Humans ; Mycobacterium tuberculosis/genetics* ; Microspheres ; Antitubercular Agents/pharmacology* ; Mutation ; Microbial Sensitivity Tests ; Fluoroquinolones ; Drug Resistance, Bacterial/genetics* ; Tuberculosis, Multidrug-Resistant/microbiology*

OBJECTIVE: To investigate the role of Numb in regulating mammalian target of rapamycin (mTOR) complex 1 (mTORC1) signaling pathway. METHODS: Male BALB/C mouse models of acute kidney injury (AKI) were subjected to intravenous injections of Numb-siRNA or NC-siRNA with or without intraperitoneal cisplatin injections. After the treatments, the expressions and distribution of Numb and megalin in the renal tissues of the mice were detected with immunohistochemistry, and the renal expressions of Numb, S6, p-S6, S6K1, p-S6K1, 4EBP1 and p-4EBP1 were examined with Western blotting. The proximal renal tubular epithelial cells were isolated from the mice transfected with Numb-siRNA for in vitro culture. In NRK-52E cells, the effects of amino acid stimulation, Numb knockdown, and V1G1 overexpression, alone or in combination, on expressions of Numb, S6 and p-S6 were detected with Western blotting; the expressions of AMPK and p-AMPK were also detected in transfected NRK-52E cells, mouse kidneys and cultured mouse renal tubular epithelial cells. RESULTS: In BALB/C mice, injection of Numb-siRNA caused significant reductions of Numb and p-S6 expressions without affecting megalin expression in the renal proximal tubules (P < 0.05). Cisplatin treatment obviously upregulated p-S6K1 and p-4EBP1 expressions in the kidneys of the mice (P < 0.05), and this effect was significantly inhibited by treatment with Numb-siRNA (P < 0.05). In NRK-52E cells, amino acid stimulation significantly upregulated the expression of p-S6 (P < 0.05), which was strongly suppressed by transfection with Numb-siRNA (P < 0.05). Numb knockdown inhibited AMPK activation in NRK-52E cells, mouse kidneys and primary proximal tubular epithelial cells (P < 0.05). Numb knockdown significantly downregulated V1G1 expression in NRK-52E cells (P < 0.05), and V1G1 overexpression obviously reversed the inhibitory effect of Numb-siRNA on S6 phosphorylation (P < 0.05). CONCLUSION Numb promotes the activation of mTORC1 signaling in proximal tubular epithelial cells by upregulating V1G1 expression.
Animals ; Male ; Mice ; Amino Acids/pharmacology* ; AMP-Activated Protein Kinases/metabolism* ; Cisplatin/pharmacology* ; Epithelial Cells ; Low Density Lipoprotein Receptor-Related Protein-2/metabolism* ; Mammals/metabolism* ; Mechanistic Target of Rapamycin Complex 1/metabolism* ; Membrane Proteins/metabolism* ; Mice, Inbred BALB C ; Nerve Tissue Proteins/metabolism* ; RNA, Small Interfering/metabolism* ; Signal Transduction ; Vacuolar Proton-Translocating ATPases/metabolism*

Arthritis, Rheumatoid/complications* ; Biomarkers ; Humans ; Lung Diseases, Interstitial/etiology* ; Prognosis

Objective: During laparoscopic pelvic operational procedure for obese patients with rectal cancer, the large amount of fat in the abdominal cavity often impairs the exposure of the surgical field, resulting in technical difficulty. In contrast, robotic surgery has the advantages of being more minimally invasive, precise, and flexible. This study compared the clinical efficacy of robotic and laparoscopic radical resection of rectal cancer for overweight and obese patients. Methods: A retrospective cohort study was conducted. Clinical data of 173 patients with rectal cancer and a body mass index (BMI) ≥ 25 kg/m(2) who received robotic or laparoscopic radical rectal resection at the First Affiliated Hospital of Nanchang University from January 2015 to February 2019 were retrospectively collected. Of 173 patients, 90 underwent robotic surgery and 83 underwent laparoscopic surgery. The intraoperative parameters, postoperative short-term and follow-up status were analyzed and compared between the two groups. The follow-up ended in December 2019. Results: Of 173 patients, 103 were male and 70 were female with a median age of 62 (range 29 to 86) years. The average BMI was (27.2±1.6) kg/m(2) in the robotic group and (27.3±1.5) kg/m(2) in the laparoscopic group. No significant differences in baseline data were observed between two groups (all P>0.05). As compared to the laparoscopic group, the robotic group had less intraoperative blood loss [(73.0±46.8) ml vs. (120.9±59.9) ml, t=-5.881, P<0.001] and higher postoperative hospitalization expense [(61±15) thousand yuan vs (52±13) thousand yuan, t=3.468, P=0.026]. The conversion rate in the robotic group was 1.1% (1/90), which was lower than 6.0% (5/83) in the laparoscopic group, but the difference was not statistically significant (P=0.106). There were no statistically significant differences between the two groups in operative time, number of intraoperative blood transfusion, number of harvested lymph nodes, time to the first flatus, postoperative hospital stay and morbidity of total postoperative complications (all P>0.05). Five (6.0%) patients in the laparoscopic group developed urinary dysfunction, while no case in the robotic group developed postoperative urinary dysfunction (P=0.024). The 173 patients were followed up for 8-59 months, with a median follow-up of 36 months. The 3-year overall survival rate of robotic group and laparoscopic group was 89.8% and 86.6%, respectively without significant difference between the two groups (P=0.638). The 3-year disease-free survival rate of the robotic group and the laparoscopic group was 85.6% and 81.5%, respectively without significant difference as well (P=0.638). Conclusions: Robotic radical surgery is safe and feasible for overweight and obese patients with rectal cancer. Compared with laparoscopic radical surgery, it has advantages of clear vision of surgical exposure, less intraoperative blood loss, less pelvic autonomic nerve damage, and operation in a narrow space.
Adult ; Aged ; Aged, 80 and over ; Feasibility Studies ; Female ; Humans ; Laparoscopy ; Male ; Middle Aged ; Obesity/complications* ; Overweight/complications* ; Rectal Neoplasms/surgery* ; Retrospective Studies ; Robotic Surgical Procedures ; Treatment Outcome

BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Aged ; Betacoronavirus ; Coronavirus Infections ; complications ; mortality ; Extracorporeal Membrane Oxygenation ; Humans ; Lung Transplantation ; methods ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; complications ; mortality ; Pulmonary Fibrosis ; mortality ; surgery ; Respiratory Distress Syndrome, Adult ; mortality ; surgery

Betacoronavirus ; genetics ; Coronavirus Infections ; diagnosis ; Fluorescence ; High-Throughput Nucleotide Sequencing ; methods ; Humans ; Pandemics ; Pneumonia, Viral ; diagnosis ; Polymerase Chain Reaction ; methods

Background:Clinical outcomes of undifferentiated arthritis (UA) are diverse,and only 40 ％ of patients with UA develop rheumatoid arthritis (RA) after 3 years.Discovering predictive markers at disease onset for further intervention is critical.Therefore,our objective was to analyze the clinical outcomes of UA and ascertain the predictors for RA development.Methods:We performed a prospective,multi-center study from January 2013 to October 2016 among Chinese patients diagnosed with UA in 22 tertiary-care hospitals.Clinical and serological parameters were obtained at recruitment.Follow-up was undertaken in all patients every 12 weeks for 2 years.Predictive factors of disease progression were identified using multivariate Cox proportional hazards regression.Results:A total of 234 patients were recruited in this study,and 17 (7.3％) patients failed to follow up during the study.Among the 217 patients who completed the study,83 (38.2％) patients went into remission.UA patients who developed RA had a higher rheumatoid factor (RF)-positivity (42.9％ vs.16.8％,x2=8.228,P=0.008),anti-cyclic citrullinated peptide (CCP) antibodypositivity (66.7％ vs.10.7％,x2 =43.897,P ＜ 0.001),and double-positivity rate of RF and anti-CCP antibody (38.1％ vs.4.1％,x2 =32.131,P ＜ 0.001) than those who did not.Anti-CCP antibody but not RF was an independent predictor for RA development (hazard ratio 18.017,95％ confidence interval:5.803-55.938;P ＜ 0.001).Conclusion:As an independent predictor of RA,anti-CCP antibody should be tested at disease onset in all patients with UA.

Objective To investigate the protective role of GPR35 inhibition on hypoxic myocardial cell line and mouse myocardial infarction (MI) model.Methods For investigating the changes of GPR35 expression in hypoxic environment,the murine myocardial cells (MCM) were divided into normoxia group and hypoxia group,the mRNA expression of GPR35 was determined by q-PCR and the protein level was measured by Western blotting 6h after incubation.For further studying the role of GPR35,MCM were divided into four groups:normoxia,hypoxia,hypoxia+vehicle,hypoxia+CID2745678 (GPR35 inhibitor,3μmol/L) group.Accordingly,the apoptosis of cardiomyocytes was measured by flow cytometer and TUNEL.For investigating the changes of GPR35 expression in the state of myocardial ischemia,the C57 male mice were divided into sham group (n=6) and MI group (n=8),the mRNA expression of GPR35 was determined by q-PCR and the protein level was measured by Western blotting 3 days after MI.For further studying the role of GPR35,the C57 mice were divided into four groups:sham (n=6),MI (n=8),MI+vehicle (n=8) and MI+CID2745678 (n=8) group.Ultrasound echocardiography was performed 4 weeks after MI.Mice were then sacrificed and the hearts were removed and stained with Masson to measure the myocardial fibrosis area.Results Compared with normoxia group,the levels of GPR35 mRNA and protein increased obviously in hypoxia group (P＜0.01,P＜0.05);Compared with hypoxia+vehicle group,the myocardial cells apoptosis in hypoxia+CID2745678 group decreased markedly (P＜0.05).Three days after MI,compared with the sham group,the levels of GPR35 mRNA and protein increased obviously (P＜0.01,P＜0.05) in MI group;Compared with MI+vehicle group,the left ventricular fraction shortening (LVFS) and left ventricular ejection fraction (LVEF) relieved obviously (P＜0.05) and myocardial fibrosis level declined markedly in MI+CID2745678 group (P＜0.05).Conclnsion Inhibition of GPR35 could decrease the apoptosis of cardiomyocytes cultured in hypoxia and attenuated the injury of myocardial ischemia.

Objective To explore the significance of modified pediatric early warning score (MPEWS) in emergency early warning triage and classification. Method Selecting ill children who came to emergency department from February of 2017 to January of 2018 as objects of study, and triage nurses of emergency department gave MPEWS to the sick children under the demand of the filed data collection. Furthermore, according to the five levels of disease severity classification, doctors gave the disease assessment and classification to the sick children, finding the relevance between the MPEWS and the severity of the disease.Result Consequently, there is a relevance between the MPEWS scores and the severity of the disease indeed (rs=-0.630, P ＜ 0.001). The data show that the higher of the scores, the lower disease level, and the higher severity of the disease. ROC areas under the curve of the subjects is 0.996, and the confidence interval is 0.993-0.999 (P ＜0.05). That indicates that MPEWS exists statistical significance of emergency children judgement. The optimal number is 4.5, the sensitivity is 96％, and the specificity is 99.9％.Conclusions MPEWS is valuable in emergency early warning triage, children emergency severity assessment and identifying critical ill children in time.

Objective: To understand the distribution and treatment of malaria patients, and the characteristics of sampled hospitals in thephase of eradication of malaria,and provide support for medical resources allocation in the later stages of malaria eradication phase. On this basis, this study aims at promoting the realization of the ultimate goal of total eradication of malaria in China by 2020. Methods : A multi-stage stratified cluster sampling method was used. A total number of 102 hospitals in Zhejiang, Jiangsu, Anhui, Henan, Sichuan and Yunnan Provinces were selected to collect original information on in-patient and out-patient of malaria in terms of medical records and treatment costs during the periodfrom January 1st 2014 toDecember 31th2016. In order to conduct accurate statistical analysis, Excel 2016, SPSS 20. 0 and other Software were used. Results: The survey results collected a total number of 1633 malaria patients, and these patients showed a W-shaped distribution during the months of treatment. Most of malaria patients from Henan and Sichuan Provinceswere diagnosed as having been affected by falciparum and vivax malaria, and their number sharply increased. This is paper also revealed the ratios of malaria patientsin terms of their choice of health services,namely from tertiary hospitals, municipal medical institutions and provincial medical institutions; those were77.10％,52.05％ and 23.58％,respectively. Conclusions : A new period of peak incidence of malariais detected from 2014 to 2016. With hospitals' line of malaria defending ability shrinking,it was found that malaria treatment capacitiesare relatively concentrated in the high level hospitals,which plays a greater role when it comes to the prevention and control of malaria. It is recommended that regional malaria treatment lines should be built,and severe malaria treatment knowledge trainingsshould be prepared and attended in mass in orderto improve malaria treatment capacities.