BACKGROUND:With the continuous advancement of medical technology,stem cell therapy has been used to treat a variety of diseases,including amyotrophic lateral sclerosis. OBJECTIVE:To review the research progress of stem cell therapy for amyotrophic lateral sclerosis,and prospect the development trend of this field. METHODS:PubMed,China National Knowledge Infrastructure(CNKI),and WanFang Data were searched for articles published from 1995 to 2024 using the key words"amyotrophic lateral sclerosis,mesenchymal stem cells,neural stem/progenitor cells,pluripotent stem cells."A total of more than 1 700 articles were retrieved,and 58 articles were finally included in this review. RESULTS AND CONCLUSION:Amyotrophic lateral sclerosis is a neurodegenerative disease that affects lower motor neurons in the brainstem and spinal cord and upper motor neurons in the motor cortex.The related research of stem cells in the treatment of amyotrophic lateral sclerosis has become a research hotspot.In this review,we summarize the application of different types of stem cells in amyotrophic lateral sclerosis research,including mesenchymal stem cells,neural stem progenitor cells,and induced pluripotent stem cells,and evaluate the key points of preclinical research such as stem cell source,cell volume,stem cell modification methods,and drug delivery routes,which lays the foundation for the future application of stem cell therapy.

Objective To investigate the value of peripheral blood soluble interleukin-2 receptor(sIL-2R),CD4+lymphocyte percentage/CD8+lymphocyte percentage ratio(hereinafter referred to as CD4+/CD8+)and tumor necrosis factor-α(TNF-α)in evaluating the efficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis.Methods A total of 102 elderly patients with newly treated active tu-berculosis admitted to the hospital from December 2019 to December 2022 were enrolled in the study as the observation group,and 102 healthy people aged 60 and older who underwent physical examination in the hos-pital during the same period were enrolled as the control group.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood were compared between the two groups,and the correlations between sIL-2R,TNF-α and CD4+/CD8+were analyzed.The observation group was treated with 2HRZE/4HR anti-tuberculosis treatment regimen.The levels of sIL-2R,TNF-α and CD4+/CD8+in peripheral blood of patients with different efficacy before treatment,1 month and 6 months after treatment in the observation group were compared.The correla-tion between sIL-2R,CD4+/CD8+,TNF-α levels and therapeutic effect was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the efficacy of indicators in evaluating the efficacy of chemo-therapy in elderly patients.Results The levels of sIL-2R and TNF-α in the observation group were higher than those in the control group,while CD4+/CD8+was lower than that in the control group,and the differ-ences were statistically significant(P＜0.05).In the observation group,sIL-2R and TNF-α were negatively correlated with CD4+/CD8+(P＜0.05),sIL-2R was positively correlated with TNF-α(P＜0.05).After 1 month and 6 months of treatment,the levels of sIL-2R and TNF-α in patients with apparent efficacy were low-er than those in patients with efficacy,and the latter were lower than those in patients with no effect,while the CD4+/CD8+in patients with apparent efficacy was higher than that in patients with efficacy,and the latter was higher than that in patients with no efficacy,and the differences were statistically significant(P＜0.05).The levels of sIL-2R and TNF-α were negatively correlated with the efficacy(P＜0.05),and CD4+/CD8+was positively correlated with the efficacy(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of sIL-2R,CD4+/CD8+,and TNF-α used in combination to assess efficacy was significantly greater than the AUCs of the single indicators used in the assessment at each time point of treatment(P＜0.05),and the AUC of the combination of the indicators was greater after 6 months of treatment than after 1 month of treatment(P＜0.05).Conclusion The levels of sIL-2R,CD4+/CD8+and TNF-α are closely related to the ef-ficacy of chemotherapy in elderly patients with newly treated active pulmonary tuberculosis,and the combina-tion of the above indicators has certain reference value in evaluating the efficacy of chemotherapy in patients.

Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.

Objective To explore the mechanism by which Sestrin2(SESN2)regulates autophagy activity of chondrocytes by mediating mammalian rapamycin target protein complex 1(mTORC1)signaling pathway.Methods The normal chondrocytes were treated with interleukin-1 β(IL-1β)to establish an osteoarthritis(OA)chondrocyte model,which was divided into the control group and the IL-1 β-treated group.Real-time quantitative PCR(qPCR)and Western blot were used to detect the expression levels of matrix metalloproteinase 13(MMP13),type Ⅱ collagen(COL2A1)and SESN2 in the two groups.The cell models of the chondrocyte overexpression SESN2 group and knockdown SESN2 group were obtained via cell transfection technology,and the expression levels of SESN2 in each group were detected by qPCR while those of SESN2,MMP13,COL2A1,mTORC1 pathway-related proteins and autophagy-related proteins in each group were detected by Western blot.The effects of SESN2 on cell proliferation and migration were detected by CCK-8 and cell scratch assay.Results(1)The expression level of MMP13 in the IL-1 β-treated group was significantly up-regulated,while the expression levels of COL2A1 and SESN2 were significantly decreased.(2)Compared with the control group,the expressions of p-mTORC1,ribosomal protein S6 kinase 1(S6K1),and MMP13 protein in OA chondrocytes in the overexpression group were significantly down-regulated,while the expressions of adenosine 5'-monophosphate(AMP)-activated protein kinase(AMPK)and chondroprotective gene COL2A1 were significantly increased,and the expression level of Beclin-1 and the ratio of microtubule associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)/(LC3-Ⅰ)were increased.Meanwhile,overexpression of SESN2 could up-regulate the proliferation and migration of chondrocytes,but the results were opposite after knockdown of SESN2.Conclusion SESN2 can enhance autophagy,proliferation and migration of chondrocytes by inhibiting mTORC1 pathway,which has provided data for revealing the pathogenesis of OA and exploring new therapeutic methods.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases. However, the role of endothelial dysfunction in pulmonary fibrosis (PF) is incompletely understood. Sphingosine-1-phosphate receptor 1 (S1PR1) is a G protein-coupled receptor highly expressed in lung ECs. Its expression is markedly reduced in patients with IPF. Herein, we generated an endothelial-conditional S1pr1 knockout mouse model which exhibited inflammation and fibrosis with or without bleomycin (BLM) challenge. Selective activation of S1PR1 with an S1PR1 agonist, IMMH002, exerted a potent therapeutic effect in mice with bleomycin-induced fibrosis by protecting the integrity of the endothelial barrier. These results suggest that S1PR1 might be a promising drug target for IPF therapy.

The Omicron family of SARS-CoV-2 variants are currently driving the COVID-19 pandemic. Here we analyzed the clinical laboratory test results of 9911 Omicron BA.2.2 sublineages-infected symptomatic patients without earlier infection histories during a SARS-CoV-2 outbreak in Shanghai in spring 2022. Compared to an earlier patient cohort infected by SARS-CoV-2 prototype strains in 2020, BA.2.2 infection led to distinct fluctuations of pathophysiological markers in the peripheral blood. In particular, severe/critical cases of COVID-19 post BA.2.2 infection were associated with less pro-inflammatory macrophage activation and stronger interferon alpha response in the bronchoalveolar microenvironment. Importantly, the abnormal biomarkers were significantly subdued in individuals who had been immunized by 2 or 3 doses of SARS-CoV-2 prototype-inactivated vaccines, supporting the estimation of an overall 96.02% of protection rate against severe/critical disease in the 4854 cases in our BA.2.2 patient cohort with traceable vaccination records. Furthermore, even though age was a critical risk factor of the severity of COVID-19 post BA.2.2 infection, vaccination-elicited protection against severe/critical COVID-19 reached 90.15% in patients aged ≽ 60 years old. Together, our study delineates the pathophysiological features of Omicron BA.2.2 sublineages and demonstrates significant protection conferred by prior prototype-based inactivated vaccines.
Humans ; Aged ; Middle Aged ; COVID-19/prevention & control* ; SARS-CoV-2 ; Pandemics/prevention & control* ; China/epidemiology* ; Disease Outbreaks/prevention & control* ; Vaccination

Objective:To explore the team construction and treatment strategy of the Diabetic Foot-Multidisciplinary Team.Methods:The clinical data of 19 patients with severe ischemic diabetic foot treated by our Diabetic Foot-Multidisciplinary Team Center from Apr 2021 to Mar 2022 were collected, and the overall amputation rate, above-ankle major amputation rate, minor amputation rate and mortality, Diabetic Foot-Multidisciplinary Team consultation discipline participation rate and treatment participation degree were retrospectively analyzed.Results:Nineteen patients (15 males and 4 females) were enrolled, aged 26 to 94 (68.6±14.2). All were with severe ischemic diabetic foot ulcer:Rutherford grade 5 or up and dysfunction in 2 or more organs. Complications included arteriosclerosis obliterans of the lower extremities in 18 cases, heart diseases in 18, hypertension in 15, and renal insufficiencies in 10. The overall amputation rate was 36.8%, major amputation rate in 21.1%, minor amputation rate in 15.8%, and mortality rate was 15.8%. A total of 16 disciplines participated in Diabetic Foot-Multidisciplinary Team; the main participating disciplines were vascular surgery (19 times), endocrinology (12 times), and cardiology (11 times). The main treatment disciplines were vascular surgery (14 times), plastic surgery (3 times), and cardiology (2 times).Conclusion:For the diagnosis and treatment of diabetic foot, it is necessary to set up a multidisciplinary team as early as possible to control the causes of diabetic foot ulcer, prevent the recurrence of diabetic foot ulcer, reduce the mortality and amputation rate, and improve the quality of life of patients.

The reform on the outpatient coordination of Employee Medical Insurance is very important in the field of medical secu-rity.It sorts out the design of outpatient treatment in areas where general outpatient coordination has been carried out before the na-tional reform of outpatient security launched in 2021,summarizes the institutional design and main characteristics of"two lines and one ratio",and provides a decision-making basis for further promoting the reform of total outpatient security in various regions.

Objective To investigate the epidemiological and pathogenic characteristics of viral diarrhea in Minhang District, Shanghai. Methods Random sampling on diarrhea was conducted in intestinal outpatient departments of 2 sentinel hospitals according to a certain sampling interval in Minhang District，Shanghai from 2014 to 2020. Real time PCR technology was used to detect Rotavirus, Norovirus, adenovirus, Astrovirus and Sapovirus in fecal samples. Results A total of 646 out of 1 839 stool specimenswere tested positive, and the positive rate was 35.13%.Five pathogenic viruses were detected , mostly norovirus (421 cases, 65.17%) followed by rotavirus (151 cases, 23.37%).The positive rate of norovirus was higher in the age group of 20- 69 years, and the positive rate of Rotavirus was higher in the age group of 0- 9 years. Conclusions Norovirus and rotavirus accounted for the majority of reported infection diarrhea cases in MinhangDistrict of Shanghai from 2014 to 2020, with significant seasonal peaks. Tailored prevention and control measures should be carried out, particularly in risk seasons.

Pathogenic microbes can induce cellular dysfunction, immune response, and cause infectious disease and other diseases including cancers. However, the cellular distributions of pathogens and their impact on host cells remain rarely explored due to the limited methods. Taking advantage of single-cell RNA-sequencing (scRNA-seq) analysis, we can assess the transcriptomic features at the single-cell level. Still, the tools used to interpret pathogens (such as viruses, bacteria, and fungi) at the single-cell level remain to be explored. Here, we introduced PathogenTrack, a python-based computational pipeline that uses unmapped scRNA-seq data to identify intracellular pathogens at the single-cell level. In addition, we established an R package named Yeskit to import, integrate, analyze, and interpret pathogen abundance and transcriptomic features in host cells. Robustness of these tools has been tested on various real and simulated scRNA-seq datasets. PathogenTrack is competitive to the state-of-the-art tools such as Viral-Track, and the first tools for identifying bacteria at the single-cell level. Using the raw data of bronchoalveolar lavage fluid samples (BALF) from COVID-19 patients in the SRA database, we found the SARS-CoV-2 virus exists in multiple cell types including epithelial cells and macrophages. SARS-CoV-2-positive neutrophils showed increased expression of genes related to type I interferon pathway and antigen presenting module. Additionally, we observed the Haemophilus parahaemolyticus in some macrophage and epithelial cells, indicating a co-infection of the bacterium in some severe cases of COVID-19. The PathogenTrack pipeline and the Yeskit package are publicly available at GitHub.
COVID-19 ; Humans ; RNA ; SARS-CoV-2/genetics* ; Single-Cell Analysis/methods* ; Transcriptome