Chronic obstructive pulmonary disease (COPD) is a heterogeneous lung condition characterized by persistent airflow obstruction caused by long-term airway inflammation or alveolar abnormalities, often manifested as chronic respiratory symptoms and decreased lung function. In recent years, experimental research has shown that mesenchymal stem cells (MSC) have anti-inflammatory, immunomodulatory, and repairing properties of lung epithelial cells, which can be used to treat various diseases including COPD. This article is mainly based on the main findings of in vitro and in vivo animal model experiments and clinical studies of MSC treatment for COPD. It summarizes and discusses the possible mechanisms of action of MSC as a new therapy, and provides new ideas for clinical treatment of COPD.

Objective:To analyze the influencing factors of genotypic drug resistance mutations in people living with human immunodeficiency virus and acquired immunodeficiency syndrome(PLWHA) who failed anti-retroviral therapy (ART) in Henan Province, in order to provide a basis for adjusting ART regimens and reducing drug resistance.Methods:PLWHA with virological failure (human immunodeficiency virus (HIV) RNA≥500 copies/mL) after receiving ART for more than 24 weeks were included in Henan Province from January 2018 to December 2022. Baseline CD4 + T lymphocyte counts, ART regimens and other clinical data were collected. HIV-1 gene subtypes and their drug resistance sequence mutations were detected in the Sixth People′s Hospital of Zhengzhou, and the sequences were submitted to the HIV Drug Resistance Interpretation System of Stanford University for comparison of test results. Genotypic drug resistance to nucleotide reverse transcriptase inhibitors (NRTI), non-nucleoside reverse transcriptase inhibitors (NNRTI), protease inhibitors (PI) and integrase inhibitors (INSTI) was determined. Multivariate logistic regression was used to analyze the influencing factors of drug resistance in patients with ART failure. Results:Among 982 PLWHA, the sequences of 899 cases were successfully amplified, and drug resistance was detected in 737 cases, with the drug resistance rate of 81.98%(737/899). The rates of resistance to NRTIs, NNRTIs, PIs and INSTIs were 71.97%(647/899), 79.31%(713/899), 5.23%(47/899) and 2.72%(20/734), respectively.The largest number of those who developed concomitant resistance to two classes of drugs was 588 cases (79.78%), mainly NRTI and NNRTI concomitant resistance in 583 cases (79.10%). There were 99 cases (13.43%) who developed resistance to only one class of drugs, and those who developed concurrent resistance to three classes of drugs were 48 cases (6.51%), and two cases (0.27%) were found to be resistant to all four classes of drugs mentioned above. A total of 10 HIV genotypes were detected, among which subtype B accounted for the most (59.73%(537/899)), followed by circulating recombinant form (CRF)01_AE subtype (21.91%(197/899)) and CRF07_BC subtype (9.45%(85/899)). The risk factors affecting the development of drug resistance were baseline CD4 + T lymphocyte counts, ART regimens and HIV-1 genotypes. The risk of drug resistance in patients with baseline CD4 + T lymphocyte counts <100/μL was 4.55 times (95% confidence interval ( CI) 2.69 to 7.70) higher than patients with CD4 + T lymphocyte counts≥250/μL, the risk of drug resistance in patients using 2NRTIs+ NNRTI regimen was 4.51 times (95% CI 1.75 to 11.63) higer than those using 2NRTIs+ INSTI regimen, and patients infected with B and CRF01_AE subtype was 2.18 times (95% CI 1.10 to 4.29) and 2.70 times (95% CI 1.26 to 5.78) higer than those with CRF07_BC subtype, respectively. Conclusions:The incidence of genotypic drug resistance in PLWHA with ART failure in Henan Province is high. Low baseline CD4 + T lymphocyte counts, 2NRTIs+ NNRTI regimens, and genotype B and CRF01_AE are risk factors for drug resistance in PLWHA.

Objective:To understand the clinical characteristics of human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) patients with renal injury after antiviral therapy in Henan Province, and to explore the risk factors of renal injury.Methods:A cross-sectional study was conducted to investigate HIV infection/AIDS patients receiving antiviral therapy in Zhengzhou Sixth People′s Hospital, Anyang Fifth People′s Hospital, Hebi Third People′s Hospital, Luo Yang Zhoushan Hospital and Lankao Central Hospital in Henan Province from April 1 to September 30, 2023. The clinical information including basic data, antiviral therapy regimens and comorbidities, and laboratory test results (blood urea nitrogen, serum creatinine, blood uric acid, urine routine, urine microalbumin, urine α 1-microglobulin (α 1-MG), urine β 2-microglobulin (β 2-MG), urine retinol binding protein (RBP), urine creatinine, HIV viral load, CD4 + T lymphocyte count) were collected. Multivariate binary logistic regression was used to analyze independent risk factors for renal injury. Results:A total of 2 526 HIV infection/AIDS patients were included, with the age of (45.52±14.28) years and 2 156 (85.4%) males. The main route of transmission was sexual transmission (91.6%, 2 314/2 526). The duration of antiviral therapy was 5.00(2.92, 8.00) years. Tenofovir (TDF)+ lamivudine (3TC)+ non-nucleoside reverse transcriptase inhibitors (NNRTI) accounted for 55.3%(1 396/2 526) of the current antiviral therapy regimen. The percentage of HIV viral load <50 copies/mL was 93.0%(2 350/2 526). The CD4 + T lymphocyte count was 476(337, 645)/μL. There were 156 patients (6.2%) complicated with hepatitis B and/or hepatitis C, 205 patients (8.1%) with diabetes, 379 patients (15.0%) with hyperlipidemia, and 189 patients (7.5%) with hyperuricemia. A total of 1 040 patients (41.2%) with renal injury were found through renal function test, including 355 cases (14.1%) with estimated glomerular filtration rate (eGFR) <60 mL/(min·1.73 m 2) or urine protein positive or urine albumin creatine ratio (UACR) ≥30 mg/g, 682 patients (27.0%) with pure tubular injury presented with only positive for urinary α 1-MG, urinary β 2-MG, or urinary RBP. eGFR< 60 mL/(min·1.73 m 2) was found in 71 cases (2.8%), eGFR from 60 to 89 mL/(min·1.73 m 2) was found in 509 cases (20.2%), and eGFR≥90 mL/(min·1.73 m 2) was found in 1 946 cases (77.0%). A total of 138 patients (5.5%) were identified as having combined chronic kidney disease (CKD). Among them, 110 patients (79.7%) were in CKD stages 1 to 2, and 117 patients (84.8%) were in urinary albumin A2 grade. Multivariate analysis of 355 patients with renal injury who had eGFR<60 mL/(min·1.73 m 2) or positive urine protein in urine routine or UACR ≥30 mg/g showed that ages of 50 to 69 years old (odds ratio( OR)=2.189, 95% confidence interval ( CI) 1.333 to 3.596, P=0.002)), ≥70 years old ( OR=5.190, 95% CI 2.912 to 9.248, P<0.001), female ( OR=1.685, 95% CI 1.241 to 2.286, P=0.001), combined opportunistic infection ( OR=2.521, 95% CI 1.567 to 4.056, P<0.001), combined hepatitis B ( OR=1.962, 95% CI 1.110 to 3.467, P=0.020), combined hepatitis C ( OR=1.883, 95% CI 1.043 to 3.400, P=0.036), combined diabetes ( OR=2.703, 95% CI 1.911 to 3.821, P<0.001), using TDF for two to four years ( OR=1.674, 95% CI 1.103 to 2.459, P=0.015), using TDF for greater than or equal to five years ( OR=1.880, 95% CI 1.287 to 2.746, P=0.001), using TDF combined with lopinavir/ritonavir (LPV/r) ( OR=3.610, 95% CI 2.273 to 5.734, P<0.001) and using TDF combined with non-LPV/r ( OR=1.495, 95% CI 1.036 to 2.157, P=0.031) were the risk factors of renal injury. Conclusions:There is a high proportion of renal injury among HIV infection/AIDS patients after antiviral therapy in Henan Province, including CKD and simple renal tubular injury. Older age, female, comorbidities, and long-term use of TDF are risk factors for renal injury.

Humans ; Adult ; Serum Albumin, Human ; Consensus ; Cardiac Surgical Procedures ; Thoracic Surgery

Objective:To explore the risk factors of death in patients receiving ECMO treatment and to construct a nomogram prediction model.Methods:The clinical data of 412 consecutive patients with acute heart and (or) pulmonary failure who received ECMO treatment between April 2018 and June 2022 were retrospectively included.According to the patients' in-hospital survival, univariate correlation analysis was used to select risk factor variables, and then Lasso regression was used to screen all variables, combined with common variables, combined with clinical practice, plotted a nomogram to predict the probability of early mortality, using the area under the ROC curve (AUC), Harrell C index and calibration curve were used to evaluate and internally validate the performance of the model.Decision curve analysis was applied to assess its clinical utility.Results:Cerebral infarction, diabetes, history of cardiopulmonary resuscitation, neurological complications, acute kidney injury, lactate, hemoglobin, albumin, and platelet count were risk factors for death in patients receiving ECMO ( P<0.05).At the same time, according to the actual situation and difference variables, we constructed a nomogram with high reliability to predict the probability of death. Conclusions:The study identified the risk factors of death in patients receiving ECMO, successfully constructed and validated a nomogram prediction model, and provided a simple and reliable tool for ECMO death prediction, which is of great significance for individualized treatment of patients.

Humans ; Mutation/genetics* ; HIV Infections/drug therapy* ; Drug Resistance ; Treatment Failure ; China ; Drug Resistance, Viral/genetics*

Objective:To analyze the drug resistance characteristics of HIV/AIDS patients in Henan Province with antiretroviral treatment (ART) failure through the genotypic drug resistance detection.Methods:Blood samples were collected from HIV/AIDS patients who received ART for more than 6 months with viral loads ≥1 000 copies/ml in 18 cities of Henan from January 2018 to May 2021. The genotypic drug resistance detection was conducted by using an In-house drug resistance detection method. The drug resistance mutation (DRM) and antiretroviral susceptibility were analyzed by submitting the determined sequences to the Stanford HIV-1 drug resistance database. The information about patients' demographic characteristics and antiviral treatment data were collected.Results:A total of 887 HIV/AIDS patients with ART failure, 812 sequences were successfully amplified with the success rate of 91.54%. In the 812 patients, 676 were drug resistant (83.25%, 676/812). The drug resistance ratesto nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs), and integrase strand transfer inhibitors (INSTIs) were 73.40% (596/812), 80.54% (654/812), 5.54% (45/812), and 2.56% (17/663), respectively. There were significant differences in drug resistance rates among four types of drugs ( χ2=1 686.34, P<0.001). The drug resistance rate to two drugs was 66.38% (539/812), and the drug resistance rate to three drugs was 5.79% (47/812). A total of 9 subtypes of HIV-1were detected, in which subtype B accounted for 59.61%(484/812), followed by subtype CRF01_AE (22.17%, 180/812) and subtype CRF07_BC (9.48%, 77/812). There were significant differences in drug resistance rate among different subtypes ( χ2=21.33, P=0.001). Among NRTIs related mutation sites, the DRM rate of M184V/I was highest (63.42%, 515/812), followed by K65R (27.46%, 223/812). The top three DRM rates were detected for K103N/S (34.98%, 284/812), G190A/S (26.11%, 212/812) and V106M/I (24.63%, 200/812) among NNRTIs related mutation sites, and M46I (4.31%, 35/812), V82A/F (3.82%, 31/812), and I54V/MV (3.69%, 30/812) among PIs related mutation sites. While among INSTIs related mutation sites, E157Q/EQ had the highest DRM rate (3.47%, 23/663), followed by R263K (0.75%, 5/663) and G140A (0.75%, 5/663). The resistance to lamivudine and emtricitabine of NRTIs was at high-level (65.52%, 532/812), and the resistance to nevirapine (77.46%, 629/812) and efavirenz (71.18%, 578/812) of NNRTIs was also at high-level. The medium/high-level resistance to lopinavir/ritonavir of PIs was only 4.19% (34/812), the medium/high-level resistance to elvitegravir and raltegravir of INSTIs was 1.66% (11/663) and 1.21% (8/663), respectively, and no high-level resistance to bictegravir or dolutegravir was found. Conclusions:The drug resistance in HIV/AIDS patients with ART failure was high in Henan, characterized by high drug resistance rates to NRTIs and NNRTIs, and diverse and complex resistance mutations. So high resistance barrier ART-regimens were recommended, and the viral load monitoring and drug resistance testing after ART should be strengthened.

Objective:To analyze the correlation between human immunodeficiency virus (HIV)-1 reservoir and poor immune reconstitution of HIV/acquired immunodeficiency syndrome (AIDS) patients, and to investigate the influence of HIV-1 reservoir on the immune reconstitution.Methods:Cross-sectional survey was conducted to measure HIV-1 RNA and T lymphocyte subsets from 219 patients with HIV/AIDS who had been treated with anti-retroviral therapy (ART) for more than two years with HIV RNA lower than the limit of detection. Among them, there are 195 patients from the Sixth People′s Hospital of Zhengzhou, 12 patients from Shangqiu Municipal Hospital and 12 patients from Zhoukou Infectious Diseases Hospital. Peripheral blood mononuclear cells (PBMC) were collected and HIV-1 DNA was detected. The measurement data of normal distribution were analyzed by two independent sample t-test. The measurement data of skewness distribution were analyzed by rank sum test. Spearman′s rank correlation was used for correlation analysis. Receiver operating characteristic curve (ROC) was used to predict the predictive value of occurrence of poor immune reconstitution AIDS patients. Results:There were 121 patients with poor immune reconstitution and 98 patients with healthy immune reconstitution. HIV-1 DNA was (2.50±0.52) copies/1×10 6 PBMC in the group with poor immune reconstitution, which was significantly higher than the healthy immune reconstitution group ((2.11±0.66) copies/1×10 6 PBMC, t=4.78, P<0.001). The CD4 + T lymphocyte counts in the group with poor immune reconstitution was 192(139, 227)/μL, which was lower than that in the healthy immune reconstitution group (573(457, 730)/μL). The difference was statistically significant ( Z=12.68, P<0.001). HIV-1 DNA was reversely correlated with CD4 + T lymphocyte counts and CD4 + /CD8 + T lymphocyte ratio (after adjusting the influence of age and ART time, r=-0.277 and -0.316, respectively, both P<0.001). The area of ROC curve for HIV-1 DNA to predict poor immune reconstitution was 0.679(95% confidence interval ( CI) 0.604 to 0.750). The HIV-1 DNA threshold value was 100 copies/1×10 6 PBMC with the sensitivity of 90.13% and specificity of 42.91%. The area of ROC curve of CD4 + /CD8 + T lymphocyte ratio to predict poor immune reconstitution was 0.905 (95% CI 0.863 to 0.942). The threshold value of CD4 + /CD8 + T lymphocyte ratio was 0.536 with the sensitivity of 77.68% and specificity of 89.84%. Conclusions:There is correlation between HIV-1 DNA and poor immune reconstitution in HIV/AIDS patients. The value of HIV-1 DNA higher than 100 copies/1×10 6 PBMC and CD4 + /CD8 + T lymphocyte ratio lower than 0.536 could be used as predictor of poor immune reconstitution.

Recombinant proteins provide new means for disease treatment, while creating considerable economic benefits. Using commercial crops (mainly tobacco), cereal crops, legumes, and vegetable crops to produce recombinant proteins with medicinal value is a hot-spot for research in "molecular farming". Although many recombinant proteins have been expressed in plants, only a small number have been successfully put into use. To overcome the problems that greatly hamper the development of recombinant protein production in plants, researchers have improved expression systems to increase the yield of recombinant proteins. Starting from analyzing the problems of low yield and/or low biological activity of recombinant proteins produced by plants, the optimization strategies to solve these problems were reviewed, and future research directions for improving the yield of recombinant proteins produced by plants were proposed.
Crops, Agricultural/genetics* ; Plant Proteins/metabolism* ; Plants, Genetically Modified/genetics* ; Recombinant Proteins ; Tobacco/genetics*

Objective:To investigate the drug resistance of patients with acquired immunodeficiency syndrome (AIDS) who failed antiviral therapy.Methods:A total of 156 AIDS patients with antiviral therapy failure at the Sixth People′s Hospital of Zhengzhou from October 2017 to December 2018 were selected. The human immunodeficiency virus (HIV)-1 ViroSeq? genotyping method was used for the detection of HIV resistance, and Stanford University HIV drug resistance database (http: ∥hivdb.stanford.edu/) was used for testing results comparison.Results:Among the 156 AIDS patients with antiviral therapy failure, 122(78.21%) developed drug resistance. One hundred and six (67.95%) cases were multi-resistant to nucleoside reverse transcriptase inhibitor (NRTI), among which, 104 (66.67%) were resistant to lamivudine, emtricitabine and abacavir. One hundred and eighteen (75.64%) were resistant to non-nucleoside reverse transcriptase inhibitor (NNRTI), and 118 (75.64%) were multi-resistant to efavirenz and nevirapine. And seven (4.49%) were resistant to protease inhibitor (PI). There were 16 resistant sites for NRTI, with 87 (71.31%) most frequent M184V/I mutations. There were 13 resistant sites for NNRTI, with 49 (40.16%) K103N/R mutations. There were 11 resistant sites for PI, with 49 (40.16%) A71V/T mutations. The antiviral drugs lamivudine and emtricitabine were moderately and highly resistant in 102 (83.61%) cases, efavirenz and nevirapine were moderately and highly resistant in 117 (95.90%) cases. Once drug resistance developed, these drugs were likely to be moderate or high resistance. There were 29 (23.77%), 48 (39.34%), and five (4.10%) cases were resistant to zidovudine, tenofovir and lopinavir/ritonavir, respectively. The resistance barrier of these drugs was relatively high.Conclusion:The incidence of drug resistance in patients with AIDS treatment failure is high, and multi-drug resistance is serious with various sites of drug resistance.