Objective:To observe the clinical efficacy of immediate repair of extracranial branch defects in the facial nerve through transplantation of the great auricular nerve.Methods:A retrospective inclusion was carried out on 17 patients with extracranial branch defects of the facial nerve caused by parotid malignant tumors and neurogenic tumors in the Department of Stomatology of Xuzhou Central Hospital from June 2021 to January 2023, including 10 males and 7 females, with the age ranged from 28 to 68 (42.4±11.4) years old. All patients underwent immediate transplantation of the greater auricular nerve during the operation. The facial nerve function was evaluated according to the House-Brackmann (HB) facial paralysis grading standard at the last follow-up. Grade Ⅰ-Ⅲ was considered effective, and grade Ⅳ-Ⅵ was considered ineffective. The quality of life was evaluated using the physical function score (FDIP) and social function score (FDIS).Results:The follow-up time was 6-30 (18.3 ±6.6) months. The facial nerve function was classified as grade Ⅰ in four cases, grade Ⅱ in six cases, grade Ⅲ in four cases, and grade Ⅳ in three cases. This resulted in an effective rate of 14/17. The FDIP score at the final follow-up was (84.7 ±9.1) points, which was higher than the (54.1 ±20.6) points recorded at the immediate moment of repair ( P<0.001). In contrast, the FDIS score was (11.8 ±8.9) points, which was lower than the (57.5 ±11.7) points recorded at the immediate moment of repair ( P<0.001). Conclusion:The transplantation of the auricular great nerve can effectively enhance facial nerve function and improve the life quality in the immediate repair of defects in the extracranial branches of the facial nerve.

Objective:To investigate the metabolic pathways and potential molecular targets associated with dapagliflozin in the treatment of type 2 diabetes mellitus.Methods:Plasma samples from patients with type 2 diabetes mellitus were collected before and after 12 months of dapagliflozin treatment and analyzed using UPLC-VION IMS Q-Tof-based metabolomics and timsTOF Pro2 diaPASEF-based proteomics. Multivariate statistical analyses were performed to identify significant differences pre- and post-treatment. Correlation analysis was then conducted to assess relationships between differentially expressed metabolites and proteins closely associated with type 2 diabetes mellitus. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were used to construct metabolic pathway maps and predict therapeutic targets.Results:After 12 months of dapagliflozin treatment, 162 differential metabolites were identified, with 59 upregulated and 103 downregulated. A total of 440 differentially expressed proteins were detected, of which 272 were upregulated and 168 were downregulated. The main classes of differential metabolites included sphingolipids, glycerophospholipids, and glycosphingolipids. Key differentially expressed proteins included importin subunit alpha-11, synemin, Janus kinase 1, and far upstream element-binding protein 2. Correlation analysis revealed 98 shared enriched pathways between differential metabolites and proteins, involving neurotrophin signaling, chemokine signaling, and B cell receptor signaling pathways. Metabolic pathway analysis suggested that dapagliflozin might regulate insulin secretion by modulating glucose-dependent insulinotropic polypeptide, calmodulin-dependent protein kinase, and diacylglycerol levels.Conclusion:Dapagliflozin may exert therapeutic effects in type 2 diabetes mellitus through multiple mechanisms, including the modulation of metabolic and proteomic profiles, participation in key cellular signaling pathways, and regulation of insulin secretion.

Objective:To investigate the metabolic pathways and potential molecular targets associated with dapagliflozin in the treatment of type 2 diabetes mellitus.Methods:Plasma samples from patients with type 2 diabetes mellitus were collected before and after 12 months of dapagliflozin treatment and analyzed using UPLC-VION IMS Q-Tof-based metabolomics and timsTOF Pro2 diaPASEF-based proteomics. Multivariate statistical analyses were performed to identify significant differences pre- and post-treatment. Correlation analysis was then conducted to assess relationships between differentially expressed metabolites and proteins closely associated with type 2 diabetes mellitus. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were used to construct metabolic pathway maps and predict therapeutic targets.Results:After 12 months of dapagliflozin treatment, 162 differential metabolites were identified, with 59 upregulated and 103 downregulated. A total of 440 differentially expressed proteins were detected, of which 272 were upregulated and 168 were downregulated. The main classes of differential metabolites included sphingolipids, glycerophospholipids, and glycosphingolipids. Key differentially expressed proteins included importin subunit alpha-11, synemin, Janus kinase 1, and far upstream element-binding protein 2. Correlation analysis revealed 98 shared enriched pathways between differential metabolites and proteins, involving neurotrophin signaling, chemokine signaling, and B cell receptor signaling pathways. Metabolic pathway analysis suggested that dapagliflozin might regulate insulin secretion by modulating glucose-dependent insulinotropic polypeptide, calmodulin-dependent protein kinase, and diacylglycerol levels.Conclusion:Dapagliflozin may exert therapeutic effects in type 2 diabetes mellitus through multiple mechanisms, including the modulation of metabolic and proteomic profiles, participation in key cellular signaling pathways, and regulation of insulin secretion.

Objective:To observe the clinical efficacy of immediate repair of extracranial branch defects in the facial nerve through transplantation of the great auricular nerve.Methods:A retrospective inclusion was carried out on 17 patients with extracranial branch defects of the facial nerve caused by parotid malignant tumors and neurogenic tumors in the Department of Stomatology of Xuzhou Central Hospital from June 2021 to January 2023, including 10 males and 7 females, with the age ranged from 28 to 68 (42.4±11.4) years old. All patients underwent immediate transplantation of the greater auricular nerve during the operation. The facial nerve function was evaluated according to the House-Brackmann (HB) facial paralysis grading standard at the last follow-up. Grade Ⅰ-Ⅲ was considered effective, and grade Ⅳ-Ⅵ was considered ineffective. The quality of life was evaluated using the physical function score (FDIP) and social function score (FDIS).Results:The follow-up time was 6-30 (18.3 ±6.6) months. The facial nerve function was classified as grade Ⅰ in four cases, grade Ⅱ in six cases, grade Ⅲ in four cases, and grade Ⅳ in three cases. This resulted in an effective rate of 14/17. The FDIP score at the final follow-up was (84.7 ±9.1) points, which was higher than the (54.1 ±20.6) points recorded at the immediate moment of repair ( P<0.001). In contrast, the FDIS score was (11.8 ±8.9) points, which was lower than the (57.5 ±11.7) points recorded at the immediate moment of repair ( P<0.001). Conclusion:The transplantation of the auricular great nerve can effectively enhance facial nerve function and improve the life quality in the immediate repair of defects in the extracranial branches of the facial nerve.

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 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 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.

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 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：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.