[摘 要] 目的：探讨干扰素刺激基因家族成员黏病毒抵抗蛋白2（MX2）在调控肿瘤细胞对呼肠孤病毒（Reo）溶瘤敏感性中的作用及其机制。方法：选取4株具有不同耐药特征的人源肿瘤细胞，通过CCK-8法评估其对Reo的溶瘤敏感性；通过转录组测序筛选出差异表达基因MX2，qPCR法及WB法验证MX2在4株人源肿瘤细胞中的表达；使用siRNA敲低溶瘤低敏感的COC1/DDP细胞中的MX2基因。在细胞感染Reo病毒后，通过CCK-8法检测细胞存活率；qPCR法检测细胞中Reo病毒S1基因表达；免疫荧光法检测细胞内Reo病毒蛋白的积累；半数组织培养感染剂量（TCID50）法测定病毒滴度；流式细胞术分别检测细胞内Reo病毒dsRNA、活性氧（ROS）水平以及细胞凋亡率；透射电镜观察细胞内质网形态变化并采用WB法检测内质网应激相关蛋白（JNK、p-JNK、eIF2α、p-eIF2α、CHOP、PERK）的表达。结果：在4株肿瘤细胞中，SKOV3细胞对Reo溶瘤作用高度敏感，而COC1/DDP、HuH-7SRB及SNU-398细胞均为溶瘤低敏感性。转录组测序结果显示，MX2在溶瘤低敏感肿瘤细胞中的表达水平显著高于溶瘤高敏感细胞（P < 0.01）；在溶瘤低敏感性的COC1/DDP细胞中，敲低MX2显著促进Reo病毒复制、诱导细胞凋亡增加，并升高细胞内活性氧水平（均P < 0.001）。透射电镜观察显示，敲低MX2的COC1/DDP细胞感染Reo病毒后出现内质网肿胀、扩张及断裂等典型内质网应激超微结构改变。WB结果显示，内质网应激关键标志物eIF2α/p-eIF2α、PERK、CHOP及凋亡相关调节蛋白JNK/p-JNK的表达均显著上调（P < 0.05或P < 0.01）。结论：肿瘤细胞对Reo的溶瘤敏感性与其细胞内MX2表达水平密切相关。敲低MX2可显著增强Reo在细胞内的复制，进而促进ROS积累，触发内质网应激并促进凋亡。病毒复制增加与细胞凋亡激活的双重作用，最终协同增强Reo的溶瘤作用。

OBJECTIVE To clarify the roles and functions of full-time pharmacists in the management of early-phase clinical trials of antineoplastic drugs， and to provide theoretical and practical support for their transformation from traditional drug managers to multi-dimensional roles in clinical research. METHODS Combined with relevant regulations such as the Good Clinical Practice （GCP） （2020 Edition）， and based on the clinical practice experience of the Phase Ⅰ Clinical Ward in our hospital， this study systematically sorted out full-time pharmacists’ roles and functions in early-phase clinical trials of antineoplastic drugs， and explored the core challenges and optimization pathways for role transformation and capacity-building of domestic full-time clinical trial pharmacists. RESULTS & CONCLUSIONS Full-time pharmacists assumed multiple roles in early-phase clinical trials of antineoplastic drugs， including providing pharmaceutical support for protocol design， implementing whole-process standardized management of clinical trial drugs， ensuring medication safety for clinical trial subjects/participants， conducting quality control throughout the clinical trial process， and serving as a bridge for interdisciplinary collaboration and communication. Currently， there are challenges in this field in China， such as unclear roles， an imperfect capacity building system， and insufficient regulatory support. This paper proposes that by establishing a standardized role framework， clarifying the core responsibilities and authorities of full-time pharmacists， and leveraging cutting-edge technologies to provide comprehensive support for their roles， so as to fully harness their pharmaceutical expertise and contribute to the standardization and efficiency of the antineoplastic new drug development process.

OBJECTIVE To provide a basis for aligning Chinese pharmacoeconomic research on heart failure （HF） with international standards. METHODS A qualitative comparison o f domestic and global HF pharmacoeconomic studies was conducted across four dimensions： research methods and model application， research perspectives and endpoints， data sources and parameter selection， and policy translation and practical impact. RESULTS & CONCLUSIONS Global studies predominantly utilize long-term dynamic models， societal perspectives， real-world data integration， and directly inform reimbursement decisions. Conversely， domestic research often relies on short-term simplified models， a single healthcare system perspectives， literature-derived data， and individual medicine recommendations. Future domestic studies should transition to long-term dynamic modeling， develop localized disease-specific utility databases via big data， establish reimbursement-linked closed-loop mechanisms， and foster multidisciplinary collaboration to optimize healthcare resource allocation.

BACKGROUND:The quadriceps strength of patients with osteoporosis and sarcopenia is significantly reduced,which can further reduce the function of the knee joint,affect the function of the lower limbs and even lead to a decrease in whole-body coordination.It is speculated that a reasonable quadriceps training program and personalized guidance are beneficial to the recovery of knee joint function in patients with osteoporosis and sarcopenia.OBJECTIVE:To observe the effect of short-term moderate-intensity resistance rehabilitation training on the mass and function of the quadriceps and knee joint function in patients with osteoporosis and sarcopenia.METHODS:Using the integrated physical examination and rehabilitation model,375 patients with osteoporosis and sarcopenia were screened at the Health Management Center of Shanghai Public Health Clinical Center.They underwent 12 weeks of combined/comprehensive exercise rehabilitation based on resistance exercise,including quadriceps resistance isotonic and isometric contraction training twice a week(3-5 sets each time,10-15 minutes per set)and aerobic exercise/balance exercise two or three times a week(30 minutes each time).Assessments and data collection were performed before rehabilitation training,12 weeks after rehabilitation training,and at follow-up 12 weeks after stopping rehabilitation training,mainly including knee joint range of motion and proprioception,quadriceps muscle strength,and cross-sectional area(magnetic resonance imaging results),pain,knee joint function(Hospital for Special Surgery score)and walking function("up-and-go"time and 6 m pace test results)as well as the patient's psychological status assessment.RESULTS AND CONCLUSION:All 375 patients completed 12 weeks of rehabilitation training and 12 weeks of follow-up without any adverse events.(1)Compared with before training,the patients' gait speed and knee range of motion increased significantly after 12 weeks of rehabilitation training(P＜0.01),the time of"stand-to-walk"decreased(P＜0.01),and the proprioception of the knee joint and the strength of the quadriceps femoris were significantly improved(P＜0.01);and at the follow-up visit 12 weeks after stopping training,the above indicators and functions of the patients were well maintained(P＞0.05).(2)Magnetic resonance imaging results showed that the effective cross-sectional area of the quadriceps femoris did not improve significantly after 12 weeks of rehabilitation training(P＞0.05);but the Hospital for Special Surgery score of knee joint function increased significantly(P＜0.01),and the visual analog pain scale score decreased significantly(P＜0.01),suggesting that this may be related to the improvement of quadriceps femoris quality by resistance rehabilitation training.(3)The results of the Hospital Anxiety and Depression Scale score showed that the anxiety and depression scores of the patients continued to decrease,both at 12 weeks of rehabilitation training and at 12 weeks after stopping training(P＜0.01).It is suggested that resistance rehabilitation training of the quadriceps can help patients with osteoporosis and sarcopenia to restore quadriceps muscle strength,increase range of motion,improve proprioception and joint stability,thereby enhancing knee joint function,reducing pain,improving depression and anxiety,and to a certain extent promoting the coordinated recovery of the musculoskeletal system.

BACKGROUND:The quadriceps strength of patients with osteoporosis and sarcopenia is significantly reduced,which can further reduce the function of the knee joint,affect the function of the lower limbs and even lead to a decrease in whole-body coordination.It is speculated that a reasonable quadriceps training program and personalized guidance are beneficial to the recovery of knee joint function in patients with osteoporosis and sarcopenia.OBJECTIVE:To observe the effect of short-term moderate-intensity resistance rehabilitation training on the mass and function of the quadriceps and knee joint function in patients with osteoporosis and sarcopenia.METHODS:Using the integrated physical examination and rehabilitation model,375 patients with osteoporosis and sarcopenia were screened at the Health Management Center of Shanghai Public Health Clinical Center.They underwent 12 weeks of combined/comprehensive exercise rehabilitation based on resistance exercise,including quadriceps resistance isotonic and isometric contraction training twice a week(3-5 sets each time,10-15 minutes per set)and aerobic exercise/balance exercise two or three times a week(30 minutes each time).Assessments and data collection were performed before rehabilitation training,12 weeks after rehabilitation training,and at follow-up 12 weeks after stopping rehabilitation training,mainly including knee joint range of motion and proprioception,quadriceps muscle strength,and cross-sectional area(magnetic resonance imaging results),pain,knee joint function(Hospital for Special Surgery score)and walking function("up-and-go"time and 6 m pace test results)as well as the patient's psychological status assessment.RESULTS AND CONCLUSION:All 375 patients completed 12 weeks of rehabilitation training and 12 weeks of follow-up without any adverse events.(1)Compared with before training,the patients' gait speed and knee range of motion increased significantly after 12 weeks of rehabilitation training(P＜0.01),the time of"stand-to-walk"decreased(P＜0.01),and the proprioception of the knee joint and the strength of the quadriceps femoris were significantly improved(P＜0.01);and at the follow-up visit 12 weeks after stopping training,the above indicators and functions of the patients were well maintained(P＞0.05).(2)Magnetic resonance imaging results showed that the effective cross-sectional area of the quadriceps femoris did not improve significantly after 12 weeks of rehabilitation training(P＞0.05);but the Hospital for Special Surgery score of knee joint function increased significantly(P＜0.01),and the visual analog pain scale score decreased significantly(P＜0.01),suggesting that this may be related to the improvement of quadriceps femoris quality by resistance rehabilitation training.(3)The results of the Hospital Anxiety and Depression Scale score showed that the anxiety and depression scores of the patients continued to decrease,both at 12 weeks of rehabilitation training and at 12 weeks after stopping training(P＜0.01).It is suggested that resistance rehabilitation training of the quadriceps can help patients with osteoporosis and sarcopenia to restore quadriceps muscle strength,increase range of motion,improve proprioception and joint stability,thereby enhancing knee joint function,reducing pain,improving depression and anxiety,and to a certain extent promoting the coordinated recovery of the musculoskeletal system.

This paper summarizes the clinical experience in the syndrome differentiation and treatment of rosacea using the method of venting heat and resolving stagnation. It is considered that the key pathogenesis of rosacea is the accumulation of heat with stagnation. Accordingly， the method of venting heat and resolving stagnation is proposed， which vents and disperses constraint heat by applying approaches such as dredging defensive qi， clearing qi， venting ying （营） level， and cooling blood， while eliminating stagnation and masses through regulating qi， resolving dampness， dispelling phlegm and removing stasis. In clinical practice， a core prescription for venting heat and resolving stagnation is formulated， with flexible modifications made according to the clinical characteristics of different rosacea subtypes， including erythematotelangiectatic， papulopustular， phymatous， and ocular types， thereby providing therapeutic insights for the treatment of rosacea with traditional Chinese medicine.

ObjectiveTo investigate the mechanism of action of remifentanil （RMZL） in alleviating lung ischemia-reperfusion injury （LIRI） in rats by inhibiting pyroptosis through modulating hypoxia inducible factor-1α （HIF-1α）/NOD-like receptor thermal protein domain associated protein 3 （NLRP3） pathway. MethodsRats were stochastically assigned into Control group， LIRI group， RMZL low-dose group， RMZL medium-dose group， RMZL high-dose group， and RMZL high-dose+HIF-1α activator dimethyloxallyl glycine （DMOG） group， with 18 rats in each group. Rats in Control group only had their left pulmonary hilum free and did not undergo ischemia-reperfusion treatment. Except for the Control group， LIRI models were constructed in all other groups. Rats in LIRI group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before constructing LIRI model； rats in Control group were intraperitoneally injected with an equal amount of physiological saline 15 minutes before freeing left pulmonary hilum； rats in other groups were intraperitoneally injected with corresponding dose of drug 15 minutes before constructing LIRI model. The wet/dry weight ratio of lungs was calculated. HE staining was used to study lung tissue pathology. Immunofluorescence staining was used to detect the relative fluorescence intensity of gasdermin D （GSDMD） and NLRP3 double positive cells in lung tissue. ELISA was used to detect interleukin-1β and IL-18 in lung tissue. Western blot was used to detect HIF-1α， NLRP3， cysteine-aspartic protease-1 （Cleaved caspase-1）， and gasdermin D-N （GSDMD-N） proteins in lung tissue. ResultsCompared to the Control group， the LIRI group showed disordered alveolar structure， thickened alveolar septa， and abundant inflammatory cell infiltration in rats. The lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， IL-1β， IL-18 levels， and HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N proteins increased （P0.05）. For the LIRI group， rats in the RMZL low， medium， and high-dose groups displayed attenuated alveolar septal thickening and reduced inflammatory cell infiltration. The lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， IL-1β， IL-18 levels， and HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N proteins declined， and the RMZL high-dose group showed the most prominent trend （P0.05）. Compared with the RMZL high-dose group， rats in the RMZL high-dose+DMOG group exhibited thickened alveolar septa and more inflammatory cell infiltration， along with increased lung wet/dry weight ratio， relative fluorescence intensity of GSDMD and NLRP3 double positive cells in lung tissue， levels of IL-1β and IL-18， and protein expression of HIF-1α， NLRP3， Cleaved caspase-1， and GSDMD-N （P0.05）. ConclusionRMZL may inhibit pyroptosis in LIRI rats by suppressing HIF-1α/NLRP3 pathway.

ObjectiveTo evaluate the predictive value of epicardial adipose tissue （EAT） parameters for microvascular obstruction （MVO） formation in patients with ST segment elevation myocardial infarction （STEMI） using cardiac magnetic resonance quantification. MethodsA total of 139 STEMI patients were included in this study， and various parameters such as EAT thickness， volume， and mass index were measured utilizing cardiac magnetic resonance. All included patients were divided into MVO group and non-MVO group according to whether MVO occurred. Differences in EAT related parameters between two groups were compared and correlation analysis was applied to evaluate the correlation between quantitative indicators of EAT and indicators such as infarct size and ejection fraction. Logistic regression analysis was used to identify the relevant risk factors for MVO formation. Receiver Operating Characteristic （ROC） curve analysis was performed to assess the predictive value of the epicardial adipose tissue （EAT） quality index and other indicators for the occurrence of MVO. ResultsCompared with non MVO group， patients in MVO group presented with higher peak troponin T levels， increase of neutrophil lymphocyte ratio （NLR） and C-reactive protein （CRP）， larger infarct size and compromised left ventricular ejection fraction （LVEF） （P<0.05）. Total EAT volume， EAT mass index， left atrioventricular EAT volume， left atrioventricular EAT mass index and thickness of EAT in the left atrioventricular groove were significantly higher in patients with MVO. Multivariate Logistic regression analysis demonstrated that NLR， peak troponin T levels and left atrioventricular EAT mass index were independent predictors of MVO. The ROC curve suggested that the left atrioventricular EAT mass index had the highest predictive power for MVO formation in STEMI patients. ConclusionThe parameters of EAT quantified by cardiac magnetic resonance serve as imaging biomarkers for predicting MVO formation in STEMI patients. These metrics enable risk stratification post-myocardial infarction and facilitate early identification of high-risk individuals， thereby supporting personalized therapeutic decision-making.

OBJECTIVE To investigate the regulatory effects of tofacitinib combined with methotrexate （MTX） on gut microbiota and the clinical efficacy of this regimen in patients with rheumatoid arthritis （RA）. METHODS A retrospective analysis was conducted on the clinical data of 182 patients with RA admitted to Xingtai People’s Hospital from January 2022 to June 2025. The patients were divided into a control group （ n ＝88， treated with MTX monotherapy） and an observation group （ n ＝94， treated with tofacitinib combined w ith MTX） based on their treatment regimen. Gut microbiota abundance， inflammatory and immunological indicators [C-reactive protein （CRP）， erythrocyte sedimentation rate （ESR）， rheumatoid factor （RF）， and anti-cyclic citrullinated peptide antibody （anti-CCP） ] ， clinical efficacy indicators [American College of Rheumatology 20% response rate （ACR20）， Disease Activity Score in 28 Joints （DAS28）， and Health Assessment Questionnaire （HAQ） score ] ， and adverse reactions during treatment were compared between the two groups before and after 12 weeks of treatment. RESULTS After treatment， the abundance of Lactobacillus and Bifidobacterium were significantly increased in both groups compared with before treatment， whereas the abundances of Enterococcus and Enterobacter ， as well as the levels of CRP， ESR， RF， anti-CCP， DAS28 score， and HAQ score， were significantly decreased （ P ＜0.05）. The degree of improvement in the observation group was significantly greater than that in the control group （ P ＜0.05）. The ACR20 response rate in the observation group was significantly higher than that in the control group （81.91% vs. 56.82%， P ＜0.05）. There was no statistically significant difference in the incidence of adverse reactions between the two groups （ P ＞0.05）， and the main adverse reactions were gastrointestinal reactions and abnormal liver function. CONCLUSIONS Tofacitinib combined with MTX can effectively improve gut microbiota balance in patients with RA by increasing the abundance of probiotics and reducing the abundance of opportunistic pathogenic bacteria， thereby improving immune and inflammatory status. In addition， this combination regimen can enhance clinical efficacy， reduce disease activity， and improve functional status， with a favorable safety profile.

ObjectiveTo investigate the therapeutic effects and mechanisms of modified Huangqi Jianzhong decoction （HQJZ） on gastric precancerous conditions （GPC）. MethodsIn the cell experiment， human gastric mucosal epithelial cells underwent malignant transformation induced by N-methyl-N′-nitro-N-nitrosoguanidine （MNNG） for the modeling of GPC （MC cells）. The cells were allocated into four groups： control ， model， low-dose HQJZ （HQJZ-L）， and high-dose HQJZ （HQJZ-H）. The control and model groups were cultured with the complete medium， while HQJZ-L and HQJZ-H groups received additional interventions with HQJZ at low （0.5 g·L^-1） and high （1.0 g·L^-1） doses， respectively. Cell counting kit-8 （CCK-8） assay was used to evaluate cytotoxicity， Transwell assay to assess cell invasion， Annexin V-FITC/PI staining to detect apoptosis， immunofluorescence assay to analyze reactive oxygen species （ROS） expression and mitochondrial autophagy， and Western blot to verify expression of proteins in key pathways. In the animal experiment， the GPC model was established in healthy BALB/c mice through MNNG induction. Twenty-four mice were allocated into four groups： control， model， HQJZ-L， and HQJZ-H. Control and model groups received normal saline （10 mL·kg^-1·d^-1） orally， while HQJZ-L and HQJZ-H groups were administrated with low-dose （6.24 g·kg^-1·d^-1） and high-dose （12.48 g·kg^-1·d^-1） HQJZ， respectively. After treatment， hematoxylin‑eosin （HE） staining and AB-PAS staining were performed to observe histopathological changes in the gastric tissue. Immunofluorescence assay was used to detect reactive oxygen species （ROS） and microtubule-associated protein 1 light chain 3 （LC3） levels in the gastric mucosa， TdT-mediated dUTP nick-end labeling （TUNEL） staining to assess apoptosis rates， and Western blotting and immunohistochemistry （IHC） to analyze the expression levels of Ki67， proliferating cell nuclear antigen （PCNA）， and foxhead box O3 （FoxO3）. ResultsCell viability assays showed that HQJZ dose-dependently reduced MC cell viability compared with the control group （P<0.05， P<0.01）. Transwell assays revealed that the model group exhibited enhanced cell invasion compared with the control group （P<0.05）. Compared with the model group， HQJZ treatment attenuated the cell invasion （P<0.05）. Gastric mucosal pathology in mice demonstrated that compared with the control group， the model group showed elevated HE and AB-PAS pathological scores （P<0.05）， while HQJZ treatment reduced these scores （P<0.05）. Transmission electron microscopy revealed increased mitochondrial number and volume in the model group compared with the control group. HQJZ treatment resulted in abnormal mitochondrial structure and significant alterations in rough endoplasmic reticulum morphology and distribution， presenting as dilated and hollow forms. Mitochondrial and apoptosis assessments indicated that compared with the control group， the model group exhibited enhanced Mito Tracker Green fluorescence （P<0.05）， no significant change in DCFH-DA fluorescence， Mito Tracker Red CMXRos fluorescence， ROS immunofluorescence， or malondialdehyde （MDA） level， increased GSH level （P<0.05）， enhanced LC3 fluorescence （P<0.05）， no significant change in apoptosis rate， and elevated ATP content in cells and mouse serum （P<0.05）. Compared with the model group， HQJZ treatment reduced Mito Tracker Green fluorescence （P<0.05）， increased DCFH-DA fluorescence， Mito Tracker Red fluorescence， MDA level， LC3 fluorescence， and apoptosis rate （P<0.05）， and decreased cellular ATP content （P<0.05）. The HQJZ-L group showed no significant change in ROS immunofluorescence or GSH level， whereas the HQJZ-H group demonstrated enhanced ROS immunofluorescence and glutathione （GSH） level （P<0.05）. Immunohistochemistry and Western blotting revealed that compared with the control group， the model group exhibited increased numbers of PCNA- and Ki67-positive cells （P<0.05） and elevated protein levels of FoxO3， sirtuin 1 （SIRT1）， and B-cell lymphoma 6 （Bcl-6） （P<0.05）. HQJZ treatment reduced the numbers of PCNA- and Ki67-positive cells （P<0.05） and lowered the protein levels of FoxO3， SIRT1， and Bcl-6 （P<0.05）. ConclusionHQJZ alleviates the progression of gastric precancerous lesions by regulating mitochondrial function via the FoxO3/ROS pathway and promoting apoptosis of GPC-malignant cells.