1.The predictive value of serum HOXA6 and HOXA10 levels for endometrial receptivity in patients with diminished ovarian reserve
Clinical Medicine of China 2025;41(6):458-465
Objective:To investigate the predictive value of serum HOXA6 and HOXA10 levels in assessing endometrial receptivity in patients with diminished ovarian reserve (DOR).Methods:A total of 248 DOR patients treated at Xi'an People's Hospital from January 2021 to October 2023 were enrolled, with 200 healthy female volunteers as controls. Serum HOXA6 and HOXA10 concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Endometrial thickness was assessed via transvaginal ultrasound on days 20-24 of the menstrual cycle, and endometrial receptivity was classified into high receptivity (≥8 mm), moderate receptivity (6-8 mm) and low receptivity (<6 mm) group. Follicle-stimulating hormone (FSH) and anti-Müllerian hormone (AMH) levels were detected by chemiluminescence immunoassay on day 3 of the menstrual cycle. Follicle count and size were recorded via transvaginal ultrasound. Normally distributed data were expressed as Mean±SD, comparison between two groups was performed by independent samples t-test, comparison among multiple groups was performed by one-way ANOVA, pairwise comparison was performed by Tukey's HSD post hoc test. Categorical data were presented as rates or percentages and analyzed by χ2 test. Logistic regression identified independent risk factors for DOR, and Pearson correlation analyzed relationships between HOXA6/HOXA10, endometrial receptivity, and ovarian reserve. Receiver operating characteristic (ROC) curves evaluated the diagnostic value of HOXA6 and HOXA10 in predicting endometrial receptivity. Results:Serum levels of both HOXA6 [(120.34±15.16) ng/L] and HOXA10 [(98.46±12.61) ng/L] in the DOR group were significantly higher than those in the control group [(80.27±10.54) ng/L and (60.36±8.80) ng/L, respectively, t=31.70, 36.20, both P<0.001]. Endometrial thickness in the DOR group [(7.4±1.3) mm] was significantly less than that in the control group [(10.0±1.1) mm]. Serum FSH levels [(12.03±2.54) U/L] were significantly higher in the DOR group compared to the control group [(8.08±2.82) U/L], while AMH levels [(1.56±0.45) μg/L] and the number of follicles [(3.52±1.63) μg/L] were significantly lower than those in the control group [(5.07±1.05) μg/L and (10.09±2.06), respectively]. The differences between the two groups for these parameters were statistically significant ( t=22.52, 15.58, 18.10, 33.58, respectively; all P<0.001). Pearson correlation analysis revealed that serum HOXA6 and HOXA10 levels were negatively correlated with endometrial thickness, AMH levels, and the number of follicles in DOR patients (HOXA6: r=-0.773, -0.647, -0.721, respectively, all P<0.001; HOXA10: r=-0.788, -0.682, -0.834, respectively, all P<0.001), and positively correlated with serum FSH levels ( r=0.667 and 0.670, respectively, both P<0.001). Multivariate logistic regression analysis indicated that serum HOXA6 ( OR=1.179, 95% CI: 1.144-1.215, P<0.001), HOXA10 ( OR=1.223, 95% CI: 1.177-1.270, P<0.001), and FSH levels ( OR=1.827, 95% CI: 1.569-2.129, P<0.001) were independent risk factors for DOR in women. Endometrial thickness ( OR=0.264, 95% CI: 0.205-0.340, P<0.001), serum AMH levels ( OR=0.126, 95% CI: 0.078-0.205, P<0.001), and the number of follicles ( OR=0.058, 95% CI: 0.024-0.143, P<0.001) were identified as protective factors against DOR. ROC curve analysis showed that the AUCs for serum HOXA6, HOXA10, and their combination in predicting poor endometrial receptivity in DOR patients were 0.770, 0.820, and 0.864, respectively. The AUC value for HOXA10 was slightly higher than that for HOXA6, and the combined prediction model had the highest AUC value. Conclusion:Serum HOXA6 and HOXA10 levels demonstrate a statistically significant association with ovarian reserve function and endometrial receptivity. These findings suggest their potential as diagnostic biomarkers for assessing endometrial receptivity in patients with diminished ovarian reserve (DOR).
2.A case report on multidisciplinary team collaborative diagnosis and treatment of severe immune checkpoint inhibitor-related myocarditis
Zhu JIXIANG ; He YIZI ; Guan QINGPEI ; Liu PANPAN ; Wang DONGHAO ; Li ZHIMING ; Zhou HUI
Chinese Journal of Clinical Oncology 2025;52(18):950-956
With the widespread useof immune checkpoint inhibitors(ICIs)in the treatment of various solid tumors,immune-related adverse events have attracted increasing clinical attention.Although ICI-associated myocarditis is rare,it typically has an insidious onset,progresses rapidly,and carries a high mortality rate,making it one of the most severe complications of ICI therapy.Early recognition and management remain challenging due to the absence of standardized diagnostic and therapeutic guidelines.ICI-associated myocarditis is characterized by the following features,with symptom onset commonly occurring within weeks of initiating ICI therapy.Its clinical manifestations are often non-specific and can be misdiagnosed as coronary artery disease or viral myocarditis.Prompt administration of high-dose corticosteroids combined with immunosuppressants,cardiac rhythm and functional support,is crucial for effective management.Although numerous stud-ies highlight the importance of early detection and multidisciplinary collaboration,there is still no consensus on standardized treatment pro-tocols.This report describes a case of acute ICI-associated myocarditis with ovarian cancer who developed symptoms after receiving com-bined apalutamide and toripalimab therapy.The patient responded well to corticosteroid pulse therapy,second-line immunosuppressants,and intensive care support.Due to recurrent ventricular arrhythmias,an implantable cardioverter defibrillator was placed,and cardiac func-tion remained stable during follow-up.Through this case and a review of the relevant literature,we discuss the clinical features,compre-hensive treatment strategies,and long-term management approaches for ICI-associated myocarditis,aiming to raise clinical awareness,pro-mote standardized multidisciplinary team collaboration,and ultimately improve patient outcomes.
3.Analysis of factors influencing the deterioration of nutritional status after radiotherapy/radiochemotherapy for esophageal cancer
Liqun CAO ; Panpan GAN ; Heling ZHU ; Han CHEN ; Nalin SUN ; Lihao CHEN ; Jiawen YU
Academic Journal of Naval Medical University 2025;46(5):674-680
Objective To analyze the factors influencing the deterioration of nutritional status after radiotherapy/radiochemotherapy for esophageal cancer,so as to provide reference for nutritional management during antitumor therapy.Methods A total of 106 patients with esophageal cancer who received radiotherapy or radiochemotherapy at Anqing First People's Hospital of Anhui Medical University from Dec.2017 to Dec.2023 were enrolled.Patients'gender,age,surgical history,timing of radiotherapy intervention,synchronous chemoradiotherapy,radiotherapy dose,clinical stage,initial nutritional status,and performance status score were collected.The patient generated subjective global assessment scale(PG-SGA)scores were monitored before and after antitumor treatment.According to the nutritional status at the beginning of enrollment and at the end of radiotherapy,the patients were assigned to deterioration group or non-deterioration(stable or improved)group.The clinical characteristics of the 2 groups were compared.The factors influencing the deterioration of nutritional status were screened by logistic regression analysis.The correlation between nutritional status deterioration and adverse reactions(radiation esophagitis,pulmonary infection,neutropenia,thrombocytopenia,and elevated aminotransferase)was analyzed by Spearman correlation analysis.Results There were no significant differences in gender,radiotherapy dose,initial nutritional status,or performance status score between the 2 groups for the deterioration of nutritional status after radiotherapy(all P>0.05).The proportions of patients with previous surgical history of esophageal cancer,synchronous chemoradiotherapy,initiation of radiotherapy at less than 90%of target calorie requirement,and clinical stage Ⅳ were significantly higher in the deterioration group than those in the non-deterioration group(all P<0.05).Logistic regression analysis showed that clinical stage Ⅳ(odds ratio[OR]=4.684,95%confidence interval[CI]1.252-17.519,P=0.022)and previous surgical history of esophageal cancer(OR=7.338,95%CI 1.878-28.666,P=0.004)were the independent adverse risk factors for the deterioration of nutritional status after radiotherapy/radiochemotherapy.The timing of radiotherapy intervention was also an independent risk factor for the deterioration of nutritional status,and taking the tolerance of 70%-90%target energy as the reference level,starting radiotherapy when the tolerance of 90%-100%target energy had the optimal protection of nutritional status(OR=0.166,95%CI 0.050-0.551,P=0.003).Spearman correlation analysis showed that the deterioration of nutritional status was positively correlated with elevated transaminases after radiotherapy(rs=0.283,P=0.003),while it was not correlated with the other adverse reactions(all P>0.05).Conclusion Under the standard nutritional intervention model,patients with previous surgery and recurrent metastatic esophageal cancer who receive radiotherapy/chemoradiotherapy are still at risk of nutritional status deterioration.Tolerance to 90%-100%target energy requirement may be a more appropriate timing for radiotherapy intervention.When the nutritional status deteriorates during treatment,it is necessary to be alert to the elevated transaminases.
4.Correlations of expression levels of microRNA-147,Ki-67 and carcinoembryonic antigen with lymph node metastasis in invasive pulmonary adenocarcinoma
Journal of Clinical Medicine in Practice 2025;29(14):7-12
Objective To explore correlations of expression levels of microRNA-147(miR-147),Ki-67 and carcinoembryonic antigen(CEA)with lymph node metastasis of invasive lung adenocarci-noma.Methods A total of 160 patients with invasive pulmonary adenocarcinoma were selected as study subjects.Based on presence of lymph node metastasis,patients were divided into lymph node metastasis group(n=74)and non-lymph node metastasis group(n=86).Immunohistochemistry was employed to detect the expression levels of miR-147 and Ki-67 in cancer tissues.The serum CEA level was measured using the chemiluminescence method.The correlations of the expression levels of miR-147,Ki-67 and serum CEA with the clinicopathological characteristics of patients were analyzed.The value of miR-147,Ki-67 and CEA in predicting lymph node metastasis was evaluated using the receiver operating characteristic(ROC)curve.Results The expression level of miR-147 in the lymph node metastasis group was significantly lower than that in the non-lymph node metastasis group,while the expression levels of Ki-67 and serum CEA were significantly higher in the lymph node me-tastasis group than in the non-lymph node metastasis group(P<0.05).Patients with a tumor diameter≥3 cm or TNM stage Ⅲ to Ⅳ had significantly lower miR-147 expression levels in cancer tissues compared to those with a tumor diameter<3 cm or TNM stage Ⅰ to Ⅱ(P<0.05).The Ki-67 ex-pression level in cancer tissues was significantly higher in patients with a tumor diameter ≥3 cm than in those with a tumor diameter<3 cm(P<0.05).The serum CEA level was significantly higher in patients with TNM stage Ⅲ to Ⅳ than in those with TNM stage Ⅰ to Ⅱ(P<0.05).The expres-sion level of miR-147 was negatively correlated with Ki-67,serum CEA and lymph node metastasis(P<0.05);Ki-67 and serum CEA were positively correlated with lymph node metastasis(P<0.05);Ki-67 was positively correlated with serum CEA(P<0.05).The areas under the ROC curves for miR-147,Ki-67 and CEA in predicting lymph node metastasis were 0.785,0.835 and 0.798,respectively(P<0.05).Conclusion The expression levels of miR-147 and Ki-67 in cancer tissues and the serum CEA level are correlated with lymph node metastasis in invasive pulmo-nary adenocarcinoma.
5.Screening and verification of oxidative stress-related genes in silicosis mouse model based on transcriptomics sequencing
Panpan ZHU ; Yuan WANG ; Chunchao ZHENG ; Hongli WANG ; Hailan HE ; Heliang LIU
China Occupational Medicine 2025;52(5):481-488
Objective To screen and analyze the differentially expressed genes (DEGs) related to oxidative stress in a silicosis mouse model using transcriptome sequencing technology. Methods i) A total of 30 workers without occupational dust-exposed history were selected as the control group and 17 patients with silicosis were selected as the silicosis group using a judgment sampling method. The levels of glutathione and malondialdehyde in the plasma of workers in the two groups were determined by enzyme-linked immunosorbent assay. ii) RAW264.7 cells in the logarithmic growth phase were randomly divided into the control group and the silica group, treated with 0 and 50 mg/L silica suspensions for 24 hours. Protein expression of superoxide dismutase 2 (SOD2), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) in the cells was determined by Western blotting. iii) The specific pathogen free male C57BL/6 mice were randomly divided into the control group and the silicosis model group, with 10 mice in each group. Mice were exposed to 50 μL of 0.9% sodium chloride solution and silica suspension at a mass concentration of 100 g/L, respectively, using a single tracheal exposure method. After 28 days of exposure, the pathological changes of mouse lung tissues were observed. Transcriptome sequencing was used to screen DEGs in the lung tissues of the silicosis mouse model, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed. The expression of DEGs was verified using quantitative real-time polymerase chain reaction (qPCR). Results i) The level of malondialdehyde in the patients′ plasma was higher (P<0.01), while the level of glutathione was lower (P<0.01) in the silicosis group than that of the control group. ii) The relative expression of SOD2 protein decreased (P<0.05), while the relative expression of IL-6 and TNF-α proteins increased (all P<0.05) in the silica group of RAW264.7 cells compared with the control group. iii) The pathological results of lung tissues showed that the alveolar structure of mice was destroyed and silicotic nodules were formed in the silicosis model group. Transcriptome sequencing identified 3 703 DEGs, of which 3 199 were significantly down-regulated and 504 were significantly up-regulated. The GO enrichment analysis results showed that the DEGs were significantly enriched in biological processes such as oxidative stress, inflammation, immunity and hypoxia, with cellular components mainly located in membranes, cytoplasm, and nucleus. Molecular functions were enriched in oxidoreductase activity, protein binding, and adenosine triphosphate binding. The KEGG enrichment analysis results showed that the DEGs were mainly involved in the phosphatidylinositol 3-kinase-protein kinase B signaling pathway, cyclic adenosine monophosphate signaling pathway, chemokine signaling pathway, and apoptosis signaling pathway. A total of 28 DEGs involved in the "oxidative stress response" pathway were screened by GO enrichment analysis. The qPCR verification results showed that the relative expression of DEGs carbonic anhydrase 3 (Car3), matrix metalloproteinase 9 (Mmp9), and MutY DNA glycosylase (Mutyh) involved in the "oxidative stress response" of lung tissues in the silicosis model group were lower than those of the control group (all P<0.05). Conclusion Oxidative stress response exists in silicosis patients. The oxidative stress-related genes Car3, Mmp9, and Mutyh are altered in the mouse lung tissues of the silicosis model through the oxidative stress pathway, suggesting that they could be new targets for the treatment of silicosis.
6.Effect of time intervals of priming continuous theta burst stimulationon on cortical plasticity induced by intermit-tent theta burst stimulation
Ayan GENG ; Qinglei WANG ; Junfan SHEN ; Shizhe ZHU ; Panpan JI ; Tong WANG ; Chuan GUO
Chinese Journal of Rehabilitation Theory and Practice 2025;31(5):607-612
Objective To investigate the effect of continuous theta burst stimulation-intermittent theta burst stimulation(cTBS-iT-BS)priming protocols with different time intervals on the plasticity of primary motor cortex(M1).Methods A total of 39 healthy young adults were recruited from Changzhou De'an Hospital from March to August,2024.Participants received cTBS-iTBS priming protocols with intervals of 5 minutes,10 minutes and 15 minutes using a randomized crossover design.Motor-evoked potential(MEP)amplitudes in M1 were recorded at baseline(before intervention)and 0 minute,10 minutes,20 minutes and 30 minutes after intervention.Results The main effects of stimulation protocol(F=19.761,P<0.001)and measurement time(F=10.224,P<0.001)were significant.At each time point after intervention,the MEP amplitude was significantly higher under the 10-minute interval than under the 5-minute and 15-minute intervals(t>3.010,P<0.05).Conclusion The 10-minute interval of cTBS-iTBS is more effective on M1 plasticity.
7.Construction and identification of recombinant fowl adenovirus 4 expressing Cap protein of goose astrovirus virus genotype 2
Xingyu LI ; Yan LI ; Panpan YANG ; Junjie LIU ; Mengjia XIANG ; Yutao ZHU ; Luyao QIU ; Qilong QIAO ; Boshun ZHANG ; Dexin BU ; Chenghao HAN ; Chunmei YU ; Yanfang CONG ; Zeng WANG ; Jianli LI ; Baiyu WANG ; Jun ZHAO
Chinese Journal of Veterinary Science 2025;45(3):443-448,513
To construct a recombinant fowl adenovirus 4(FAdV-4)expressing the Cap protein of goose astrovirus genotype 2(GoAstV-2),the expression cassette of Cap gene was inserted into the natural 1 966 bp deletion region of the FAdV-4 genome in the infectious clone p15A-cm-FAdV4-HNJZ.The resulted recombinant plasmid p15A-cm-FAdV4-HNJZ-Cap/GoAstV-2 was linearized with restriction enzyme and transfected into chicken hepatoma cell line(LMH)to rescue the recombinant FAdV-4 expressing the Cap protein of GoAstV-2,rF Ad V4-Cap/GoAstV-2.After 15 passages in LMH cells,the recombinant rFAdV4-Cap/GoAstV-2 was identified by PCR using primers flanking the insertion site of the Cap gene expression cassette and using viral genome DNA extracted from rFAdV4-Cap/GoAstV-2 infected LMH cells as template.LMH cells were in-fected with 15th passage rFAdV4-Cap/GoAstV-2 and indirect immunofluorescence was performed with a polyclonal antibody against Cap protein as the primary antibody.Western blot was carried out with lysates of rFAdV4-Cap/GoAstV-2 infected LMH cells.The in vitro replication dynamic of the 15th passage of the rFAdV4-Cap/GoAstV-2 was also investigated in LMH cells.The results demonstrated that the Cap gene of GoAstV-2 was presented in the genome of the recombinant vi-rus rF AdV4-Cap/Go Ast V-2,and could be expressed stably.The prepared recombinant virus in this study will lay a foundation for developing inactivated bivalent vaccine candidate against co-in-fection of FAdV-4 and GoAstV-2 in goose.
8.Distribution of infectious keratitis pathogens and drug resistance in Nantong, China in recent 10 years
Panpan LI ; Huaijin GUAN ; Yangchen GUO ; Qi CAI ; Yan ZHU ; Mudong XU ; Yong WANG
Chinese Journal of Experimental Ophthalmology 2025;43(8):722-729
Objective:To investigate the ocular pathogen spectrum and drug sensitivity characteristics of patients to be diagnosed with infectious keratitis within 10 years in two tertiary hospitals in Nantong City, Jiangsu Province, eastern China.Methods:A cross-sectional study was conducted.Microbial culture specimens from consecutive 1 404 patients with suspected infectious keratitis admitted to the Department of Ophthalmology at the First People's Hospital of Nantong City and Nantong University Affiliated Hospital from January 2014 to October 2023 were collected.The patients' general data, etiology and drug sensitivity test results were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Nantong First People's Hospital (No.2021KT273) and Nantong University Affiliated Hospital (No.2019-K068).Results:Among 1 404 patients with suspected infectious keratitis, the positive rate of microbial culture was 37.04%(520/1 404).A total of 537 strains were isolated and cultured, with fungi accounting for 69.09%(371/537) and bacteria accounting for 30.91%(166/537).The common bacterial genera in fungal keratitis were Fusarium (47.17%, 175/371), Alternaria (15.90%, 59/371), Aspergillus (14.56%, 54/371), Certospora (10.78%, 40/371) and Penicillium (3.50%, 13/371).The annual composition ratio of Fusarium showed a downward trend, while Certospora showed an upward trend.The common bacteria in bacterial keratitis were Staphylococcus epidermidis (24.10%, 40/166), Streptococcus pneumoniae (17.47%, 29/166), Pseudomonas aeruginosa (13.25%, 22/166), Staphylococcus aureus (6.63%, 11/166) and Corynebacterium macginleyi (4.22%, 7/166).The annual composition ratio of Pseudomonas aeruginosa showed an increasing trend.The resistance rates of gram-positive bacteria to levofloxacin and vancomycin were 36.26% and 0% respectively, and the resistance rates of gram-negative bacteria to aminoglycosides and ceftazidime were <10%.A total of 61 bacterial strains (40.94%) were multi-drug resistant. Conclusions:Fusarium is common in fungal keratitis, and Corynebacterium macginleyi in bacterial keratitis may be a microbial feature in Nantong City.Levofloxacin may no longer be suitable as a first-line antibiotic for topical ocular use.
9.Distribution of infectious keratitis pathogens and drug resistance in Nantong, China in recent 10 years
Panpan LI ; Huaijin GUAN ; Yangchen GUO ; Qi CAI ; Yan ZHU ; Mudong XU ; Yong WANG
Chinese Journal of Experimental Ophthalmology 2025;43(8):722-729
Objective:To investigate the ocular pathogen spectrum and drug sensitivity characteristics of patients to be diagnosed with infectious keratitis within 10 years in two tertiary hospitals in Nantong City, Jiangsu Province, eastern China.Methods:A cross-sectional study was conducted.Microbial culture specimens from consecutive 1 404 patients with suspected infectious keratitis admitted to the Department of Ophthalmology at the First People's Hospital of Nantong City and Nantong University Affiliated Hospital from January 2014 to October 2023 were collected.The patients' general data, etiology and drug sensitivity test results were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Nantong First People's Hospital (No.2021KT273) and Nantong University Affiliated Hospital (No.2019-K068).Results:Among 1 404 patients with suspected infectious keratitis, the positive rate of microbial culture was 37.04%(520/1 404).A total of 537 strains were isolated and cultured, with fungi accounting for 69.09%(371/537) and bacteria accounting for 30.91%(166/537).The common bacterial genera in fungal keratitis were Fusarium (47.17%, 175/371), Alternaria (15.90%, 59/371), Aspergillus (14.56%, 54/371), Certospora (10.78%, 40/371) and Penicillium (3.50%, 13/371).The annual composition ratio of Fusarium showed a downward trend, while Certospora showed an upward trend.The common bacteria in bacterial keratitis were Staphylococcus epidermidis (24.10%, 40/166), Streptococcus pneumoniae (17.47%, 29/166), Pseudomonas aeruginosa (13.25%, 22/166), Staphylococcus aureus (6.63%, 11/166) and Corynebacterium macginleyi (4.22%, 7/166).The annual composition ratio of Pseudomonas aeruginosa showed an increasing trend.The resistance rates of gram-positive bacteria to levofloxacin and vancomycin were 36.26% and 0% respectively, and the resistance rates of gram-negative bacteria to aminoglycosides and ceftazidime were <10%.A total of 61 bacterial strains (40.94%) were multi-drug resistant. Conclusions:Fusarium is common in fungal keratitis, and Corynebacterium macginleyi in bacterial keratitis may be a microbial feature in Nantong City.Levofloxacin may no longer be suitable as a first-line antibiotic for topical ocular use.
10.Effect of time intervals of priming continuous theta burst stimulationon on cortical plasticity induced by intermit-tent theta burst stimulation
Ayan GENG ; Qinglei WANG ; Junfan SHEN ; Shizhe ZHU ; Panpan JI ; Tong WANG ; Chuan GUO
Chinese Journal of Rehabilitation Theory and Practice 2025;31(5):607-612
Objective To investigate the effect of continuous theta burst stimulation-intermittent theta burst stimulation(cTBS-iT-BS)priming protocols with different time intervals on the plasticity of primary motor cortex(M1).Methods A total of 39 healthy young adults were recruited from Changzhou De'an Hospital from March to August,2024.Participants received cTBS-iTBS priming protocols with intervals of 5 minutes,10 minutes and 15 minutes using a randomized crossover design.Motor-evoked potential(MEP)amplitudes in M1 were recorded at baseline(before intervention)and 0 minute,10 minutes,20 minutes and 30 minutes after intervention.Results The main effects of stimulation protocol(F=19.761,P<0.001)and measurement time(F=10.224,P<0.001)were significant.At each time point after intervention,the MEP amplitude was significantly higher under the 10-minute interval than under the 5-minute and 15-minute intervals(t>3.010,P<0.05).Conclusion The 10-minute interval of cTBS-iTBS is more effective on M1 plasticity.

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