BACKGROUND: Temozolomide (TMZ) resistance is a significant challenge in treating glioblastoma (GBM). Collagen remodeling has been shown to be a critical factor for therapy resistance in other cancers. This study aimed to investigate the mechanism of TMZ chemoresistance by GBM cells reprogramming collagens. METHODS: Key extracellular matrix components, including collagens, were examined in paired primary and recurrent GBM samples as well as in TMZ-treated spontaneous and grafted GBM murine models. Human GBM cell lines (U251, TS667) and mouse primary GBM cells were used for in vitro studies. RNA-sequencing analysis, chromatin immunoprecipitation, immunoprecipitation-mass spectrometry, and co-immunoprecipitation assays were conducted to explore the mechanisms involved in collagen accumulation. A series of in vitro and in vivo experiments were designed to assess the role of the collagen regulators prolyl 4-hydroxylase subunit alpha 1 (P4HA1) and yes-associated protein (YAP) in sensitizing GBM cells to TMZ. RESULTS: This study revealed that TMZ exposure significantly elevated collagen type I (COL I) expression in both GBM patients and murine models. Collagen accumulation sustained GBM cell survival under TMZ-induced stress, contributing to enhanced TMZ resistance. Mechanistically, P4HA1 directly binded to and hydroxylated YAP, preventing ubiquitination-mediated YAP degradation. Stabilized YAP robustly drove collagen type I alpha 1 ( COL1A1) transcription, leading to increased collagen deposition. Disruption of the P4HA1-YAP axis effectively reduced COL I deposition, sensitized GBM cells to TMZ, and significantly improved mouse survival. CONCLUSION P4HA1 maintained YAP-mediated COL1A1 transcription, leading to collagen accumulation and promoting chemoresistance in GBM.
Temozolomide ; Humans ; Glioblastoma/drug therapy* ; Animals ; Mice ; Cell Line, Tumor ; Drug Resistance, Neoplasm/genetics* ; YAP-Signaling Proteins ; Hydroxylation ; Dacarbazine/pharmacology* ; Adaptor Proteins, Signal Transducing/metabolism* ; Transcription Factors/metabolism* ; Collagen/biosynthesis* ; Collagen Type I/metabolism* ; Prolyl Hydroxylases/metabolism* ; Antineoplastic Agents, Alkylating/therapeutic use*

Objective:Explore the effect of modified position on correction of breech presentation and the ma-ternal and infant outcomes in primiparas at 30-34 weeks of gestation in the midwifery clinic.Methods:From Jan-uary to December2024,274 primiparas at30-34 weeks of gestation who visited the midwifery clinic of The Gener-al Hospital of Northern Theater Command were selected.They were randomly divided into two groups according to the coin-tossing method.Through the inclusion exclusion,and elimination criteria,the selected pregnant women were finally categorized into the knee-chest position group(control group,n=126)and the modified position group(observation group,n=140).The success rate of breech presentation correction,delivery mode,duration of labor,1-minute and 5-minute Apgar scores of vaginally delivered infants,umbilical artery blood gas,postpartum re-covery,and postpartum depression incidence were compared between the two groups.Results:The success rate of breech presentation correction in the observation group was significantly higher than that in the control group(77.9%vs 58.7%,P<0.05).After breech presentation correction,the vaginal delivery rate was higher in the ob-servation group than in the control group(80.7%vs 66.2%,P<0.05).Among women who achieved vaginal de-livery,the intrapartum complication rate was significantly lower in the observation group than in the control group(22.7%vs.46.9%,P<0.05).The duration of the first stage of labor(557.7±195.5 min vs.629.6±208.2 min)and the second stage of labor(67.7±11.4 min vs.79.6±10.3 min)was significantly shorter in the observation group than in the control group(P<0.05).The pH of umbilical artery blood gas of newborns in the observation group delivered vaginally was significantly higher than that in the control group(7.367±0.028 vs.7.322±0.027,P<0.05).There were no statistically significant differences in the1-minute and5-minute Apgar scores of vaginally delivered infants,base excess,and lactate between the two groups(P>0.05).The initial time of lactation(21.7±4.4 h vs.23.5±4.1 h),time to ambulation(8.2±1.2 d vs.9.2±1.4 d),time for lochia to subside(29.6±4.8 d vs.34.1±4.8 d),and postpartum hemorrhage(298.1±56.1 ml vs.362.9±42.6 ml)in the observation group were significantly lower than those in the control group(P<0.05).There were no statistically significant differ-ences in the depression scores(EPDS)at 1 week and 6 weeks postpartum between the two groups of women with vaginal delivery(P>0.05).Conclusions:The modified position in the midwifery clinic significantly improves the success rate of breech presentation correction for primiparas at 30-34 weeks of gestation,good maternal and infant outcomes,and could be widely applied in clinical practice.

Objective:By reviewing the experiences and challenges of assessing the value of ophthalmic gene therapy,it aimed to provide references for optimizing the reimbursement of this kind of drug.Methods:Based on case analysis,it summarized the key considerations and challenges faced by Health Technology Assessment(HTA)agencies conducting technical reviews of gene therapy for ophthalmic conditions in typical countries,including the US.,Canada,the UK.,France,and the Netherlands.Results:Disease severity and medical demand,drug safety,efficacy,cost-effectiveness,budget impact,and social value are the factors for HTA institutions to evaluate the value of ophthalmic gene therapy,patient participation and ethical fairness were taken into account by some institutions.HTA agencies generally put forward the following problems:large uncertainty of the long-term benefits,the difficulty of evaluating the value for caregivers,and the uncertainty of the discount rate.Providing methodological guidance for extrapolating clinical benefits of gene therapy,incorporating a wide range of value elements such as disease severity,and introducing innovative payment agreements are common responses.Conclusion:It is proposed to adjust the threshold for willingness to pay,consider the diversified value domains,gradually introducing finance-based or performance-based innovative payment models,and optimize value assessment and medical insurance access pathways.

Objective:Explore the effect of modified position on correction of breech presentation and the ma-ternal and infant outcomes in primiparas at 30-34 weeks of gestation in the midwifery clinic.Methods:From Jan-uary to December2024,274 primiparas at30-34 weeks of gestation who visited the midwifery clinic of The Gener-al Hospital of Northern Theater Command were selected.They were randomly divided into two groups according to the coin-tossing method.Through the inclusion exclusion,and elimination criteria,the selected pregnant women were finally categorized into the knee-chest position group(control group,n=126)and the modified position group(observation group,n=140).The success rate of breech presentation correction,delivery mode,duration of labor,1-minute and 5-minute Apgar scores of vaginally delivered infants,umbilical artery blood gas,postpartum re-covery,and postpartum depression incidence were compared between the two groups.Results:The success rate of breech presentation correction in the observation group was significantly higher than that in the control group(77.9%vs 58.7%,P<0.05).After breech presentation correction,the vaginal delivery rate was higher in the ob-servation group than in the control group(80.7%vs 66.2%,P<0.05).Among women who achieved vaginal de-livery,the intrapartum complication rate was significantly lower in the observation group than in the control group(22.7%vs.46.9%,P<0.05).The duration of the first stage of labor(557.7±195.5 min vs.629.6±208.2 min)and the second stage of labor(67.7±11.4 min vs.79.6±10.3 min)was significantly shorter in the observation group than in the control group(P<0.05).The pH of umbilical artery blood gas of newborns in the observation group delivered vaginally was significantly higher than that in the control group(7.367±0.028 vs.7.322±0.027,P<0.05).There were no statistically significant differences in the1-minute and5-minute Apgar scores of vaginally delivered infants,base excess,and lactate between the two groups(P>0.05).The initial time of lactation(21.7±4.4 h vs.23.5±4.1 h),time to ambulation(8.2±1.2 d vs.9.2±1.4 d),time for lochia to subside(29.6±4.8 d vs.34.1±4.8 d),and postpartum hemorrhage(298.1±56.1 ml vs.362.9±42.6 ml)in the observation group were significantly lower than those in the control group(P<0.05).There were no statistically significant differ-ences in the depression scores(EPDS)at 1 week and 6 weeks postpartum between the two groups of women with vaginal delivery(P>0.05).Conclusions:The modified position in the midwifery clinic significantly improves the success rate of breech presentation correction for primiparas at 30-34 weeks of gestation,good maternal and infant outcomes,and could be widely applied in clinical practice.

Objective:By reviewing the experiences and challenges of assessing the value of ophthalmic gene therapy,it aimed to provide references for optimizing the reimbursement of this kind of drug.Methods:Based on case analysis,it summarized the key considerations and challenges faced by Health Technology Assessment(HTA)agencies conducting technical reviews of gene therapy for ophthalmic conditions in typical countries,including the US.,Canada,the UK.,France,and the Netherlands.Results:Disease severity and medical demand,drug safety,efficacy,cost-effectiveness,budget impact,and social value are the factors for HTA institutions to evaluate the value of ophthalmic gene therapy,patient participation and ethical fairness were taken into account by some institutions.HTA agencies generally put forward the following problems:large uncertainty of the long-term benefits,the difficulty of evaluating the value for caregivers,and the uncertainty of the discount rate.Providing methodological guidance for extrapolating clinical benefits of gene therapy,incorporating a wide range of value elements such as disease severity,and introducing innovative payment agreements are common responses.Conclusion:It is proposed to adjust the threshold for willingness to pay,consider the diversified value domains,gradually introducing finance-based or performance-based innovative payment models,and optimize value assessment and medical insurance access pathways.

In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50％of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.

Objective To evaluate the predictive value of a combined model based on clinical and radiomics features for the invasiveness of lung adenocarcinoma manifesting as ground glass nodule(GGN).Methods Clinical data of patients with GGN-type lung adenocarcinoma who underwent chest CT and were confirmed by surgical pathology at some hospital from January to December 2019 were analyzed retrospectively,and the extraction of imaging histological features was performed using Python-based open resource Pyradiomics.A clinical model was constructed based on independent risk factors obtained from univariate and multivariate analyses,a radiomics model was built using the screened radiomics features,and a combined model was established with the predictive values of the clinical models and radiomics scores(Radscore).The predictive performance of the three models in the training and test sets was assessed using ROC curves,the statistical significance of the differences in the ROC curves of the three models for predicting GGN-type lung adenocarcinoma was assessed using the Delong test,and the net benefits of the models were analyzed using clinical decision curves.Results Logistic multifactor analysis showed that age(P=0.020 2)and vascular characteristics(P=0.002 2)were the independent predictors of the degree of the invasiveness of lung adenocarcinoma.The AUCs of the radiomics model,clinical model and combined model were 0.876,0.867 and 0.904 on the training set,and 0.828,0.828 and 0.864 on the test set,respectively.The difference between the ROC curves of the combined model and the clinical and radiomics models was not statistically significant(P>0.05)on the test set.Clinical decision curves showed a higher clinical benefit when using the combined model to predict the invasiveness under most conditions of threshold probability.Conclusion The combined model based on clinical and radiomics features enhances the predictive performance for the invasiveness of GGN-type lung adenocarcinoma.

The larvae of Echinococcus (hydatidcyst) can parasitize humans and animals, causing a serious zoonotic disease-echinococcosis. The life history of Echinococcus is complicated, and as the disease progresses slowly after infection, early diagnosis is difficult to establish. Due to the limitations of imaging and immunological diagnosis in this respect, domestic and foreign scholars have established a variety of molecular detection techniques for the pathogen Echinococcus over recent years, mainly including nested polymerase chain reaction (PCR), multiplex PCR, real-time quantitative PCR, and nucleic acid isothermal amplification technology. In this article, the research progress of molecular detection technology for Echinococcus infection currently was reviewed and the significance of these methods in the detection and diagnosis of hydatid and hydatid diseases was also discussed.

Objective:To investigate the clinical efficacy of different grade transoral atlantoaxial release for the treatment of irreducible atlantoaxial dislocation.Methods:From January 2010 to December 2019, 297 patients with irreducible atlantoaxial dislocation treated by different grade releases were retrospectively analyzed, including 132 males and 165 females, aged 42.3±12.14 years (range, 10-63 years). All cases were treated by different grade releases, Grade I (196, 66.0%), Grade II (54, 18.2%), Grade III (28, 9.4%) and Grade IV (19, 6.4%). The American Spinal Injury Association (ASIA) grade and Japanese Orthopedic Association (JOA) score were recorded as the clinical evaluation index. The clivus-canal angle (CCA) and cervico-medullary angle (CMA) were measured to evaluate the reduction. The surgery time, blood loss, duration of bony fusion and complications were also analyzed.Results:The follow-up time was 14.8±10.2 months (range, 9-36 months). The surgery time of Grade I-IV were 2.02±0.35 min, 3.00±0.36 min, 4.07±0.96 min and 5.24±0.83 min, respectively ( F=385.43, P<0.001), blood loss was 84.08±27.21 ml, 153.61±31.36 ml, 268.93±48.94 ml and 444.21±109.51 ml, respectively ( F=582.39, P<0.001). The preoperative ASIA motor score of Grade I-IV were 83.85±6.68, 84.06±5.47, 84.07±5.99 and 85.00±4.11, respectively. The last follow-up were 98.34±2.38, 98.67±1.79, 98.86±1.58 and 98.32±2.11, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative JOA score of Grade I-IV were 11.44±1.73, 11.59±1.72, 11.61±1.47 and 11.32±1.80, respectively. The last follow-up were 16.22±1.00, 16.28±1.02, 16.14±1.04 and 16.16±1.07, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative CCA of Grade I-IV were 110.19°±8.76°, 112.48°±7.66°, 106.61°±6.54° and 109.05°±7.79°, respectively. The last follow-up were 140.22°±8.04°, 141.86°±7.04°, 142.35°±8.62° and 140.15°±6.49°, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative CMA of Grade I-IV were 113.48°±9.54°, 116.03°±8.38°, 109.55°±7.13°, and 112.46°±8.33°, respectively. The last follow-up were 144.28°±7.75°, 146.40°±6.98°, 145.81°±8.27° and 143.24°±6.36°, respectively, with statistically significant differences from preoperative ( P<0.05). Solid bony fusion was obtained except for 3 cases, the fusion time was 9.71±2.55 months (range 3-14 months). Altogether 33 complications occurred in all cases (11.1%), including 3 fusion failure, 3 cerebrospinal leak, 3 wound infection, 2 death (1 case caused by cerebrospinal leak), 11 pharyngeal discomfort, 4 postoperative pain surrounding iliac crest, and 8 malunion of iliac crest. Conclusion:Transoral stepped atlantoaxial release theory could provide guidelines for atlantoaxial dislocation treatment, and make the transoral release technique more effective and safer.

Objective: To analyze the course of disease and epidemiological parameters of COVID-19 and provide evidence for making prevention and control strategies. Methods: To display the distribution of course of disease of the infectors who had close contacts with COVID-19 cases from January 1 to March 15, 2020 in Guangdong Provincial, the models of Lognormal, Weibull and gamma distribution were applied. A descriptive analysis was conducted on the basic characteristics and epidemiological parameters of course of disease. Results: In total, 515 of 11 580 close contacts were infected, with an attack rate about 4.4%, including 449 confirmed cases and 66 asymptomatic cases. Lognormal distribution was fitting best for latent period, incubation period, pre-symptomatic infection period of confirmed cases and infection period of asymptomatic cases; Gamma distribution was fitting best for infectious period and clinical symptom period of confirmed cases; Weibull distribution was fitting best for latent period of asymptomatic cases. The latent period, incubation period, pre-symptomatic infection period, infectious period and clinical symptoms period of confirmed cases were 4.50 (95%CI:3.86-5.13) days, 5.12 (95%CI:4.63-5.62) days, 0.87 (95%CI:0.67-1.07) days, 11.89 (95%CI:9.81-13.98) days and 22.00 (95%CI:21.24-22.77) days, respectively. The latent period and infectious period of asymptomatic cases were 8.88 (95%CI:6.89-10.86) days and 6.18 (95%CI:1.89-10.47) days, respectively. Conclusion: The estimated course of COVID-19 and related epidemiological parameters are similar to the existing data.
COVID-19 ; Cohort Studies ; Contact Tracing ; Humans ; Incidence ; Prospective Studies