Ruxolitinib， a small molecule inhibitor， selectively targets Janus kinase （JAK） by competitively binding to adenosine triphosphate on the catalytic site of the JAK1 and JAK2 domain， thereby inhibiting JAK activation and signal transducer and activator of transcription （STAT） phosphorylation and prevents the expressions of the JAK-STAT signaling pathway. Oral ruxolitinib has demonstrated promising efficacy for myelofibrosis and polycythemia vera. The topical Ruxolitinib cream， approved by the US FDA as the first non-segmental vitiligo home treatment drug， is set to be launched in domestic medical pioneer areas in August 2023 and is expected to bring about a breakthrough in the treatment of vitiligo. Clinical cases have also shown that Ruxolitinib cream has significant curative effects on atopic dermatitis， alopecia areata， and other conditions， indicating great application prospects.

Objective:To explore the efficacy of precise and empirical bismuth-containing quadruple therapy guided by clarithromycin sensitivity testing in the first eradication of Helicobacter pylori ( H. pylori) in Ningxia. Methods:From August 12, 2022 to March 22, 2023, 600 patients diagnosed as H. pylori-positive by 14C-urea breath test ( 14C-UBT) for the first time in People′s Hospital of Ningxia Hui Autonomous Region, Ningnan Hospital of People′s Hospital of Ningxia Hui Autonomous Region, Zhongwei People′s Hospital, Yanchi County People′s Hospital, and Pingluo People′s Hospital were selected, and divided into empirical treatment group (hereinafter referred to as the empirical group), genetic testing group (hereinafter referred to as the genetic group), and drug sensitivity testing group (hereinafter referred to as the drug sensitivity group) by using random number table with 200 patients in each group. The empirical group did not undergo drug sensitivity testing and genetic testing, while the genetic and drug sensitivity groups were confirmed to be sensitive to clarithromycin through genetic testing and drug sensitivity testing, and the patients with drug-resistant were excluded, respectively. All the patients of the 3 groups received the same clarithromycin bismuth-containing quadruple therapy. Intention-to-treat (ITT) and per-protocol (PP) analyses were performed to compare the eradication rates of H. pylori among 3 groups. Cost-effectiveness ratio (CER) and incremental cost-effectiveness ratio (ICER) were used for cost-effectiveness and sensitivity analysis based on the ITT. Chi-square test was used for statistical analysis. Results:There were 200, 126, and 168 patients included in the empirical group, genetic group, and drug sensitivity group in ITT analysis, and 190, 123, and 164 patients were enrolled in the 3 groups in PP analysis, respectively. The results of ITT analysis showed that the eradication rates of H. pylori in the empirical group, genetic group, and drug sensitivity group were 80.5% (161/200), 94.4% (119/126), and 95.2% (160/168), respectively. The results of PP analysis indicated that the eradication rates of H. pylori in the 3 groups were 84.7% (161/190), 96.7% (119/123), and 97.6% (160/164), respectively, and the differences were statistically significant ( χ2=25.39 and 24.93, both P<0.001). The H. pylori eradication rates of genetic group and drug sensitivity group were both higher than that of empirical group in ITT and PP analysis( χ2=12.40, 17.80, 11.42, and 17.13; all P<0.001). The cost-effectiveness analysis showed that the direct treatment cost of the empirical group, genetic group, and drug sensitivity group was 400.8, 729.2, and 779.2 yuan, respectively, and the CER was 4.98, 7.72, and 8.18 yuan/%, respectively. Compared to the empirical group, the ICER of the genetic group and drug sensitivity group was 23.6 and 25.7 yuan/%, respectively. The sensitivity analysis demonstrated that, when the cost of genetic testing reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 21.8 or 25.5 yuan/%, respectively. When the cost of drug sensitivity testing reduced or increased by 20%, the ICER of the drug sensitivity group compared to the empirical group was 23.3 or 28.2 yuan/%. When the cost of gastroscopy reduced or increased by 20%, the ICER of the genetic group compared to the empirical group was 20.8 or 26.5 yuan/%, and the ICER of the drug sensitivity group compared to the empirical group was 23.0 or 28.4 yuan/%, respectively. Conclusion:In Ningxia, if the clarithromycin bismuth-containing quadruple regimen is applied as the first H. pylori eradication regimen, in order to achieve the clinical eradication efficacy of H. pylori, and the patients can accept an additional payment of 23.6 or 25.7 yuan for each 1% increasing in the H. pylori eradication rate, then the precision treatment after clarithromycin resistance test is recommended.

Purpose: Inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal malignancy that occurs primarily in children and adolescents. The clinical and pathological features of IMT in adult patients are not well understood. Materials and Methods: We retrospectively searched for records of adult patients with IMT at Fudan University Shanghai Cancer Center from 2006 to 2021. Clinicopathological data, treatments, and outcomes were collected and analyzed. Results: Thirty adult patients with IMT, mostly women (60.0%), were included. The median age of the patients was 38 (21-77). The most common primary site was abdominopelvic region (53.3%), followed by lungs (20.0%). Seven patients had an abdominal epithelioid inflammatory myofibroblast sarcoma (EIMS). The positivity rate of anaplastic lymphoma kinase (ALK) was 81.5% (22/27). Sixteen patients with advanced ALK-positive disease received crizotinib, with an objective response rate (ORR) of 81.3% and a disease control rate of 87.5%. The median progression-free survival was 20.8 months. EIMS was associated with more aggressive behavior; however, the prognosis was similar to that of non-EIMS patients after treatment with an ALK inhibitor. At a median follow-up time of 30 months (95% confidence interval [CI], 13.6 to 46.4), the 5-year overall survival was 77% (95% CI, 66 to 88) in all patients. Conclusion Adult IMTs appeared more aggressive, with a higher incidence of recurrence and metastases, and patients with EIMS had more aggressive cases. Treatment with ALK inhibitors resulted in a high ORR and a durable response, which suggested that ALK inhibitors could be used as a first-line treatment option in adult patients with ALK-positive advanced IMT.

Objective:To explore the etiology, pathogenesis, clinical features, diagnosis and treatment of hepatic sinus obstruction syndrome(HSOS)after orthotopic liver transplantation(OLT).Methods:Clinical data were reviewed for 3 HSOS patients after OLT.Baseline profiles, primary disease, onset, clinical manifestations, abdominal imaging and pathological changes were recorded for summarizing the key points of diagnosis, treatment and outcomes of HSOS after OLT.Results:HSOS was an extremely rare complication after OLT with an incidence of 2%(2/117)and a median onset of 15(13-50)days.The major clinical manifestations were hepatic pain, abdominal distension, poor appetite, fatigue, jaundice, oliguria, peritoneal effusion and pleural effusion.Some of them were complicated with acute renal insufficiency.Abdominal ultrasonography revealed that blood stream of hepatic and portal veins was smooth but rather slow and hepatic parenchyma showed uneven echo changes.Abdominal enhanced computed tomography(CT)demonstrated " mosaic" and " map-like" uneven enhancement in portal vein and balance phases.The pathological manifestations of liver biopsy included obvious dilation and congestion of hepatic sinuses, swelling and necrosis of hepatic cells, thickening of hepatic venules and luminal stenosis or occlusion.All of them received immunosuppressants.Tacrolimus was switched to sirolimus, low molecular weight heparin or plus rivaroxaban anticoagulant thrombolytic therapy, methylprednisolone regulatory immunotherapy, albumin supplementation, diuresis, hepatic protection and fluid replacement.Afterward clinical symptoms of 2 patients improved, became cured and discharged.One case died from gastrointestinal hemorrhage and acute renal failure secondary to multiple organ failure.Conclusions:HSOS is an extremely rare but severe complication after OLT.Early diagnosis and fine-tuning of treatment protocols can avoid poor prognosis such as liver and kidney failure and significantly improve patient survival.

Objective:To examine the long-term survival outcomes and identify mortality risk factors for coronary artery bypass grafting patients who received venoarterial extracorporeal membrane oxygenation(VA-ECMO) for postcardiotomy cardiogenic shock.Methods:Data from 121 consecutive venoarterial extracorporeal membrane oxygenation-treated coronary artery bypass grafting(CABG) patients at Beijing Anzhen Hospital between June 2012 and December 2016 were analyzed. There were 84 males and 24 females. The median age was 62(55, 67) years, and the median body mass index was 25(23, 27)kg/m 2. Thirty-seven patients(34%) had left main artery disease, and 56 patients(52%) underwent off-pump CABG. According to the 3 year survival outcome after ECMO, patients were divided into survival group(35 cases) and non-survival group(73 cases). The differences of clinical indicators between the two groups were compared and analyzed. Multivariable Cox regression modeling was used to identify factors independently associated with 36 month mortality. Results:Sixty-five patients(60%) could be weaned from VA-ECMO, 49 patients(45%) survived to hospital discharge, and 35 patients(32%) survived to 3 years. The median( IQR) time on VA-ECMO support was 4(3, 5) days. The median( IQR) length of ICU stay and hospital stay duration were 8(5, 12) and 20(13, 29) days, respectively. Older age( HR=1.06, 95% CI: 1.03-1.10, P<0.001), left main coronary artery disease( HR=1.62, 95% CI: 1.00-2.60, P=0.048), and vasoactive inotropic score( HR=1.09, 95% CI: 1.03-1.17, P=0.007)were independent risk factors associated with 3-year mortality. The area under the receiver operating characteristic curve for the model, which was constructed with age≥60years, left main coronary artery disease, and vasoactive inotropic score>60, was 0.88(95% CI: 0.80-0.95). Conclusion:Long-term survival of patients who survive to discharge appears favorable. Older age, left main coronary artery disease, and vasoactive inotropic score were associated with 3-year mortality in coronary artery bypass grafting patients who received VA-ECMO.

Background::The heavy metals cadmium (Cd) and mercury (Hg) are known to be widespread environmental contaminants and high occupational exposure adversely affects the risk of chronic kidney disease (CKD). However, evidence from epidemiological studies linking low Cd and Hg exposure (or non-industrial) to the risk of progression to CKD are conflicting. This study aimed to explore the association of low Cd and Hg exposure with the risk of CKD in Chinese adults aged ≥80 years.Methods::The participants were recruited for the Healthy Aging and Biomarkers Cohort Study in 2017, an ongoing perspective survey conducted in longevity areas in China initially involving 3016 older adults. We used logistic regression models to estimate odds ratios (ORs) with 95% confidence intervals of CKD setting Cd and Hg as categorical variables. Logistic regression with restricted cubic spline was used to characterize a dose-response relationships between Cd or Hg concentrations and the risk of CKD in the study population.Results::The ORs for the risk of CKD comparing the fourth to the first quartile of blood Cd, blood Hg, urine Cd, and urine Hg were 1.77, 1.57, 2.03, and 1.50, respectively. Restricted cubic spline models showed that blood Cd and urine Hg were significantly linearly correlated with the risk of CKD, while blood Hg and urine Cd were non-linearly correlated with the risk of CKD with a steeper slope at concentrations <2.30 μg/L and 3.30 μg/g creatinine.Conclusions::Our findings suggest that even low Cd and Hg exposure (or non-industrial) were associated with increased risk of CKD in Chinese oldest old, although we did not find a significant multiplicative and additive interaction between Cd and Hg levels in relation to the risk of CKD.

目的：探讨成纤维细胞生长因子 13（fibroblast growth factor 13，FGF13）对非小细胞肺癌 A549 细胞活性氧（reactive oxygen species，ROS）的生成和凋亡的影响及其调控机制。方法：WB 法检测 FGF13 在人正常肺上皮细胞 BEAS-2B 和肺癌 A549、H460 细胞中的本底表达量。采用 FGF13 过表达载体转染 BEAS-2B 和 A549 细胞；设计两组靶向 FGF13 的 shRNA 序 列，构建慢病毒干扰载体，包装病毒后侵染 A549 细胞，采用 qPCR 和 WB 法检测干扰效果，DCFH-DA 探针结合荧光酶标仪分 析敲减 FGF13 对 A549 细胞内 ROS 水平的影响，MitoSOX 与 WB 法检测对线粒体 ROS 水平及烟酰胺腺嘌呤二核苷酸磷酸氧 化酶 4（nicotinamide adenine dinucleotide phosphate oxidase 4，NOX4）蛋白表达量的影响，Annexin V-FITC-PI 双染法检测对细胞 凋亡和 Caspase-3 及 Cleaved Caspase-3 蛋白表达的影响。结果：与 BEAS-2B 细胞相比，FGF13 蛋白在两种肺癌细胞中均高表 达（均 P<0.05）。成功构建 FGF13 过表达、低表达的 A549 细胞系。过表达 FGF13 后，BEAS-2B 和 A549 细胞内 ROS 水平显著 降低（P<0.05）；敲减 FGF13 表达后，A549 细胞内 ROS 水平显著升高（P<0.05）；然而过表达及干扰 FGF13 对 A549 细胞内线粒 体 ROS 水平无显著影响，但 NOX4 蛋白表达量显著下调（P<0.05）及显著上调（P<0.05）。FGF13 干扰后 A549 细胞凋亡率显著 升高（P<0.01），Caspase-3 及 Cleaved Caspase-3 蛋白表达量显著上调（P<0.05）。结论：FGF13 可能通过 NOX 家族途径调控 ROS 的生成，并通过 ROS/Caspase-3 通路调控 A549 细胞凋亡。

Objective:To examine the association of blood uric acid (UA) and cognitive impairment (CI) among oldest-old adults in China.Methods:Data was collected in 9 longevity areas of China from Healthy Aging and Biomarkers Cohort Study (HABCS) conducted during 2017-2018. Finally,1, 622 elderly aged 80 years and older with complete information on blood UA and cognitive function score were included in this study. Information on demographic characteristics, lifestyle, and health status were collected through questionnaire and physical examination. Venous blood samples of the participants were collected to test blood UA level. Cognitive impairment (CI) was assessed using the Chinese Mini-Mental State Examination (MMSE) according to personal educational level. Generalized Estimating Equations (GEE) model for binary data was used to analyze the association of blood UA and CI, and further compared the associations among different age and body mass index (BMI) groups.Results:Of the 1 622 oldest-old, the mean age was (92.2±8.1) years, 656 (40.4%) were male, the mean level of blood UA was (343.3±86.2) μmol/L, and 482 (29.7%) oldest-old had CI. Compared with the lowest quartile of UA, the risks of CI in the second, third and highest quartiles were gradually reduced, the corresponding ORs and 95% CI were 0.99 (0.71-1.33), 0.87 (0.68-0.94) and 0.69 (0.48-0.85), respectively; and the linear trend test was statistically significant ( P<0.001). Subgroup analysis showed that the effects of higher UA associated with lower risk of CI were stronger in younger oldest-old (aged 80-89 years) and thinner group (BMI<24) ( Pinteraction<0.05). Conclusions:Blood UA was negatively associated with the risk of having CI in the oldest-old among the nine longevity areas of China.

Objective:To investigate the association of blood oxidative stress level with hypertriglyceridemia in the elderly aged 65 years and older in China.Methods:A total of 2 393 participants aged 65 years and older were recruited in 9 longevity areas from Heathy Aging and Biomarkers Cohort Study, during 2017 to 2018. Information on demographics characteristic, life style and health status were collected by questionnaire and physical examination, and venous blood was collected to detect the levels of blood oxidative stress and hypertriglyceridemia. The linear or non-linear association between oxidative stress and hypertriglyceridemia was described by restrictive cubic splines (RCS) fitting multiple linear regression model. The generalized linear mixed effect model was conducted to assess the association between oxidative stress and hypertriglyceridemia.Results:A total of 2 393 participants, mean age was 84.6 years, the youngest was 65 and the oldest was 112, the male was 47.9%(1 145/2 393), the triglyceride level was (1.4±0.8) mmol/L. The hypertriglyceridemia detection rate was 9.99%(239/2 393). The results of multiple linear regression model with restrictive cubic spline fitting showed that MDA level was linear association with triglyceride level; SOD level was nonlinear association with triglyceride level. MDA level had significantly association with hypertriglyceridemia, and the corresponding OR value was 1.063 (95% CI: 1.046,1.081) with 1 nmol/ml increment of blood MDA; SOD level had significantly association with hypertriglyceridemia, and the corresponding OR value was 0.986(95% CI: 0.983,0.989) with 1 U/ml increment of blood SOD. Conclusion:Among the elderly aged 65 and older in 9 longevity areas in China, MDA and SOD levels were associated with the risk of hypertriglyceridemia.

Objective:To investigate the relationship between the neutrophil-to-lymphocyte ratio (NLR) and the risk of depression symptoms among older adults aged 65 and above in 9 longevity areas of China.Methods:Data was collected in 9 longevity areas of China from Healthy Aging and Biomarkers Cohort Study (HABCS) conducted between 2017 and 2018. Finally,2018 elderly aged 65 years and above with complete information on neutrophil count, lymphocyte count and depressive symptoms were included in this study. Information on demographic characteristics, lifestyle, and health status was collected through questionnaire and physical examination. Complete blood counts which included lymphocytes and neutrophils were obtained by testing venous blood samples. Participants were divided into four groups by the quartile of NLR level, i.e. Q1, Q2, Q3, Q4. Logistic regression model was applied to analyze the association of NLR with depression symptoms. Results:Among 2 018 older adults, the mean(±SD) age was 82.6(±10.73), 1 032(51.14%) were male, 390(19.33%) were detected with depressive symptoms. Compared with participants of NLR in the 1 st quartile, the OR(95% CI) of risk for depressive symptoms was 1.47 (0.99, 2.19), 1.67 (1.13, 2.47) and 1.95 (1.32, 2.89), respectively. Conclusion:Increased NLR level is significantly related to depressive symptoms among elderly aged 65 years and above in 9 longevity areas in China.