OBJECTIVE To investigate the application and influencing factors of sodium-dependent glucose transporters 2 inhibitors（SGLT-2i） in patients with heart failure with preserved ejection fraction（HFpEF） in the real world. METHODS Data from 358 patients with HFpEF who were hospitalized at the First Affiliated Hospital of Chongqing Medical University from May 2023 to May 2024 were retrospectively collected. The patients were divided into the SGLT-2i group and the non-SGLT-2i group based on whether they were prescribed SGLT-2i upon discharge. Baseline characteristics， comorbidities， and differences in drug treatment were compared between the two groups. Based on univariate analysis， multivariate Logistic regression analysis was performed to identify independent influencing factors of SGLT-2i use in patients with HFpEF， followed by further stratified analysis. RESULTS Among 358 HFpEF patients， the overall utilization rate of SGLT-2i was 33.5%. Combined with type 2 diabetes [OR＝9.063，95%CI（4.924-16.679） ] ， atrial fibrillation [OR＝3.135，95%CI（1.590-6.178） ] ， coronary artery heart disease [OR＝1.888，95%CI（1.072-3.327） ] and the use of loop diuretics [OR＝3.822， 95%CI （1.588-9.200） ] were all independent influencing factors for the use of SGLT-2i in patients with HFpEF （ P ＜0.05）. The results of the stratified descriptive analysis were consistent with those of the multivariate analysis， showing a higher utilization rate of SGLT-2i among patients with concomitant T2DM，atrial fibrillation， coronary artery heart disease， and those receiving loop diuretics （ P ＜0.05）； whereas the utilization rate of SGLT-2i was comparable across patients with different levels of renal function （ P ＞0.05）. CONCLUSIONS In the real-world clinical practice， the utilization of SGLT-2i in patients with HFpEF remains suboptimal， and treatment coverage still needs to be improved. Their use of SGLT-2i is primarily influenced by the presence of type 2 diabetes， atrial fibrillation， coronary artery heart disease， and the use of loop diuretics.

Objective To longitudinally investigate the characteristics of postoperative weight changes in patients with esophageal cancer and analyze its influencing factors, which can provide certain guidance for nutritional intervention in patients with esophageal cancer. Methods Patients with esophageal cancer who underwent surgical treatment at the Sichuan Cancer Hospital from December 2020 to February 2022 were prospectively included. The general information questionnaire and body composition analyzer were used to longitudinally investigate the patients’ weight and body composition before surgery (T0), 1 month after surgery (T1), 3 months after surgery (T2) and 6 months after surgery (T3), and the change characteristics were analyzed. The generalized estimating equation was used to analyze the influencing factors for postoperative weight changes in patients with esophageal cancer. Results A total of 130 patients were enrolled, including 110 males and 20 females, aged 42-79 (63.33±8.16) years. The weight and body composition of patients with esophageal cancer showed a continuous slow downward trend within 6 months after surgery. The weight loss rate of patients at 1, 3, and 6 months after surgery was 5.10%, 7.76%, and 9.86%, respectively. The analysis results of the influencing factors for postoperative weight showed that patients with the following characteristics had more weight loss: female (β=−7.703, P=0.001), ≥60 years (β=−3.657, P=0.010), smoking (β=4.622, P=0.010), low tumor differentiation degree (β=4.314, P=0.039), and high frequency of eating (β=−3.400, P=0.008). Conclusion Weight loss is an important health problem for patients with esophageal cancer after surgery, and patients have a continuous downward trend in weight within 6 months after surgery. Medical staff should pay special attention to the patients who are female, ≥60 years, having smoking history and low tumor differentiation degree.

ObjectiveTo investigate the reversal effect of Cordyceps sinensis extract on immunotherapy resistance of non-small cell lung cancer （NSCLC）. MethodsELISA， flow cytometry， and co-culture assays were performed to evaluate the effects of Cordyceps sinensis extract on cytokine secretion， proliferation， and tumor cell killing activity of Jurkat （JKT） cells. Furthermore， the therapeutic effect of Cordyceps sinensis extract on programmed cell death ligand 1 （PD-L1） resistant lung cancer was evaluated through in vivo experiments both alone and in combination with anti-PD-L1 monoclonal antibody. ResultsCordyceps sinensis extract enhanced the secretion of cytokines interferon gamma（IFN-γ）， tumor necrosis factor-alpha（TNF-α） and interleukin-2 （IL-2）in JKT cells， promoted cell proliferation （P=0.006）， and boosted their killing function against tumors （P＜0.001）. Compared with the control group， in vivo study demonstrated that Cordyceps sinensis extract monotherapy effectively inhibited the growth of PD-L1-resistant tumors ［tumor growth inhibition value （TGI）=26.1%， P=0.090］， while its combination with anti-PD-L1 antibody significantly reversed PD-L1 resistance （TGI=50.6%， P＜0.001）. ConclusionThis study provides certain data support for the activation of anti-tumor immunity by Cordyceps sinensis extract， and offers a new treatment strategy for enhancing anti-tumor immunity and reversing immune resistance in lung cancer.

Objective:To investigate alterations in the immune lineage of T-cell large granular lymphocytic leukemia (T-LGLL) at the single-cell transcriptome level and to elucidate its pathogenic mechanisms.Methods:Peripheral blood samples were collected from 5 T-LGLL patients before and after treatment (from June 2019 to December 2020) and 3 healthy controls at the Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC. Single-cell transcriptome sequencing libraries were prepared and sequenced using 10× Genomics technology. Differentially expressed genes in immune cells were compared between patients and healthy donors, followed by pathway enrichment analyses.Results:Profiling 67,237 immune cells revealed that, in T-LGLL: 1) Effector CD8+ T cells exhibited increased numbers, enhanced cytotoxicity, and greater proliferative capacity. Following effective immunosuppressive therapy, both the proliferative capacity and effector functions of these cells significantly decreased ( P<0.05). 2) The proportion of regulatory T (Treg) cells was reduced, accompanied by increased apoptosis. After effective immunosuppressive therapy leading to remission, Treg cell proportions increased, and apoptotic pathways were downregulated ( P<0.05). 3) Antigen-presenting cells (APCs) showed enhanced functionality. Monocytes and dendritic cells were enriched in antigen synthesis and presentation pathways, while B cells displayed increased antigen-binding capacity and were enriched in pathways related to T-cell activation ( P<0.05). 4) Natural killer (NK) cells exhibited attenuated cytotoxic function but demonstrated an enhanced regulatory capacity over T cells ( P<0.05) . Conclusions:T-LGLL patients present a characteristic immunological profile marked by an imbalance in immune homeostasis. This profile includes abnormal activation and expansion of effector CD8 + T cells, and a reduction in Treg cell numbers accompanied by functional impairment. Furthermore, APCs and NK cells were found to positively regulate T-lymphocyte activation, differentiation, and proliferation.

Objective:To evaluate the efficacy of cyclophosphamide in patients with T-cell large granular lymphocytic leukemia (T-LGLL) and the maintenance of treatment-free remission (TFR) following drug discontinuation.Methods:Clinical data were collected from 37 patients with T-LGLL who received oral cyclophosphamide at the Regenerative Medicine Clinic of the Institute of Hematology and Blood Diseases Hospital between June 2019 and March 2024. Patient clinical characteristics, treatment efficacy, and long-term TFR were analyzed.Results:The median age of the 37 patients was 60 years (range: 37-86), and 22 (59.5%) were male. Anemia was observed in 30 patients (81.1%), and 28 (75.7%) met the diagnostic criteria for secondary pure red cell aplasia. Neutropenia occurred in 15 patients (40.5%), lymphocytosis in 11 (29.7%), and thrombocytopenia in three (8.1%). Sixteen patients (43.2%) had not received prior immunosuppressive therapy (treatment-naive group), while 21 patients (56.8%) were refractory to or had relapsed after immunosuppressive treatment (refractory/relapsed group). All patients met the treatment criteria and received oral cyclophosphamide at doses of 50-100 mg/day. Among the 36 evaluable patients, hematologic remission was achieved in 25 (69.4%), with a median time of 2.0 months (range: 0.7-7.0). There was no statistically significant difference in remission rates between the treatment-naive and refractory/relapsed groups (68.5% vs. 66.7%, P=0.589). Among the 25 patients who achieved hematologic remission, 24 discontinued cyclophosphamide. With a median follow-up of 39.0 months (range: 8.0-56.0), the median TFR duration was not reached. The estimated TFR rates were (90.87± 6.16) % at 12 months and (75.72±11.04) % at 36 months. No significant difference in TFR was observed between the treatment-naive and refractory/relapsed groups ( P=0.451) . Conclusion:Oral cyclophosphamide is effective in the treatment of T-LGLL, and patients may maintain long-term TFR following drug discontinuation.

BACKGROUND: The effects of human umbilical cord-derived mesenchymal stem cell (UC-MSC) treatment on coronavirus disease 2019 (COVID-19) patients have been preliminarily characterized. However, real-world data on the safety and efficacy of intravenous transfusions of MSCs in hospitalized COVID-19 patients at the convalescent stage remain to be reported. METHODS: This was a single-arm, multicenter, real-word study in which a contemporaneous external control was included as the control group. Besides, severe and critical COVID-19 patients were considered together as the severe group, given the small number of critical patients. For a total of 110 patients, 21 moderate patients and 31 severe patients were enrolled in the MSC treatment group, while 26 moderate patients and 32 severe patients were enrolled in the control group. All patients received standard treatment. The MSC treatment patients additionally received intravenous infusions of MSCs at a dose of 4 × 10 7 cells on days 0, 3, and 6, respectively. The clinical outcomes, including adverse events (AEs), lung lesion proportion on chest computed tomography, pulmonary function, 6-min walking distance (6-MWD), clinical symptoms, and laboratory parameters, were measured on days 28, 90, 180, 270, and 360 during the follow-up visits. RESULTS: In patients with moderate COVID-19, MSC treatment improved pulmonary function parameters, including forced expiratory volume in the first second (FEV1) and maximum forced vital capacity (VCmax) on days 28 (FEV1, 2.75 [2.35, 3.23] vs . 2.11 [1.96, 2.35], P  = 0.008; VCmax, 2.92 [2.55, 3.60] vs . 2.47 [2.18, 2.68], P  = 0.041), 90 (FEV1, 2.93 [2.63, 3.27] vs . 2.38 [2.24, 2.63], P  = 0.017; VCmax, 3.52 [3.02, 3.80] vs . 2.59 [2.45, 3.15], P  = 0.017), and 360 (FEV1, 2.91 [2.75, 3.18] vs . 2.30 [2.16, 2.70], P  = 0.019; VCmax,3.61 [3.35, 3.97] vs . 2.69 [2.56, 3.23], P  = 0.036) compared with the controls. In addition, in severe patients, MSC treatment notably reduced the proportion of ground-glass lesions in the whole lung volume on day 90 ( P  = 0.045) compared with the controls. No difference in the incidence of AEs was observed between the two groups. Similarly, no significant differences were found in the 6-MWD, D-dimer levels, or interleukin-6 concentrations between the MSC and control groups. CONCLUSIONS: Our results demonstrate the safety and potential of MSC treatment for improved lung lesions and pulmonary function in convalescent COVID-19 patients. However, comprehensive and long-term studies are required to confirm the efficacy of MSC treatment. TRIAL REGISTRATION Chinese Clinical Trial Registry, ChiCTR2000031430.
Humans ; COVID-19/therapy* ; Female ; Male ; Mesenchymal Stem Cell Transplantation/adverse effects* ; Middle Aged ; Adult ; Umbilical Cord/cytology* ; Mesenchymal Stem Cells/cytology* ; SARS-CoV-2 ; Aged ; Treatment Outcome

Objective To investigate the epidemiological characteristics and effectiveness of emergency responses to epidemic foci in Guangzhou City in 2024, so as to optimization of the dengue fever control strategy in Guangzhou City. Methods All data pertaining to dengue fever cases in Guangzhou City in 2024 were collected from the National Notifiable Infectious Disease Surveillance Information Reporting System. The temporal, spatial and population distributions of dengue fever cases and sources of infections were descriptively analyzed, and the effectiveness of emergency responses to epidemic foci of dengue fever was evaluated through standard space index (SSI), the interval from disease onset to case reporting and the percentage of isolation in hospital. Results A total of 3 656 dengue fever cases were reported in Guangzhou City in 2024, including 3 102 local cases and 554 imported cases. Of all cases, 67.86% (2 481 cases) occurred at ages of 20 to 59 years, and the three most common occupations included housework/unemployment (793 cases, 21.69%), business servants (744 cases, 20.35%) and retirees (669 cases, 18.30%). The peak of dengue fever epidemics was concentrated during the period from the 39th to the 45th weeks in 2024, when a total of 2 317 local cases were reported, accounting for 74.69% of all local cases in 2024. Dengue fever cases were reported across all 11 districts in Guangzhou City in 2024, with local cases concentrated in Baiyun District (754 cases, 24.31%), Liwan District (398 cases, 12.83%), Panyu District (365 cases, 11.77%), Haizhu District (332 cases, 10.70%) and Tianhe District (328 cases, 10.57%). Imported dengue fever cases were predominantly domestically imported (492 cases, 88.81%), with the majority imported from Foshan City (377 cases), and overseas imported cases were predominantly imported from southeastern Asian countries. The mean proportion of case isolation in hospital was 9.16% (284/3 102), and the mean interval from disease onset to case reporting was (3.99 ± 2.70) days, while the percentages of mosquito density meeting the required standard were 61.68% (462/ 749) and 66.32% (126/190) on the 4th and 7th day of emergency responses to epidemic foci, respectively. Conclusions The prevention and control cycle of dengue fever in Guangzhou in 2024 took longer than in previous years, with a larger scale of the epidemic. Although some progress has been made in epidemic management, there are still problems such as unsustainable mosquito vector control and low hospitalization isolation rates for cases. Further optimization of control measures in mosquito vector control, case monitoring and management is required to improve the effectiveness of dengue fever control measures.

Objective:To explore the correlation between phase angle, determined by bioelectrical impedance analysis, and common chronic metabolic diseases in centrally obese individuals, aiming to assess the role of phase angle as a potential biomarker in screening for and preventing common chronic metabolic diseases associated with central obesity.Methods:In this retrospectivel study, body composition measurement was conducted among centrally obese patients attending the outpatient clinic of the Department of Clinical Nutrition of the First Affiliated Hospital of Xinjiang Medical University from July 2022 to May 2024, along with the collection of current medical histories. The subjects were divided into three groups from Q1 to Q3 according to the tertiles of phase angle (Q1 group: phase angle<5.1°; Q2 group: phase angle≥5.1° but <5.6°; and Q3 group: phase angle>5.6°), and the prevalence of metabolic diseases and the differences in body compositions were compared among these three groups. Pearson's correlation was used to analyse the potential associations of phase angle and each body composition with common chronic metabolic diseases.Results:A total of 3 476 centrally obese individuals (1 141 males and 2 335 females) were included in the study. The Q1 group had significantly older age [(45.0±15.1) years vs. (36.1±10.0) years], higher prevalence of type 2 diabetes mellitus (T2DM) (23.9% vs. 17.3%), higher body fat percentage [(41.80%±6.36%) vs. (36.81%±7.21%)], and larger visceral fat area [(171.43±43.46) cm2 vs. (157.57±47.05) cm2] but significantly lower body mass index [(29.98±4.93) kg/m2 vs. (32.57±4.94) kg/m2], basal metabolic rate [(5 692.12±653.33) kJ/d vs. (6 809.04±923.49) kJ/d], skeletal muscle index [(7.16±0.86) kg/m2 vs. (8.60±0.94) kg/m2], body cell mass [(29.47±4.63)(38.18±6.70) kg], and waist-to-hip ratio [(0.972±0.069) vs. (0.977±0.063)] than the Q3 group (all P<0.001). However, there were no significant differences in the prevalence rates of hypertension and dyslipidemia among the three groups (all P>0.05). Among female centrally obese patients, those with all three metabolic diseases had significantly smaller phase angle (4.85°±0.54°) than those with 1-2 metabolic diseases (5.10°±0.62°) and those without metabolic diseases (5.17°±0.55°) (both P<0.001). Among T2DM patients receiving different treatment regimens, phase angle was significantly smaller in the insulin treatment group and the combined treatment group than in the lifestyle intervention group and oral hypoglycemic medication group (all P<0.05). Conclusions:Phase angle is an effective indicator of T2DM in centrally obese individuals and has potential clinical value in the screening and evaluation of metabolic diseases in centrally obese individuals.

AIM:To investigate the effects and underlying mechanisms of paeoniflorin(PF)on lipopolysac-charide(LPS)-induced intestinal injury in septic mice,using a combination of network pharmacology,molecular docking,and animal experiments.METHODS:Network pharmacology was used to identify key active components and therapeutic targets of Red Peony for treating sepsis.Molecular docking was performed to explore the binding affinity be-tween PF and silent information regulator 1(SIRT1).An LPS-induced mouse model of sepsis with intestinal injury was es-tablished.Samples were collected 24 h after modeling,and hematoxylin-eosin(HE)staining was performed to observe pathological changes in intestinal tissues.Chiu's scoring system was utilized to evaluate the extent of intestinal injury.En-zyme-linked immunosorbent assay(ELISA)was employed to measure levels of inflammatory factors in intestinal tissues,including interleukin-1β(IL-1β)and IL-18,as well as indicators of intestinal permeability such as diamine oxidase(DAO)and intestinal-type fatty acid-binding protein(I-FABP),alongside serum levels of D-lactate and the aerobic gly-colysis product L-lactate.Western blot analysis was performed to assess changes in protein levels of SIRT1,M2-type pyru-vate kinase(PKM2),and NOD-like receptor protein 3(NLRP3)in intestinal tissues.RESULTS:Network pharmacolo-gy suggested that paeoniflorin,an active component of Red Peony,treats sepsis by targeting SIRT1 among other proteins.Molecular docking revealed a strong binding affinity of PF with SIRT1.In vivo experimentation revealed significant patho-logical damage in intestinal tissues in the LPS group compared to the control group as evidenced by HE staining.Chiu's score,along with levels of IL-1β,IL-18,D-lactate,and L-lactate were significantly elevated,while DAO and I-FABP levels were reduced(P＜0.05).SIRT1 expression decreased,while PKM2 and NLRP3 levels increased(P＜0.05).In contrast,the LPS+PF group displayed reduced intestinal histopathological injury,lower Chiu's scores,and decreased levels of IL-1β,IL-18,D-lactate,and L-lactate,along with increased DAO and I-FABP levels(P＜0.05).Notably,SIRT1 protein expression increased while PKM2 and NLRP3 levels decreased(P＜0.05).Furthermore,compared to the LPS+PF group,the LPS+PF+EX527 group exhibited exacerbated intestinal histopathological injury,increased Chiu's scores,as well as elevated levels of IL-1β,IL-18,D-lactate,and L-lactate,alongside reduced DAO and I-FABP levels(P＜0.05),decreased SIRT1 expression,and increased PKM2 and NLRP3 levels(P＜0.05).CONCLUSION:Paeoni-florin effectively alleviates intestinal injury in mice with sepsis,potentially through the upregulation of SIRT1 expression and the inhibition of PKM2-mediated aerobic glycolysis,which subsequently reduces the activation of NLRP3 inflamma-somes,mitigates the release of inflammatory factors,and lessens intestinal inflammation.

A 77-year-old male patient was admitted to the hospital with the main cause of memory loss, visual hallucination for more than one year, aggravated for two months with sensitivity and paranoia. The patient exhibited signs of loss of smell, axial hypertonia, upper limb hypertonia, slow start, and propulsive gait. Cranial MRI suggested cerebral atrophy, bilateral hippocampal atrophy, and multiple cavernous cerebral infarcts. Severe memory deficits, moderate intellectual deficits, MMSE score of 12, mildly abnormal electroencephalography, and polysomnographic monitoring suggested a high likelihood of apnea syndrome. Prior to the onset of the disease, the patient had a history of swinging, shouting, and cursing during nighttime sleep, according to his family members. The final diagnosis was Lewy body dementia.