1.Zuogui Wan Improve Ovarian Inflammatory Microenvironment and Stemness of Ovarian Germline Stem Cells in Ovarian Aging via cGAS/STING Signaling Pathway
Yunling ZHENG ; Xinyi PAN ; Zuang LI ; Yixuan WANG ; Junyi AN ; Yuxin ZOU ; Mengting XIAO ; Zheng CHEN ; Ling ZHU
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(7):1-10
ObjectiveTo investigate the mechanism of Zuogui Wan (ZGW) in improving ovarian inflammatory microenvironment and stemness of ovarian germline stem cells (OSCs) for treating ovarian aging via the cyclic guanosine monophosphate/adenosine monophosphate synthase (cGAS)/stimulator of interferon genes (STING) signaling pathway. MethodsForty C57BL/6 female mice were randomly divided into a blank group, a model group, a low-dose ZGW group (2.7 g·kg-1), a high-dose ZGW group (5.4 g·kg-1), and an estradiol valerate group (0.15 mg·kg-1), with 8 mice in each group. Except the blank group, all other groups received a single intraperitoneal injection of cyclophosphamide at 120 mg·kg-1 to establish an ovarian aging mouse model. After successful modeling, each group was continuously administered for 4 weeks, once daily. The physiological status of the mice was observed, and the ovarian index was calculated. The estrus cycle of the mice was monitored. Hematoxylin-eosin (HE) staining was used to observe pathological changes in ovarian tissue. Enzyme-linked immunosorbent assay (ELISA) was used to detect serum sex hormone levels. Serum inflammatory factors interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and mouse interleukin-6 (IL-6) levels were detected using kits. Western blot was used to detect the protein expression of ovarian cGAS, STING, p-STING, TANK-binding kinase 1 (TBK1), p-TBK1, interferon-induced transmembrane protein 3 (Fragilis), and Vasa homolog protein (MVH). Quantitative real-time polymerase chain reaction (Real-time PCR) was used to detect the mRNA expression of inflammatory factors in ovarian tissue. Immunofluorescence double labeling was performed to locate OSCs in ovarian tissues, and fluorescence intensities of OSCs markers MVH and octamer binding transcription factor 4 (Oct4) were calculated. ResultsCompared with the blank group, the model group showed reduced body weight, ovarian wet weight, and ovarian index (P<0.01) and a disordered estrus cycle (P<0.01). In addition, the levels of serum follicle-stimulating hormone (FSH), TNF-α, IL-6, and IL-1β were increased (P<0.01), while anti-Müllerian hormone (AMH) and estradiol (E2) levels were decreased (P<0.01). The protein expression of cGAS, p-STING/STING, and p-TBK1/TBK1 in ovarian tissue was increased (P<0.05, P<0.01), while that of OSCs stemness factors MVH and Fragilis was reduced (P<0.01). Immunofluorescence indicated a reduction in MVH and Oct4 expression in OSCs (P<0.01). The mRNA expression of inflammatory factors TNF-α, IL-6, and IL-1β in ovarian tissue was increased (P<0.05, P<0.01). Compared with the model group, the treatment groups exhibited improved body weight, ovarian wet weight, and ovarian index (P<0.05) and a reduced rate of estrus cycle disorder (P<0.05, P<0.01). The levels of serum FSH, TNF-α, IL-6, and IL-1β were decreased (P<0.05, P<0.01), while AMH and E2 levels were increased (P<0.01). The protein expression levels of cGAS, p-STING/STING, and p-TBK1/TBK1 in ovarian tissue were decreased (P<0.05), while the protein expression of MVH and Fragilis was increased (P<0.05), and the fluorescence intensities of MVH and Oct4 were increased (P<0.05, P<0.01). The mRNA expression of inflammatory factors in ovarian tissue was decreased (P<0.05). ConclusionZGW alleviate ovarian inflammatory response, regulate ovarian microenvironment homeostasis, and maintain stemness of OSCs in ovarian aging mice probably by modulating the cGAS-STING signaling pathway, thereby improving ovarian function and delaying ovarian aging.
2.Impact of Nutritional Support on Antitumor Efficacy in the Era of Immunotherapy
Xiaojun QIAN ; Ling LU ; Xuecheng HU ; Shiwei LI ; Wenjun GAO ; Li PAN ; Yubei SUN ; Suyi LI
Cancer Research on Prevention and Treatment 2026;53(2):89-95
Despite breakthroughs in immunotherapy for solid tumors, significant variations in treatment efficacy persist. Up to 80% of cancer patients suffer from malnutrition, which leads to: lymphoid atrophy and reduced T-cell reserves; deficiency of substrates required for T-cell activation and expansion; concurrent inflammation hindering T-cell infiltration into tumors; and cachexia accelerating PD-1 antibody clearance. Clinical studies confirm that severe malnutrition significantly impairs immune responses and increases the risk of treatment toxicity. Therefore, implementing standardized nutritional therapy is crucial for optimizing the reserve, activation, expansion, and infiltration capacity of immune cells, thereby providing a sound immune system foundation for immunotherapy. Immunonutrition therapy, by enhancing immunonutrients such as arginine, omega-3 polyunsaturated fatty acids, and nucleotides, reduces the secretion of pro-inflammatory mediators and promotes T-cell activation and proliferation. This enhances anti-tumor immune responses, prolongs survival, and advances cancer treatment towards multimodal combination and precision approaches.
3.Role of endoplasmic reticulum stress-mediated DEAD-box helicase 3 X-linked in a mouse model of concanavalin A-induced immune-mediated liver injury
Zhenzhen PAN ; Ling XU ; Xianru ZHU ; Zihao FAN ; Yaling CAO ; Yinkang MO ; Sai YAN ; Feng REN
Journal of Clinical Hepatology 2026;42(1):134-142
ObjectiveTo investigate the role of DEAD-box helicase 3 X-linked (DDX3X) in immune-mediated liver injury (ILI), and to clarify its mechanism by regulating endoplasmic reticulum stress (ERS)-dependent apoptotic pathway and its association with the clinical progression of hepatitis B. MethodsMice were given injection of concanavalin A (ConA) via the caudal vein to establish a model of ILI, PBS (control group) and different concentrations of ConA were injected into the tail vein of hepatocyte-specific DDX3X-knockout mice (DDX3XΔHep and DDX3X-flox mice (DDX3Xfl/fl), respectively.. The log-rank survival analysis, measurement of the serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT), and HE staining of liver tissue were performed to assess liver injury, and qRT-PCR and Western Blot were used to measure the mRNA and protein expression levels of glucose-regulated protein 78 (GRP78), CCAAT/enhancer-binding protein homologous protein (CHOP), and DDX3X in liver tissue. Intraperitoneal injection of 4-phenylbutyric acid (4-PBA, 100 mg/kg) was performed to inhibit ERS. Serum samples (n=30) and liver tissue samples (n=6) were collected from healthy controls, chronic hepatitis B (CHB) patients, and hepatitis B virus-associated liver failure (HBV-LF) patients; ELISA was used to measure the serum level of DDX3X, and qRT-PCR/Western Blot was used to analyze the expression of targets in liver tissue. A one-way analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. ResultsCompared with the control group of mice, the expression of DDX3X in the liver of mice induced by ConA was significantly increased after liver injury (P<0.05), and hepatocyte-specific DDX3X knockout increased the 72-hour survival rate of mice by 55% (compared with 20% in the DDX3Xfl/fl group), with significant reductions in the serum levels of ALT and AST (P<0.000 1) and the expression levels of the ERS markers GRP78 and CHOP (P<0.05). After ERS was inhibited by 4-PBA, there was alleviation of liver injury (with reductions in ALT and AST, P <0.001) and a reduction in DDX3X expression (P<0.01). The analysis of clinical samples showed that the mRNA and protein expression levels of liver DDX3X in CHB patients and HBV-LF patients were significantly higher than those in healthy controls (all P<0.01), and there was a significant increase in the serum level of DDX3X in HBV-LF patients (P<0.000 1). ConclusionDDX3X exacerbates ILI by regulating the ERS-dependent apoptotic pathway (GRP78/CHOP), and its expression is associated with the progression of hepatitis B. Therefore, it can be used as a potential therapeutic target.
4.Clinical practice guidelines for intraoperative cell salvage in patients with malignant tumors
Changtai ZHU ; Ling LI ; Zhiqiang LI ; Xinjian WAN ; Shiyao CHEN ; Jian PAN ; Yi ZHANG ; Xiang REN ; Kun HAN ; Feng ZOU ; Aiqing WEN ; Ruiming RONG ; Rong XIA ; Baohua QIAN ; Xin MA
Chinese Journal of Blood Transfusion 2025;38(2):149-167
Intraoperative cell salvage (IOCS) has been widely applied as an important blood conservation measure in surgical operations. However, there is currently a lack of clinical practice guidelines for the implementation of IOCS in patients with malignant tumors. This report aims to provide clinicians with recommendations on the use of IOCS in patients with malignant tumors based on the review and assessment of the existed evidence. Data were derived from databases such as PubMed, Embase, the Cochrane Library and Wanfang. The guideline development team formulated recommendations based on the quality of evidence, balance of benefits and harms, patient preferences, and health economic assessments. This study constructed seven major clinical questions. The main conclusions of this guideline are as follows: 1) Compared with no perioperative allogeneic blood transfusion (NPABT), perioperative allogeneic blood transfusion (PABT) leads to a more unfavorable prognosis in cancer patients (Recommended); 2) Compared with the transfusion of allogeneic blood or no transfusion, IOCS does not lead to a more unfavorable prognosis in cancer patients (Recommended); 3) The implementation of IOCS in cancer patients is economically feasible (Recommended); 4) Leukocyte depletion filters (LDF) should be used when implementing IOCS in cancer patients (Strongly Recommended); 5) Irradiation treatment of autologous blood to be reinfused can be used when implementing IOCS in cancer patients (Recommended); 6) A careful assessment of the condition of cancer patients (meeting indications and excluding contraindications) should be conducted before implementing IOCS (Strongly Recommended); 7) Informed consent from cancer patients should be obtained when implementing IOCS, with a thorough pre-assessment of the patient's condition and the likelihood of blood loss, adherence to standardized internally audited management procedures, meeting corresponding conditions, and obtaining corresponding qualifications (Recommended). In brief, current evidence indicates that IOCS can be implemented for some malignant tumor patients who need allogeneic blood transfusion after physician full evaluation, and LDF or irradiation should be used during the implementation process.
5.Spatio-temporal clustering analysis of mumps in Wenzhou City from 2010 to 2023
LI Ling ; WEI Jingjiao ; PAN Qiongjiao ; LI Wancang ; WANG Jian
Journal of Preventive Medicine 2025;37(3):284-287
Objective:
To identify the spatio-temporal clustering analysis of mumps in Wenzhou City, Zhejiang Province from 2010 to 2023, so as to provide the basis for improving mumps prevention and control strategies.
Methods:
Data of mumps cases in Wenzhou City from 2010 to 2023 were collected from the Monitoring and Reporting Management System of Chinese Disease Prevention and Control Information System. The spatio-temporal clustering characteristics of mumps incidence were identified using spatial autocorrelation analysis and spatio-temporal scan analysis.
Results:
A total of 20 455 mumps cases were reported in Wenzhou City from 2010 to 2023, with an average annual incidence of 17.54/105. There were 12 919 male and 7 536 female cases, with a male-to-female ratio of 1.71∶1. The children aged 5-<10 years had the highest incidence of mumps at 135.29/105. The incidence of mumps showed a downward trend from 46.82/105 in 2010 to 3.59/105 in 2023 (P<0.05). The incidence of mumps peaked from May to July and from November to January during 2010 and 2012, the winter peak became less evident after 2013, and no seasonal trends were observed after 2020. Spatial autocorrelation analysis showed there was a positive spatial correlation of mumps of other years, with the exception of 2018 (all Moran's I >0, all P<0.05). Lucheng District, Longwan District, Ouhai District, Cangnan County and Rui'an City were high-high clustering sites. Spatio-temporal scan analysis showed that the primary clustering area was centered in Nanbaixiang Street, Ouhai District, covering 50 towns (streets), with the clustering time from April 2010 to August 2013; the secondary clustering area was centered in Zaoxi Town, Cangnan County, covering 24 towns (streets), with the clustering time from January 2010 to June 2013.
Conclusions
The incidence of mumps in Wenzhou City from 2010 to 2023 showed a downward trend. The urban areas, Cangnan County and Rui'an City were the clustering areas.
6.Analysis of red blood cell transfusion reactions in China from 2018 to 2023
Bo PAN ; Xiaoyu GUAN ; Jue WANG ; Yunlong PAN ; Liu HE ; Haixia XU ; Xin JI ; Li TIAN ; Ling LI ; Zhong LIU
Chinese Journal of Blood Transfusion 2025;38(5):704-710
Objective: To analyze the demographic characteristics of patients with red blood cell transfusion reactions, the usage of red blood cell preparations, and the differences in the composition ratio of adverse reactions based on multi-center data from the Haemovigilance Network, in order to reveal the clinical characteristics of red blood cell transfusion and its underlying issues. Methods: Clinical data of patients who experienced transfusion reactions after red blood cell transfusion in the Haemovigilance Network from 2018 to 2023 were collected. The demographic characteristics of patients who experienced transfusion reactions with different types of red blood cell preparations, the utilization of these preparations, and the differences of the composition ratios of transfusion reactions were analyzed. Count data were expressed as numbers (n) or percentages (%), and comparisons between groups were performed using the Chi-square test. Results: Red blood cell transfusion reactions were more common in females (53.56%), with the majority of patients aged 50-69 years (35.54%). The Han polulation accounted for the vast majority of patients (92.77%), and patients in the hematology and obstetrics/gynecology departments had a relatively high proportion of transfusion reactions (13.26% and 14.26%, respectively). Leukocyte-reduced red blood cells and suspended red blood cells were the most common types of transfusion reactions reported among red blood cell preparations. Allergic reactions and non-hemolytic febrile reactions were the most common transfusion reactions, and there were significant differences in the composition ratios of allergic reactions (χ
=869.89, P<0.05) and non-hemolytic febrile reactions (χ
=812.75, P<0.05) across various types of red blood cell preparations. Conclusion: There are differences in the demographic characteristics and composition ratio of transfusion reactions among different red blood cell preparations. The management of red blood cell transfusion reactions should be tailored to patient characteristics and conditions, and the selection and use of blood products should be optimized to reduce or avoid the occurrence of transfusion reactions, such as considering the use of washed red blood cells for patients with a history of transfusion allergies or those prone to allergies.
7.Research Progress of mRNA Chimeric Antigen Receptor Cell Therapy
Xiao ZHOU ; Sheng PAN ; Sunbin LING ; Xiao XU ; Qiang WEI
China Cancer 2025;34(2):152-158
In recent years,viral vector-mediated chimeric antigen receptor(CAR)cell therapy has emerged as a prominent topic in the field of cancer treatment and has demonstrated significant clinical efficacy in patients with hematological malignancies.However,the permanent expression of CAR induced by this therapy may give rise to severe adverse reactions.In contrast,messenger RNA(mRNA)chimeric antigen receptor therapy is anticipated to become a new generation of safer and more effective treatments due to its lack of insertional mutagenesis and minimal risk of off-tar-get toxicity.This therapeutic approach involves transfecting effector immune cells with CAR-en-coding mRNA to elicit an immune response within the body.It has been employed for treating B-cell malignancies,lymphoma,acute myelogenous leukemia(AML),and other cancers.The continuous optimization of mRNA purification,modification,and transfection technology enhances CAR ex-pression durability,while increasing killing efficiency and expanding the range of action.This pa-per reviews the research advances on CAR-encoding mRNA delivery,its application and advan-tages in cancer therapies.
8.Value of the five-sectional screening method of the central nervous system in the first trimester
Lingling SUN ; Chunya JI ; Jun ZHANG ; Qi PAN ; Zhong YANG ; Chen LING ; Linliang YIN ; Xuedong DENG
Chinese Journal of Ultrasonography 2025;34(5):383-390
Objective:To investigate the value of the five-sectional screening method of the central nervous system(CNS)in early detection of fetal CNS abnormalities during the first trimester.Methods:The data of pregnant women who underwent nuchal translucency(NT)screening at the Affiliated Suzhou Hospital of Nanjing Medical University from September 2018 to September 2023 were retrospectively analyzed. And a five-sectional screening method of CNS was performed in all fetuses at the meantime. The five-sectional screening protocol in the first trimester consists of the mid-sagittal plane of the fetal head,trans-ventricular plane,trans-thalamus plane,axial plane of the fetal head at the posterior fossa level,and the sagittal plane of the fetal spine. All fetuses underwent ultrasound screening during the second trimester and the third trimester sequentially after NT screening. All the ultrasound findings were tracked,and all fetuses were followed up until delivery or after induction. Fetuses with CNS abnormalities found or suspected in the first trimester were reviewed by at least one senior physician,and follow-up examinations were routinely performed after 2 weeks to further confirm the diagnosis or find other abnormalities that may be present.Results:A total of 13 679 fetuses were screened,included 11 415 singleton pregnancies and 1 132 twin pregnancies. Among them,there were 289 cases of missed follow-up and unexplained fetal death,included 263 singleton pregnancies and 13 twin pregnancies. A total of 13 390 fetuses were finally included,among which,35 cases developed CNS abnormalities with 34 cases detected by prenatal ultrasound and 1 case of closed spina bifida missed in prenatal diagnosis,and the detection rate of CNS malformation by prenatal ultrasound was 97.14%(34/35). Of the 35 fetuses with CNS abnormalities,24 were detected by the CNS five-sectional screening method in the first trimester,with a sensitivity of 68.57%,a specificity of 100%,a positive predictive value of 100%,and a negative predictive value of 99.92%. Among them,there were 2 cases of anencephaly,3 cases of exencephaly and 6 cases of encephalocele were all detected in the first trimester. In addition,6 cases of holoprosencephaly,3 cases of severe ventriculomegaly,2 cases of open spina bifida,and 2 cases of Dandy-Walker malformation were detected in the first trimester. In this study,1 case of agenesis of corpus callosum(ACC),1 case of arachnoid cyst,1 case of lissencephaly,1 case of schizencephaly,and 1 case of mega cisterna magna were not detected in early pregnancy.Conclusions:The fetal five-sectional screening method of CNS in the first trimester has high specificity,positive predictive value and negative predictive value for the detection of fetal CNS abnormalities,but the sensitivity is moderate. The five-sectional screening method for CNS in early pregnancy may be an effective method for early detection of fetal CNS abnormalities.
9.Diagnostic value of fetal cardiac ultrasound screening views in the first trimester for congenital heart disease
Chengcheng WU ; Chunya JI ; Liqun FENG ; Wei SHAO ; Naimin SUN ; Jun ZHANG ; Zhong YANG ; Chen LING ; Lingling SUN ; Qi PAN ; Xuedong DENG ; Linliang YIN
Chinese Journal of Ultrasonography 2025;34(9):799-804
Objective:To investigate the diagnostic value of fetal cardiac ultrasound view visualization in the first trimester for congenital heart disease(CHD).Methods:A retrospective analysis was performed on 13 323 singleton fetuses who underwent first-trimester(11-13 +6 weeks)ultrasound screening at the Ultrasound Medicine Center,the Affiliated Suzhou Hospital of Nanjing Medical University from January 2018 to June 2024. Cardiac views including the four-chamber view(4CV),left ventricular outflow tract view(LVOT),and Results:The study group showed significantly higher rates of "poorly visualized" 4CV,LVOT,and 3VT than the control group(2.70% vs. 0.14%, P=0.005;36.49% vs. 4.76%, P<0.001;36.49% vs.2.46%, P<0.001). The efficacies of combination 1(any view abnormal)and combination 2(any view "poorly visualized" or "abnormal")were comparable,with AUCs of 0.86 and 0.85( P=0.424). The AUCs of combination 3(3VT "poorly visualized" or any view "abnormal")and combination 4(4CV "poorly visualized" or any view "abnormal")were 0.88 and 0.86( P=0.424),all significantly higher than combination 5(LVOT "poorly visualized" or any view "abnormal",AUC=0.84,all P<0.05). Conclusions:"Poorly visualized" cardiac views in the first trimester demonstrate good diagnostic efficacy for CHD,particularly when 3VT or 4CV are affected,warranting heightened clinical vigilance for fetal cardiac anomalies.
10.Comparison of arthroscopic en masse repair versus modified separate repair for type Ⅰ delaminated rotator cuff tears
Hongwu ZHUO ; Ling PAN ; Yushun WU ; Jian LI
Chinese Journal of Orthopaedic Trauma 2025;27(8):689-694
Objective:To compare the outcomes between the arthroscopic en masse repair and the modified separate repair for type Ⅰ delaminated rotator cuff tears.Methods:This retrospective study analyzed the clinical data of 46 patients who had been treated for delaminated rotator cuff tears at Department of Sports Medicine, The Second People's Hospital of Fujian Province from January 2021 to January 2023. This cohort consisted of 15 males and 31 females, with an age of (58.2±9.0) years. Their delaminated rotator cuff tears were all classified as typeⅠ according to Choo et al. According to different surgical methods, they were divided into 2 groups: group A (22 cases) was treated by arthroscopic en masse repair while group B (24 cases) by arthroscopic modified separate repair. The 2 groups were compared in terms of forward flexion, external rotation, internal rotation, visual analogue scale (VAS) for pain, American Shoulder and Elbow Surgeons (ASES) score, and Constant-Murley score at preoperation and the last follow-up. MRI was used to evaluate the healing status of rotator cuff at the last follow-up.Results:There was no significant difference in the baseline data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up for 26.0 (24.0, 28.0) months. At the last follow-up, the external rotation (57.3°±15.7°), ASES score [(97.5±3.6) points] and Constant-Murley score [(93.7±3.0) points] in group B were significantly better than those in group A [40.9°±17.7°, (85.5±18.3) points, and (78.6±22.7) points] ( P<0.05), but the differences in forward flexion, internal rotation or VAS pain score were not significantly different between the 2 groups ( P>0.05). In both groups A and B, significant improvements were achieved at the last follow-up in forward flexion, external rotation, internal rotation, VAS pain score, ASES score, and Constant-Murley score compared with the preoperative period ( P<0.05). At the last follow-up, in group A and group B respectively, the rotator cuff was completely healed in 9 and 18 cases, partially healed in 10 and 6 cases, and re-torn in 3 and 0 cases, showing significant differences in the healing status between the 2 groups ( P<0.05). Conclusion:In the treatment of type Ⅰ delaminated rotator cuff tears, the modified separate repair can obtain significantly better external rotation, ASES score, Constant-Murley score, and healing status of rotator cuff than the arthroscopic en masse repair.


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