well as packaging plasmids(pGag/Pol,pRev,pVSV-G)were co-transfected into human embryonic kidney cell line(HEK 293T)cells(pLV-SOX3 group),and pLV-EF1a-GFP-2A-Puro and packaging plasmids(pGag/Pol,pRev,pVSV-G)were co-transfected into HEK 293T cells(pLV-NC group),the lentiviral particles of both groups were collected and the titers of the viruses were measured after 48 h of transfection,the lentiviruses of the two groups were infected into KGN cells,and the stably expressed cell lines were obtained after puromycin screening for 2 weeks;real-time fluorescence quantitative PCR(RT-qPCR)and Western blot were used to detect the SOX3 mRNA and protein levels in the two groups;CCK-8 assay was used to detect the proliferative ability of the cells in the two groups;ELISA was used to determine the concentration of estradiol in the two groups.Results The identification of PCR products and sequencing results showed that the SOX3 gene fragment was amplified successfully,and the enzyme digestion and sequencing results indicated that the construction of overexpression lentiviral recombinant plasmid was completed;green fluorescence could be detected after lentiviral infection of HEK 293T cells,which indicated that lentiviral packaging was successful;the lentivirus was screened by puromycin after lentiviral infection of KGN cells,and the cells were observed to express green fluorescence under the fluorescence microscope;RT-qPCR and Western blot assays both showed that the expression level of SOX3 in the pLV-SOX3 group was significantly higher than that in the pLV-NC group(P<0.05).CCK-8 assay results showed that the proliferation ability of the cells in the pLV-SOX3 group significantly increased compared with that in the pLV-NC group(P<0.01).ELISA results showed that estradiol concentration was elevated in the pLV-SOX3 group com-pared with the pLV-NC group(P<0.05).Conclusion Overexpression of the transcription factor SOX3 can pro-mote the proliferation and estradiol secretion of human ovarian granulosa cells KGN.

[Objective] To investigate the clinical manifestations and explore the experience of diagnosis and treatment of spontaneous perirenal urine extravasation after urinary tract obstruction so as to improve the understanding of the disease. [Methods] The clinical data of 23 patients with spontaneous perirenal urine extravasation after obstruction treated at our hospital during 2018 and 2020 were retrospectively analyzed, including the primary diseases, clinical manifestations, imaging examination, treatment and prognosis. The key points of diagnosis and treatment were summarized. [Results] Of the 23 patients, there were 15 males and 8 females, with an average age of 43.4 years. These cases were diagnosed by imaging tests such as ultrasound, computed tomography urography (CTU) and CT. Ureteroscopic lithotripsy was performed in 3 patients with ureteral calculi, retrograde ureteral catheterization in 4 patients and percutaneous nephrostomy in 13 patients. Afterwards, a second phase surgery was performed based on the patients' condition. Of the 3 patients with tumor metastasis who underwent retrograde ureteral catheterization, 2 operation were successful, and 1 operation failed and then converted to nephrostomy and drainage under B-ultrasound localization. [Conclusion] CTU should be performed as soon as possible to make a definite diagnosis. Treatment can be achieved with ureteral retrograde catheterization or percutaneous nephrostomy to achieve local decompression, followed by secondary surgery to treat the primary cause of obstruction.

Objective:To follow-up the previous phase Ⅲ clinical trial of recombinant human follicle-stimulating hormone (Follitrope ?), and to evaluate the cumulative pregnancy rate, the cumulative live birth rate, and the neonatal outcomes of subjects. Methods:The phase Ⅲ clinical study of Follitrope ? in China (CTR20150341/CTR20150341, May 15, 2015—June 27, 2016) was followed up until December 31, 2022. Patients were divided into Follitrope ? group and Gonal-F ? group. According to the age, patients were divided into three subgroups: 20-30 years old subgroup, 31-35 years old subgroup and 36-39 years old subgroup. Cumulative pregnancy rate, cumulative live birth rate, number of embryos transferred per cycle, live births per embryo transfer cycle, live births per oocyte retrieved, and neonatal characteristics were analyzed. Results:A total of 446 patients were included in the analysis, of which 336 (75.3%) were in the Follitrope ? group and 110 (24.7%) in the Gonal-F ? group, with a follow-up period of 6.5 years. There were no statistically significant differences between the Follitrope ? group and the Gonal-F ? group in terms of cumulative pregnancy rate and cumulative live birth rate (all P>0.05). Similar cumulative pregnancy rates and cumulative live birth rates were observed between the two groups within each age subgroup (all P>0.05). In the 36-39 years old subgroup, the Follitrope ? group showed a trend towards higher cumulative pregnancy rate [60.0% (12/20)] and cumulative live birth rate [55.0% (11/20)] compared with the Gonal-F ? group [28.6% (2/7), 14.3% (1/7)], however, none of the differences were statistically significant (all P>0.05). Twin pregnancy rates, live births per embryo, live birth per oocyte, newborn gender, birth weight, and birth defect rates were similar between the Follitrope ? group and the Gonal-F ? group without statistically significant differences (all P>0.05). Conclusion:The safety and effectiveness of Follitrope ? in controlled ovarian hyperstimulation are similar to those of Gonal-F ?. Compared with Gonal-F ?, there is a trend toward higher cumulative pregnancy rates and cumulative live birth rates in elderly patients with Follitrope ?, although there is no statistical difference.

Objective:To follow-up the previous phase Ⅲ clinical trial of recombinant human follicle-stimulating hormone (Follitrope ?), and to evaluate the cumulative pregnancy rate, the cumulative live birth rate, and the neonatal outcomes of subjects. Methods:The phase Ⅲ clinical study of Follitrope ? in China (CTR20150341/CTR20150341, May 15, 2015—June 27, 2016) was followed up until December 31, 2022. Patients were divided into Follitrope ? group and Gonal-F ? group. According to the age, patients were divided into three subgroups: 20-30 years old subgroup, 31-35 years old subgroup and 36-39 years old subgroup. Cumulative pregnancy rate, cumulative live birth rate, number of embryos transferred per cycle, live births per embryo transfer cycle, live births per oocyte retrieved, and neonatal characteristics were analyzed. Results:A total of 446 patients were included in the analysis, of which 336 (75.3%) were in the Follitrope ? group and 110 (24.7%) in the Gonal-F ? group, with a follow-up period of 6.5 years. There were no statistically significant differences between the Follitrope ? group and the Gonal-F ? group in terms of cumulative pregnancy rate and cumulative live birth rate (all P>0.05). Similar cumulative pregnancy rates and cumulative live birth rates were observed between the two groups within each age subgroup (all P>0.05). In the 36-39 years old subgroup, the Follitrope ? group showed a trend towards higher cumulative pregnancy rate [60.0% (12/20)] and cumulative live birth rate [55.0% (11/20)] compared with the Gonal-F ? group [28.6% (2/7), 14.3% (1/7)], however, none of the differences were statistically significant (all P>0.05). Twin pregnancy rates, live births per embryo, live birth per oocyte, newborn gender, birth weight, and birth defect rates were similar between the Follitrope ? group and the Gonal-F ? group without statistically significant differences (all P>0.05). Conclusion:The safety and effectiveness of Follitrope ? in controlled ovarian hyperstimulation are similar to those of Gonal-F ?. Compared with Gonal-F ?, there is a trend toward higher cumulative pregnancy rates and cumulative live birth rates in elderly patients with Follitrope ?, although there is no statistical difference.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems