Abstract: Objective　To investigate the allelic mutations of kdr and ace-1 in Anopheles gambiae s.l., providing a scientific basis for mosquito-borne disease prevention and control in the region. Methods Mosquitoes were collected from six villages in two malaria-prone areas, Est-mono (Ogou koulidé, Kepssi, Igbomedji) and Anié (Kolocopé, Bana, Afolé). All mosquitoes were used for DNA extraction, species identification, and genotyping of kdr and ace-1. Results An. coluzzii and An. gambiae, two closely related species within the An. gambiae complex, were identified across six collection sites, with An. gambiae being predominant, constituting approximately 96.53% of the samples. Among all mosquito samples detected, high-frequency mutations were observed at the kdr 1014 locus in the An. gambiae complex, with mutation frequencies reaching 100.0% in Ogou koulidé, Bana, and Afolé, 97.5% in Kepssi and Igbomedji, and 91.1% in Kolocopé district. The allelic frequency of 1014F ranged from 85.5% to 100%. Mutation frequency of An. coluzzii 1014 locus in all three regions was 100%, with an allelic frequency of 1014F ranging from 90% to 100%, indicating a high rate of homozygosity. The kdr 1575 mutation frequency in An. gambiae ranged from 6.6% to 24.3%, with the allelic frequency of 1575Y ranging from 3.2% to 12.2%, all detected mutations were heterozygous, and no mutations were detected at the 1575 locus in An. coluzzii. Mutations at the ace-1 G119 locus were also observed in the An. gambiae complex, with mutation frequencies in An. gambiae ranging from 8.8% to 15% and the allelic frequency of 119S from 4.4% to 7.5%. In An. coluzzii, mutation frequencies ranged from 0 to 20.0%, with an allelic frequency of 119S from 0 to 10%, and all detected 119S mutations were heterozygous. Conclusions The high frequencies of the Anopheles gambiae kdr mutation observed suggest that malaria mosquito vectors in Togo may have developed a high level of resistance to pyrethroid insecticides and possibly a moderate resistance to organophosphorus or carbamate insecticides. This indicates that local vector management authorities should prioritize insecticide resistance issues in future malaria vector control and resistance management planning, and conduct regular monitoring.

Objective:To investigate the correlation of preoperative platelet distribution width (PDW) with clinical features and prognosis of patients with medullary thyroid carcinoma (MTC) .Methods:The clinical data of 160 MTC patients admitted to Zhejiang Cancer Hospital in Department of Head and Neck Surgery from Jun. 2007 to Sep. 2021 were retrospectively collected. There were 74 males and 86 females, aging 8-77 years (mean 48.73±13.76). The median was used to determine the cut-off value of PDW and divided into low PDW group and high PDW group. The correlation between preoperative PDW and clinicopathological features of MTC patients was analyzed by Chi-square test and Spearman correlation test. The relationship of preoperative PDW with overall survival (OS) and disease free survival (DFS) of patients were analyzed by Kaplan-meier and Log-rank test. Univariate and multivariate Cox regression analyses were used to analyze the risk factors for DFS in MTC patients.Results:The preoperative PDW level was closely correlated with the tumor size ( χ2=4.46, P=0.035), TNM stage ( χ2=5.02, P=0.025), bilateral lesions ( χ2=4.94, P=0.026) ,multiple lesions ( χ2=5.19, P=0.023), capsular invasion ( χ2=5.75, P=0.017), extrandular invasion ( χ2=4.27, P=0.039), and vascular tumor thrombus ( χ2=4.48, P=0.034) in MTC patients ( P<0.05). Spearman correlation test showed that preoperative PDW level was negatively correlated with clinical stage ( r=-0.166, P=0.036), lymph node metastasis ( r=-0.187, P=0.018), multiple lesions ( r=-0.176, P=0.026) and vascular tumor thrombus ( r=-0.220, P=0.005) in MTC patients ( P<0.05). Survival analysis showed that reduced PDW predicted worse DFS for MTC ( χ2=9.989, P=0.002). Multivariate Cox regression analysis showed that low PDW ( OR=0.847, 95% CI:0.724-0.992, P=0.040) and lymph node metastasis ( OR=4.913, 95% CI:2.415-9.995, P<0.001) were independent risk factors for DFS in MTC patients. Conclusion:Preoperative decreased PDW is a high risk factor for poor prognosis of MTC and can be used as an indicator to predict recurrence in MTC patients.

Objective:To evaluate the efficacy and safety of quadruple therapy involving radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX (oxaliplatin and gemcitabine) chemotherapy (quadruple therapy) in treatment cohort of patients with unresectable intrahepatic cholangiocarcinoma (ICC).Methods:The patients with recurrent, metastatic, or unresectable ICC underwent quadruple therapy at Zhongshan Hospital, Fudan University between September 2018 and May 2022 were selected. The data about efficacy and safety of quadruple therapy were collected in the hospital electronic medical record system. All patients were followed up regularly to obtain the long-term prognostic data until December 31, 2022. The efficacy, prognosis, and toxicity data were collected and analyzed.Results:A total of 41 patients were included in the analysis. After a median follow-up period of 15 months, disease progression was diagnosed in 36 patients (18 patients died), while 3 patients were lost to follow-up. The causes of death included liver failure induced by intrahepatic tumor progression ( n=6), distant metastases (lungs or brain, n=6), abdominal lymph node metastases ( n=3), cancer cachexia ( n=2), and unknown cause ( n=1). The median progression-free survival (PFS) was 11 months (95% CI: 9.2-12.8), and the median overall survival (OS) was 35 months (95% CI: 17.0-52.0). All patients experienced treatment-related adverse events (AEs) during the study treatment period. Of the 41 patients, 13 patients experienced at least once grade 3 or worse treatment-related AE, but all were manageable with symptomatic treatment. No treatment-related deaths were reported during the follow-up period. Conclusions:Radiotherapy (RT), lenvatinib, anti-PD-1 antibody and GEMOX in the treatment of unresectable ICC shows significant efficacy and good safety, which is worthy of clinical application.

Objective:To analyze the characteristics of prescription about Lingnan Traditional Chinese Medicine (TCM) masters for Biqiu treatment based on data mining, so as to provide reference for the clinical practice and patent drug research and development of rhinorrhea in Lingnan district.Methods:By searching journal documents and medical records in CNKI, VIP, Wanfang, Chinese BioMedical Database (SinoMed) and Duxiu Data Retrieval Platform, we selected the articles and famous TCM medical records that met the criteria on the TCM medical rules of treating Biqiu. We screened database in strict accordance with inclusion and exclusion criteria and extracted prescription information from medical cases. The software Ancient and Modern Consilia Cloud Platform (V 1.5) was used for data mining analysis and medical case standardization, and SPSS Clementine 12.0 software were used to conduct frequency statistics, association analysis and cluster analysis of drugs in medical cases. Results:A total of 31 articles and 42 medical cases including 73 prescriptions were screened. The frequency results showed that there were 40 kinds of high frequency TCMs (frequency more than 5), mainly including drugs for benefiting the qi and strengthening the spleen, medicine to relieve cold and promote nasal passages, which was the same as the frequency statistics of the effects of herbal medicine. Seven drug groups were obtained by cluster analysis. The results of rule analysis showed that 16 association rules for drug pairs and 18 association rules for 3 TCMs pairs were obtained.Conclusions:While treating allergic rhinitis, Lingnan medical doctors focus on tonifying spleen qi, dispersing wind and cold, and promoting the nasal passages, which reflect the treatment theory of cultivating earth and generating gold, and attacking and tonifying. Lingnan medical doctors commonly used Guangdong medicinal herbs, which have distinct regional characteristics. The data mining methods can comprehensively summarize and explore the potential rules of Lingnan prominent practitioners' treatment of allergic rhinitis, and provide reference for guiding the treatment of congested nose and congested nose in TCM.

Objective:To investigate the levels of serum pyrolysis-related factors cysteine protease-1 (caspase-1) and interleukin-18 (IL-18) in patients with gestational diabetes mellitus (GDM) and their relationship with insulin resistance (IR) .Methods:A total of 102 GDM patients admitted to Kaifeng Traditional Chinese Medicine Hospital from Apr. 2019 to Mar. 2021 were selected as the GDM group, and 102 healthy pregnant women undergoing obstetric examination in the same period were included as the normal group. The age, gestational week, fasting insulin (FINS) , pre-pregnancy body mass index (BMI) , triglycerides (TG) , fasting blood glucose (FBG) , total cholesterol (TC) , and homeostatic model insulin resistance index (HOMA-IR) and other materials were compared between the GDM group and the normal group. Enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of serum caspase-1 and IL-18; Pearson method was used to analyze the correlation between serum caspase-1 and IL-18 levels and HOMA-IR in GDM patients; Logistic regression method was used to analyze the influencing factors of GDM.Results:The levels of TG [ (2.94±0.99) mmol/L vs (2.09±0.70) mmol/L], FBG [ (5.87±1.94) mmol/L vs (4.90±1.67) mmol/L], TC [ (5.72±1.92) mmol/L vs (5.03±1.68) mmol/L], FINS [ (11.45±3.87) mIU/L vs (6.92±2.34) mIU/L], HOMA-IR [ (3.05±0.78) vs (1.51±0.40) ] and levels serum caspase-1 [ (86.27±28.78) pg/mL vs (40.98±13.54) pg/mL] and IL-18 [ (44.26±14.56) pg/L vs (30.45±10.12) pg/L] in the GDM group were higher than those in the normal group (t=7.080, 3.827, 2.731, 10.116, 17.743, 14.381, 7.866, P<0.05) ; the levels of serum caspase-1 and IL-18 in GDM patients were positively correlated with HOMA-IR ( r=0.518, 0.555, P<0.05) ; FBG, TG, FINS, HOMA-IR, caspase-1, IL-18 were risk factors affecting the occurrence of GDM (95% CI=1.578-3.826, 1.454-3.311, 1.477-3.405, 1.678-4.265, 1.406-3.141, 1.511-3.551, P<0.05) . Conclusions:The levels of serum caspase-1 and IL-18 in patients with GDM are relatively high, which are significantly related to IR. Caspase-1 and IL-18 may be potential targets for the treatment of GDM.

Malignant hepatobiliary tumors mainly include hepatocellular carcinoma (HCC) and biliary tract cancer (BTC) and are common malignancies in China that seriously threaten the life and health of the Chinese people. Malignant hepatobiliary tumors often have an insidious onset, and most patients have lost the opportunity for surgery due to the advanced stage at initial diagnosis. The treatment of advanced HCC mainly depends on systemic therapy such as sorafenib, lenvatinib, donafenib, regorafenib, apatinib, and systemic chemotherapy, but such treatment often has a limited effect. The treatment of advanced BTC mainly relies on systemic chemotherapy, which often has an unsatisfactory effect. The advent of the era of immunotherapy brings new hope to the treatment of advanced malignant hepatobiliary tumors. Atezolizumab combined with bevacizumab and sintilimab combined with a bevacizumab biosimilar IBI305 have been approved as the first-line treatment of advanced HCC. The treatment regimens, such as Chemotherapy-based immune checkpoint inhibitor (ICI) or ICI combined with targeted drugs, have made great progress in the treatment of advanced BTC, and although these regimens can significantly improve the overall survival of patients, they often bring obvious and even life-threatening adverse reactions, which should be taken seriously by clinicians. In addition, further studies are needed to investigate the value of ICI-based combination therapy in the perioperative treatment of malignant hepatobiliary tumors.

Biliary malignant tumors have an insidious onset and rapid development, and most patients have lost the opportunity for radical surgery at initial diagnosis and often have poor prognosis. Gemcitabine-based chemotherapy is the first-line treatment for biliary malignant tumors, but with a limited clinical effect. The improvement in next-generation sequencing technology provides the possibility for the precise treatment of biliary malignant tumors, but the application and development of the precise treatment of biliary malignant tumors are limited by the low positive rate of targets and the poor accessibility of therapeutic drugs. The advent of the era of immunotherapy represented by the immune checkpoint inhibitor PD1/PD-L1 monoclonal antibody brings a promising future for the treatment of malignant tumors, including biliary malignant tumors. Combined chemotherapy and/or targeted therapy based on immune checkpoint inhibitors has shown a good effect in the treatment of biliary malignant tumors, which is the direction of the treatment of advanced biliary malignant tumors in the future.

The clinical application of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of hepatocellular carcinoma (HCC) patients. With the widespread applica-tion of ICIs in HCC, the management of immune-related adverse events (irAE) gained more and more attention. However, the complicated disease characteristics and various combination therapies in HCC throw out challenges to irAE management. Therefore, the editorial board of the 'Chinese expert consensus on the management of immune-related adverse events of hepatocellular carcinoma treated with immune checkpoint inhibitors (2021 edition)' organizes multidisciplinary experts to discuss and formulate this consensus. The consensus focuses on issues related to HCC irAE manage-ment, and puts forward suggestions, in order to improve standardized and safety clinical medication, so as to maximize the benefits of immunotherapy for patients.

Objective:To investigate the value of visfatin in the differential diagnosis of benign and malignant breast tumors and the feasibility of visfatin as a molecular marker of breast cancer.Methods:A total of 195 breast cancer patients hospitalized in the Cancer Hospital of The University of Chinese Academy of Sciences from December 2017 to July 2018 were selected as the breast cancer group, all of them were women. 80 patients with benign breast diseases in the same period were randomly selected as the breast benign disease group, all of them were women. 80 female employees with normal physical examination in the same year were selected as the normal control group. Enzyme linked immunosorbent assay (ELISA) was used to detect the serum level of visfatin. Logistic regression was used to analyze the relationship between visfatin and clinicopathological features of breast cancer. Receiver operating characteristic (ROC) curve was drawn to get area under curve (AUC) value, and the diagnostic efficacy was analyzed.Results:The serum visfatin level in breast cancer group was significantly higher than that in benign breast disease group and normal control group ( P<0.05). Univariate analysis showed that the serum visfatin level was related to lymph node metastasis, tumor node metastasis (TNM) stage and body mass index (BMI) (all P<0.05). The serum visfatin level was positively correlated with TNM stage and lymph node metastasis of breast cancer patients ( r=0.336, P=0.043; r=0.632, P=0.027, respectively). Multivariate regression analysis showed that lymph node metastasis was a risk factor for serum visfatin [ OR=1.098, 95% CI(1.073, 1.226), P=0.02]. According to the ROC curve of serum visfatin level in benign breast disease group and normal group, the AUC of serum visfatin were 0.652 and 0.701, respectively. When the Youden index was the highest, the sensitivity was 52.30% and 55.90% respectively, and the specificity was 73.10% and 75.0% respectively. Conclusions:Serum visfatin level can be used to distinguish benign and malignant breast cancer patients. It has a certain clinical value in the auxiliary diagnosis of breast cancer, and may be used as a potential molecular marker of breast cancer.

Objective:To explore the risk factors influencing the prognosis for patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation and summarize the relevant diagnostic and therapeutic experiences.Methods:The clinicopathological features with diagnosis and treatment plan of 102 recurrent HCC patients fulfilling the Fudan Criteria were compared for survival rate (univariate analysis) and independent prognostic indicators were obtained by Cox multivariate analysis.Results:The 1/3/5-year overall survival rates were 92.2%, 48.6% and 34.6% and the 1/3/5-year survival rates with tumor were 63.2%, 31.0% and 16.7% respectively. Cox regression analysis indicated that patient age, whether tumor can be surgically resected or not and personalized diagnostic & therapeutic plan based upon targeted therapy were independent prognostic factors affecting the overall survival rates and survival rates with tumor.Conclusions:Although HCC recurrence and metastasis after liver transplantation seriously influence patient prognosis, satisfactory outcomes may be obtained for some patients through active, effective and precise managements.