Chimeric antigen receptor (CAR)-T cell therapy has achieved remarkable success in the treatment of hematological malignancies. Based on the immunomodulatory capability of CAR-T cells, efforts have turned toward exploring their potential in treating autoimmune diseases. Bibliometric analysis of 210 records from 128 academic journals published by 372 institutions in 40 countries/regions indicates a growing number of publications on CAR-T therapy for autoimmune diseases, covering a range of subtypes such as systemic lupus erythematosus, multiple sclerosis, among others. CAR-T therapy holds promise in mitigating several shortcomings, including the indiscriminate suppression of the immune system by traditional immunosuppressants, and non-sustaining therapeutic levels of monoclonal antibodies due to inherent pharmacokinetic constraints. By persisting and proliferating in vivo, CAR-T cells can offer a tailored and precise therapeutics. This paper reviewed preclinical experiments and clinical trials involving CAR-T and CAR-related therapies in various autoimmune diseases, incorporating innovations well-studied in the field of hematological tumors, aiming to explore a safe and effective therapeutic option for relapsed/refractory autoimmune diseases.

Tetrandrine(TET),a natural bisbenzyl isoquinoline alkaloid extracted from Stephania tetrandra S.Moore,has diverse pharmacological effects.However,its effects on melanoma remain unclear.Cellular prolif-eration assays,multi-omics analyses,and xenograft models were used to determine the effect of TET on melanoma.The direct target of TET was identified using biotin-TET pull-down liquid chromatograph-mass spectrometry(LC-MS),cellular thermal shift assays,and isothermal titration calorimetry(ITC)analysis.Our findings revealed that TET treatment induced robust cellular autophagy depending on activating transcription factor 6(ATF6)-mediated endoplasmic reticulum(ER)stress.Simultaneously,it hindered autophagic flux by inducing cytoskeletal protein depolymerization in melanoma cells.TET treatment resulted in excessive accumulation of reactive oxygen species(ROS)and simultaneously triggered mitophagy.Sirtuin 5(SIRT5)was ultimately found to be a direct target of TET.Mechanistically,TET led to the degradation of SIRT5 via the ubiquitin(Ub)-26S proteasome system.SIRT5 knockdown induced ROS accumulation,whereas SIRT5 overexpression attenuated the TET-induced ROS accumula-tion and autophagy.Importantly,TET exhibited anti-cancer effects in xenograft models depending on SIRT5 expression.This study highlights the potential of TET as an antimelanoma agent that targets SIRT5.These findings provide a promising avenue for the use of TET in melanoma treatment and underscore its potential as a therapeutic candidate.

With the recent ongoing autumn/winter 2022 COVID-19 wave and the adjustment of public health control measures, there have been widespread SARS-CoV-2 infections in Chinese mainland. Here we have analyzed 369 viral genomes from recently diagnosed COVID-19 patients in Shanghai, identifying a large number of sublineages of the SARS-CoV-2 Omicron family. Phylogenetic analysis, coupled with contact history tracing, revealed simultaneous community transmission of two Omicron sublineages dominating the infections in some areas of China (BA.5.2 mainly in Guangzhou and Shanghai, and BF.7 mainly in Beijing) and two highly infectious sublineages recently imported from abroad (XBB and BQ.1). Publicly available data from August 31 to November 29, 2022 indicated an overall severe/critical case rate of 0.035% nationwide, while analysis of 5706 symptomatic patients treated at the Shanghai Public Health Center between September 1 and December 26, 2022 showed that 20 cases (0.35%) without comorbidities progressed into severe/critical conditions and 153 cases (2.68%) with COVID-19-exacerbated comorbidities progressed into severe/critical conditions. These observations shall alert healthcare providers to place more resources for the treatment of severe/critical cases. Furthermore, mathematical modeling predicts this autumn/winter wave might pass through major cities in China by the end of the year, whereas some middle and western provinces and rural areas would be hit by the upcoming infection wave in mid-to-late January 2023, and the duration and magnitude of upcoming outbreak could be dramatically enhanced by the extensive travels during the Spring Festival (January 21, 2023). Altogether, these preliminary data highlight the needs to allocate resources to early diagnosis and effective treatment of severe cases and the protection of vulnerable population, especially in the rural areas, to ensure the country's smooth exit from the ongoing pandemic and accelerate socio-economic recovery.

OBJECTIVE To investigate the effects of total glucosides of paeony （TGP） on enhancing efficacy and reducing toxicity of Tripterygium wilfordii polyglycoside （TWP） in the treatment of eczema. METHODS Totally 50 SD male rats were collected to establish eczema model by sensitizing with 2，4-dinitrofluorobenzene-acetone olive oil solution （volume ratio was 4∶1） on the abdominal area and provoking on the back and ear. Model rats were randomly divided into model group， loratadine group （0.9 mg/kg）， TWP group （9.45 mg/kg）， TGP group （162 mg/kg） and compatibility group （TWP 9.45 mg/kg+TGP 162 mg/kg）， with 10 rats in each group. Other 10 rats were collected to set as normal group. Three days after the first sensitization， administration groups were given relevant medicine intragastrically， and normal group and model group were given constant volume of 0.1% CMC-Na solution intragastrically， once a day， for consecutive 21 d. Twenty-four hours later after the final administration， the general condition of rats in each group was observed， and the eczema area and severity index （EASI） were scored； ear swelling degree of rats was measured， and the skinhistomorphology observation and pathological score were performed； protein expressions of p38 mitogen-activated 13938427612@126.com protein kinase （p38 MAPK）， phosphorylated p38 MAPK （p- MAPK） and phosphorylation level of p38 MAPK in rat skin tissue were detected； the levels of inflammatory indexes （interleukin-4， interferon- γ）， liver and kidney function indexes [glutamic-pyruvic transaminase （GPT）， glutamic-oxaloacetic transaminase （GOT）， serum creatinine （SCr） and blood urea nitrogen （BUN）] and oxidant stress indexes [total superoxide dismutase （T-SOD） and malondialdehyde （MDA）] were measured. RESULTS Compared with normal group， EASI score， ear swelling degree， pathological score， protein expressions of p38 MAPK and p-p38 MAPK， phosphorylation level of p38 MAPK， the levels of inflammatory indexes and BUN were all increased significantly in model group （P＜0.05）. Compared with model group， EASI scores， ear swelling degree， pathological scores， protein expressions of p38 MAPK and p-p38 MAPK， phosphorylation levels of p38 MAPK and levels of inflammatory indexes were all improved significantly in administration groups （P＜0.05）. The levels of GPT， GOT， SCr and BUN were increased significantly in TWP group， while the serum levels of GOT and SCr in TGP group and serum level of SCr in loratadine group were all decreased significantly （P＜0.05）. The levels of T-SOD in liver and kidney tissue were all decreased significantly in TWP group and compatibility group， while the levels of MDA were increased significantly （P＜0.05）. The compatibility group showed more obvious effect in improving the ear swelling degree， pathological score， p38 MAPK expression and its phosphorylation level and levels of inflammatory indexes， and could reverse the abnormality of liver and kidney indexes caused by TWP （P＜0.05）. CONCLUSIONS The combination of TGP and TWP has the effects of anti-inflammatory， synergistic and hepatorenal detoxification in eczema model rats. Its mechanism may be associated with down-regulating the expression of serum proinflammatory indexes and inhibiting the activation of p38 MAPK pathway.

【Objective】 To explore the application of matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) in the genotyping of difficult blood typing samples, and to provide evidence for clinical blood transfusion. 【Methods】 Three ambiguous blood group samples, submitted to Shanghai Blood Center by Shanghai regional hospitals, were studied, of which Sample1 included the proband and his parents. Serological methods were used to perform blood group typing, direct antibody test, unexpected antibody screening and identification test. Blood group genotyping was performed by using the MALDI-TOF MS detection systeme stablished in our laboratory. Sanger sequencing was used to confirm gene mutation sites, and serological or flow methods were used to verify specific samples′ phenotype. 【Results】 Serological results indicated the existence of antibodies against high frequency antigens in sample 1 (including proband and her mother), 2 and 3. The genotyping results of MALDI-TOF MS showed that the proband of sample 1 was Di(a+ b+ ), her father was Di(a-b+ ), her mother was Di(a+ b-), sample 2 was p, and sample 3 was Jr(a-). Sequencing results of three samples were consistent with mass spectrometry typing results. Serological results showed that sample 2 had a p phenotype. The flow cytometry results suggested that sample 3 had a Jr(a-) phenotype. 【Conclusion】 For the first time, we applied MALDI-TOF MS technology to blood type genotyping of ambiguous clinical samples in China. Compared with other genotyping methods such as PCR-SSP, MALDI-TOF MS has the advantages of rapid detection, high throughput and high specificity, which would contribute to identification of difficult blood typing samples in the future, as well as rare blood group screening.

OBJECTIVE To study the intervention effect of Bushen qiangshen tablet on polycystic ovary syndrome （PCOS） model rats and its mechanism . METHODS Totally 50 rats were given letrozole suspension （1 mg/kg，once a day ，for consecutive 21 d） instragastrically to induce PCOS model . Model rars were randomly divided into model group ，positive control group （Ethinylestradiol and cyproterone acetate tables 0.2 mg/kg+Metformin hydrochloride tables 230 mg/kg），Bushen qiangshen tablet low-dose，medium-dose and high -dose groups （189，378，756 mg/kg），with 10 rats in each group . Another 10 healthy rats were included in normal group . Each group was given the corresponding drugs ，once a day ，for consecutive 30 d. Twenty-four hours after the last administration ，serum levels of estrogen （E2），testosterone（T），gonadotropin-releasing hormone （GnRH），follicle- stimulating hormone （FSH）and luteinizing hormone （LH）were measured . The ovary index was calculated ，and pathological changes of ovary were observed . The protein expressions of phosphoinositide 3-kinase（PI3K），phosphorylated protein kinase B （p- Akt），phosphorylated mammalian target of rapamycin （p-mTOR）and glucose transporter 4（GLUT4）in ovary were detected ，and mRNA expressions of PI 3K，Akt，mTOR and GLUT 4 in ovary were detected . RESULTS Compared with normal group ，ovarian index and ovarian cystic disease score were significantly increased in model group （P＜0.05），and serum levels of T ，GnRH and LH were significantly increased （P＜0.05）；serum levels of FSH and E 2，protein expressions of PI 3K，p-Akt，p-mTOR and GLUT4，and mRNA expression of PI 3K，AKT，mTOR and GLUT 4 in ovarian tissue were all significantly decreased in the model group （P＜0.05）；in ovarian tissue ，the number of atresia follicles and non -cumulus cystic follicles increased ，and the number of granulosa cell layers decreased . Compared with model group ， above indexes of Bushen qiangshen tablet medium-dose and high -dose g roups were reversed significantly 86550201。E-mail：mary868@163.com （P＜0.05），and most above indexes of low -dose group were reversed significantly （P＜0.05），the pathological changes of ovarian tissue were improved to varying degrees . CONCLUSIONS Bushen qiangshen tablet can regulate the secretion of sex hormones in PCOS model rats and improve ovarian cystic lesions . Its mechanism may be related to the upregulation of PI 3K/Akt/mTOR and PI 3K/Akt/GLUT4 signaling pathways .

OBJECTIVE To investigate the effect of Compound danshen tablet s o n improving the blood lipid levels and the mechanism of protecting renal functions in hyperlipidemia model rats. METHODS Sixty male SD rats were divided into normal group，model group ，simvastatin combined with （2S）-N-[N-（3，5-difluorophenylacetyl）-L-alanyl]-2-phenylglycine tert butyl （DAPT）group and low-dose ，medium-dose and high-dose groups of Compound danshen tablets ，with 10 rats in each group. Rats in the normal group received routine diet. The other 5 groups were intraperitoneally injected with 75％ yolk emulsion 10 mL/kg， fasting and drinking freely. After 16 h，they were fed high-fat diet for 4 weeks. Simvastatin combined with DAPT group was given simvastatin 0.002 g/kg and DAPT 0.012 g/kg at the same time of modeling. The low-dose ，medium-dose and high-dose groups of Compound danshen tablets were given Compound danshen tablets 0.25，0.5 and 1 g/kg respectively at the same time of modeling ， the normal group and model group were given equal volume of distilled water ，once a day ，for 4 weeks. The serum levels of total cholesterol（TC），triglyceride（TG），creatinine（Cr）and urea nitrogen （BUN）in serum were detected by biochemical method ； kidney coefficient of rats was calculated ；histopathological changes of rat kidney were observed by HE staining ，and the renal injury was scored according to the degree of renal tubular injury and glomerular sclerosis in renal cortex ；expression levels of Notch signal receptor 1（Notch 1），Notch signal ligand 1（Jagged1）and hairy division associated enhancer 1（Hes1）in kidney were detected by immunohistochemistry ；mRNA expressions of Notch 1，Jagged1 and Hes 1 in renal tissue were detected by real-time fluorescence quantitative polymerase chain reaction. RESULTS Compared with normal group ，the serum levels of TG ， TC，Cr and BUN were increased significantly in model group （P＜0.05）；renal coefficient increased significantly （P＜0.05）； pathological changes occurred in renal tissue ，and the scores of renal tubular injury and glomerular sclerosis increased significantly （P＜0.05）；protein and mRNA expressions of Notch1， Jagged1， Hes1 in renal tissue were increased significantly（P＜0.05）. Compared with model group ，serum levels of TG ，TC，Cr and BUN ，renal coefficient ，the scores of renal tubular injury and glomerular sclerosis ，protein and mRNA expression of Notch 1，Jagged1 and Hes 1 in renal tissue were all decreased in low-dose ，medium-dose and high-dose groups of Compound danshen tablets （P＜0.05），and most indexes showed a dose-dependent trend ；the degree of renal lesions was reduced. CONCLUSIONS Compound danshen tablets possess obvious hypolipidemic effect ，and can protect the renal function of hyperlipidemia model rats by down-regulating Notch 1/Jagged1 signal pathway.

Objective:To investigate the efficacy and safety of different stents assisted embolization in the treatment of subarachnoid hemorrhage(SAH) caused by V4 dissecting aneurysm of vertebral artery.Methods:The clinical data of 39 patients with spontaneous SAH V4 dissecting aneurysm treated at the Department of Neurosurgery, the Northern Theater General Hospital from January 2016 to June 2019 were analyzed retrospectively.There were 21 males and 18 females, aged (48±17) years(range:35 to 68 years).There were 24 cases of HUNT-HESS grade Ⅰ and 15 cases of grade Ⅱ.Among them, 20 cases were treated with single stent-assisted embolization, 9 cases with multi-stent-assisted embolization, 9 cases with semi-dense mesh-assisted embolization, and 1 case with dense-mesh stent-assisted embolization.The perioperative and postoperative complications, postoperative recurrence were collected.Results:Intraoperative complications included 2 cases of aneurysm rupture and 2 cases of acute thrombosis.All aneurysms were densely packed according to the angiography performed immediately after operation.Postoperative complications included 3 cases of long-term responsible vascular ischemia(modified Rankin score<2). The patients were followed up for 15.1 months(range: 12 to 29 months). At the last follow-up, aneurysms recurrence occured in 10 cases, the recurrence rate was 25.6%(10/39). There were 6 cases of recurrence and 2 cases of complications in 20 cases with single stent-assisted embolization, 3 cases of recurrence and 4 cases of complications in 9 cases with multi-stent-assisted embolization, 1 case of recurrence and 1 case of complications in 9 cases with semi-dense mesh stent.Conclusion:Endovascular treatment is feasible for patients with vertebral artery dissecting aneurysm, and the appropriate surgical method should be selected according to the vascular structure and the location of the aneurysm.

Objective:To investigate the efficacy and safety of different stents assisted embolization in the treatment of subarachnoid hemorrhage(SAH) caused by V4 dissecting aneurysm of vertebral artery.Methods:The clinical data of 39 patients with spontaneous SAH V4 dissecting aneurysm treated at the Department of Neurosurgery, the Northern Theater General Hospital from January 2016 to June 2019 were analyzed retrospectively.There were 21 males and 18 females, aged (48±17) years(range:35 to 68 years).There were 24 cases of HUNT-HESS grade Ⅰ and 15 cases of grade Ⅱ.Among them, 20 cases were treated with single stent-assisted embolization, 9 cases with multi-stent-assisted embolization, 9 cases with semi-dense mesh-assisted embolization, and 1 case with dense-mesh stent-assisted embolization.The perioperative and postoperative complications, postoperative recurrence were collected.Results:Intraoperative complications included 2 cases of aneurysm rupture and 2 cases of acute thrombosis.All aneurysms were densely packed according to the angiography performed immediately after operation.Postoperative complications included 3 cases of long-term responsible vascular ischemia(modified Rankin score<2). The patients were followed up for 15.1 months(range: 12 to 29 months). At the last follow-up, aneurysms recurrence occured in 10 cases, the recurrence rate was 25.6%(10/39). There were 6 cases of recurrence and 2 cases of complications in 20 cases with single stent-assisted embolization, 3 cases of recurrence and 4 cases of complications in 9 cases with multi-stent-assisted embolization, 1 case of recurrence and 1 case of complications in 9 cases with semi-dense mesh stent.Conclusion:Endovascular treatment is feasible for patients with vertebral artery dissecting aneurysm, and the appropriate surgical method should be selected according to the vascular structure and the location of the aneurysm.

Objective To investigate the safety and feasibility of the modified terminal cannula ileostomy in laparoscopic anus-preserving operation of low rectal cancer (RC).Methods The retrospective cross-sectional study was conducted.The clinicopathological data of 15 patients who underwent laparoscopic radical resection of RC + terminal cannula ileostomy in the Subei People's Hospital of Jiangsu Province between September 2016 and June 2017 were collected.The patients underwent laparoscopic low anterior resection of RC,intra-abdominal sigmoid colon-rectum end-to-end anastomosis after extracting tumor specimens,and terminal cannula ileostomy in vitro.Observation indicators:(1) intraoperative situations:operation time,time of cannula ileostomy,volume of intraoperative blood loss,number of lymph node dissected,surgical margin;(2) postoperative situations:time to initial anal exsufflation,recovery time of defecation,time of tube removal,closing time of stoma,postoperative complications,duration of hospital stay;(3) follow-up situations.Follow-up using outpatient examination and telephone interview was performed to detect the anastomotic leakage-related complications up to December 2017.Measurement data with normal distribution were represented as (x)±s.Results (1) Intraoperative situations:all the 15 patients underwent successful laparoscopic radical resection of RC + terminal cannula ileostomy,without conversion to open surgery and death.The operation time,time of cannula ileostomy,volume of intraoperative blood loss and number of lymph node dissected were respectively (170 ± 34) minutes,(23 ± 4) minutes,(59 ± 27)mL and (13 ± 5) per case.No residual cancer cells were found in resection margins.(2) Postoperative situations:time to initial anal exsufflation and recovery time of defecation in 15 patients were respectively (6± 1) days and (7 ± 1) days.The stoma was automatically closed after tube removal,and time of tube removal and closing time of stoma after tube removal were respectively (23 ± 2) days and (3 ± 1) days.The incidence of postoperative complications was 1/15.One patient with catheterization-related complications was improved by strengthening dressing and antibiotic use,and the stoma was healed at 8 days after tube removal.There was no anastomotic leakage-related complications and death.The duration of hospital stay was (15±3) days.(3) Followup situations:all the 15 patients were followed up for 6-12 months.During the follow-up,there were no anastomotic leakage-related complications and death.Conclusion The modifyied terminal cannula ileostomy is safe and feasible,and is also an ideal surgical method for preventing anastomotic leakage in the laparoscopic anuspreserving operation of low RC.