[摘 要] 嵌合抗原受体基因修饰T（CAR-T）细胞免疫治疗被认为是最有前景的肿瘤治疗方法之一，效应CAR-T细胞的数量是决定CAR-T细胞疗法治疗效果的关键因素。CAR-T细胞的体外扩增耗时耗力，回输体内后，CAR-T细胞大量耗竭且难以浸润实体瘤，导致能有效抑制实体瘤的CAR-T细胞数量大幅下降。目前，CAR-T细胞的扩增方法在提高扩增特异性和治疗安全性等方面均存在问题，为CAR-T细胞疗法的临床转化造成困难。近年来，新型免疫激动剂及其下游信号的发现为CAR-T细胞扩增方案提供了更多选择，免疫激动剂给药方式的更新迭代进一步提高了其在体内扩增CAR-T细胞的安全性。本文分析了目前扩增CAR-T细胞面临的挑战，系统阐述了近年来在体内外扩增CAR-T细胞的新策略，为CAR-T细胞疗法的疗效和产能优化提供了新思路。

Objective To explore the postoperative characteristics and management experience of patients with coronavirus disease 2019 (COVID-19) undergoing cardiac and vascular surgery. Methods From December 7, 2022 to January 5, 2023, the patients with COVID-19 who were admitted to Cardiovascular Hospital Affiliated to Kunming Medical University and underwent cardiac and vascular surgery were selected. The clinical history, surgical information, postoperative recovery process and treatment plan were analyzed retrospectively. Results There were 18 patients in this group, including 11 (61.1%) males and 7 (38.9%) females, with an average age of 58.1±10.9 years. There were 7 patients of hypertension, 5 patients of diabetes, 3 patients of respiratory diseases, and 2 patient of chronic renal insufficiency. There were 5 (27.8%) patients receiving emergency operations and 13 (72.2%) elective operations. All the 18 patients underwent cardiac and vascular surgery in the period of COVID-19, and the time between the last positive nucleic acid test and the surgery was 1.50 (1.00, 6.25) days. There were 8 patients of pulmonary imaging changes, including 3 patients with chest patch shadow, 3 patients with thickened and disordered lung markings, and 2 patients with exudative changes before operation. Antiviral therapy was not adopted in all patients before operation. Three patients were complicated with viral pneumonia after operation, including 2 patients with high risk factors before operation, who developed into severe pneumonia after operation, and underwent tracheotomy. One patient with thrombus recovered after anticoagulation treatment. Another patient of mild pneumonia recovered after antiviral treatment. The other 15 patients recovered well without major complications. There was no operation-related death in the whole group. One patient died after surgery, with a mortality rate of 5.6%. Conclusion Patients with COVID-19 are at high risk of cardiac and vascular surgery, and patients with high-risk factors may rapidly progress to severe pneumonia. Patients with preoperative lung imaging changes or other basic visceral diseases should consider delaying the operation. Early antiviral combined with immunomodulation treatment for emergency surgery patients may help improve the prognosis.

Objective To explore the postoperative characteristics and management experience of patients with coronavirus disease 2019 (COVID-19) undergoing cardiac and vascular surgery. Methods From December 7, 2022 to January 5, 2023, the patients with COVID-19 who were admitted to Cardiovascular Hospital Affiliated to Kunming Medical University and underwent cardiac and vascular surgery were selected. The clinical history, surgical information, postoperative recovery process and treatment plan were analyzed retrospectively. Results There were 18 patients in this group, including 11 (61.1%) males and 7 (38.9%) females, with an average age of 58.1±10.9 years. There were 7 patients of hypertension, 5 patients of diabetes, 3 patients of respiratory diseases, and 2 patient of chronic renal insufficiency. There were 5 (27.8%) patients receiving emergency operations and 13 (72.2%) elective operations. All the 18 patients underwent cardiac and vascular surgery in the period of COVID-19, and the time between the last positive nucleic acid test and the surgery was 1.50 (1.00, 6.25) days. There were 8 patients of pulmonary imaging changes, including 3 patients with chest patch shadow, 3 patients with thickened and disordered lung markings, and 2 patients with exudative changes before operation. Antiviral therapy was not adopted in all patients before operation. Three patients were complicated with viral pneumonia after operation, including 2 patients with high risk factors before operation, who developed into severe pneumonia after operation, and underwent tracheotomy. One patient with thrombus recovered after anticoagulation treatment. Another patient of mild pneumonia recovered after antiviral treatment. The other 15 patients recovered well without major complications. There was no operation-related death in the whole group. One patient died after surgery, with a mortality rate of 5.6%. Conclusion Patients with COVID-19 are at high risk of cardiac and vascular surgery, and patients with high-risk factors may rapidly progress to severe pneumonia. Patients with preoperative lung imaging changes or other basic visceral diseases should consider delaying the operation. Early antiviral combined with immunomodulation treatment for emergency surgery patients may help improve the prognosis.

Objective To construct a MRI-based radiomics nomogram for predicting the Cyelin-Dependent Kinase Inhibitor 2A/B(CDKN 2A/B)homozygous deletion status in patients with isocitrate dehydrogenase(IDH)-mutant astrocytoma.Methods A total of 200 patients with IDH-mutant astrocytoma(103 CDKN 2A/B homozygous deletion and 97 CDKN 2A/B non-homozygous dele-tion)were enrolled in a training cohort(n=140)and a test cohort(n=60).A total of 1 946 features were respectively extracted in tumor edema area and tumor parenchyma area,and 3 892 features were extracted in overall tumor area.All features were extracted from T2 fluid attenuated inversion recovery(T2 FLAIR)and T1 WI contrast enhancement sequences.The t test and the least absolute shrinkage and selection operator(LASSO)model were used to select radiomics features,and a radiomics nomogram was constructed by using age,gen-der and the above radiomics features.Results The t test concluded that the overall tumor radiomics signature had the best perform-ance[area under the curve(AUC):training cohort=0.951,test cohort=0.779]and the radiomics nomogram had a good ability to pre-dict the CDKN 2A/B homozygous deletion in IDH-mutant astrocytoma.The clinical usefulness of the nomogram in predicting the CDKN 2A/B homozygous deletion was further confirmed by decision curve analysis(DCA).Conclusion The nomogram combined with age,gender,and the radiomics features provides a clinically useful approach to predict the CDKN 2A/B homozygous deletion and facilitated MRI-based clinical decision-making in patients with IDH-mutant astrocytoma.

Objective To investigate the correlation between salivary cystatin D level and salivary gland injury in patients with primary Sj?gren syndrome(pSS).Methods A total of 51 pSS patients admitted in the Department of Rheumatology and Immunology of the First Affiliated Hospital of Xi'an Jiaotong University from September 1,2022 to June 30,2023,and 51 age-and gender-matched healthy individuals who took physical examination in the hospital during same period were enrolled in the study.The level of salivary cystatin D was detected,and the difference in the level between the 2 groups was compared using an independent-samples t test.Pearson correlation analysis was applied to analyze the correlation between salivary cystatin D and clinical parameters in the patients.Results The pSS patients had significantly lower cystatin D level than the healthy controls(206.55±108.11 vs 374.32±172.24 pg/mL,P＜0.01).The cystatin D level in the pSS patients was positively correlated with both static(r=0.433,P=0.002)and dynamic salivary flow rates(r=0.363,P=0.009).The patients with higher score of salivary gland ultrasonography(SGUS)had obviously lower cystatin D than those with lower SGUS score(parotid gland:160.75±85.56 vs 290.53±95.17 pg/mL,P＜0.01;submandibular gland:157.76±87.59 vs 276.25±97.06 pg/mL,P＜0.01).The cystatin D level was also negatively correlated with peripheral blood IL-6 level(r=-0.453,P=0.001)and CD4+T cell count(r=-0.396,P=0.005)in the pSS patients.Conclusion Salivary cystatin D level can be used as an indicator of salivary gland damage for pSS patients.

AIM:To investigate the molecular mechanism of long noncoding RNA(lncRNA)SNHG1 in regu-lating ferroptosis to alleviate inflammation in CHME-5 human microglia induced by HIV-1 gp120 V3 loop.METHODS:CHME-5 human microglia were cultured in vitro,and were divided into 7 groups:blank group,random peptide group,gp120 V3 loop group(HIV-1 gp120 group),HIV-1 gp120+shCon group,HIV-1 gp120+SNHG1 sh2 group,HIV-1 gp120+SNHG1 sh2+ferrostatin-1(Fer-1;ferroptosis inhibitor)group,and HIV-1 gp120+SNHG1 sh2+EX527(Sirt1 in-hibitor)group.Normal CHME-5 cells were treated with random peptide or gp120 V3 loop for 24 h.After pretreatment of SNHG1 sh2 cells with inhibitors for 2 h,the cells were then treated with gp120 V3 loop for 24 h.The levels of inflammato-ry cytokines in the cell supernatants were detected by ELISA.Western blot was used to detect the protein expression levels of solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),Sirt1 and p53.Microplate reader was used to detect the levels of intracellular ferrous ion(Fe2+)and malondialdehyde(MDA).RESULTS:(1)The results of ELISA showed that the expression levels of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and IL-1β in HIV-1 gp120 group were significantly higher than those in blank group(P<0.05).Compared with HIV-1 gp120 group,the ex-pression levels of inflammatory cytokines in HIV-1 gp120+SNHG1 sh2 group were significantly decreased(P<0.05).Compared with HIV-1 gp120+SNHG1 sh2 group,the expression levels of inflammatory factors in HIV-1 gp120+SNHG1 sh2+Fer-1 were significantly decreased(P<0.05),but those in HIV-1 gp120+SNHG1 sh2+EX527 group were significant-ly increased(P<0.01).(2)The results of Western blot showed that compared with blank group,the expression levels of ferroptosis-related proteins SLC7A11 and GPX4 in HIV-1 gp120 group were significantly down-regulated(P<0.01).Com-pared with HIV-1 gp120 group,the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2 group were sig-nificantly up-regulated(P<0.01).Compared with HIV-1 gp120+SNHG1 sh2 group,the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2+Fer-1 group were significantly up-regulated(P<0.05),but the expression levels of SLC7A11 and GPX4 in HIV-1 gp120+SNHG1 sh2+EX527 group were significantly down-regulated(P<0.01),and the expression level of p53 was significantly up-regulated(P<0.05).(3)Compared with blank group,the levels of Fe2+and MDA in HIV-1 gp120 group were significantly increased(P<0.05).Compared with HIV-1 gp120 group,the levels of Fe2+and MDA in HIV-1 gp120+SNHG1 sh2 group were significantly decreased(P<0.01).Compared with HIV-1 gp120+SNHG1 sh2 group,Fe2+and MDA in HIV-1 gp120+SNHG1 sh2+Fer-1 group were significantly decreased(P<0.05),but those in HIV-1 gp120+SNHG1 sh2+EX527 group was significantly increased(P<0.05).CONCLUSION:Knockdown of SNHG1 can attenuate the inflammation in microglia induced by HIV-1 gp120 V3 loop,which may be achieved by regulating ferrop-tosis-related signaling molecules through the Sirt1/p53 signaling pathway.

Objective To analyze the clinical characteristics and genotype of a patient with congenital systemic lip-odystrophy(CGL)type 1 associated with exudative xanthoma caused by AGPAT2 gene mutation,and to provide ev-idence for clinical and genetic diagnosis of the disease.Methods Clinical data of the patient such as medical histo-ry,physical examination and laboratory examination were collected.Peripheral venous blood was collected for whole exome sequencing analysis and Sanger sequencing verification,and treatment was provided to patients according to the changes of condition.Results The clinical manifestations of the patient were subcutaneous fat reduction,fatty liver,spleen enlargement,kidney enlargement,high blood sugar and lipids,severe insulin resistance,scattered yellow rash on limbs,which was confirmed as xanthoma.The results of whole exon sequencing showed that the AGPAT2 gene of the patient had a heterozygous nonsense mutation of c.202C＞T:p.R68?and c.646A＞T:p.K216?,and the former was the pathogenic mutation site.Follow-up therapy covers improvement of lifestyle,low-fat diet and regular exercise.The rashes subsided after active lipid-lowering therapy.Conclusions Apart from typical lipody-strophy,the patient was accompanied by exanthemous xanthoma.No CGL1 patient with exanthemous xanthoma has been reported in the domestic literature database up to now,and the genetic test results showed that there was a c.202C＞T heterozygous mutation of AGPAT2 gene.This gene site has not been reported in the literature,and its functional verification needs to be further studied.

Objective:To predict and analyze the number of acute pancreatitis (AP) inpatients based on time series model, and to explore the predictive efficiency of the model.Methods:Clinical data of AP inpatients in the Affiliated Hospital of Southwest Medical University from January 2014 to December 2019 were collected. R software was used to collect the time series of AP inpatients, and the trend and seasonal characteristics of AP inpatients from 2014 to 2018 were analyzed. Furthermore, the autoregressive moving average (ARIMA) model was established through stationarity test, model ordering and model testing steps, and the best selected model was used to predict the monthly number of inpatients in 2019 to verify its prediction efficiency.Results:A total of 3 939 AP patients were included in the study. The most common etiology for AP was cholestrogenic (48.2%), followed by hyperacylglyceremia (36.3%). The peak age of hospitalization was from 40 to 60 years old. Time series analysis showed that the number of AP inpatients increased year by year. The highest peak of the disease was from February to March, followed by September to November; and there was seasonal variation and the incidence was relatively small in summer. The established original training set sequence did not pass the stationarity test ( P=0.061), so the ARIMA model was established after it was transformed into a stationarity sequence by first-order difference. According to the criterion of minimum AIC value, ARIMA(2, 1, 1)(1, 1, 1) 12 was selected as the best model. The model was used to predict the number of AP inpatients in 2019, showing that it could better fit the trend of onset time and had good short-term prediction effect. The mean root error and absolute error were 6.8790 and 4.7783, respectively. Conclusions:The number of AP inpatients increases year by year with seasonal changes. ARIMA model is effective in predicting the number of AP inpatients and can be used for short-term prediction.

ObjectiveTo investigate the effect of Chaihu Guizhitang on triple-negative breast cancer （TNBC） cells based on hypoxia-inducible factor-1α （HIF-1α）/vascular endothelial growth factor A （VEGFA） signaling pathway. MethodTNBC xenograft model was established and the cells were randomized into model group， capecitabine group （0.2 mg·kg^-1）， Chaihu Guizhitang low-dose group， medium-dose group， and high-dose group （10.62， 21.23， 42.46 g·kg^-1）， with 10 mice in each group. After 21 days of medication， the content of tumor necrosis factor-α （TNF-α） in serum was detected by enzyme-linked immunosorbent assay （ELISA）. The expression of HIF-1α mRNA was detected by real-time fluorogenic quantitative polymerase chain reaction （real-time PCR）. Immunohistochemistry （IHC） was employed to detect the expression of HIF-1α， TNF-α， and VEGFA in tumor tissues， and CD34 staining to examine the angiogenesis in tumor tissues. Microvessel density （MVD） was calculated， and the protein expression of HIF-1α， VEGFA， and epidermal growth factor receptor （EGFR） in tumor tissues was measured by Western blot. ResultCompared with the model group， the rest four groups showed low levels of TNF-α （P<0.01）， HIF-1α mRNA （P<0.01）， expression of HIF-1α， TNF-α， VEGFA， and CD34 in cells， and MVD （P<0.05， P<0.01）， and low protein levels of HIF-1α， VEGFA， and EGFR （P<0.01）. Compared with capecitabine group， medium-dose and high-dose Chaihu Guizhitang decreased the level of TNF-α （P<0.01）， HIF-1α mRNA （P<0.01）， expression of HIF-1α， TNF-α， and VEGFA in cells （P<0.01）， CD34 expression， MVD， and protein levels of HIF-1α， VEGFA， and EGFR （P<0.01）. ConclusionChaihu Guizhitang may inhibit the angiogenesis in TNBC cells by regulating the expression of HIF-1α/VEGFA signaling pathway， thus exerting anti-tumor effect.

Objective:To access the efficacy of monoenergetic imaging from spectral CT combined with metal artifact reduction for orthopedic implants (O-MAR) on reducing contrast hardening artifacts in the vein on the injection side, and determining the optimal monoenergetic spectral range to improve the display of axillary lymph node.Methods:A total of 35 patients with breast cancer who underwent chest-enhanced CT scans were enrolled in this retrospective study. The original data were reconstructed to obtain a total of 35 sets of images, including one conventional image, 17 groups of monoenergetic images, and 17 groups of monoenergetic+O-MAR images. The areas of interest were delineated in the high and low-density artifact area on the injection side of the same layer contrast agent, and the contralateral ectopectoralis. The CT value and its standard deviation (SD) were recorded respectively, the artifact area was measured, and the number of axillary lymph nodes was recorded. The difference in CT values (ΔCT 1, ΔCT 2) and the artifact index (AI1 and AI 2) of the high and low-density artifact areas relative to the contralateral ectopectoralis in the same layer were calculated respectively. Friedman test and Wilcoxon signed-rank test were used to compare the differences of ΔCT, AI, artifact area, and number of lymph nodes among the three imaging modalities, and the Kappa test was used to compare the differences in subjective evaluation. Results:As the energy level increased, compared to the conventional image, monoenergetic image, ΔCT 1 absolute value, ΔCT 2 absolute value, AI 1, and AI 2 showed a trend of initially low and then high, artifact area decreased, and the number of detected lymph nodes increased ( P<0.01). Compared to other energy levels, when the monoenergetic image was 100 keV, ΔCT 1 value, 140 keV for ΔCT 2 value, 120 keV for AI 1 value, and 130 keV for AI 2 value were close to zero, and the number of detected lymph nodes was highest at 110-200 keV. In contrast, in the monoenergetic+O-MAR images, ΔCT 1 absolute value showed a trend of initially low and then high, but, ΔCT 2 absolute value, AI 1, AI 2, and artifact area all significantly decreased, whereas the number of detected lymph nodes significantly increased (χ 2 values were 916.23, 895.93, 387.08, 519.41, 890.10, and 1027.98, respectively. All P<0.01). Compared to other energy levels, when the monoenergetic+O-MAR image was at 100 keV, ΔCT 1 value was close to zero, while ΔCT 2 value became close to zero with increasing energy level, and the number of detected lymph nodes was highest at 110-200 keV. As the energy level increased, the ΔCT 1, AI 1, AI 2, and artifact area of monoenergetic+O-MAR images were significantly smaller than those of monoenergetic images at the same energy level, and the number of detected lymph nodes was significantly higher than that of monoenergetic images ( P<0.01). The subjective scores for 110-200 keV monoenergetic images and 100-200 keV monoenergetic+O-MAR images were both higher than 4, and the score for monoenergetic+O-MAR images was significantly higher than that of single-energy spectrum images. The agreement between the two radiologists in assessing subjective scores was good. Conclusion:At 100-120 keV level, spectral CT monoenergetic combined with O-MAR imaging technique has the best performance in removing hardening-induced artifacts of chest-enhanced CT contrast agent and detecting and displaying axillary lymph nodes.