Objective: To analyze the timeliness of antir-etroviral therapy (ART) and its influencing factors among newly reported HIV/AIDS cases in Wenzhou City, Zhejiang Province from 2016 to 2023, so as to provide a reference for improving the ART effect of HIV/AIDS cases. Methods: Newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were selected as the research subjects. Demographic information, the situation of the first CD4+ T lymphocyte (CD4 cell) test, baseline CD4 cell count, and ART situation were collected through the Chinese Disease Prevention and Control Information System. The timely rate of ART was analyzed, and the influencing factors for timely ART among HIV/AIDS cases were analyzed using a multivariable logistic regression model. Results: A total of 4 500 newly reported HIV/AIDS cases in Wenzhou City from 2016 to 2023 were included, among which 3 679 were males, accounting for 81.76%, and 821 were females, accounting for 18.24%. The median age was 46.24 (interquartile range, 26.23) years. Among these cases, 3 606 received timely ART, with a timely rate of 80.13%. The timely rate of ART increased from 57.54% in 2016 to 91.97% in 2023 (P<0.05). Multivariable logistic regression analysis showed that unmarried/divorced/widowed (OR=0.769, 95%CI: 0.641-0.922), detainees (OR=0.492, 95%CI: 0.269-0.900), untimely first CD4 cell test (OR=0.278, 95%CI: 0.234-0.330), baseline CD4 cell count ≥200 cells/µL (OR=0.709, 95%CI: 0.595-0.843) or undetected (OR=0.131, 95%CI: 0.080-0.213) were associated with a lower timeliness for ART among HIV/AIDS cases. Conclusion From 2016 to 2023, the timely rate of ART among newly reported HIV/AIDS cases in Wenzhou City showed an upward trend, which was mainly affected by marital status, case source, timeliness of the first CD4 cell test, and baseline CD4 cell count.

The elevated polyamines, amine-rich molecules with diverse functions in pathophysiology processes, are implicated in contributing to tumorigenesis and progression. Whether and how they affect the efficacy of chemotherapy is incompletely understood. Our screening assays reveal that the supplement with a low dose of spermidine (Spd), one of the polyamines, enhances ferroptosis in prostate cancer cells as evidenced by increased lipid peroxidation and intracellular Fe²⁺ levels in vitro. Combination treatment with Spd and a low dose of ferroptosis inducer erastin synergistically augments anti-tumor efficacy with undetectable toxicity in mice. Analysis of RNA-seq data indicates that heme oxygenase 1 (HMOX1), an enzyme that catalyzes the cleavage of heme to release Fe²⁺, is significantly upregulated in response to Spd and erastin cotreatment. Spd mediated the hypusine modification of the eukaryotic initiation factor 5A (EIF5A) promotes the translation of the nuclear factor erythroid 2-related factor 2 (NRF2), subsequently leading to elevation of HMOX1. Moreover, Spd and erastin significantly inhibit proteasome activity which results in a decrease in proteasomal degradation of NRF2, although many proteasome-related genes are induced either by Spd or Spd plus erastin. Thus, in addition to its pro-oncogenic activity, the supplement of Spd improves antitumor activity in combination with ferroptosis inducers and offers an optional approach to cancer treatment.

Objective:To evaluate the efficacy of curative esophagectomy versus definitive chemoradiotherapy (dCRT) in patients with clinical T1bN0M0 thoracic esophageal cancer.Methods:The propensity score matching (PSM) and retrospective cohort study was conducted. The clinico-pathological data of 163 patients with clinical T1bN0M0 thoracic esophageal cancer who were admitted to Henan Provincial People′s Hospital from January 2014 to December 2020 were collected. There were 125 males and 38 females, aged (58.9±7.0)years. Of 163 patients, 124 cases undergoing curative transthoracic esophagectomy were allocated into the radical resection group, 39 cases undergoing dCRT were allocated into the dCRT group. Observation indicators:(1) PSM and compari-son of clinicopathological characteristics of patients between the two groups after matching; (2) complications in the radical resection group and treatment status in the dCRT group; (3) survival analysis; (4) analysis of factors influencing patients′ prognosis. Comparison of measurement data with normal distribution between groups was conducted using the Welch t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Cox proportional hazard model was used for univariate and multivariate analyses. The Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. PSM was performed using the 2∶1 nearest neighbor matching method. The caliper value was set as 0.05. Results:(1) PSM and comparison of clinicopathological charac-teristics of patients between the two groups after matching. Of the 163 patients, 117 cases were successfully matched, with 78 cases in the radical resection group and 39 cases in the dCRT group. After PSM, the elimination of tumor differentiation degree confounding bias ensured comparability. (2) Complications in the radical resection group and treatment status in the dCRT group.Among the 78 patients in the curative esophagectomy group, 22 cases developed complications within 30 days after surgery. There was no death within 30 days after surgery. Among the 39 patients in the dCRT group, 25 cases received concurrent chemoradiotherapy alone, 8 cases received induction chemo-therapy followed by concurrent chemoradiotherapy, 3 cases received sequential chemoradiotherapy, and 3 cases received radiotherapy alone. Among the 33 patients who received concurrent chemo-radiotherapy, 29 cases were treated with the XP regimen, and 4 cases with the FP regimen. Efficacy evaluation showed that 37 patients achieved complete remission, and 2 patients had residual lesions. Twenty-two patients developed treatment-related adverse reactions. (3) Survival analysis. After PSM, the follow-up duration was 58(range, 13-125)months in the radical resection group and 56(range, 10-129)months in the dCRT group. The postoperative 5-year overall survival rates were 95.7% and 97.1% in the radical resection group and dCRT group, respectively, showing no significant difference between the two groups ( χ2=0.001, P>0.05). The postoperative 5-year disease-free progression survival rates were 88.2% and 94.2% in the radical resection group and dCRT group, respectively, showing no significant difference between the two groups ( χ2=0.652, P>0.05). (4) Analysis of factors influencing patients prognosis. Age and pathological TNM stage were indepen-dent influencing factors for overall survival time in patients with clinical T1bN0M0 thoracic esophageal cancer ( hazard ratio=1.312, 2.945, 95% confidence interval as 1.042-1.711, 2.204-5.517, P<0.05). Age and pathological TNM stage were independent influencing factors for disease-free survival time in patients with clinical T1bN0M0 thoracic esophageal cancer ( hazard ratio=1.215, 3.301, 95% confidence interval as 1.012-1.699, 2.012-6.321, P<0.05). Conclusions:There is no significant difference in overall survival and disease-free survival between patients with clinical T1bN0M0 thoracic esophageal cancer undergoing curative esophagectomy and dCRT. The treatment modality is not an independent prognostic factor.

Objective To investigate the effect of T2-fluid attenuated inversion recovery(T2-FLAIR)sequence on the appearance of ivy sign in patients with moyamoya disease under different imaging conditions.Methods Coronal T2-FLAIR scans were performed in 51 consecutive adult patients with moyamoya disease who had not undergone surgery and had their first visit to this hospital between March and July of 2024.According to the scanning conditions,the patients were divided into 19 and 14 of the echo train length in two groups,and 103,144,and 195 ms of the time of echo(TE)in three groups,respectively.The left and right cerebral hemispheres and whole brains were scored according to the cerebral vascular anatomy,and scores of the ivy sign of left and right cerebral hemispheres and whole brain were compared.Results There was no statistical significance in the ivy sign scores of right and left cerebral hemispheres and whole brain between the two groups with 19 and 14 of the echo train length(P＞0.05).Comparison of ivy sign scores in right and left cerebral hemispheres and whole brain was statistically significant among the three groups of TE at 144,103 and 195 ms(P＜0.05).Conclusion The best appearance of ivy sign in patients with moyamoya disease is seen under the condition of TE at 195 ms,so appropriately extending the TE time is helpful for ivy sign display.

Objective:The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation.Methods:A male proband who presented with bilateral sensorineural hearing loss at Henan Children′s Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family.Results:In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion:The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.

Objective:To evaluate the efficacy of curative esophagectomy versus definitive chemoradiotherapy (dCRT) in patients with clinical T1bN0M0 thoracic esophageal cancer.Methods:The propensity score matching (PSM) and retrospective cohort study was conducted. The clinico-pathological data of 163 patients with clinical T1bN0M0 thoracic esophageal cancer who were admitted to Henan Provincial People′s Hospital from January 2014 to December 2020 were collected. There were 125 males and 38 females, aged (58.9±7.0)years. Of 163 patients, 124 cases undergoing curative transthoracic esophagectomy were allocated into the radical resection group, 39 cases undergoing dCRT were allocated into the dCRT group. Observation indicators:(1) PSM and compari-son of clinicopathological characteristics of patients between the two groups after matching; (2) complications in the radical resection group and treatment status in the dCRT group; (3) survival analysis; (4) analysis of factors influencing patients′ prognosis. Comparison of measurement data with normal distribution between groups was conducted using the Welch t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the Mann-Whitney U test. The Cox proportional hazard model was used for univariate and multivariate analyses. The Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. PSM was performed using the 2∶1 nearest neighbor matching method. The caliper value was set as 0.05. Results:(1) PSM and comparison of clinicopathological charac-teristics of patients between the two groups after matching. Of the 163 patients, 117 cases were successfully matched, with 78 cases in the radical resection group and 39 cases in the dCRT group. After PSM, the elimination of tumor differentiation degree confounding bias ensured comparability. (2) Complications in the radical resection group and treatment status in the dCRT group.Among the 78 patients in the curative esophagectomy group, 22 cases developed complications within 30 days after surgery. There was no death within 30 days after surgery. Among the 39 patients in the dCRT group, 25 cases received concurrent chemoradiotherapy alone, 8 cases received induction chemo-therapy followed by concurrent chemoradiotherapy, 3 cases received sequential chemoradiotherapy, and 3 cases received radiotherapy alone. Among the 33 patients who received concurrent chemo-radiotherapy, 29 cases were treated with the XP regimen, and 4 cases with the FP regimen. Efficacy evaluation showed that 37 patients achieved complete remission, and 2 patients had residual lesions. Twenty-two patients developed treatment-related adverse reactions. (3) Survival analysis. After PSM, the follow-up duration was 58(range, 13-125)months in the radical resection group and 56(range, 10-129)months in the dCRT group. The postoperative 5-year overall survival rates were 95.7% and 97.1% in the radical resection group and dCRT group, respectively, showing no significant difference between the two groups ( χ2=0.001, P>0.05). The postoperative 5-year disease-free progression survival rates were 88.2% and 94.2% in the radical resection group and dCRT group, respectively, showing no significant difference between the two groups ( χ2=0.652, P>0.05). (4) Analysis of factors influencing patients prognosis. Age and pathological TNM stage were indepen-dent influencing factors for overall survival time in patients with clinical T1bN0M0 thoracic esophageal cancer ( hazard ratio=1.312, 2.945, 95% confidence interval as 1.042-1.711, 2.204-5.517, P<0.05). Age and pathological TNM stage were independent influencing factors for disease-free survival time in patients with clinical T1bN0M0 thoracic esophageal cancer ( hazard ratio=1.215, 3.301, 95% confidence interval as 1.012-1.699, 2.012-6.321, P<0.05). Conclusions:There is no significant difference in overall survival and disease-free survival between patients with clinical T1bN0M0 thoracic esophageal cancer undergoing curative esophagectomy and dCRT. The treatment modality is not an independent prognostic factor.

Objective:The aim of this study is to analyze the clinical characteristics and genetic variants of a late-onset auditory neuropathy pedigree caused by maternally inherited- mitochondrial mutation.Methods:A male proband who presented with bilateral sensorineural hearing loss at Henan Children′s Hospital in September 2023 was chosen, along with his family members (4 generations, 20 individuals) as the study subjects. Data from this pedigree were collected, organized, and analyzed for clinical genetic characteristics. Medical histories were obtained from family members, pedigree charts were drawn, audiological, imaging, and physical examinations were conducted. Pathogenic genes and mutations were screened using high-throughput sequencing. Sanger sequencing was employed for variant confirmation and segregation validation in the family.Results:In this family, a total of 12 members (10 members collected) had sensorineural hearing loss, characterized by late-onset hearing impairment with an onset age ranging from 9 to 30 years. The patients exhibited poor speech recognition rates, and audiometric examinations are consistent with auditory neuropathy. There was no history of ototoxic drug use. High-throughput sequencing identified the variant NC_012920.1:m.7471dup in the mitochondrial MT-TS1 gene as the pathogenic variant. Sanger sequencing results confirmed that the pathogenic gene mutation site perfectly co-segregated with the auditory neuropathy phenotype in this family. According to the classification criteria and guidelines for genetic variations by the American College of Medical Genetics and Genomics, the variant was classified as a pathogenic mutation. Conclusion:The mitochondrial MT-TS1 gene mutation m.7471dup is considered to be the pathogenic cause in this late-onset auditory neuropathy pedigree.

AIM:To investigate the impact and regulatory mechanisms of zinc finger protein 36-like protein 1(ZFP36L1)on pancreatic carcinoma cell growth.METHODS:The ZFP36L1 expression in pancreatic carcinoma and its correlation with patient prognosis were analyzed using online databases UALCAN and GEPIA.Western blot was utilized to detect ZFP36L1 protein expression in pancreatic ductal cells(HPNE)and three different pancreatic carcinoma cell lines.CCK-8 and cell colony formation assays were performed to evaluate the effects of ZFP36L1 on pancreatic cancer cell prolif-eration.Wound healing and Transwell assays were used to assess the impact of ZFP36L1 expression changes on pancreatic carcinoma cell migration and invasion.Flow cytometry experiments were used to analyze the effect of ZFP36L1 on the pan-creatic carcinoma cell cycle process.Bioinformatics analysis was conducted to predict potential ZFP36L1 interacting pro-teins.Co-immunoprecipitation experiments were carried out to confirm the interaction between ZFP36L1 and mitogen-acti-vated protein kinase 14(MAPK14).Rescue experiments were performed to assess the function of MAPK14 in ZFP36L1-regulated pancreatic carcinoma cell growth.RESULTS:(1)ZFP36L1 is highly expressed in pancreatic carcinoma and is positively correlated with poor prognosis in pancreatic carcinoma patients.Compared to HPNE,ZFP36L1 is highly ex-pressed in MIA PaCa-2 and ASPC-1 cells,but relatively low in PANC-1 cells.(2)ZFP36L1 overexpression significantly increased the cell viability,colony formation,migration,and invasion abilities of PANC-1 and MIA PaCa-2 cells,while siRNA interference of ZFP36L1 led to opposite results.(3)ZFP36L1 promotes the entry of pancreatic carcinoma cells into the S phase of the cell cycle.(4)ZFP36L1 interacts with MAPK14 to regulate pancreatic cancer cell growth.MAPK14 overexpression reversed the cell viability and migration abilities of pancreatic carcinoma cells overexpressing ZFP36L1.Furthermore,it also decreased the cell viability and migration abilities of pancreatic carcinoma cells with ZFP36L1 inter-ference.CONCLUSION:ZFP36L1 is a potential oncogene in pancreatic carcinoma growth and may regulate pancreatic carcinoma cell growth through cell cycle modulation and interaction with MAPK14.

Objective:To compare the difference of tumor control probability (TCP) and normal tissue complication probability (NTCP) between different radiotherapy schemes bases on biological model of non-small cell lung cancer(NSCLC) that used in assessing radiotherapy. Methods:The radiotherapy data of 15 NSCLC patients who admitted to Tianjin Medical University General Hospital from April 2021 to July 2022 were collected. The low resolution Poisson (TCP Poisson LQ) model,Zaider Minerbo (TCP-ZM) model and TCP Logit model were respectively adopted to fit TCP curve for all patients. Lyman-Kutcher-Burman (LKB) model and linear quadratic (LQ) model were adopted to fit NTCP curves for comparing applicability of several models in tumor control rate,radiation pneumonitis and radiation pericarditis,and the differences in TCP and NTCP among conventional radiotherapy regimen (scheme 1),regimen of maximum gain ratio of treatment (scheme 2),and maximum segmentation frequency regimen (scheme 3) as mean lung dose (MLD)<20 Gy. Results:The average TCP of the TCP Poisson LQ model was (87.2±11.92)％ at 60-70 Gy,which met the requirement of clinical dose. The incidence rate of radiation pneumonitis,which was calculated by the NTCP-LQ model,was higher than that by the NTCP-LKB model when the average radiation dose of whole lung was less than 26 Gy. In the comparison of different schemes,the TCP mean of scheme 3 was (81.56±11.20)％,which was respectively higher than that of other two schemes (60.28±8.04)％ and (69.46±18.09)％,and the differences of them were statistically significant (t=-6.196,-1.969,P<0.05). The average incidence of radiation pneumonitis in Scheme 3 was (19.24±0.43)％,which was respectively higher than that in Scheme 1 and Scheme 2[(15.07±3.24)％ and (15.89±4.55)％],respectively,and the differences of them were statistically significant (t=-5.878,-2.386,P<0.05). Conclusion:It is reasonable to use Poisson-LQ model and NTCP-LQ model to calculate TCP,and incidence of radiation pneumonitis in NSCLC patients. The maximum segmentation frequency scheme (Scheme 3) can effectively improve TCP under the premise of ensuring treatment safety when MLD<20 Gy.

AIM: To investigate the effects of hypobaric hypoxia in plateau on tear indexes and related anatomical structures in rabbits.METHODS: A total of 18 healthy New Zealand rabbits were selected and randomly divided into plateau group and control group, with 9 rabbits(18 eyes)in each group. The plateau group was housed in the Simulated Climate Cabin for Special Environment of Northwest of China, simulating hypobaric hypoxia at an altitude of 6 000 m. The control group was housed in a clean animal room with atmospheric pressure and oxygen. Changes in the tear meniscus height and non-invasive tear break-up time were detected by using RHCT-1 corneal topographer dry eye comprehensive analysis system, changes in tear secretion was measured by Schirmer Ⅰ test, before intervention and on the 3, 7 d, 2 and 4 wk. Meanwhile, the changes in tear composition before and after intervention in the plateau environment were analyzed using Raman Spectroscopy. The histopathological changes of the lower lid conjunctiva, cornea, lacrimal gland, and Hardarian gland were observed by hematoxylin-eosin(HE)staining after 4 wk of intervention, and the expression of mucin 5AC(MUC5AC)in conjunctiva was detected by immunohistochemistry.RESULTS: Compared with the control group, Schirmer Ⅰ test, tear meniscus height, first and average non-invasive tear break-up time in the plateau group decreased significantly since 3 d, and the difference was significant with the extension of observation time(P<0.05). The above indexes increased from 2 wk. After 4 wk of intervention, the protein and lipid content of the tear composition of rabbits in the plateau group increased, and the nucleic acid content decreased compared with the pre-intervention period. Compared with the control group, rabbits in the plateau group showed thickening of corneal stromal edema, an increase in the number of conjunctival cup cells, increase in the level of expression of MUC5AC, an increase in the level of expression of MUC5AC, an atrophy and flattening of cytoplasm in lacrimal epithelial cells, an enlargement of glandular lumen, and no obvious destructive changes in the Hardarian glands.CONCLUSION: Acute plateau environment can destroy the homeostasis of rabbit ocular surface, so that the tear secretion and the tear film stability decreases, but within a certain period of time, rabbits undergo compensation with the habituation to the hypobaric hypoxia environment, which can increase the tear secretion to a certain extent and restore the tear film stability.