OBJECTIVE To study the effects of ethanol on markers of gastric stem cells and epithe-lial cells,and explore the related signal pathways for stem cells differentiation in a mouse gastric mucous injury model.METHODS Male C57BL/6 mice were randomly divided into normal control and ethanol groups.The mice in the control group were given normal drinking water while those in the ethanol group were gavaged with 10 ml·kg-1 50%(V/V)ethanol on day 1,and drinking water containing 10%(V/V)ethanol was given on day 2-9.On the 10th day,stomach tissues were collected.HE staining was used to detect pathological changes in the stomach.Immunohistochemistry(IHC)staining was used to detect changes of such cell markers as mucin 5AC,H+/K+ATPase β and pepsin C.Immunofluorescence(IF)staining was employed to analyze changes in expression of cell markers such as H+/K+ATPase β,pepsin C and gastrin.ELISA assay was used to measure gastrin,somatostatin and interleukin 1β(IL-1β)concentrations in gastric tissue homogenates.Flow cytometry was adopted to measure the number of leucine rich repeat containing G protein-coupled receptor 5 positive(LGR5+)stem cells in gastric glands.Organoids was constructed to characterize stem cell activity.RNA sequencing and bioinformatics analysis were conducted to analyze the inflammatory pathways and differentiation signaling pathways during mice gastric mucous injury.RESULTS H&E results showed multifocal necrosis of the mucosal layer appeared in the ethanol group,accompanied by pyknosis,lysis and detachment of mucosal epithelial cells and gastric gland cells.IHC results showed decreased expressions of mucin 5AC and increased expressions of H+/K+ATPase β and pepsin C.IF results revealed increased expressions of H+/K+ATPase β,pepsin C,and gastrin after ethanol treatment.ELISA results demonstrated significant increases in gastrin,somatostatin and IL-1β levels in gastric tissues of the ethanol group.Flow assay results suggested that the number of LGR5+stem cells significantly decreased in ethanol treated gastric tissues.Stem cells from stomach tissues treated with ethanol did not grow into organoids.RNA sequencing and bioinformatics analyses revealed enrichment of TNF,NF-κB and Notch pathways in the ethanol group.CONCLUSION Administration of 50%ethanol solution on day 1,followed by continuous admin-istration of 10%ethanol solution on day 2-9 can induce histopathological injury to the gastric gland and stem cells,and an increase in epithelial cells.These changes may be related to the up-regulation of inflammatory pathways and Notch signaling pathways triggered by ethanol.

This consensus will introduce the characteristics of fillers used in the surgical cavities of domestic nasal surgery patients based on relevant literature and expert opinions. It will also provide recommendations for the selection of cavity fillers for different nasal diseases, with chronic sinusitis as a representative example.
Humans ; Nasal Cavity/surgery* ; Nasal Surgical Procedures ; China ; Consensus ; Sinusitis/surgery* ; Dermal Fillers

OBJECTIVE To study the effects of ethanol on markers of gastric stem cells and epithe-lial cells,and explore the related signal pathways for stem cells differentiation in a mouse gastric mucous injury model.METHODS Male C57BL/6 mice were randomly divided into normal control and ethanol groups.The mice in the control group were given normal drinking water while those in the ethanol group were gavaged with 10 ml·kg-1 50%(V/V)ethanol on day 1,and drinking water containing 10%(V/V)ethanol was given on day 2-9.On the 10th day,stomach tissues were collected.HE staining was used to detect pathological changes in the stomach.Immunohistochemistry(IHC)staining was used to detect changes of such cell markers as mucin 5AC,H+/K+ATPase β and pepsin C.Immunofluorescence(IF)staining was employed to analyze changes in expression of cell markers such as H+/K+ATPase β,pepsin C and gastrin.ELISA assay was used to measure gastrin,somatostatin and interleukin 1β(IL-1β)concentrations in gastric tissue homogenates.Flow cytometry was adopted to measure the number of leucine rich repeat containing G protein-coupled receptor 5 positive(LGR5+)stem cells in gastric glands.Organoids was constructed to characterize stem cell activity.RNA sequencing and bioinformatics analysis were conducted to analyze the inflammatory pathways and differentiation signaling pathways during mice gastric mucous injury.RESULTS H&E results showed multifocal necrosis of the mucosal layer appeared in the ethanol group,accompanied by pyknosis,lysis and detachment of mucosal epithelial cells and gastric gland cells.IHC results showed decreased expressions of mucin 5AC and increased expressions of H+/K+ATPase β and pepsin C.IF results revealed increased expressions of H+/K+ATPase β,pepsin C,and gastrin after ethanol treatment.ELISA results demonstrated significant increases in gastrin,somatostatin and IL-1β levels in gastric tissues of the ethanol group.Flow assay results suggested that the number of LGR5+stem cells significantly decreased in ethanol treated gastric tissues.Stem cells from stomach tissues treated with ethanol did not grow into organoids.RNA sequencing and bioinformatics analyses revealed enrichment of TNF,NF-κB and Notch pathways in the ethanol group.CONCLUSION Administration of 50%ethanol solution on day 1,followed by continuous admin-istration of 10%ethanol solution on day 2-9 can induce histopathological injury to the gastric gland and stem cells,and an increase in epithelial cells.These changes may be related to the up-regulation of inflammatory pathways and Notch signaling pathways triggered by ethanol.

Objective:To follow-up the previous phase Ⅲ clinical trial of recombinant human follicle-stimulating hormone (Follitrope ?), and to evaluate the cumulative pregnancy rate, the cumulative live birth rate, and the neonatal outcomes of subjects. Methods:The phase Ⅲ clinical study of Follitrope ? in China (CTR20150341/CTR20150341, May 15, 2015—June 27, 2016) was followed up until December 31, 2022. Patients were divided into Follitrope ? group and Gonal-F ? group. According to the age, patients were divided into three subgroups: 20-30 years old subgroup, 31-35 years old subgroup and 36-39 years old subgroup. Cumulative pregnancy rate, cumulative live birth rate, number of embryos transferred per cycle, live births per embryo transfer cycle, live births per oocyte retrieved, and neonatal characteristics were analyzed. Results:A total of 446 patients were included in the analysis, of which 336 (75.3%) were in the Follitrope ? group and 110 (24.7%) in the Gonal-F ? group, with a follow-up period of 6.5 years. There were no statistically significant differences between the Follitrope ? group and the Gonal-F ? group in terms of cumulative pregnancy rate and cumulative live birth rate (all P>0.05). Similar cumulative pregnancy rates and cumulative live birth rates were observed between the two groups within each age subgroup (all P>0.05). In the 36-39 years old subgroup, the Follitrope ? group showed a trend towards higher cumulative pregnancy rate [60.0% (12/20)] and cumulative live birth rate [55.0% (11/20)] compared with the Gonal-F ? group [28.6% (2/7), 14.3% (1/7)], however, none of the differences were statistically significant (all P>0.05). Twin pregnancy rates, live births per embryo, live birth per oocyte, newborn gender, birth weight, and birth defect rates were similar between the Follitrope ? group and the Gonal-F ? group without statistically significant differences (all P>0.05). Conclusion:The safety and effectiveness of Follitrope ? in controlled ovarian hyperstimulation are similar to those of Gonal-F ?. Compared with Gonal-F ?, there is a trend toward higher cumulative pregnancy rates and cumulative live birth rates in elderly patients with Follitrope ?, although there is no statistical difference.

Objective:To systematically evaluate and compare the efficacy and safety of oxcarbazepine and carbamazepine in the treatment of vestibular paroxysmia (VP).Methods:Randomized controlled trials (RCTs) of oxcarbazepine versus carbamazepine in the treatment of VP, in which the outcome measures included response rate, visual analogue scale for vertigo and the attack frequency, and incidence of adverse events/reactions were collected by searching relevant databases at home and abroad (up to March 2023). The Cochrane Collaboration′s tool for assessing risk of bias was used to evaluate the quality of the included studies. RevMan 5.3 software was used for meta-analysis. The effect sizes of counting data were odds ratio ( OR) and its 95% confidence interval ( CI), and those of the measurement data were mean difference ( MD) and its 95% CI. Results:A total of 7 RCTs and 476 patients were entered in the analysis, including 236 in the oxcarbazepine group and 240 in the carbamazepine group. Meta analysis showed that there were no significant differences in the total effective rate of oxcarbazepine and carbamazepine in the treatment of VP [85.7% (168/196) vs. 85.0% (170/200), OR=1.07, 95% CI: 0.61-1.86], the decrease of visual analogue scale for vertigo after treatment ( MD=0.40, 95% CI: -0.52-1.32) or the reduction of vertigo frequency after treatment ( MD=1.15, 95% CI:-1.78-4.08). However, compared to the carbamazepine group, the overall incidence of adverse events/reactions, the incidence of dizziness/ataxia, and incidence of nausea/vomiting in oxcarbazepine group was significantly lower [13.6% (32/236) vs. 30.8% (74/240), OR=0.34, 95% CI: 0.22-0.55, P<0.001; 2.1%(5/236) vs. 7.9%(19/240), OR=0.32, 95% CI: 0.13-0.76, P=0.01; 2.4%(5/211) vs. 7.1%(15/211), OR=0.38, 95% CI: 0.15-0.95, P=0.04]. Conclusion:Oxcarbazepine and carbamazepine have similar efficacy in the treatment of VP, but oxcarbazepine has better safety with lower incidence of adverse reactions in the nervous system and digestive system.

Objective:To systematically evaluate and compare the efficacy and safety of oxcarbazepine and carbamazepine in the treatment of vestibular paroxysmia (VP).Methods:Randomized controlled trials (RCTs) of oxcarbazepine versus carbamazepine in the treatment of VP, in which the outcome measures included response rate, visual analogue scale for vertigo and the attack frequency, and incidence of adverse events/reactions were collected by searching relevant databases at home and abroad (up to March 2023). The Cochrane Collaboration′s tool for assessing risk of bias was used to evaluate the quality of the included studies. RevMan 5.3 software was used for meta-analysis. The effect sizes of counting data were odds ratio ( OR) and its 95% confidence interval ( CI), and those of the measurement data were mean difference ( MD) and its 95% CI. Results:A total of 7 RCTs and 476 patients were entered in the analysis, including 236 in the oxcarbazepine group and 240 in the carbamazepine group. Meta analysis showed that there were no significant differences in the total effective rate of oxcarbazepine and carbamazepine in the treatment of VP [85.7% (168/196) vs. 85.0% (170/200), OR=1.07, 95% CI: 0.61-1.86], the decrease of visual analogue scale for vertigo after treatment ( MD=0.40, 95% CI: -0.52-1.32) or the reduction of vertigo frequency after treatment ( MD=1.15, 95% CI:-1.78-4.08). However, compared to the carbamazepine group, the overall incidence of adverse events/reactions, the incidence of dizziness/ataxia, and incidence of nausea/vomiting in oxcarbazepine group was significantly lower [13.6% (32/236) vs. 30.8% (74/240), OR=0.34, 95% CI: 0.22-0.55, P<0.001; 2.1%(5/236) vs. 7.9%(19/240), OR=0.32, 95% CI: 0.13-0.76, P=0.01; 2.4%(5/211) vs. 7.1%(15/211), OR=0.38, 95% CI: 0.15-0.95, P=0.04]. Conclusion:Oxcarbazepine and carbamazepine have similar efficacy in the treatment of VP, but oxcarbazepine has better safety with lower incidence of adverse reactions in the nervous system and digestive system.

Objective:To evaluate the efficacy and safety of transepithelial photorefractive keratectomy (Trans-PRK) combined with accelerated corneal cross-linking (CXL) for refractive error in patients with thin or irregular corneas, excluding keratoconus.Methods:An observational case series study was performed.Fifty-five right eyes of 55 myopic patients diagnosed with thin or irregular corneas, who underwent Trans-PRK combined with prophylactic CXL surgery, were included at Baotou Chaoju Eye Ophthalmic Hospital from August 2017 to July 2018.Uncorrected distance visual acuity (UDVA) of the operated eye was measured using international standard visual acuity charts, and refractive diopters were measured by computer and comprehensive refraction before surgery and at 1 week, 1, 3, 6, and 12 months after surgery.Corneal morphology was assessed with the Pentacam anterior segment analyzer before surgery and at 3, 6, and 12 months after surgery.Intraocular pressure (IOP) was measured with a non-contact tonometer before surgery and at 1, 3, 6, and 12 months after surgery.The incidence of postoperative complications was recorded.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Baotou Chaoju Ophthalmic Hospital (No.btcj-u-1). Written informed consent was obtained from each subject.Results:Preoperative, 1-week, 1-, 3-, 6-, and 12-month postoperative UDVA (LogMAR) were 0.52(0.55, 0.78), 0.22(0.12, 0.17), 0.10(0.04, 0.07), 0.00(-0.04, -0.16), -0.08(-0.05, -0.03) and -0.08(-0.06, -0.04), respectively, showing a statistically significant overall difference ( Z=249.44, P<0.001). UDVA at each postoperative time point was improved compared to preoperative, and UDVA at 3, 6, and 12 months postoperatively was significantly improved compared to 1 week and 1 month postoperatively (all at P<0.001). The spherical diopter at each postoperative time point decreased significantly compared to preoperative, with the spherical diopter at 1, 3, 6, and 12 months postoperatively being lower than that at 1 week postoperatively, and the 12-month postoperative spherical diopter being lower than that at 3 and 6 months postoperatively, showing statistically significant differences (all at P<0.001). The cylindrical degree at 1, 3, 6, and 12 months postoperatively was lower than that at preoperative and 1 week postoperatively, with statistically significant differences (all at P<0.05). After the operation, the spherical equivalent of the operated eye gradually decreased with time, tending toward emmetropia.The spherical equivalent at each postoperative time point decreased compared to preoperative, with the spherical equivalent at 1, 3, 6, and 12 months postoperatively being lower than that at 1 week postoperatively, and the spherical equivalent at 12 months postoperatively being lower than that at 3 and 6 months postoperatively, showing statistically significant differences (all at P<0.001). The corneal K1 and K2 values at 3, 6, and 12 months postoperatively were significantly lower than preoperatively (all at P<0.001), and the corneal K1 and K2 values at 3 months postoperatively tended to stabilize.The IOP of the operated eye at 3, 6, and 12 months postoperatively was significantly lower than preoperatively, and the IOP at 6 and 12 months postoperatively was lower than that at 1 and 3 months postoperatively, with statistically significant differences (all at P<0.001). One eye developed grade 0.5 corneal haze at 1 week postoperatively, which spontaneously resolved to transparency at 1 month postoperatively. Conclusions:Trans-PRK combined with accelerated CXL has good efficacy, stability and safety for refractive error patients with thin or irregular corneas, except for keratoconus.

Objective:To construct and analyze the visual nomogram predictive model for the prognosis of elderly advanced lung adenocarcinoma patients after surgery based on the Surveillance, Epidemiology, and End Results (SEER) database.Methods:SEER*Stat8.4.0.1 software was used to screen out the data from 17 register in SEER database between 2000 and 2019, and finally 4 453 lung adenocarcinoma patients aged ≥ 65 years who underwent surgical treatment and were diagnosed as stage Ⅲ and Ⅳ according to the 7th edition of the American Joint Committee on Cancer (AJCC) staging criteria were enrolled. The data were randomly divided into the training set (3 117 cases) and the validation set (1 336 cases) in a 7:3 ratio; the epidemilogical data and clinicopathological characteristics of the two groups were compared. LASSO regression was used for data dimensionality reduction to select the best predictors from the prognostic factors of patients. Cox proportional risk model was used to perform univariate and multivariate analyses of the screened variables, and based on R software rms package and the prognostic independent risk factors, the nomogram was constructed to predict the 1-, 3-, and 5-year cancer-specific survival (CSS) rates of the patients. The validation set was validated by using Bootstrap method with 1 000 equal repeated samples with playback, and the accuracy of the nomogram model was verified by using the C-index, receiving operating characteristic (ROC) curves and calibration curves.Results:There were no statistically significant differences in age, gender, race, tumor location, Grade grading, surgery methods, the number of lymph node dissection, radiotherapy, tumor diameter, tumor metastasis, marriage, living condition, TNM staging, radiochemotherapy of training set and validation set (all P > 0.05). In training set, 18 variables were included into LASSO regression analysis and were performed with dimensionality reduction; ultimately, 11 optimal predictive variables were selected, including age ≥ 85 years ( HR = 2.34, 95% CI: 1.803-3.037, P < 0.01), male ( HR = 1.326, 95% CI: 1.228-1.432, P < 0.01), Grade grading Ⅲ-Ⅳ ( HR = 1.333, 95% CI: 0.844-2.105, P < 0.01), undissected lymph nodes ( HR = 2.261, 95% CI: 2.023-2.527, P < 0.01), tumor diameter ≥3.7 cm ( HR = 1.445, 95% CI: 1.333-1.566, P < 0.01), bone metastasis ( HR = 1.535, 95% CI: 1.294-1.819, P < 0.01), brain metastasis ( HR = 1.308, 95% CI: 1.117-1.532, P < 0.01), lung metastasis ( HR = 1.229, 95% CI: 1.056-1.431, P = 0.01), living in rural areas ( HR = 1.215, 95% CI: 1.084-1.363, P < 0.01), TNM staging Ⅳ ( HR = 1.155, 95% CI: 1.044-1.278, P = 0.01), postoperative radiotherapy ( HR = 1.148, 95% CI: 1.054-1.250, P < 0.01); lung adenocarcinoma patients with the above 11 factors had worse prognosis. Based on the variables, the nomogram predictive model was constructed to predict 1-, 3-, and 5-year CSS rates of elderly advanced lung adenocarcinoma patients. Bootstrap method was used for repeated sampling for 1 000 times to verify the modeling effect of nomogram. In the model group, C-index was 0.654 (95% CI: 0.641-0.668), 0.666 (95% CI: 0.646-0.685), respectively in the training set and the validation set. The nomogram was drawn to predict ROC curves of 1-, 3-, and 5-year CSS rates for elderly advanced lung adenocarcinoma patients after operation in the training set and validation set; the area under the curve (AUC) of 1-year, 3-year, and 5-year CSS rates was 0.730 (95% CI: 0.708-0.754) and 0.689 (95% CI: 0.672-0.710), 0.687 (95% CI: 0.668-0.711) and 0.731 (95% CI: 0.697-0.765), 0.712 (95% CI:0.684-0.740) and 0.714 (95% CI: 0.683-0.745), respectively in the training and validation sets. The calibration curve showed a high consistency between the predicted probability of the model and the actual probability. Conclusions:The nomogram model constructed by optimal predictive variables for predicting the prognosis of elderly advanced lung adenocarcinoma patients after surgery may be a convenient tool for survival prediction of these patients.

OBJECTIVE To provide a reference for improving the relevant standard operating procedures （SOP） and biological sample management in drug clinical trials. METHODS According to Good Clinical Practice， Data On-site Verification Points of Drugs Clinical Trials， Human Genetic Resources Management Regulations Implementation Rules， Qualification Examination Rules of Drug Clinical Trials Institution， based on the experience of managing clinical trials programs， the irregularities in biological samples management were analyzed by using statistical quality control tables and protocol deviation （PD） reported by sponsors， in the context of the quality control of drug clinical trials projects managed by the author from July 2016 to May 2023. The precautions in various aspects of sample management were put forward. RESULTS & CONCLUSIONS A total of 101 biospecimen- related irregularities were found in the 60 drug clinical trials projects. Biological sample collection， preservation， and handling were the aspects with the highest incidence of irregular operations in biological sample management， accounting for 37.62%， 25.74%， and 21.78%， respectively. Regulating the management of biospecimens requires multiple efforts. The institutional office and the ethics committee carefully reviewed the consistency of the protocols， informed consent， and genetic office application involving biospecimen collection and handling when the project was initiated. Institutional office quality controllers should pay attention to the attendance and training of authorized personnel at project initiation. The principal investigator， research nurse， collector， handler， transporter， relevant personnel of the central laboratory， and institutional office quality controller have their roles during the project implementation phase. On this basis， all parties involved in the management of biological samples should do a good job of effective communication， find problems and report them in time， and conduct special studies on key aspects.

OBJECTIVE To investigate the current situation of clinical trial institutions in Chongqing after the recording system of clinical trial institutions, and to put forward suggestions. METHODS A total of 34 clinical trial institutions in Chongqing were selected as the research objects. The research contents mainly included the basic situation of the institutions, staffing, hardware and software construction, project operation and work difficulties, etc. Combined with the research results, suggestions were put forward for the difficulties of the new and old institutions in the operation of clinical trial institutions. RESULTS A total of 29 questionnaires were collected and 29 were valid. The release of clinical trial resources in Chongqing were not sufficient and uniform, there were problems such as insufficient incentive policies, lack of information platform construction, and the number and professional degrees of practitioners need to be improved. The new institutions had certain advantages in project load, office space and willingness to undertake, but it was restricted by principle investigator qualification, project experience and institutional reputation. CONCLUSION It is suggested to clarify the incentive mechanism, enhance the enthusiasm of clinical trials and establish a standardized training mechanism for clinical trial professionals. Make full use of the information platform to improve the efficiency of clinical trials, build a regional information platform to share information and resources, and accelerate the development of regional clinical trials.