Objective To assess the impact of cytokines on pulmonary arterial hypertension using a bi-directional Mendelian randomization(MR)approach.Methods The data for 41 cytokines were derived from a genome-wide association study(GWAS)dataset consisting of 8,293 individuals of European descent,and the genetic data for pulmonary arterial hypertension were obtained from a GWAS dataset comprising 11,744 indi-viduals of European descent;the potential impact of cytokines on pulmonary arterial hypertension was ex-plored using MR analysis.Results The inverse variance weighted(IVW)analysis revealed a potential causal relationship between IL-9 and pulmonary arterial hypertension(OR=0.63,95%CI:0.50 to 0.78,P<0.001),and a potential causal relationship between β-NGF and pulmonary arterial hypertension(OR=1.34,95%CI:1.01 to 1.79,P=0.049).Multivariable MR analysis demonstrated an association between IL-9 and pulmonary arterial hypertension(OR=0.57,95%CI:0.44 to 0.72,P<0.001),as well as between β-NGF and pulmonary arterial hypertension(OR=1.47,95%CI:1.10 to 1.97,P=0.009).Conclusion Elevated IL-9 levels may be causally associated with a reduced risk of pulmonary arterial hypertension,while increased β-NGF levels may elevate the risk of pulmonary arterial hypertension.

Pheochromocytomas and paragangliomas(PPGLs)cause symptoms by altering the circulation levels of catecholamines and peptide hormones.Currently,the diagnosis of PPGLs relies on diagnostic imaging and the detection of catecholamines.In this study,we used ultra-performance liquid chromatography(UPLC)/quadrupole time-of-flight mass spectrometry(Q-TOF MS)analysis to identify and measure the perioperative differential metabolites in the plasma of adrenal pheochromocytoma patients.We identified differentially expressed genes by comparing the transcriptomic data of pheochromocytoma with the normal adrenal medulla.Through conducting two steps of metabolomics analysis,we identified 111 differential metabolites between the healthy group and the patient group,among which 53 metabolites were validated.By integrating the information of differential metabolites and differentially expressed genes,we inferred that the cysteine-methionine,pyrimidine,and tyrosine metabolism pathways were the three main metabolic pathways altered by the neoplasm.The analysis of transcription levels revealed that the tyrosine and cysteine-methionine metabolism pathways were downregulated in pheochromocytoma,whereas the pyrimidine pathway showed no significant difference.Finally,we developed an optimized diagnostic model of two metabolites,L-dihydroorotic acid and vanylglycol.Our results for these metabolites suggest that they may serve as potential clinical biomarkers and can be used to supplement and improve the diagnosis of pheochromocytoma.

Background::Although overnight fasting is recommended prior to endoscopic retrograde cholangiopancreatography (ERCP), the benefits and safety of high-carbohydrate fluid diet (CFD) intake 2 h before ERCP remain unclear. This study aimed to analyze whether high-CFD intake 2 h before ERCP can be safe and accelerate patients’ recovery.Methods::This prospective, multicenter, randomized controlled trial involved 15 tertiary ERCP centers. A total of 1330 patients were randomized into CFD group ( n = 665) and fasting group ( n = 665). The CFD group received 400 mL of maltodextrin orally 2 h before ERCP, while the control group abstained from food/water overnight (>6 h) before ERCP. All ERCP procedures were performed using deep sedation with intravenous propofol. The investigators were blinded but not the patients. The primary outcomes included postoperative fatigue and abdominal pain score, and the secondary outcomes included complications and changes in metabolic indicators. The outcomes were analyzed according to a modified intention-to-treat principle. Results::The post-ERCP fatigue scores were significantly lower at 4 h (4.1 ± 2.6 vs. 4.8 ± 2.8, t = 4.23, P <0.001) and 20 h (2.4 ± 2.1 vs. 3.4 ± 2.4, t= 7.94, P <0.001) in the CFD group, with least-squares mean differences of 0.48 (95% confidence interval [CI]: 0.26–0.71, P <0.001) and 0.76 (95% CI: 0.57–0.95, P <0.001), respectively. The 4-h pain scores (2.1 ± 1.7 vs. 2.2 ± 1.7, t = 2.60, P = 0.009, with a least-squares mean difference of 0.21 [95% CI: 0.05–0.37]) and positive urine ketone levels (7.7% [39/509] vs. 15.4% [82/533], χ2 = 15.13, P <0.001) were lower in the CFD group. The CFD group had significantly less cholangitis (2.1% [13/634] vs. 4.0% [26/658], χ2 = 3.99, P = 0.046) but not pancreatitis (5.5% [35/634] vs. 6.5% [43/658], χ2 = 0.59, P = 0.444). Subgroup analysis revealed that CFD reduced the incidence of complications in patients with native papilla (odds ratio [OR]: 0.61, 95% CI: 0.39–0.95, P = 0.028) in the multivariable models. Conclusion::Ingesting 400 mL of CFD 2 h before ERCP is safe, with a reduction in post-ERCP fatigue, abdominal pain, and cholangitis during recovery.Trail Registration::ClinicalTrials.gov, No. NCT03075280.

Objective To analyze the efficacy,safety,and survival of laparoscopic cholecystectomy(LC)combined with lymph node dissection in the treatment of elderly primary gallbladder cancer.Methods 59 elderly patients with primary gallbladder cancer who underwent open cholecystectomy combined with lymph node dissection from January 2018 to July 2021 were selected as the control group,and 59 elderly patients with primary gallbladder cancer who underwent LC combined with lymph node dissection were selected as the study group.The clinical efficacy,perioperative indicators,and T cell subsets were compared between the two groups CD4+、CD4+/CD8+]、Quality of life(SF-36).Results The difference in recent treatment effectiveness between the research group and the control group is relatively small,(94.0％VS 72.5％,x2=0.209,P=0.648).The time required for lymph node dissection was(39.27±5.63)min and surgery time was(235.16±31.37)min in the study group,which was longer than that in the control group[(35.61±4.75)min and(194.59±30.82)min(P＜0.05).In the study group,the intraoperative bleeding volume was(32.63±5.42)ml and first exhaust time was(3.18±0.72)d,gastrointestinal function recovery time was(3.98±1.04)d,and hospitalization time was(6.24±1.25)d,which were shorter than those in the control group[(61.27±7.85)ml,(4.02±0.83)d,(4.65±1.18)d,(10.41±2.18)d,respectively,(P＜0.05)].After surgery,the levels of CD3+(16.52％±5.24％),CD4+(15.79％±3.83％),and CD4+/CD8+(0.47％±0.11％)in the study group were higher than those in the control group(13.74％±4.30％,10.83％±3.14％and 0.29％±0.05％)(P＜0.05).One month after surgery,the total quality of life score(SF-36)of the observation group(90.86±3.75)was higher than that of the control group(86.85±3.14)(P＜0.05).The incidence of complications in the study group was lower than that in the control group(7.01％VS 23.73％,x2=4.627,P＜0.05).The median survival time of the study group was(13.8±1.50)months,which was significantly higher than that of the control group[(12.5±1.25)months,P＞0.05].Conclusion LC combined with lymph node dissection is a safe and effective treatment for elderly primary gallbladder cancer,without affecting long-term prognosis and survival.

Objective By population survey,to explore the epidemiological characteristics of gastric precancerous lesions in Lishui District of Nanjing and provide objective basis for the prevention and treatment of early gastric cancer.Methods From July 2021 to December 2022,21 977 patients who received endoscopy and/or 13C-UBT in Lishui District People's Hospital and 6 medical community units in Nanjing City were retrospectively analyzed for demography characteristics,detection rate of gastric precancerous lesions,and H.Pylori infection rate.Results(1)590 cases of gastric precancerous lesions were detected(detection rate 2.68%);(2)The total detection rate of precancerous lesions and three pathological types in males were all higher than those in females(all P<0.001);(3)The minimum age for the total detection rate of precancerous lesions in males and the mini-mum age for each pathological type were lower than in females(P<0.001,0.009,0.005,0.002);(4)The popu-lation total H.pylori infection rate was 23.10%,the H.pylori infection rate in patients with precancerous lesions was higher than that in non-precancerous lesions(P<0.001),both H.pylori infection rate of male and female in precancerous lesions were all higher than those of non-precancerous lesions of the same sex(all P<0.001),in addition,the H.pylori infection rate of male whether in precancerous or non-precancerous lesions was higher than that of female(all P<0.001);(5)The precancerous lesions detection rate in male,female,and the overall age range of 20～29 to 70～79 years is positively correlated with age growth(P<0.001),and rapidly decreases after the age of 79,the of H.pylori infection rate was also positively correlated with age growth(P<0.001),and the trend of age change(P<0.001)was parallel to the precancerous lesions detection rate.Conclusions The detec-tion rate of gastric precancerous lesions in this region is above the average level in China;the total H.pylori infec-tion rate is at a relatively low level in China;the H.pylori infection rate is parallel to the age trend of the detection rate of gastric precancerous lesions,and increases with age.

Objective:To investigate the unqualified hepatitis C virus (HCV) detection result of blood donors from the served area of blood institutions.Methods:The data related to HCV markers detected of the first and repeat blood donors were collected from the system of practice comparison for the Chinese mainland blood institutions from 2017 to 2021. The anti-HCV reactive rate and the rates of anti-HCV negative but HCV-RNA reaction and all the relationship between rates and the annual, regional and different blood donors were statistically analyzed.Results:During 2017-2021, the number of anti-HCV reactive per 100 000 blood donors decreased from 444.3 to 250.44 in the served area of 22 blood institutions ( χ2=49.677, P<0.05). The number of HCV RNA detected positive per 100 000 anti-HCV negative increased from 0.69 to 2.05 year by year, but there was no statistical significance ( χ2=0.643, P>0.05). The anti-HCV unqualified rate was significantly different among regions ( χ2=3 260.283, P<0.05). The anti-HCV unqualified rate of the first blood donors was significantly higher than that of the repeated blood donors ( F=130.993, P < 0.05). The annual number of HCV RNA detected positive per 100 000 anti-HCV negative blood samples from donors ranged from 0 to 17.28. Conclusions:The anti-HCV unqualified rate of blood donors in the served area of 22 blood institutions decreased year by year. Compared with repeated blood donors, HCV infection should be emphasized in first-time blood donors. The implementation of HCV RNA test can detect out much more HCV infections and reduce the risk of transfusion transmitted infectious HCV.

Community health institutions have entered a new development stage of featured specialty construction. After 12 years of development, rehabilitation medicine now is the featured specialty of Fenglin Community Health Service Center. This article presents the train of thought and key points of specialty construction in primary care institutions based on the Fenglin′s experience. The positioning of featured specialty should be based on the community. The construction process should include 7 elements, namely, the standard operation procedure(SOP)of service system construction, the detailed publicity and implementation of the collaboration of specialists, prevention and control knowledge promotion for general practitioners, prevention and control knowledge education for community residents, service list, clinical efficacy evaluation, and clinical database. In the later iterations, the head of the department should always focus on the service system construction SOP and clinical database construction, and the rest parts can be assigned to the relevant team members.

The construction of featured specialties is the current development strategy of community health service institutions to improve the service scope and to meet the health needs of residents. The rehabilitation medicine has undergone 12 years of development and become a relatively mature featured specialty in Fenglin Community Health Service Center. Based on the Fenglin′s experience, this article discusses the development status and restriction bottlenecks of general practice, and the development status and trend of rehabilitation medicine in the community; and also explores the integrated development model of community-featured specialty with general practice.

Objective To investigate gene pathways associated with severe acne.Methods Kyoto encyclopedia of genes and genomes (KEGG)-based pathway analysis was conducted using the genome-wide association study (GWAS) data on 1 056 patients with severe acne and 1 056 healthy controls,and each testee was tested for 900 015 SNPs.A hypergeometric distribution test was used to analyze the relationship between each pathway and severe acne,and the false discovery rate (FDR) to correct for multiple testing.Any pathway with an adjusted P value of ＜ 0.05 was considered to be associated with severe acne.Results Twelve genes were identified to be associated with severe acne (P ＜ 0.001),including TMPRSS11E,DDB2,RIC1,CLLU1OS,IL3,PLA2G4B,SLC16A14,SOX17,FAHD2A,ENTPD7,MRPL50 and TXLNB.Pathway analysis revealed 5 pathways associated with severe acne (adjusted P ＜ 0.05),including the prolactin signaling pathway,hepatitis C,renal cell carcinoma,high affinity receptor for immunoglobulin E (Fc epsilon RI) signaling pathway,and tyrosine metabolism.Conclusion The 5 identified pathways are associated with severe acne,which affect the endocrine,immune and metabolic processes in the human body.

Objective To compare the effects of intensive blood pressure (BP) lowering and guideline-recommended standard BP lowering on the early reperfusion and prognosis after intravenous thrombolysis in patients with acute ischemic stroke. Methods This is a randomised controlled trial consisting of 118 consecutive patients who came from Department of Neurology, Nanjing First Hospital from July 2012 to April 2016, accepting intravenous recombinant tissue plasminogen activator thrombolysis with the systolic blood pressure (SBP) being 150-185 mmHg(1 mmHg=0.133 kPa). The patients with ischemic stroke were diagnosed by multi-mode MRI and confirmed to have ischemic penumbra. The SBP of patients randomly assigned to intensive BP lowering group and guideline BP lowering group was maintained in 140-150 mmHg or below 180 mmHg respectively for 72 h and all patients needed to reexamine multi-mode MRI at 24 h. The primary endpoints were the neurologic function at early stage, modified Rankin Scale (mRS) score and the mortality at 90 d;the secondary endpoints were the volume of infarction and hypoperfusion area, the rate of reperfusion, hemorrhagic transformation (HT) and syptomatic intracerebral hemorrhage (sICH). Results Forty-nine cases in intensive BP lowering group and 56 cases in guideline BP lowering group acquired the available images. The volume of infarction was increased both in these two groups, and there was no statistically significant difference in the increased values ((13.21±9.51) cm3 vs (12.95±9.68) cm3). There were no statistically significant differences in the volume of hypoperfusion, reperfusion rate, neurologic function at early stage, the mRS scores and mortality at 90 d, the incidence of sICH except the rate of HT (9.4%, 5/53 vs 23.1%, 15/65, χ2=3.860, P=0.049) between the two groups.Conclusion Early intensive BP-lowering treatment has no adverse effects on the transformation of ischemic penumbra and prognosis after intravenous thrombolysis in patients with acute ischemic stroke and may decrease the the rate of HT in some degree.