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 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 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.

Objective To explore the protective effect of wogonin on retinal ganglion cells(RGC)in mice with glau-coma and its related mechanism.Methods Ten(10 eyes)C57BL/6J mice were included in the control group,and 40(40 eyes)DBA/2J mice were selected to prepare glaucoma models,which were divided into the model group,experiment 1,2 and 3 groups,with 10 mice per group.Mice in the control and model groups were given normal saline intragastrically,and mice in the experiment 1,2 and 3 groups were intragastrically given 50,100 and 150 mg·kg-1 wogonin,respectively.The right eyes were selected as experimental eyes.The intraocular pressure(IOP)of mice was compared among the five groups before and after 2,4 and 8 weeks of intragastric administration.The RGC number and retinal thickness of mice in each group were compared after hematoxylin-eosin staining.The levels of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)and nitric oxide synthase(NOS)in the retinal tissues of mice were detected by colorimetry.The levels of inter-leukin(IL)-6,IL-1 β and tumor necrosis factor-α(TNF-α)in the retinal tissues of mice were detected by enzyme-linked im-munosorbent assay.The expression levels of nucleotide oligomerization domain-like receptor family 3(NLRP3),Caspase-1 and apoptosis-associated speck-like protein(ASC)in the retinal tissues of mice were detected by Western blot.Results Compared with the control group,IOP in the model group and the experiment 1,2 and 3 groups increased(all P＜0.05)before intragastric administration.After 2,4 and 8 weeks of intragastric administration,IOP in the model group and the ex-periment 1,2 and 3 groups increased compared with the control group(all P＜0.05);IOP in the experiment 1,2 and 3 groups decreased compared with the model group(all P＜0.05);IOP in the experiment 2 and 3 groups decreased compared with the experiment 1 group(both P＜0.05);IOP in the experiment 3 group decreased compared with the experiment 2 group(P＜0.05).Compared with the control group,the number of RGC,retinal thickness,SOD and GSH-Px levels in the model group and the experiment 1,2 and 3 groups decreased,while the expression levels of NOS,IL-6,IL-1 β,TNF-α,and NLRP3,Caspase-1 and ASC proteins increased,and the differences were statistically significant(all P＜0.05).Compared with the model group,the number of RGC,retinal thickness,SOD and GSH-Px levels in the experiment 1,2 and 3 groups increased,while the expression levels of NOS,IL-6,IL-1β,TNF-α,and NLRP3,Caspase-1 and ASC proteins decreased,and the differences were statistically significant(all P＜0.05).Compared with the experiment 1 group,the number of RGC,retinal thickness,SOD and GSH-Px levels in the experiment 2 and 3 groups increased,while the expression levels of NOS,IL-6,IL-1 β,TNF-α,and NLRP3,Caspase-1 and ASC proteins decreased(all P＜0.05);compared with the experi-ment 2 group,the number of RGC,retinal thickness,SOD and GSH-Px levels in the experiment 3 group increased,while the expression levels of NOS,IL-6,IL-1β,TNF-α,and NLRP3,Caspase-1 and ASC proteins decreased(all P＜0.05).Conclusion Wogonin can improve the retinal thickness of mice with glaucoma and alleviate retinal oxidative damage and inflammatory reaction,which may be related to inhibiting the activation of NLRP3 inflammasomes.

Objective To observe the impact of cold circulation liquid temperature on ablation focus morphology of microwave ablation(MWA)for in vitro porcine liver tissue.Methods Twenty in vitro fresh porcine liver blocks were randomly divided into ice water circulation group(group A)and normal temperature circulation group(group B),respectively.Ten target ablations in each subgroups in group A and group B,i.e.A1 and B1(50 W,1 min),A2 and B2(50 W,5 min),A3 and B3(60 W,1 min),A4 and B4(60 W,5 min),A5 and B5(70 W,1 min)as well as A6 and B6(70 W,5 min)subgroups were performed using different ablation power(50,60,70 W)and ablation time(1,5 min),respectively.Then the morphology indexes of ablation foci,including longitudinal diameter(LD),transverse diameter(TD),roundness index(RI)and volume(V)were compared between subgroups in group A and B,also among subgroups within group A and B.Results Under the same ablation power and time,LD of ablation foci in subgroups of group A were all smaller than those of group B(all P＜0.05).Significant differences of RI of ablation foci were found between A1 and B1,A2 and B2,A4 and B4,A5 and B5 as well as A6 and B6 subgroups(all P＜0.05),but not between A3 and B3 subgroups(P＞0.05).However,the main effect of cold circulation liquid temperature on ablation focus TD(F=1.125)nor V(F=3.332)was not significant(both P≥0.05).Under the same cold circulation liquid temperature,significant differences of the morphology indexes of ablation foci were detected between A1 and A2,A3 and A4 as well as A5 and A6 subgroups,also between corresponding subgroups in group B(all P＜0.05).Conclusion During MWA for in vitro porcine liver tissue under constant ablation power and time,taken ice water as the cold circulation liquid was benefit to ablation focus shaped spherically.With the extension of ablation time,the larger the ablation focus,the higher the RI.

OBJECTIVE To explore the role of clinical pharmacists in the treatment of critical patients with acute heart failure after percutaneous coronary intervention （PCI）， and to provide reference for drug treatment and monitoring of such patients. METHODS Clinical pharmacists participated in the treatment of a critical patient with acute heart failure after PCI， and assisted physicians to jointly develop individualized medication plans based on domestic and foreign literature： it was suggested to give imipenem and cilastatin for anti-infective therapy， adjust drug dose according to renal function， and timely descend step therapy； Levetiracetam tablets were selected to prevent epilepsy； the differential diagnosis and treatment of rhabdomyolysis possibly caused by Atorvastatin calcium tablets were performed； the whole process of pharmaceutical care was conducted. RESULTS Physicians adopted the suggestions of clinical pharmacists. The acute heart failure of the patient was controlled， the pulmonary infection was improved， the adverse reaction symptoms were relieved， and the patient was successfully transferred out of the ICU. CONCLUSIONS For severe patients， when giving imipenem and cilastatin for anti-infection treatment，the clinical pharmacist should adjust the dose according to the patient’s renal function and be alert to the possible neurotoxicity. During the treatment with Atorvastatin calcium tablets，the clinical pharmacist should comprehensively analyze the risk of rhabdomyolysis. For the adverse reactions that have occurred， clinical pharmacist should promptly address symptomatic issues to ensure the safety and effectiveness of medication for patients.

Objective : To study the effect of lipopolysaccharide ( LPS) -induced immune system activation on syn- aptic structure and DISC1. Methods : 40 rats were divided into 4 groups，which were PBS group，PBS + MK-801 group，LPS group and LPS + MK-801 group．The rats in LPS group and LPS + MK-801 group were administrated with LPS solution (0. 2 mg / kg，i．p．BIW) for 6 times in total， the rats in PBS group and PBS + MK801 group were administrated with PBS．At the third time when the rats were administrated with LPS solution，the rats in PBS + MK-801 group and LPS + MK-801 group were administrated with MK-801 solution (0. 5 mg / kg，i．p．BIW) for a total of 4 times，the rats in PBS group and LPS group were adminis- trated with saline．The head shaking and the open field tests were then evaluated in the rats．Immediately，the rats were sacrificed，and their brain were saved for testing. RT-qPCR , Golgi staining，immunohistochemistry and ELISA kits were used to detect DISC1 gene expression，dendritic spine status，microglia activation and inflammatory cytokine content in cortex，respectively. gene expression in the cortex of rats with schizophrenia． Results : Compared with the PBS group，the expression of DISC1 gene of the rats in the PBS + MK-801 group increased (P ＜0. 01) ，the score of head shaking increased (P ＜0. 01) ，and the distance of the open field increased (P ＜0. 000 1) ; As well as the LPS + MK-801 group，compared with the LPS group，the expression of DISC1 gene increased (P＜0. 000 1) ，the head shaking score and the distance of the open field increased (P＜0. 000 1) . In addition，compared with the PBS + MK-801 group，the expression of DISC1 gene， the shaking head score and the open field distance of the LPS + MK-801 group further improved (P ＜0. 000 1) . Furthermore，compared with PBS group and PBS + MK-801 group，the content of iba1 in the cortex of LPS group and LPS + MK-801 group significantly increased (P ＜0. 05 ) ，the content of inflammatory cytokines significantly increased (P＜0. 05) ，and the length and density of dendritic spines significantly decreased (P＜0. 05) ． Conclusion The activation of the immune system induced by LPS can contribute to the susceptibility of schizophrenia model， and the possible mechanism is that it cooperates with MK-801 to increase the expression of DISC1 gene，which ulti- mately leads to abnormal mental behavior in rats.

Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

To evaluate the clinical significance of nerve growth factor（NGF） in patients with cerebral small vessel disease（CVSD） and explore the relationship between NGF and the pathogenesis of depression after CVSD（CVSD-D）. Methods 80 Patients with first-onset CSVD were recruited. The CSVD were confirmed by MRI. Forty age and gender matched healthy people were selected as the control group. One month later，the diagnosis of post-stroke depression（PSD） was performed according to the American Classification and Diagnostic Criteria for Mental Disorders（DSM-IV）. Depressive symptoms are scored according to the 17-item Hamilton Depression Scale（HAMD-17 items）. The cubital venous blood was drawn within 24 hours after the depression scale was scored，and the serum NGF was detected by enzyme-linked immunosorbent assay（ELISA）. Results The serum NGF in patients with csvd were higher than those of normal patients，But in the CSVD patients，the serum NGF in patients with CSVD-D was lower than those of non CSVD-D group. The difference was statistically significant. Correlation analysis showed that there is no correlation between serum NGF and HAMD score（r=02096，P=0.3752）. Conclusion The occurrence of depression after cerebrovascular disease is closely related to the serum NGF level. But the degree of depression has no correlation with the NGF level.