To evaluate the effectiveness and safety of implantable D-shant atrial shunt device in patients with severe pulmonary arterial hypertension(PAH)and right heart failure.A 53-year-old female patient diagnosed with severe idiopathic PAH and right heart failure,her WHO FC grade was Ⅳ.The right heart catheter and implantation of D-shant atrial shunt device were performed under local anesthesia on November 30,2021.A 6 mm×4 cm peripheral artery balloon was selected to dilate the atrial septum and a D-shant atrial shunt device with a fixed 4 mm diameter orifice was implanted into the heart.The clinical symptoms and hemodynamics of the patient was improved after the intervention.Implantation of atrial shunt device as a palliative therapy to established a right to left shunt is another strategy for treating patients with severe PAH in late period,which has good effectiveness and safety.It could be the last replacement therapy to improve symptoms and prolonged lives to drug resistant and severe PAH patients.

Investigating the species/biovars,distribution patterns,and genetic correlations of Brucella from sheep in north-west China is critical to reveal the population and epidemiological characteristics of the Brucella melitensis.In this study,con-ventional identification and AMOS-PCR were used to determine the species/biovars of Brucella isolated from 13 regions in northwest China.MLST and MLVA-16 genotyping methods were used to analyze the genetic characteristics of the strains.Con-ventional identification and AMOS-PCR detection revealed that 59 Brucella melitensis were isolated in this study,in-cluding 22 strains from Inner Mongolia,17 strains from Xin-jiang,13 strains from Gansu,and 7 strains from Qinghai,of which 58 strains were B.melitensis biovar 3,and one strain was B.melitensis biovar 1.MLST analysis indicated that 90％(53/59)of B.melitensis were of ST8 sequence type,the dominant epidemic population.The MLVA-11 survey demonstrated that 59 B.melitensis strains clustered into six MLVA-11 genotypes,and 87％of the strains were of MLVA-11 genotype 116.Therefore,the predominant strains in the northwest region were from the Eastern Mediterranean lineage.MLVA-16 divided 59 strains of B.melitensis into 40 gen-otypes,eight of which were shared genotypes.Each genotype was composed of two to seven strains from the same region,thereby indicating that the cases of each shared genotype were outbreaks from a common source of infection.All shared MLVA-16 genotypes comprised strains from the same province,thus indicating apparent regional clustering characteristics of strains in each province.In a genetic comparison between populations and isolated strains from the spleens of sheep,multiple identical MLVA-16 genotypes were found to be composed of strains from different hosts.These findings indicated a transmission path-way from sheep/goats to humans.B.melitensis biovar 3 was the main pathogen causing animal brucellosis in the northwest re-gion,and infected sheep were the main brucellosis infection source in the regional population.The ST8 strains were the domi-nant epidemic population,and the MLVA genotype of strains in each region showed clear regional clustering characteristics.

Objective To explore the effect of 4-week repetitive downhill treadmill running on the mi-tochondrial structure,function,and autophagy in skeletal muscle of rats,so as to analyze the role of FKBP8-mediated mitophagy in exercise-induced mitochondrial damage in their skeletal muscles.Meth-ods Thirty-two male adult Sprague-Dawley rats were randomly divided into a 2-week quiet control group(2C group,n=8),a 4-week quiet control group(4C group,n=8),a 2-week exercise group(2E group,n=8)and a 4-week exercise group(4E group,n=8).Rats in 2E and 4E groups performed dai-ly 90-minute downhill treadmill running(-16°,16 m/min)5 days a week for two and four weeks,re-spectively.Then,they rested for 24 hours and received an exhaustive exercise test.Running distance and blood lactate were measured prior to and at the time of exercise cessation.Moreover,mitochondri-al ultrastructural changes in soleus muscles were observed by using a transmission electron microscope.The protein expression of mitochondrial succinate dehydrogenase subunit B(SDHB),cytochrome C oxi-dase subunit 1(MTCO1),FK506 binding protein 8(FKBP8)and microtubule associated protein 1 light chain 3(LC3)in the soleus muscle were measured using Western blotting.Meanwhile,the co-localiza-tion of FKBP8 with LC3 and cytochrome C oxidase subunit Ⅳ(COXⅣ)with LC3,lysosomal associat-ed membrane protein 2(LAMP2)were detected by the immunofluorescence double labeling technique.Results(1)The running distance of one exhaustive exercise and the blood lactate before and after the test in 2E group were significantly higher than 2C and 4E groups(P<0.05 or P<0.01),and the run-ning distance of 4E group was significantly higher than 4C group(P<0.01).However,there was no sig-nificant difference between 4E and 4C groups in the blood lactate before and after the exhaustive exer-cise test(P>0.05).(2)In both 2E and 4E groups,significant mitochondrial swelling and accumulation under cell membrane,as well as a number of mitophagosomes and mitophagolysosomes were observed,together with a significant reduce in the number of mitochondria(P<0.05),which was more severe in 2E group than 4E group.(3)The protein expression of mitochondrial SDHB and MTCO1 in 2E and 4E groups were lower than 2C and 4C groups,respectively,with significantly greater changes of these proteins in 4E group than 2E group(P<0.05 or P<0.01).(4)The protein expression of mitochondrial FKBP8 and LC3,as well as the co-localization of FKBP8 with LC3 and COXⅣ with LC3,LAMP2 in 2E and 4E groups were higher than 2C and 4C groups,respectively,with significantly greater changes in 4E group than 2E group(P<0.05 or P<0.01).Conclusion After 4-week downhill treadmill running,the structure,quantity and function of mitochondria in skeletal muscle are impaired.FKBP8-mediated mitophagy is activated,but is insufficient to degrade the damaged mitochondria,leading to muscular damage,as well as the increasing and falling down of running capacity.

Objective:To investigate the clinical effect of extraperitoneal robot-assisted laparoscopic modified Y-V plasty(LMYVP)in the treatment of refractory bladder neck contracture(BNC).Methods:We retrospectively analyzed the clinical data on 10 cases of refractory BNC after transurethral resection of the prostate between September 2020 and January 2023,all with a history of recurrent urethral dilatation and at least two failures in transurethral surgical treatment of scarring.After definite diagnosis and re-moval of some of the scar tissues to flatten the elevated bladder neck under the cystoscope,we performed robot-assisted LMYVP using the da Vinci Si robotic system and a four-port extraperitoneal approach.The surgical procedure involved an inverted T-shaped incision in the bladder neck and urethral stricture ring,an inverted V-shaped excision of the scar area at the 3-9 o'clock position on the ventral side of the prostatic urethra,continuous full-layer suturing of the bladder neck and inverted V-shaped urethra with 3-0 barbed thread,and indwelling of an F20 silicone catheter for 2 weeks.At 3 months after surgery,we performed cystoscopic examination,measured the maximum urinary flow rate(Qmax),and obtained the IPSS and quality of life(QOL)scores of the patients.Results:Operations were successfully completed in all the cases.At 3 months after surgery,the patients showed significantly increased Qmax([3.65±1.27]vs[20.3±1.77]ml/s,P＜0.05),IPSS(5.9±2.02 vs 30±1.15,P＜0.05)and QOL score(1.3±0.95 vs 5.2±0.79,P＜0.05)compared with the baseline.Cystoscopy revealed a wide and flat bladder neck with good survival and hemody-namics of the bladder flap.All the patients met the criteria for clinical cure at a median follow-up of 13.2 months.Conclusion:Extraper-itoneal robot-assisted LMYVP provides a new strategy for urinary tract reconstruction in the management of refractory BNC,with the ad-vantages of minimal invasiveness,high efficiency and high success rate.

Objective:To investigate the prognosis of patients with initially resectable gastric cancer liver metastasis (GCLM) who were treated by different modalities, and analyze the influencing factors for prognosis of patients.Methods:The retrospective cohort study was conducted. The clinicopathological data of 327 patients with initially resectable GCLM who were included in the database of a nationwide multicenter retrospective cohort study on GCLM based on real-world data from January 2010 to December 2019 were collected. There were 267 males and 60 females, aged 61(54,68)years. According to the specific situations of patients, treatment modalities included radical surgery combined with systemic treatment, palliative surgery combined with systemic treatment, and systemic treatment alone. Observation indicators: (1) clinical characteristics of patients who were treated by different modalities; (2) prognostic outcomes of patients who were treated by different modalities; (3) analysis of influencing factors for prognosis of patients with initially resectable GCLM; (4) screening of potential beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3), and comparison between groups was conducted using the rank sum test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to calculate survival rate and draw survival curve, and Log-Rank test was used for survival analysis. Univariate and multivariate analyses were conducted using the COX proportional hazard regression model. The propensity score matching was employed by the 1:1 nearest neighbor matching method with a caliper value of 0.1. The forest plots were utilized to evaluate potential benefits of diverse surgical combined with systemic treatments within the population. Results:(1) Clinical characteristics of patients who were treated by different modalities. Of 327 patients, there were 118 cases undergoing radical surgery plus systemic treatment, 164 cases undergoing palliative surgery plus systemic treatment, and 45 cases undergoing systemic treatment alone. There were significant differences in smoking, drinking, site of primary gastric tumor, diameter of primary gastric tumor, site of liver metastasis, and metastatic interval among the three groups of patients ( P<0.05). (2) Prognostic outcomes of patients who were treated by different modalities. The median overall survival time of the 327 pati-ents was 19.9 months (95% confidence interval as 14.9-24.9 months), with 1-, 3-year overall survival rate of 61.3%, 32.7%, respectively. The 1-year overall survival rates of patients undergoing radical surgery plus systemic treatment, palliative surgery plus systemic treatment and systemic treatment alone were 68.3%, 63.1%, 30.6%, and the 3-year overall survival rates were 41.1%, 29.9%, 11.9%, showing a significant difference in overall survival rate among the three groups of patients ( χ2=19.46, P<0.05). Results of further analysis showed that there was a significant difference in overall survival rate between patients undergoing radical surgery plus systemic treatment and patients undergoing systemic treatment alone ( hazard ratio=0.40, 95% confidence interval as 0.26-0.61, P<0.05), between patients undergoing palliative surgery plus systemic treatment and patients under-going systemic treatment alone ( hazard ratio=0.47, 95% confidence interval as 0.32-0.71, P<0.05). (3) Analysis of influencing factors for prognosis of patients with initially resectable GCLM. Results of multivariate analysis showed that the larger primary gastric tumor, poorly differentiated tumor, larger liver metastasis, multiple hepatic metastases were independent risk factors for prognosis of patients with initially resectable GCLM ( hazard ratio=1.20, 1.70, 1.20, 2.06, 95% confidence interval as 1.14-1.27, 1.25-2.31, 1.04-1.42, 1.45-2.92, P<0.05) and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy were independent protective factors for prognosis of patients with initially resectable GCLM ( hazard ratio=0.60, 0.39, 0.46, 95% confidence interval as 0.42-0.87, 0.25-0.60, 0.30-0.70, P<0.05). (4) Screening of potentinal beneficiaries in patients who were treated by radical surgery plus systemic treatment and patients who were treated by palliative surgery plus systemic treatment. Results of forest plots analysis showed that for patients with high-moderate differentiated GCLM and patients with liver metastasis located in the left liver, the overall survival rate of patients undergoing radical surgery plus systemic treatment was better than patients undergoing palliative surgery plus systemic treatment ( hazard ratio=0.21, 0.42, 95% confidence interval as 0.09-0.48, 0.23-0.78, P<0.05). Conclusions:Compared to systemic therapy alone, both radical and palliative surgery plus systemic therapy can improve the pro-gnosis of patients with initially resectable GCLM. The larger primary gastric tumor, poorly differen-tiated tumor, larger liver metastasis, multiple hepatic metastases are independent risk factors for prognosis of patients with initial resectable GCLM and immunotherapy or targeted therapy, the treatment modality of radical or palliative surgery plus systemic therapy are independent protective factors for prognosis of patients with initially resectable GCLM.

Objective To study the effect and mechanism of action of Yi Sui Sheng Xue Fang(YSSX)in ameliorating chemotherapy-induced renal injury in mice through The Kelch-like ECH-associated protein 1(KEAP1)/Nuclear factor erythroid-derived 2-like 2(NRF2)signalling pathway.Methods A mouse kidney injury model was induced by intraperitoneal injection of carboplatin(40 mg·kg-1).C57BL/6 mice were randomly divided into blank group(0.9％NaCl),model group(kidney injury model)and experimental-L,experimental-M,experimental-H groups(0.53,1.05 and 2.10 g·kg-1·d-1 YSSX by gavage for 7 d).Keap1 and Nrf2 were determined by Western blot;superoxide dismutase(SOD)and malondialdehyde(MDA)activities were determined by spectrophotometry.Results The protein expression levels of Keap1 in blank group,model group and experimental-L,experimental-M,experimental-H groups were 0.26±0.02,0.64±0.03,0.59±0.01,0.45±0.05 and 0.34±0.02;the protein expression levels of Nrf2 were 0.69±0.06,0.35±0.01,0.36±0.01,0.48±0.02 and 0.56±0.01;the enzyme activities of catalase(CAT)were(572.49±912.92),(334.60±4.92),(402.76±9.80),(475.35±5.21)and(493.00±12.03)U·mg-1;glutathione(GSH)were(2.79±0.06),(0.51±0.01),(0.59±0.07),(1.29±0.04)and(1.70±0.08)μmol·L1;SOD were(477.00±4.32),(260.67±6.13),(272.67±2.87),(386.33±3.68)and(395.00±12.25)U·mL-1;MDA were(3.89±0.02),(7.32±0.03),(6.94±0.14),(4.60±0.01)and(4.34±0.02)nmol·mg prot-1.The differences of the above indexes in the model group compared with the blank group were statistically significant(P＜0.01,P＜0.001);the differences of the above indexes in experimental-M,experimental-H groups compared withe model group were statistically significant(P＜0.01,P＜0.001).Conclusion YSSX can activate Keap1/Nrf2 signaling pathway and regulate the oxidative stress state of the organism,thus improving the renal injury caused by chemotherapy in mice.

Objective To investigate the preventive effects of puerarin apioside on a non-alcoholic fatty liver disease(NAFLD)mouse model and its influence on hepatic lipid metabolism.Methods Thirty-two male C57BL/6J mice were randomly divided into the normal group,model group and experimental-L,-H groups,with 8 mice in each group.The normal group was given regular maintenance feed;the other 3 groups were fed to construct NAFLD model.Experimental-L,-H groups were given 5 and 10 mg·kg-1 puerarin apioside by gavage.Normal and model groups were treated with an equal amount of dimethylsulfoxide by gavage.Four groups were administered once a day for 8 weeks.Changes in mouse body weight were measured.Serum levels of glutamic-pyruvic transaminase(GPT)and glutamic-oxaloacetic transaminase(GOT)and the levels of total cholesterol(TC)and triglycerides(TG)in hepatic tissue were determined by kit.Western blot was used to evaluate the expression levels of acetyl-coenzyme A carboxylase 1(ACC1)and phosphorylated 5'-adenosine monophosphate-activated protein kinase(p-AMPK).Results The body weights of mice in the normal,model and experimental-L,-H groups were(32.69±1.37),(45.51±3.29),(41.18±3.22)and(38.28±2.62)g;serum GPT levels were(36.53±6.44),(134.56±39.91),(121.54±43.38)and(75.92±25.98)U·L-1;serum GOT levels were(60.81±8.74),(188.51±39.70),(156.02±41.67)and(126.79±16.49)U·L-1;hepatic TC levels were(2.17±0.24),(6.46±1.22),(5.86±0.66)and(3.62±0.45)mmol·L-1;hepatic TG levels were(0.57±0.09),(1.39±0.27),(1.28±0.34)and(0.73±0.19)mmol·L-1;the relative expression levels of ACC1 protein were 1.01±0.04,2.00±0.02,1.47±0.08 and 1.20±0.09;the relative expression levels of p-AMPK protein were 1.03±0.09,0.33±0.02,0.66±0.04 and 0.95±0.08,respectively.The differences between the model group and the normal and experimental-H groups were statistically significant for all the above indicators(all P＜0.05).Conclusion Puerarin apioside can improve the hepatic lipid metabolism in NAFLD mice by regulating the AMPK signaling pathway.

The pathogenesis of osteoarthritis (OA) is related to a variety of factors such as mechanical overload, metabolic dysfunction, aging, etc., and is a group of total joint diseases characterized by intra-articular chondrocyte apoptosis, cartilage fibrillations, synovial inflammation, and osteophyte formation. At present, the treatment methods for osteoarthritis include glucosamine, non-steroidal anti-inflammatory drugs, intra-articular injection of sodium hyaluronate, etc., which are difficult to take effect in a short period of time and require long-term treatment, so the patients struggle to adhere to doctor’s advice. Some methods can only provide temporary relief without chondrocyte protection, and some even increase the risk of cardiovascular disease and gastrointestinal disease. In the advanced stages of OA, patients often have to undergo joint replacement surgery due to pain and joint dysfunction. Mitochondrial dysfunction plays an important role in the development of OA. It is possible to improve mitochondrial biogenesis, quality control, autophagy balance, and oxidative stress levels, thereby exerting a protective effect on chondrocytes in OA. Therefore, compared to traditional treatments, improving mitochondrial function may be a potential treatment for OA. Here, we collected relevant literature on mitochondrial research in OA in recent years, summarized the potential pathogenic factors that affect the development of OA through mitochondrial pathways, and elaborated on relevant treatment methods, in order to provide new diagnostic and therapeutic ideas for the research field of osteoarthritis.

Objective:To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM).Methods:This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging ( M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results:(1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95% CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference ( P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options ( HR=1.98, 95% CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients′ prognosis ( HR=2.01, 95% CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors ( HR=2.84, 95% CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver ( HR=2.06, 95% CI 1.19 to 3.57, P=0.010). Conclusions:In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

A decline in mucosal vascularity is a histological hallmark of oral submucous fibrosis(OSF),a premalignant disease that is largely induced by betel quid chewing.However,the lack of available models has challenged studies of angiogenesis in OSF.Here,we found that the expression of thrombospondin 1(THBS1),an endogenous angiostatic protein,was elevated in the stroma of tissues with OSF.Using a fibroblast-attached organoid(FAO)model,the overexpression of THBS1 in OSF was stably recapitulated in vitro.In the FAO model,treatment with arecoline,a major pathogenic component in areca nuts,enhanced the secretion of transforming growth factor(TGF)-β1 by epithelial cells,which then promoted the expression of THBS1 in fibroblasts.Furthermore,human umbilical vein endothelial cells(HUVECs)were incorporated into the FAO to mimic the vascularized component.Overexpression of THBS1 in fibroblasts drastically suppressed the sprouting ability of endothelial cells in vascularized FAOs(vFAOs).Consistently,treatment with arecoline reduced the expression of CD31 in vFAOs,and this effect was attenuated when the endothelial cells were preincubated with neutralizing antibody of CD36,a receptor of THBS1.Finally,in an arecoline-induced rat OSF model,THBS1 inhibition alleviated collagen deposition and the decline in vascularity in vivo.Overall,we exploited an assembled organoid model to study OSF pathogenesis and provide a rationale for targeting THBS1.