We reported a case of polyglandular syndrome induced by programmed death-1(PD-1) inhibitors. The patient was a 51-years-old male with non-small cell lung cancer, treated with PD-1 inhibitor nivolumab/pembrolizumab because of postoperative subcarinal lymph node metastasis indicated by PET-CT. During 14 cycles of PD-1 inhibitor treatment, the patient successively developed primary hypothyroidism, and type 1 diabetes mellitus(T1DM). More than five months after the withdrawal of pembrolizumab, the patient experienced recurrentce. Laboratory examinations showed mild hyponatremia and hypopituitarism including ACTH and growth hormone(GH)/insulin-like growth factor-1(IGF-1) insufficiency. This is the first report of a patient diagnosed as polyglandular syndrome caused by PD-1 inhibitor. In particularly, the hypothyroidism and T1DM did not improve after drug withdrawal, while hypopituitarism was further aggravated. This case reminds us that we should pay more attention to the changes of endocrine function during and after the treatment of PD-1 inhibitor, so that we can make the correct diagnosis and take proper medical measures timely, to avoide missed diagnosis, and improper treatment.

Objective: To explore the effects of hnRNP E1 and both early genes E2 and E6 of HPV16 as well as their interactions in the progression of cervical carcinogenesis. Methods: Subjects of this study included 56 women with normal cervix (NC), 58 patients with low-grade cervical intraepithelial neoplasm (CINⅠ) and 50 patients with high-grade cervical intraepithelial neoplasm (CINⅡ/Ⅲ) who were all recruited from the 'Cervical Lesions Study Cohort Project’ in Jiexiu of Shanxi province from June to September, 2014. Another 40 patients with cervical squamous cell carcinoma (SCC) were from the Shanxi Tumor Hospital during the same period. Information related to cervical lesions were collected, using a structured questionnaire, with cervical tissues and cervical exfoliated cells gathered from all the participants. HPV infection was detected by flow-through hybridization, while the levels of expression on hnRNP E1, HPV16 E2 and E6 protein were measured by Western Blot. Kruskal-Wallis H test, χ² test, trend χ² test were analyzed by SPSS 22.0 software, while interaction was evaluated by generalized multifactor dimensionality reduction (GMDR). Results: The overall infection rates of HPV16 related to CINⅠ (15.52%, 9/58), CINⅡ/Ⅲ (40.00%, 20/50) and SCC (67.50%, 27/40) groups were all higher than that of the NC group (8.93%, 5/56) and with an increasing trend on the severity of cervical lesions (trend χ²=43.613, P<0.001). The levels of expression on hnRNP E1 protein were significantly different in the groups with different cervical lesions (H=9.98, P=0.019), showing a decreasing trend with the severity of cervical lesions (trend χ²=9.495, P=0.002). The levels of expression on HPV16 E2 (H=16.20, P=0.001) and HPV16 E6 (H=15.44, P=0.001) were significantly different in groups with different cervical lesions. Results of GMDR showed that the best interaction model in both groups of CINⅡ/Ⅲ and SCC appeared as hnRNP E1 low expression, HPV16 E2 low expression and HPV16 E6 high expression. However, no similar interaction was seen in CINⅠ (P>0.05). Conclusions Both low expressions of hnRNP E1 and abnormal expression of HPV16 E2 and E6 could increase the risk of high-grade CIN and cervical cancer. It seemed that they might have an important synergistic effect on the progression of cervical cancer.

Objective: To investigate the role of human papillomavirus (HPV) 16 early genes E2 and E6 and heterogeneous nuclear ribonucleoprotein (hnRNP) E2 and their interaction effects in the progression of the cervical cancer. Methods: Women with normal cervix (NC), low cervical intraepithelial neoplasia (CIN Ⅰ) and high cervical intraepithelial neoplasia (CIN Ⅱ/Ⅲ) from the cervical lesions cohort in Jiexiu County of Shanxi Province from June 2014 to September 2014, and patients with cervical squamous cell carcinoma (SCC) treated at the Second Hospital of Shanxi Medical University in the same period were enrolled in this study. There were 257 participants, about 67 NC cases (26.07%), 69 CIN Ⅰ cases (26.85%), 68 CIN Ⅱ/Ⅲ cases (26.46%), and 53 SCC cases (20.62%), respectively. The information of demographic characteristics, life health habits and cervical lesions were collected by using the structured questionnaire. Cervical exfoliated cells and cervical biopsy tissues were collected to detect the infection of HPV16 and the protein expression levels of hnRNP E2, HPV16 E2 and E6. According to the median-value of the protein expression levels of hnRNP E2, HPV16 E2 and E6 and E2/E6 ratio in the NC group, the study participants were divided into the high and low expression groups/ratio groups. The multivariate logistic regression model was used to analyze the correlation between HPV16 early gene E2 and E6, hnRNP E2 and cervical cancer. The interaction effect was analyzed by using the generalized multifactor dimensionality reduction (GMDR) model. Results: The ages of NC, CIN Ⅰ, CIN Ⅱ/Ⅲ and SCC groups were (47.00±9.07), (47.64±7.35), (46.37±8.67) and (51.26±8.03) years old, respectively. The multivariate logistic regression model analysis showed that the HPV16 E2 low expression, E6 high expression and E2/E6 low ratio could increase the risk of CIN Ⅱ/Ⅲ, about OR (95%CI) values 11.11 (1.63-75.56), 8.00 (1.28-50.04), and 9.75 (1.22-77.72), respectively and SCC, about OR (95%CI) values 14.22 (2.11-95.88), 10.33 (1.67-64.00), and 12.38 (1.56-97.91), respectively. The hnRNP E2 low expression could increase the risk of CIN Ⅱ/Ⅲ and SCC, about OR (95%CI) values 3.35 (1.39-8.10) and 5.53 (1.54-19.88). The result of GMDR showed that there were interaction effects of the hnRNP E2 low expression, HPV16 E2 low expression and HPV16 E6 high expression in both CIN Ⅱ/Ⅲ and SCC groups. Conclusion The HPV16 E2 low expression, HPV16 E6 high expression and hnRNP E2 low expression could increase the risk of high-grade cervical intraepithelial neoplasia and cervical cancer, and they might have an important interaction effect in the progression of the cervical cancer.

BACKGROUND:Previous literature reported that the fusion cage moved more than 2 mm from its original position,which means that the fusion cage moved backward.At present,clinical observation has found that the factors leading to the displacement of the fusion cage are complex,and the relationship between these factors and the cage retropulsion is not clear. OBJECTIVE:To explore the risk factors related to cage retropulsion after lumbar interbody fusion. METHODS:Retrospective analysis was conducted in 200 patients who underwent transforaminal lumbar interbody fusion surgery with a polyetheretherketone interbody fusion from February 2020 to February 2022.According to the distance from the posterior edge of the vertebral fusion cage to the posterior edge of the vertebral body after the operation(the second day after the removal of the drainage tube)and 1,3,6 and 12 months after the operation,patients were divided into cage retropulsion group(≥2 mm)and cage non-retropulsion group(<2 mm).The factors that may affect cage retropulsion,such as age,gender,body mass index,bone mineral density,operation time,bleeding,endplate injury,preoperative and postoperative interbody height,cage implantation depth,cage size,and segmental anterior convexity angle,were analyzed by univariate and logistic regression analysis. RESULTS AND CONCLUSION:(1)Posterior displacement of the fusion cage occurred in 15 cases(15/200).The differences in basic information such as age and body mass index between the two groups were not statistically significant.(2)The results of the univariate analysis were that gap height difference,time to wear a brace,segmental anterior convexity angle difference,bone mineral density,and age were related to posterior migration of the cage.(3)The results of logistic regression analysis were that cage size,endplate injury condition,and depth of cage implantation were risk factors for cage retropulsion.(4)These findings suggest that cage retropulsion after lumbar interbody fusion is caused by multiple factors,including segmental anterior convexity angle difference,bone mineral density,cage size,endplate damage,time to wear a brace,and depth of cage implantation.

OBJECTIVE：To understand the current status of clinical understanding of “prohibiting”“avoiding”“using caution ” in the application of TCM ，and to provide reference for standardizing the connotation and rational application of “prohibiting” “avoiding”“using caution ”of TCM. METHODS ：Based on the theory of “knowledge-attitude-behavior”，doctor-pharmacist questionnaires and patient questionnaires were designed on the basis of literature research and clinical practice. Through the “Tencent questionnaire ”platform，800 doctor-pharmacist questionnaires were distributed to nearly 300 medical institutions from 32 provinces（cities，autonomous regions ）and 800 patient questionnaires were distributed to public patiants who had used TCM nationwide by anonymous online method. After dimensionality reduction of the questionnaire from three dimensions of cognition ， attention and behavior ，the cognition ，attention and behavior of “prohibiting”“avoiding”“using caution ”in the application of TCM were evaluated by 10 points system. RESULTS ：A total of 703 doctor-pharmacist questionnaires were collected ，including 638 valid questionnaires with recovery rate of 87.9％ and effective rate of 90.8％；Cronbach alpha coefficient was 0.90. A total of 644 patient questionnaires were collected ，including 621 valid questionnaires with recovery rate of 80.5％ and effective rate of 96.4％ . The cognition score of doctors and pharmacists to the terms of “prohibiting”“avoiding”“using caution ”in clinical application of TCM was （7.94±1.21），and that of patients was （5.64±1.54）. The score of doctors and pharmacists ’attention to the above terms was （9.47±1.15）（Spearman Rho correlation coefficient with cognition score was 0.077，P＞0.05），and the score of behavioral ability of patients was （7.01±1.71）（Spearman Rho correlation coefficient with cognition score was －0.021，P＞ 0.05）. The score of behavior ability was （7.43 ± 1.72） （Spearman Rho correlation coefficient with cognition score was 0.233，P＜0.01）. TCM textbooks （89.2％），trainingmeetings （66.5％） and herbal prescriptions （58.2％） were the main ways for doctors and pharmacists to learn the above taboos. Medical staff （74.2％）and internet （52.5％）were the main ways for patients to understand the above taboos. CONCLUSIONS ：Doctors，pharmacists and patients pay more attention to the terms of “prohibiting”“avoiding”“using caution ”in the clinical application of TCM ，but their cognition and executive power were low. Clinical cognition of “prohibiting”“avoiding”“using caution ”in the application of TCM is relatively vague，and the corresponding clinical practice behavior is lacking. It is yet to establish clinical specialist consensus in the field of TCM and publicize it actively to improve the level of clinical rational drug use.