Objective To analyze the epidemic characteristics of multidrug-resistant tuberculosis(MDR-TB)in Hunan Province from 2013 to 2016,and provide theoretical basis for the prevention and control of tuberculosis.Methods Information about TB patients in Hunan Province reported by China Information System for Disease Control and Prevention between January 2013 and December 2016 was analyzed retrospectively.Results From 2013 to 2016,the total drug resistance registration rate in Hunan Province was 5.53/million(1 496/270 330 000),multidrug registration rate was 5.40/million(1 459/270 330 000),drug resistance rate and multidrug resistance rate showed an upward trends(trend x2 =113.605,96.590,respectively,both P<0.001).Among MDR-TB patients,male were more than females(74.09%vs 25.91%),most were more than 25 years of age,especially 45～age group(27.07%);the proportion of patients with MDR-TB retreatment was higher than that of the initial treatment(69.91%vs 30.09%).From 2013 to 2016,distribution range of MDR registration rates in different regions were 4.07/million-7.23/million.Conclusion MDR-TB in Hunan Province in 2013-2016 is increasing year by year,and mainly concentrate on young people over 20 years old.There are more cases of male and retreatment;it is necessary to strengthen regular treatment and prevention of key population,enhance the ability to identify and diagnose MDR-TB patients,and reduce the spread of MDR-TB.

OBJECTIVESTo evaluate the safety and define the contraindication of regional citrate anticoagulation treatment on various critically ill patients being treated by continuous blood purification, who also had bleeding tendencies.

METHODSForty critically ill patients being treated by continuous blood purification (CBP) were involved in this study. Due to their bleeding tendencies, regional citrate anticoagulation treatment was given to all of them. Those with hepatic function impairment (n = 10) were classified as Group A, those with hypoxemia were classified as Group B (n = 10), and the others as Group C (n = 20). Blood samples were collected before treatment, and at 4, 12, 24, 36, and 48 hour intervals during CBP. These samples then were used arterial blood gas analysis, whole blood activated clotting time (WBACT) pre- and post-filter, and serum ionized calcium examination.

RESULTSWBACT pre-filter showed little fluctuant through the 48 hr period of CBP, and WBACT post-filter showed obvious prolongation than that of the pre-filter (P < 0.05) at all time points. Metabolic acidosis was found in Group A patients before CBP, and improved during CBP. Normal acid-base conditions of patients were disturbed and deteriorated in Group B during CBP, but not in Group C. Serum ionized calcium was maintained at a normal range during CBP in Group A and C patients, but declined significantly in Group B patients (vs. pre-treatment, P < 0.05).

CONCLUSIONSRegional citrate anticoagulation can be safely used in conjunction with CBP treatment for patients with hepatic function impairment, but may induce acidosis and a decline in serum ionized calcium when used with hypoxemic patients.

Adult ; Aged ; Anticoagulants ; administration & dosage ; Calcium ; blood ; Citric Acid ; administration & dosage ; adverse effects ; Critical Illness ; Female ; Hemofiltration ; Humans ; Male ; Middle Aged

Objective To evaluate the effect of microRNA-182-5p (miR-182-5p) on proliferation and apoptosis of non-small cell lung cancer (NSCLC) A549 cells by targeting forkhead box O3a (FOXO3a).Methods The difference of miR-182-Sp expression between human normal lung epithelial cells BEAS-2B and NSCLC cells A549 was compared.The A549 cells were chosen,and miR-182-Sp mimic (miR-182-Sp mimic group),miR-182-Sp inhibitor (miR-182-5p inhibitor group),negative control mimic (NC mimic group) and negative control inhibitor (NC inhibitor group) were transfected respectively.The expression of miR-182-Sp was detected by reverse transcription-polymerase chain reaction (RT-PCR).The protein expression of FOXO3a was detected by Western blotting.The cell proliferation activity was detected by methyl thiazolyl tetrazolium (MTT) method.The cell apoptosis was detected by flow cytometry.The targeted relationship between miR-182-5p and FOXO3a was detected by dual-luciferase experiment.Results The miR-182-5p expression of A549 cells and BEASo2B cells respectively was 3.21 ±0.24 and 1.01 ±0.11,and the difference was statistically significant (t =14.209,P＜0.001).The miR-182-5p expression of NC mimic group,miR-182-5p mimic group,NC inhibitor group and miR-182-5p inhibitor group respectively was 1.09 ± 0.20,12.80 ± 1.10,1.03 ± 0.11and 0.47 ± 0.08,and the difference was statistically significant (F =87.872,P ＜ 0.001).The FOXO3a expression of the above four groups respectively was 118.34 ± 16.71,50.89 ± 11.58,125.33 ± 20.87 and 289.26 ± 34.51,and the difference was statistically significant (F =62.125,P ＜ 0.001).The 72 h proliferation activity of the four groups respectively was 1.12 ± 0.13,1.70 ± 0.14,1.07 ± 0.13 and 0.71 ± 0.11,and the difference was statistically significant (F =31.336,P ＜ 0.001).The proliferation activity of miR-182-5p mimic group was significantly higher than that of NC mimic group (P ＜ 0.05),and the proliferation activity of miR-182-5p inhibitor group was significantly lower than that of NC inhibitor group (P ＜0.05).The apoptosis rate of the four groups respectively was (5.51 t±1.80)％,(1.41 ±0.50)％,(6.24 ± 1.71)％ and (47.93 ± 5.12) ％,and the difference was statistically significant (F =211.081,P ＜ 0.001).The apoptosis rate of miR-182-5p mimic group was significantly lower than that of NC mimic group (P ＜ 0.05),and the apoptosis rate of miR-182-5p inhibitor group was significantly higher than that of NC inhibitor group (P ＜0.001).The miRNA target genes prediction software test results showed that miR-182-5p could act on FOXO3a 3' untranslated region (UTR).Compared with transfection NC mimic,co-transfection miR-182-5p mimic and FOXO3a-Wt could make luciferase activity of A549 significantly decreased (1.20 ±0.14 vs.0.62 ±0.10;t =5.839,P =0.004).Conclusion miR-182-5p can enhance proliferation and inhibit apoptosis of A549 cell by targeting FOXO3a.

Accurate identification of compound-protein interactions (CPIs) in silico may deepen our understanding of the underlying mechanisms of drug action and thus remarkably facilitate drug discovery and development. Conventional similarity-or docking-based computational methods for predicting CPIs rarely exploit latent features from currently available large-scale unlabeled com-pound and protein data and often limit their usage to relatively small-scale datasets. In the present study, we propose DeepCPI, a novel general and scalable computational framework that combines effective feature embedding (a technique of representation learning) with powerful deep learning methods to accurately predict CPIs at a large scale. DeepCPI automatically learns the implicit yet expressive low-dimensional features of compounds and proteins from a massive amount of unla-beled data. Evaluations of the measured CPIs in large-scale databases, such as ChEMBL and Bind-ingDB, as well as of the known drug-target interactions from DrugBank, demonstrated the superior predictive performance of DeepCPI. Furthermore, several interactions among small-molecule compounds and three G protein-coupled receptor targets (glucagon-like peptide-1 recep-tor, glucagon receptor, and vasoactive intestinal peptide receptor) predicted using DeepCPI were experimentally validated. The present study suggests that DeepCPI is a useful and powerful tool for drug discovery and repositioning. The source code of DeepCPI can be downloaded from https://github.com/FangpingWan/DeepCPI.

Objective To investigate the efficacy of continuous renal replacement therapy(CRRT)versus intermittent hemodialysis(IHD)in patients with severe acute renal failure(ARF).Methods One hundred and ninety -three severe ARF patients who received renal support between December 1978 and December 1998 were involved in this study.Of them,101(52.3%)were treated with CRRT(CRRT group),and 92(47.7%)with IHD(IHD group).Results Sixty(59.4%)patients in the CRRT group got through the acute phase of disease and 41 (40.6%)patients did not survive while in the IHD group 59(64.1%)patients survived and 33(35.9%)patients did not.No significant difference in survival rate was found between the two groups.24 of 64 patients(37.5%)in the CRRT group with multiple organ dysfunction syndrome(MODS)survived,while in the IHD group,8 out of 44(27.3%)survived,their survival rate was much lower than that in the CRRT group.Patients in CRRT group were more severely iii,as manifested by lower mean arterial pressure,higher APACHE Ⅱ score,more dysfunctioned organs and requiring mechanical ventilation and vasopressor support as compared with patients in the IHD group,CRRT was found to improve hemodynamic stability with a better fluid balance and control of biochemical status,increased nutritional intake and a shorter duration of acute renal failure(P ＜ 0.05).Conclusion CRRT perhaps may be the best choice in the treatment of severe ARF patients,for it can offer several distinct advantages compared to IHD.These may contribute to improving the survival rate of ARF patients,particularly those that are critically ill patients.

OBJECTIVETo investigate the effectiveness of using continuous veno venous hemofiltration (CVVH) in the treatment of acute necrotizing pancreatitis (ANP).

METHODSThirteen ANP patients were involved in this study, including 4 females and 9 males, averaging 50.6 +/- 10.8 years old. CT scans upon admission revealed 33% necrosis involving the body of the pancreas in 2 patients, 67% necrosis in 3 patients and 100% necrosis in the other 8; the CT severity score was 8.9 +/- 2.1. CVVH was maintained for at least 72 hours and the AN69 hemofilter (1.2 m(2)) was changed every 24 hours. The ultrafiltration rate during CVVH was 2993.9 +/- 983.0 ml/h, the blood flow rate was 250 - 300 ml/min, and the substitute fluid was infused in a pre-diluted manner. Low molecular weight heparin was used as anticoagulant.

RESULTSCVVH was well tolerated in all the patients. Bloody abdominal cavity drainage fluid was observed in 2 patients, but no other side-effects related with CVVH were observed. Two patients died of systemic fungal infections and another died of intracranial fungi infection, resulting in an ICU mortality of 23.1%. Ten of the patients survived in the ICU, but one of them died for other reasons unrelated to the SAP before discharge. The APACHE II score before CVVH was 15.2 +/- 6.5, but decreased significantly to 8.1 +/- 5.3, 7.5 +/- 4.9 and 8.0 +/- 5.2 at the 24th, 48th and 72nd hour after CVVH, respectively (P < 0.01). Serum concentration of IL-1beta and TNFalpha decreased to the trough at the 6th hour after a new hemofilter was used and increased slowly to pre-CVVH levels 12 hours later. After CVVH had ceased, the serum levels of two cytokines increased to their peaks at the 120th hour and decreased eventually at the 144th hour. The sieving coefficient (SC) of IL-1beta and TNFalpha was 0.33 +/- 0.11 and 0.16 +/- 0.08.

CONCLUSIONCVVH offered therapeutic options for ANP and was well tolerated resulting in clearance of IL-1beta and TNFalpha; CVVH at early stages of SAP may contribute to the improvement of outcome.

Adult ; Aged ; Female ; Hemofiltration ; adverse effects ; Humans ; Interleukin-1 ; analysis ; Male ; Middle Aged ; Pancreatitis, Acute Necrotizing ; therapy ; Tumor Necrosis Factor-alpha ; analysis

Objective:To carry out cytogenetic and molecular genetic analysis for two infertile patients carrying rare small supernumerary marker chromosomes (sSMC).Methods:Two infertile patients who received reproductive and genetic counseling at CITIC Xiangya Reproductive and Genetic Hospital on October 31, 2018 and May 10, 2021, respectively were selected as the study subjects. The origin of sSMCs was determined by conventional G banding, fluorescence in situ hybridization (FISH) and copy number variation sequencing (CNV-seq). Microdissection combined with high-throughput whole genome sequencing (MicroSeq) was carried out to determine the fragment size and genomic information of their sSMCs. Results:For patient 1, G-banded karyotyping and FISH revealed that he has a karyotype of mos47, XY, del(16)(p10p12), + mar[65]/46, XY, del(16)(p10p12)[6]/48, XY, del(16)(p10p12), + 2mar[3].ish mar(Tel 16p-, Tel 16q-, CEP 16-, WCP 16+ ). CNV analysis has yielded a result of arr[GRCh37]16p12.1p11.2(24999364_33597595)×1[0.25]. MicroSeq revealed that his sSMC has contained the region of chromosome 16 between 24979733 and 34023115 (GRCh37). For patient 2, karyotyping and reverse FISH revealed that she has a karyotype of mos 47, XX, + mar[37]/46, XX[23].rev ish CEN5, and CNV analysis has yielded a result of seq[GRCh37]dup(5)(p12q11.2)chr5: g(45120001_56000000)dup[0.8]. MicroSeq results revealed that her sSMC has contained the region of chromosome 5 between 45132364 and 55967870(GRCh37). After genetic counseling, both couples had opted in vitro fertilization (IVF) treatment and preimplantation genetic testing (PGT). Conclusion:For individuals harboring sSMCs, it is vital to delineate the origin and structural characteristics of the sSMCs for their genetic counseling and reproductive guidance. Preimplantation genetic testing after microdissection combined with high-throughput whole genome sequencing (MicroSeq-PGT) can provide an alternative treatment for carrier couples with a high genetic risk.

Chaigui granules(CG)are a compound composed of six herbal medicines with significant antidepressant effects.However,the antidepressant mechanism of CG remains unclear.In the present study,we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling.First,the regulatory effect of CG on purine metabolites in the prefrontal cortex(PFC)of chronic unpredictable mild stress(CUMS)rats was analyzed by ultra high-performance liquid chro-matography tandem mass spectrometry(UHPLC-MS/MS)targeted quantitative analysis.Meanwhile,purinergic receptors(P2X7 receptor(P2X7R),A1 receptor(A1R)and A2A receptor(A2AR))and signaling pathways(nod-like receptor protein 3(NLRP3)inflammasome pathway and cyclic adenosine mono-phosphate(cAMP)-protein kinase A(PKA)pathway)associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay(ELISA).Besides,antidepressant mecha-nism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of puri-nergic receptors in vitro.An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG.Additionally,purinergic re-ceptors(P2X7R,A1R and A2AR)and related signaling pathways(NLRP3 inflammasome pathway and cAMP-PKA pathway)were also significantly regulated by CG.The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway,and the reduction of adenosine and inosine inhibited the A1R-cAMP-PKA pathway,which was significantly ameliorated by CG.Overall,CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A1R-cAMP-PKA pathway.

Objective:To explore potential predictors of refractory Mycoplasma pneumoniae pneumonia (RMPP) in early stage. Methods:The prospective multicenter study was conducted in Zhejiang, China from May 1 st, 2019 to January 31 st, 2020. A total of 1 428 patients with fever >48 hours to <120 hours were studied. Their clinical data and oral pharyngeal swab samples were collected; Mycoplasma pneumoniae DNA in pharyngeal swab specimens was detected. Patients with positive Mycoplasma pneumoniae DNA results underwent a series of tests, including chest X-ray, complete blood count, C-reactive protein, lactate dehydrogenase (LDH), and procalcitonin. According to the occurrence of RMPP, the patients were divided into two groups, RMPP group and general Mycoplasma pneumoniae pneumonia (GMPP) group. Measurement data between the 2 groups were compared using Mann-Whitney U test. Logistic regression analyses were used to examine the associations between clinical data and RMPP. Receiver operating characteristic (ROC) curves were used to analyse the power of the markers for predicting RMPP. Results:A total of 1 428 patients finished the study, with 801 boys and 627 girls, aged 4.3 (2.7, 6.3) years. Mycoplasma pneumoniae DNA was positive in 534 cases (37.4%), of whom 446 cases (83.5%) were diagnosed with Mycoplasma pneumoniae pneumonia, including 251 boys and 195 girls, aged 5.2 (3.3, 6.9) years. Macrolides-resistant variation was positive in 410 cases (91.9%). Fifty-five cases were with RMPP, 391 cases with GMPP. The peak body temperature before the first visit and LDH levels in RMPP patients were higher than that in GMPP patients (39.6 (39.1, 40.0) vs. 39.2 (38.9, 39.7) ℃, 333 (279, 392) vs. 311 (259, 359) U/L, both P<0.05). Logistic regression showed the prediction probability π=exp (-29.7+0.667×Peak body temperature (℃)+0.004×LDH (U/L))/(1+exp (-29.7+0.667×Peak body temperature (℃)+0.004 × LDH (U/L))), the cut-off value to predict RMPP was 0.12, with a consensus of probability forecast of 0.89, sensitivity of 0.89, and specificity of 0.67; and the area under ROC curve was 0.682 (95% CI 0.593-0.771, P<0.01). Conclusion:In MPP patients with fever over 48 to <120 hours, a prediction probability π of RMPP can be calculated based on the peak body temperature and LDH level before the first visit, which can facilitate early identification of RMPP.