Objective To investigate the relationship between the expression of NF-κB and Pglycoprotein(P-gp) in cervical cancer tissue before and after neoadjuvant chemotherapy(NACT). Methods The mRNA and the protein expression levels of NF-κB and P-gp were determined by Real time-PCR and immunohistochemical assay respectively in cancer specimens from 40 cevical cancer patients, which were collected before and after NACT. Results The mRNA expression levels of NF-κB were 50. 340 ± 0. 780 and 67. 595 ± 0. 914 before and after NACT respectively, which showed significant difference statistically ( t = -73. 384 ,P ＜ 0. 01 ). We also found significant difference in the comparison between MDR1 mRNA expression before and after NACT(45. 800 ±0. 636 vs 62. 381 ±0. 743 ,t = -66. 582,P ＜0. 01 ). The positive rate of NF-κB protein expression before and after NACT were 50% ( 20/40 ), 80% ( 32/40 ) respectively, which showed significant difference statistically( χ2 = 7. 912, P = 0. 005 ). The positive rate of P-gp protein expression after NACT was significantly higher than that before NACT [ 40% ( 16/40 ) vs 70% ( 28/40 ), χ2 = 7. 273, P = 0. 007 ]The mRNA and protein expressions of NF-κB were positively correlated with those of P-gp before and after NACT( r = 0. 408,r = 0. 327 respectively, Ps ＜ 0. 05 ). Conclusion NF-κB and P-gp may play an important role in multi-drug resistance of cervical carcinoma. Chemotherapy drugs in our NACT strategy may induce the activation of NF-κB and multi-drug resistance. Activation of NF-κB may correlate with multi-drug resistance mediated by P-gp.

Objective To investigate the relationship between clinical presentation and pathological characteristics in HBeAg negative chronic hepatitis B(CHB) patients with steatosis, and to find out the predictors of hepatic inflammation and fibrosis. Methods HgeAg negative CHB patients with (n=56) or without (n=60) steatosis confirmed clinically and pathologically were enrolled in the study. All patients were examined for fasting blood glucose(FBG), fasting insulin (FINS), triglyceride (TG), cholesterol (TC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyhransferase (GGT), alkaline phosphatase (ALP) albumin (Alb), globulin(Glb), homeostatic model assessment of insulin resistance (HOMA-IR), HBV-DNA and body mass index(BMI). The association of above parameters with hepatic inflammation, fibrosis and fatty deposition were analyzed statistically. Results It was demonstrated that BMI, FBG, FINS, TG, TC, GGT, ALP , Glb and HOMA-IR were significantly higher in HBeAg negative CHB patients with steatosis than those without steatosis (P<0.05). Whereas the levels of HBV-DNA, Alb, ALT and AST were significantly lower in HBeAg negative CHB patients with steatosis compared with those without steatosis (P<0.05). The hepatic inflammation and fibrosis were aggravated in patients with steatosis. It was implicated that BMI,FBG, FINS, TG, TC, GGT and HOMA-IR(all P values 0.05) were significant predictors for hepatic steatosis, while ALT, AST, Glb and HBV-DNA(all P values <0.05) were significant predictors for hepatic inflammation. And the predictors for hepatic fibrosis were ALT, AST, Alb, Glb and HBV-DNA(all P values <0.05). Conclusions Hepatic steatosis is common in HBeAg negative CHB patients which is positively associated with parameters including BMI, FBG, FINS, TG, TC, GGT, ALP and HOMA-IR. Besides steatosis, the hepatic inflammation and fibrosis are also aggravated in these patients.

Objective To estimate the bladder symptoms, and explore its impact on patients′ quality of life in type 2 diabetes mellitus. Methods Overactive bladder symptom score (OABSS) was used to evaluate patients′ bladder symptoms, and Medical Outcome Study 12-Item Short Form Health Survey Scale (SF-12), Overactive Bladder Questionnaire Short Form(OABq-SF)were conducted to test the effect of bladder symptoms on general and disease-specific quality of life. Results Among the four bladder symptoms, nocturia was the most prevalent symptom (46.7%,479/1025 ), followed by urinary frequency (14.9%,153/1025 ),urinary urgency (14.2%,146/1025 ), urge urinary incontinence (7.9%, 81/1025). Nocturia and urge urinary incontinence significantly increased symptom bother (nocturia B=0.337,P<0.01;urge urinary incontinence B=0.437,P<0.01) and decreased disease-specific quality of life (nocturia B=-0.364,P<0.01;urge urinary incontinence B=-0.346, P<0.01) in these patients. Meanwhile, urge urinary incontinence was negatively associated with general mental health (B=-0.255, P=0.011). Conclusions The prevalence of bladder symptoms in type 2 diabetes patients was high, and was found to be associated with patients′general and disease-specific quality of life. Health care providers should be aware of the high prevalence of bladder symptoms and its impact on QOL to facilitate early diagnosis and treatment of bladder symptoms during diabetic care.

Objective: Predefining the most effective treatment for patients with depressive disorders remains a problem. We will examine the differential brain regions of gray matter (GM) in major depressive disorder (MDD) patients and the relationship between changes in their volume and the efficacy of early antidepressant treatment using magnetic resonance imaging (MRI). Methods: 159 never-medicated patients with first-episode MDD and 53 normal control subjects (NCs) were enrolled. The brains were scanned by MRI and measured with the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and after 2 weeks of treatment with selective serotonin reuptake inhibitor (SSRI)s, and the non-responder group and responder group were obtained. The patients were analyzed by voxel-based morphological (VBM) and SPSS software. Receiver operator characteristics (ROC) analysis was performed for the difference between the responder group and the non-responder group in the differential brain regions, and Pearson correlations were computed between volume size and HAMD score reduction rate. Results: Smaller GM volume of the right superior temporal gyrus (STG), and the orbital parts of the right medial frontal gyrus and right inferior frontal gyrus were observed in MDD versus the NCs. The non-responder group demonstrated a significant volume reduction at the right STG compared with the responders, but no corresponding change in orbital part of right medial frontal gyrus and right inferior frontal gyrus. ROC analysis showed that Accuracy=71.2%. There was a positive correlation between the STG gray matter volume and the HAMD-17 score reduction rate (r=0.347, p=0.002). Conclusion The study results confirmed the local changes in brain structure in MDD and may initially predict the early treatment response produced by SSRIs as antidepressants.

Objective:To study the radiation dose rate and effective dose in ambient environment due to 125I seed implantation in the treatment of the patients suffering abdominal and pelvic tumors, so as to provide reference for occupational protection of different groups. Methods:Within 24 hours after operation, the radiation dose rate to 42 patients with abdominal and pelvic tumor with 125I seed implantation was monitored by using pocket dosimeter. The relationships between the total activity in the implanted particles and the measured dose rate, as well as between the implanted depth and the dose rate under the standard activity, were obtained by curve fitting. According to the formula, the relationship between the dose rate and the warning time was calculated. Results:The dose rates at 30 cm, 50 cm and 100 cm of vertical particle implantation site were (6.92±2.87), (4.10±1.62) and (1.30±0.48) μSv/h, respectively ( χ2=73.71, P<0.05). The dose rates on the left and right sides were (0.378±0.156) and (0.384±0.153) μSv/h at 30 cm, (0.170±0.089) and (0.17±0.086) μSv/h at 50 cm, (0.039 ±0.014) and (0.043±0.017) μSv/h at 100 cm, respectively ( χ2=76.19, 76.33, P<0.05). There was a linear relationship between the dose rate at the vertical particle implantation site and the total activity in the implanted particles, and between the dose rate and the implantation depth under the standard activity. The relationship between the warning time and the dose rate to adults in the same bed, co-workers, minors in the same bed and pregnant women were as follows: t ( d)=-106.616+ 83.779ln D( t), t ( d)=26.556+ 85.933ln D ( t), t( d)=3.088+ 85.017ln D( t). Conclusions:After 125I seed implantation, the radiation dose in the ambient environment is low, ensuring the radiation safety; and the measured dose rate decreases with the decrease in the total activity in the implanted particle and the increase in the implantation depth; at the same time, the warning time for different groups is calculated according to the measured dose rate or the total activity in the implanted particle and the depth of the implanted particle, so as to carry out individualized protection.

Objective The aim of this study was to investigate the effects of general practice mode combined with duloxetine on psychological status,sleep quality and serum inflammatory cytokines in patients with Fibromyalgia Syndrome(FMS).Methods A total of 105 FMS patients in Chengde Central Hospital from January 2019 to December 2021 were divided into the combined group(53 cases)and the control group(52 cases)by the random number table method.The two groups were treated with general practice mode combined with duloxetine or duloxetine alone.The single course of treatment lasted for 4 weeks.Their efficacy and safety were evaluated after 2 courses of intervention.Visual analogue scale(VAS),Hamilton Anxiety assessment scale(HAMA),Hamilton Depression Scale(HAMD)and Pittsburgh Sleep Quality Index(PSQI)were performed before and after treatment.The pain,psychological status and sleep quality of the patients were evaluated.Blood samples were taken to measure the serum levels of tumor necrosis factor-α(TNF-α),interleukin-1(IL-1)and IL-6 before and after treatment.Results The total effective rate in the study group was 96.23%,which was higher than that in the control group(82.69%,P<0.05).Compared with those before treatment,VAS,HAMA,HAMD and PSQI scores,serum TNF-α,IL-1 and IL-6 levels in the two groups were all decreased after treatment,and those in the study group were lower than those in the control group(P<0.05).There was no statistically significant difference in the incidence of adverse reactions between two groups(7.55%vs.19.23%,P>0.05).Conclusion General practice mode combined with duloxetine was safe and effective in the treatment of FMS,which could significantly relieve anxiety and depression of patients,improve their sleep quality,and reduce the level of serum inflammatory cytokines.

Objective:To summarize the application of pectoralis major flap in complex defects after maxillofacial " frozen neck" surgery.Methods:The clinical data of 7 patients with maxillofacial " frozen neck" admitted to the Department of Stomatology of the Xuzhou Central Hospital from October 2020 to October 2022 were retrospectively analyzed. The pectoralis major flap was used to repair the complex defects after surgery and the treatment effect was observed.Results:All 7 patients had survived flap transplantation with no serious complications. After 3 to 24 months of follow-up, the patients were basically satisfied with the treatment effect.Conclusions:The pectoralis major flap has reliable blood supply, abundant tissue, and can be applied flexibly with a high survival rate and significant repair effect. It is a good choice for repairing complex defects after " frozen neck" surgery, and it has clinical application value.

OBJECTIVE：To evaluate the econo mics of pembrolizumab in the second-line treatment of advanced hepatocellular carcinoma in China. METHODS ：From the perspective of Chinese healthcare system ，a three-state PartSA model and Markov model were established ；the cost and utility for the second-line treatment of advanced hepatocellular carcinoma in China were compared between pembrolizumab and placebo. The circulation cycle of the model was 3 weeks and the study time limit was lifetime；one-way sensitivity analysis ，probability sensitivity analysis and scenario analysis were used to verify the robustness of the base-case analysis results. RESULTS ：PartSA results showed that the ICER for the second-line treatment of advanced hepato- cellular carcinoma with pembrolizumab was 1 266 846.18 yuan/QALY，which is far more than 1-3 times of China ’s per capita GDP in 2020. The results of one-way sensitivity analysis showed that the three parameters that had the greatest impact on ICER were the PFS status utility of the placebo group ，the PFS status utility of the pembrolizumab group ，and the cost of pembrolizumab. The results of probability sensitivity analysis verified the robustness of the base-case analysis. The scenario analysis showed that the treatment cost of pembrolizumab had dropped significantly when the charity donation of pembrolizumab was considered. Although it was still not economical ，ICER was close to 3 times of per capita GDP of China in 2020. When WTP threshold was 1 and 3 times of China ’s per capita GDP ，the economic prices of pabolizumab （100 mg）were 4 157.67 and 5 829.24 yuan，respectively. The results of Markov model were similar to those of PartSA model. CONCLUSIONS ：Under the WTP threshold of 1-3 times China ’s per capita GDP in 2020，pembrolizumab is not economical for second-line treatment of advanced hepatocellular carcinoma.

OBJECTIVE：To provide referenc e for selectin g antitumor drugs economic evaluation models and improving the quality of evidence for antitumor drugs economics evaluation in China. METHODS ：A systematic search of the antitumor drug health technology evaluation （pCODR）reports were conducted on the official website of the Canadian Agency for Drugs and Technologies in Health （CADTH）. The search time was limited to Jan. 1st，2015 to Sep. 6th，2020. The basic information ，model types and structure ，and key limitations were extracted and summarized. RESULTS & CONCLUSIONS ：A total of 185 pCODR reports were finally retrieved ，involving 114 types of tumor indications and 98 types of antitumor drugs. The number of CADTH antitumor drugs economics evaluations in the past 5 years had shown an increasing trend. Among 137 pCODR reports with final economic guidance report ，98 reports（71.5％）adopted the PartSA model ，21 reports（15.3％）used the Markov model ，and some reports（6 reports，4.3％）used both PartSA and Markov models to explore the uncertainty of the model structure. In terms of model health status setting ，86 reports（62.8％）used three-state models to evaluate the economy of different anti tumor drugs ，and 16 reports（11.7％）used no less than four health states to simulate the outcome of disease state. However ，there were still some problems in CADTH models ，such as the unreasonable choice of research time limit ，the unreasonable extrapolation method or uncertain extrapolation results of efficacy （survival）data，the uncertainty of efficacy data obtained by indirect comparison ，and some assumptions or parameter settings did not conform to the actual diagnosis and treatment environment. In view of the advantages of PartSA model ，it is suggested that PartSA model or Markov model combined with PartSA model should be used first to verify the uncertainty of model structure in the future economic evaluation of antitumor drugs ；reasonable settings of key model parameters should be considered to improve the quality of evidence for antitumor drugs economics evaluation in China.

OBJECTIVE To ev aluate the economical efficiency of nivolumab versus everolimus in the second-line treatment of metastatic clear cell renal cell carcinoma. METHODS From the perspective of China ’s health system ，cost-effectiveness analysis of the two therapies was carried out by developing a three-state partitioned survival model. The clinical parameters were from the updated CheckMate 025 study，and the cost and health utility were from relevant websites and published literatures. The model adopted a 2-week cycle and a lifetime research time. The robustness of the results was verified by sensitivity analysis. The economical efficiency of two therapy schemes were evaluated in the scenario of model simulation time of 80 months and charitable drug donation scheme. RESULTS The results of basic analysis showed that compared with everolimus ，the incremental cost-effectiveness ratio （ICER）of nivolumab was 586 982.60 yuan/quality-adjusted life year （QALY），which was far higher than 3 times of China ’s per capita gross domestic product （GDP）in 2020. The results of single-factor sensitivity analysis showed that the 3 parameters that had the greatest impact on the economic evaluation results were the cost of nivolumab ，the utility value of nivolumab group and everolimus group in progressive disease state. The results of probability sensitivity analysis verified the robustness of the basic analysis results. Results of scenario analysis showed that in the first scenario analysis ，in which model simulation time lasted for 80 months，ICER of nivolumab was 417 204.52 yuan/QALY；in the second scenario analysis ，in which nivolumab charitable drug donation program for low-income people was considered ，ICER of nivolumab was 124 988.58 yuan/QALY. CONCLUSIONS Under the threshold of 1-3 times of China ’s per capita GDP in 2020，compared with everolimus ，it is not economical to use nivolumab as the second-line treatment for metastatic clear cell renal cell carcinoma ； nivolumab is economical when considering its charitable drug donation program for low-income people.