Myelodysplastic syndrome (MDS), a myeloid tumor derived from the malignant clones of hematopoietic stem cells, has an annually increasing incidence. The contemporary research direction has shifted to analyzing the synergistic effect of immune surveillance collapse and abnormal bone marrow microenvironment in the pathological process of MDS. Against this backdrop, the immune checkpoint molecule TIM3 has emerged as a key target because of its persistently high expression on the surface of important immune cells such as T and NK cells. The abnormal activation of the TIM3 pathway is the mechanism by which solid tumors and hematological malignancies achieve immune escape and is a key hub in the formation of immune exhaustion phenotypes. This work integrates the original discoveries of our team with the latest international progress, systematically demonstrating the bidirectional regulatory network of TIM3 between the malignant clone proliferation of MDS and the immunosuppressive microenvironment. Integrating the evidence from emerging clinical trials allows us to consider the clinical significance of TIM3-targeted blocking for MDS, providing a transformative path to overcome the resistance of traditional treatments and marking a new chapter in the active immune reconstitution of MDS treatment.

ObjectiveTo evaluate the clinical efficacy and safety of Tongluo Mingmu capsules in the treatment of diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome. MethodA randomized， double-blind， positive-control， and multi-center clinical trial design method was used. 416 patients with diabetic retinopathy with blood stasis， collateral obstruction， and Qi and Yin deficiency syndrome in four test centers were included （the ratio of the treatment group to the control group was 3∶1）. On the basis of standardized hypoglycemic treatment， the treatment group was given both four Tongluo Mingmu capsules and two Calcium Dobesilate capsule agents three times a day， while the control group were given both two Calcium Dobesilate capsules and four Tongluo Mingmu capsule agents three times a day. The course of treatment was 12 weeks. The curative effect of Tongluo Mingmu capsules was evaluated by comparing the comprehensive curative effect of diabetic retinopathy， traditional Chinese medicine（TCM） syndrome score， corrected visual acuity， fundus changes， fundus fluorescence angiography， and other curative effect indexes before and after treatment in the two groups. At the same time， general examination， laboratory examination， and adverse events were performed to evaluate the safety of the drug. ResultThe baseline demographic data and disease characteristics of the treatment group and the control group were balanced and comparable， with the difference not statistically significant. After 12 weeks of treatment， the total effective rate of the comprehensive curative effect of diabetic retinopathy in the treatment group （61.0%， 189/310） was better than that in the control group （44.1%， 45/102）， and the difference was statistically significant （χ²=8.880， P<0.01）. The total effective rate of TCM syndromes in the treatment group （88.4%， 259/293） was better than that in the control group （69.9%， 65/93）， and the difference was statistically significant （χ²=17.927， P<0.01）. The disappearance rate of dry eyes （χ²=8.305）， dull complexion （χ²=4.053）， lassitude （χ²=10.267）， shortness of breath （χ²=8.494）， and dry stool （χ²=8.657） in the treatment group was higher than that in the control group， and the difference between the groups was statistically significant （P<0.05， P<0.01）. In terms of improving corrected visual acuity （χ²=8.382）， fundus changes （χ²=6.026） ， the treatment group was significantly better than the control group （P<0.05）. During the trial， the incidence of adverse events in the treatment group and the control group was 1.3% and 2.9%， respectively. There was no significant difference between the two groups. In addition， there were no serious adverse events and adverse events leading to withdrawal in both groups. ConclusionTongluo Mingmu capsules can improve the comprehensive curative effect of diabetic retinopathy and enhance the efficacy of TCM syndromes， visual acuity， fundus changes， and fundus fluorescein angiography， with great safety. Therefore， it can provide a new alternative therapeutic drug for patients with diabetic retinopathy.

Objective To explore the application value of ultrasound-guided use of bupivacaine for subarachnoid block in hip replacement surgery for elderly femoral neck fractures.Methods A total of 108 elderly patients who underwent hip replacement surgery at Ganzhou Traditional Chinese Medicine Hospital from March 2020 to March 2022 were selected as the study subjects.They were divided into conventional anesthesia group and ultrasound guided anesthesia group by means of random number table,54 cases in each group.Patients in the conventional anesthesia group received routine general anesthesia;Patients in the ultrasound guided anesthesia group received unilateral lumbar anesthesia with bupivacaine under ultrasound-guided guidance.Compare the effectiveness of two anesthesia methods during surgery.Results Compared with the conventional anesthesia group,the anesthesia effect of the ultrasound guided anesthesia group was better(P<0.05);The surgery time,amount of bleeding during surgery,postoperative recovery time,and length of hospital stay in the ultrasound guided anesthesia group were all lower than those in the conventional anesthesia group(P<0.05).The ultrasound guided anesthesia group performed better in terms of hemodynamic stability,with a smaller range of changes,and significantly lower pain scores at different postoperative time points compared to the conventional anesthesia group(P<0.05).Conclusion In elderly patients undergoing hip replacement surgery,using ultrasound-guided bupivacaine for subarachnoid block can achieve ideal anesthesia and analgesic effects compared to traditional general anesthesia,shorten drug onset time,alleviate pain in elderly patients,maintain hemodynamic stability,and have significant clinical application effects.

Objective To analyze the effect of circLRP6 on high glucose-induced renal tubular epithelial cell injury via miR-31-5p/high mobility group protein A1(HMGA1)axis regulation.Methods Human renal tubular epithelial HK-2 cells were cultured in vitro and divided into eight groups:control,high glucose,high glucose+si-NC,high glucose+si-circLRP6,high glucose+si-circLRP6+miR-NC,high glucose+si-circLRP6+miR-31-5p inhibitor,high glucose+si-circLRP6+miR-31-5p inhibitor+si-NC,and high glucose+si-circ-LRP6+ miR-31-5p inhibitor+si-HMGA1.The circLRP6,miR-31-5p,and HMGA1 mRNA levels were determined using real-time quantitative PCR.Cell supernatant IL-6 and tumor necrosis factor-α(TNF-α)levels,lactate dehydrogenase(LDH)activity,and malondialdehyde(MDA)content were also determined.Furthermore,flow cytometry was used to observe cell apoptosis.HMGA1,Bax,and Bcl-2 protein expression was detected by Western blotting.Finally,dual luciferase assay was used to report the targeting relationship of miR-31-5p with circLRP6 and HMGA1.Results Compared with the high glucose group,the HK-2 cell proliferation inhibition rate;cell superserum IL-6,TNF-α,LDH,and MDA levels;apoptosis rate;and Bax protein expression in the high glucose+si-circLRP6 group decreased significantly,whereas Bcl-2 protein expression increased significantly(all P＜0.05).Consequently,miR-31-5p downregulation possibly weakened the protective effect of si-circLRP6 on high glucose-induced renal tubular epithelial cell injury.HMGA1 expression inhibition reversed the effect of the si-circLRP6+miR-31-5p inhibitor on high glucose-induced renal tubular epithelial cell injury.Finally,miR-31-5p exhibited a targeting relationship with circLRP6 and HMGA1.Conclusion Si-circLRP6 protects high glucose-induced renal tubular epithelial cell injury via miR-31-5p upregulation and HMGA1 expression inhibition.

Objective:To study the effects and potential mechanisms of the combination of dihydroartemisinin and carfilzomib on the activity, proliferation, and apoptosis of multiple myeloma ARD cell lines.Methods:In vitro cultivation of multiple myeloma ARD cells involved treating the cells with dihydroartemisinin at concentrations of 0, 5, 10, 20, 40, and 80 μg/ml, and with carfilzomib at concentrations of 0, 5, 10, 20, 40, and 80 nmol/L. The ARD cells were divided into a control group (no treatment) , a dihydroartemisinin group (2 μg/ml) , a carfizomib group (8 nmol/L) , and a combination group (dihydroartemisinin 2 μg/ml + carfizomib 8 nmol/L) . Cell activity and proliferation were assessed by MTT assay and EdU-488 assay; cell apoptosis was evaluated using live cell/dead cell dual staining and flow cytometry. The expression levels of apoptosis-related proteins were examined using Western blotting analysis. Results:The cell survival rates of ARD cells treated with 0, 5, 10, 20, 40, and 80 μg/ml dihydroartemisinin were (100.00±2.18) %, (50.22±3.09) %, (37.39±2.34) %, (30.42±1.79) %, (23.80±1.12) %, and (18.04±0.79) %, respectively, and there was a statistically significant difference ( F=653.30, P<0.001) . With the increase of drug concentration, ARD cell activity decreased gradually (all P<0.05) . The cell survival rates of ARD cells treated with 0, 5, 10, 20, 40, and 80 nmol/L carfilzomib were (100.00±1.12) %, (83.98±2.95) %, (67.27±2.10) %, (58.24±2.02) %, (46.34±1.14) %, and (37.47±1.36) %, respectively, and there was a statistically significant difference ( F=227.40, P<0.001) . With the increase of drug concentration, ARD cell activity decreased gradually (all P<0.05) . The cell survival rates for the control group, dihydroartemisinin group, carfilzomib group, and combination group were (100.00±2.67) %, (67.23±0.57) %, (76.23±2.83) %, and (27.06±1.09) %, respectively, and there was a statistically significant difference ( F=655.60, P<0.001) . There were statistically significant differences in the dihydroartemisinin group, carfilzomib group, and combination group compared with control group (all P<0.001) . There were statistically significant differences in the dihydroartemisinin group and carfilzomib group compared with combined group (both P<0.001) . The EdU-488 experiment showed that the EdU-positive rates of ARD cells in the control group, dihydroartemisinin group, carfilzomib group, and combination group were (100.00±8.17) %, (68.07±6.14) %, (85.04±2.78) %, and (19.62±3.83) %, respectively, and there was a statistically significant difference ( F=115.20, P<0.001) . There were statistically significant differences in the dihydroartemisinin group, carfilzomib group, and combination group compared with control group ( P<0.001; P=0.047; P<0.001) . There were statistically significant differences in the dihydroartemisinin group and carfilzomib group compared with combined group (both P<0.001) . The live cell/dead cell dual staining experiment showed, under bright-field observation, the cell morphology was intact in the control group. In all the drug groups, the cell morphology became irregular, reduced in size with condensed cytoplasmic, and apoptotic vesicles with irregular morphology were seen around the cells, among which the most obvious changes were seen in the combination group. Under fluorescence observation, the cells in the control group only displayed green fluorescence. In all drug-treated groups, cells with red fluorescence were observed, with the combination group having the highest percentage of cells with red fluorescence among the total cell population. The apoptosis rates for the control group, dihydroartemisinin group, carfilzomib group, and combination group were (9.06±2.95) %, (29.50±1.34) %, (20.77±3.00) %, and (58.23±5.13) %, respectively, and there was a statistically significant difference ( F=115.80, P<0.001) . There were statistically significant differences in the dihydroartemisinin group, carfilzomib group, and combination group compared with control group ( P<0.001; P=0.012; P<0.001) . There were statistically significant differences in the dihydroartemisinin group and carfilzomib group compared with combined group (both P<0.001) . There were statistically significant differences in the relative expression levels of P53, Cleaved-Caspase-3, Bcl-2, and Bax proteins among the control group, dihydroartemisinin group, carfilzomib group, and combination group ( F=21.76, P<0.001; F=42.87, P<0.001; F=44.27, P<0.001; F=163.50, P<0.001) . There were statistically significant differences in the dihydroartemisinin group, carfilzomib group, and combination group compared with control group (all P<0.05) . There were statistically significant differences in the dihydroartemisinin group and carfilzomib group compared with combined group (both P<0.05) . Conclusion:The combination of dihydroartemisinin and carfilzomib can synergistically inhibit the activity and proliferation of multiple myeloma ARD cells, and promote apoptosis, and the underlying mechanism may be associated with the mitochondrial apoptosis pathway.

Objective:To analyze the differentially expressed genes (DEGs) in visceral adipose tissue of patients with type 2 diabetes mellitus (T2DM) based on bioinformatics.Methods:The microarray dataset GSE78721 was downloaded from the Gene Expression Omnibus (GEO) database, including visceral fat samples data from 19 T2DM patients and 16 non-diabetic subjects. The analysis of transcriptomic profiling results from tissue samples was conducted, and a comparison between different groups of samples based on gender was performed. The online Xintao Academic Database was utilized for the analysis, employing the "limma" package in R language to filter DEGs. Subsequently, the DEGs were visualized, and Gene Ontology (GO) functional annotation along with Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were carried out and visualized. Based on the Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database, a protein-protein interaction network (PPI) of DEGs was constructed and key differentially expressed genes were identified and visualized using Cytoscape software.Results:Analysis of visceral adipose tissue gene expression profiles revealed 168 DEGs (|log 2FC|≥1, P<0.05). In females, 42 mRNAs were up-regulated, 3 were down-regulated; in males, 105 were up-regulated, 37 were down-regulated, 19 genes were shared by the two groups. GO analysis linked DEGs to insulin-like growth factor receptor signaling and regulation, nutrient response, and leukocyte migration. KEGG analysis implicated extracellular matrix receptor interactions and leukocyte transendothelial migration. The PPI network unveiled 10 key genes, including COL1A1, COL1A2, TGFB3, PCOLCE, TIMP1, COL6A2, COMP, COL14A1, VCAM1 and THY1. Conclusion:Bioinformatics technology can effectively analyze and screen DEGs in visceral adipose tissue of T2DM patients, providing useful clues for further exploring its molecular mechanism and finding therapeutic targets.

Objective:To compare the efficacy and impact on the quality of life of elderly patients of minimally invasive percutaneous nephrolithotomy(MPCNL)and retrograde intrarenal surgery(RIRS)in the treatment of unilateral upper ureteral calculi larger than 1.0 cm in diameter.Methods:A total of 104 patients were prospectively collected from January 2021 to December 2022 in the First Hospital of Shanxi Medical University.Based on the inclusion and exclusion criteria, 88 patients were finally included, 32 patients in the MPCNL group and 56 patients in the RIRS group, and the independent samples t-test, χ2 test, or Fisher's exact probability method were used to compare the differences in the general information, stone characteristics, and intraoperative and postoperative indexes between the two groups, and the quality-of-life scores were applied with the SF-36 Health Survey form. Results:There were no significant differences in age[(67.52±7.41)years and(67.38±7.25)years], gender[male/female: 19/13 cases and 36/20 cases], body mass index[(23.74±2.93)kg/m 2 and(23.70±2.57)], stone location(left/right: 20/12 cases and 38/18 cases), degree of hydronephrosis(mild/moderate/severe: 9/20/3 cases and 16/38/2 cases), stone maximum diameter[(14.12±3.69)mm and(13.34±2.99)mm], stone CT values[(1 035.7±275.7)HU and(973.3±253.8)HU]and postoperative complications[15.6%(5/32)and 14.3%(8/56)]between the two groups of patients( P>0.05).However, there were significant difference in stone clearance rate[96.9%(31/32) vs.80.4%(45/56)], and the operation time[(44.44±9.91)min vs.(54.69±11.94)min]between the two groups.The hospital stay in the RIRS group was shorter than that in the MPCNL group[(5.27±2.27)d vs.(8.00±2.19)d, P<0.05].There was no significant difference in the scores of eight dimensions between the two groups before surgery( P<0.05).At the day of discharge, patients in the MPCNL group had significantly lower mean scores than the RIRS group on six different subscales of the SF-36 questionnaire, namely, physical functioning, role-physical, bodily pain, social functioning, role-emotional and mental health.No differences in the mean scores for general health and vitality between the two groups were noted.In terms of SF-36 scores at one month after operation, the MPCNL group had lower scores in physical pain and social function than the RIRS group and the difference was statistically significant( P<0.05).No differences in the mean scores for other domains at one month after operation between patients undergoing MPCNL and those undergoing RIRS were noted. Conclusions:For patients with unilateral upper ureteral calculi larger than 1.0 cm in diameter, MPCNL has higher stone-free rate and shorter operation time than RIRS, but longer hospitalization time, and MPCNL has a greater impact on the quality of life of patients with ureteral calculi than RIRS in many aspects.

Actinomycosis is a rare chronic granulomatous disease characterized by granuloma formation and tissue fibrosis with sinus tracts,often misdiagnosed due to its similarity to many infectious and non-infectious diseases.This report presents a case of a 60-year-old female with more than 10 years history of rheumatoid arthritis who developed actinomycosis infection after long-term treatment with immunosuppressants and biologics,including methotrexate,leflunomide,and infliximab,leading to recurrent joint pain,poorly controlled rheumatoid arthritis activity,and persistent elevation of white blood cell counts.Abdominal CT revealed a pelvic mass and right ureteral dilation.Pathological examination of cervical tissue showed significant neutrophil infiltration and sulfur granules,indicating actinomycosis.The patient received 18 months of doxycycline treatment for the infection and continued rheumatoid arthritis therapy with leflunomide,hydroxychloroquine sulfate,and tofacitinib,resulting in improved joint symptoms and normalized white blood cell counts.After 2 years of follow-up,the patient remained stable with no recurrence.This case highlights the importance of clinicians being vigilant for infections,particularly chronic,occult infections from rare pathogens,in rheumatoid arthritis patients on potent immunosuppressants and biologics,advocating for early screening and diagnosis.

Objective To explore the effect of circFAT1 on myocardial injury in rats with diabetic cardiomyopathy(DCM)and the regu-latory mechanism of circFAT1 on the miR-211-5p/CCND2 axis.Methods A DCM rat model was established by injecting rats with high glucose and high fat feed combined with STZ.The rats were randomly separated into DCM,circ-NC,circFAT1,circFAT1+agomir-NC,and circFAT1+miR-211-5p agomir groups,with 20 rats in each group;rats fed regular feed were used as control.Real-time PCR was used to detect the levels of circFAT1,miR-211-5p,and CCND2in myocardial tissue and Western blotting was used to detect CCND2 expression in myocardial tissue.The levels of fasting blood glucose(FBG),total cholesterol(TC),and triglycerides(TG)of rats were recorded.Car-diac ultrasound was used to detect the cardiac function of rats.Furthermore,HE and Masson staining were used to observe the pathological morphology of myocardial tissue and TUNEL staining was used to detect myocardial apoptosis.Additionally,ELISA was used to detect the levels of interleukin-1β(IL-1β),IL-6,and tumor necrosis factor-α(TNF-α).Double luciferase reporter gene assay was used to verify the targeting relationship among circFAT1,miR-211-5p,and CCND2.Results Compared with the control group,the expression of circFAT1 and CCND2mRNA and protein and the levels of LVEF and LVFS decreased in the DCM group(P<0.05)whereas,the levels of FBG,TC,TG,LVEDd,LVEDs,CVF,cell apoptosis rate,IL-1β,IL-6,and TNF-αincreased(P<0.05).Compared with the DCM group,the levels of circFAT1,CCND2mRNA and protein,LVEF,and LVFS increased in the circFAT1 group(P<0.05),whereas the levels of FBG,TC,TG,LVEDd,LVEDs,CVF,cell apoptosis rate,IL-1β,IL-6,and TNF-α decreased(P<0.05).Furthermore,miR-211-5p agomir reversed the protective effect of circFAT1 on DCM myocardial injury,and the expression of CCND2mRNA and protein decreased(P<0.05).Conclu-sion circFAT1 alleviates myocardial tissue damage in rats with DCM by regulating the miR-211-5p/CCND2 axis.

Objective:To investigate the per capita expenses of physical examination and its related factors in health examination (management) institutions in 2019.Methods:Using the census method, the basic information, including the name, address, nature, level and operation nature of the institutions, and per capita expenses of physical examination in provincial health examination (management) institutions in 2019 were collected by questionnaire survey. Rank sum test and Spearman correlation analysis were used to analyze the data.Results:In 2019, the top three provinces in terms of per capita expenses of physical examination were Shanghai, Inner Mongolia Autonomous Region and Beijing, with 612.00 yuan, 547.90 yuan and 528.83 yuan, respectively; Guizhou Province, Xinjiang Uygur Autonomous Region and Guangdong Province ranked the last three, with 255.25 yuan, 244.00 yuan and 235.10 yuan, respectively. There were significant differences in per capita expenses of physical examination among different health examination (management) institutions in different regions and of different institutional nature, institutional level and business nature (all P<0.05). The per capita expenses of physical examination was positively correlated with the local per capita health care expenditure, the proportion of local population aged 15-64 years and the proportion of local people with education of college and above ( r=0.465, 0.374 and 0.401, all P<0.05). Conclusions:There are differences in the per capita expenses of physical examination in health examination (management) institutions among different regions, institutional nature, institutional level and business nature in 2019, and it is related to the per capita health care expenditure, age and educational level of the local people.