As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Objective To investigate the growth, development and health status of primary and secondary school students in Xinzhou District of Wuhan, and analyze the detection and change trend of common diseases in primary and secondary school students, and to provide a basis for relevant departments to formulate prevention and control measures of common diseases in students. Methods The monitoring data of common diseases and health influencing factors of primary and secondary school students in Xinzhou District from 2019 to 2022 were analyzed and compared according to different genders, different grades and ages. SPSS 20.0 software was used to analyze the data of detection rates of myopia, dental caries, obesity, malnutrition and abnormal spinal curvature. Results The overall detection rates of myopia, dental caries, malnutrition, obesity and abnormal spinal curvature were 57.00%, 58.45%, 4.60%, 14.91%, and 6.33%, respectively, in Xinzhou District from 2019 to 2022. The annual change rates were 7.22%, 15.10%, -2.72%, 13.29%, and 4.91%, respectively. The detection rates of myopia, dental caries, obesity and abnormal spinal curvature showed an increasing trend in each year (χ² ≥17.22, P<0.001). The detection rates of myopia and malnutrition increased with the increase of age and school level (both χ²≥42.37, P<0.001), while the opposite was true for the detection rates of dental caries and obesity (both χ²≥14.26, P<0.001). The detection rates of myopia and dental caries were higher in girls than in boys (both χ²≥33.66, P<0.001), while the detection rates of obesity and abnormal spinal curvature were higher in boys than in girls (both χ²≥8.22, P<0.005). The detection rates of myopia, dental caries, obesity and abnormal spinal curvature in 2019 were lower than those in 2020-2022 (χ²≥4.11, P<0.05), while the detection rates of malnutrition had decreased. Conclusion The growth, development and health status of primary and secondary school students in Xinzhou District are serious. The detection rate of common diseases such as myopia, dental caries, obesity and abnormal curvature of the spine is on the rise, which should be the focus of the surveillance work of common diseases in primary and secondary school students in the future, and comprehensive intervention measures are urgently needed to prevent and control these common diseases.

Objective:To investigate the association between social support and subjective and objective cognitive functions among the middle-aged and elderly population in Pingyin County, Jinan City, Shandong Province.Methods:Employing a multi-stage cluster random sampling method, a cross-sectional study was conducted in 2023 by selecting people aged 45-70 years from seven villages in three towns within Pingyin County, Jinan City, as survey respondents. Social Support Rating Scale (SSRS), Subjective Cognitive Decline-Questionnaire 9 (SCD-Q9) and Montreal Cognitive Assessment-Basic (MoCA-B) were used to assess the social support and cognitive status of interviewees, and a self-developed questionnaire was used to collect other basic information. Pearson correlation analysis, multiple linear regression and multifactorial logistic regression were used to explore the relationship between social support and subjective and objective cognitive functions.Results:A total of 1 891 subjects were finally included in the study, with 45.52±6.99 for the SSRS total score, an abnormal rate of 43.68% (826/1 891) for the SCD-Q9 score and an abnormal rate of 60.02% (1 135/1 891) for the MoCA-B score. The SSRS total score, subjective support score, objective support score and support utilization score were negatively correlated with SCD-Q9 scores and positively correlated with MoCA-B scores (all P<0.05). An increase in SSRS total score ( β=-0.034, 95% CI: -0.051--0.017, P<0.001) and objective support score ( β=-0.074, 95% CI: -0.121--0.027, P=0.002) can lower SCD-Q9 scores. Compared to those who had only 1 source of financial support or help with practical problems when experiencing an acute situation, those with 2-4 ( OR=0.53, 95% CI: 0.34-0.82), 5 ( OR=0.46, 95% CI: 0.27-0.79), or 6-7 ( OR=0.42, 95% CI: 0.22-0.81) sources of help were more likely to have normal SCD-Q9 scores. Compared to individuals with ≤2 close friends who provided support and help, those with 3-5 ( OR=0.67, 95% CI: 0.50-0.91) or ≥6 friends ( OR=0.72, 95% CI: 0.54-0.97) were more likely to have normal MoCA-B scores. Moreover, compared to individuals who never participated in group activities, those who actively participated ( OR=0.59, 95% CI: 0.42-0.81) were more likely to have normal MoCA-B scores. Conclusions:Social support has protective effects on subjective and objective cognitive functions, and various social support conditions have different protective effects on subjective and objective cognitive functions among middle-aged and older people. Improving social support conditions for middle-aged and elderly individuals may delay the process of cognitive decline.

Objective:To investigate the association between social support and subjective and objective cognitive functions among the middle-aged and elderly population in Pingyin County, Jinan City, Shandong Province.Methods:Employing a multi-stage cluster random sampling method, a cross-sectional study was conducted in 2023 by selecting people aged 45-70 years from seven villages in three towns within Pingyin County, Jinan City, as survey respondents. Social Support Rating Scale (SSRS), Subjective Cognitive Decline-Questionnaire 9 (SCD-Q9) and Montreal Cognitive Assessment-Basic (MoCA-B) were used to assess the social support and cognitive status of interviewees, and a self-developed questionnaire was used to collect other basic information. Pearson correlation analysis, multiple linear regression and multifactorial logistic regression were used to explore the relationship between social support and subjective and objective cognitive functions.Results:A total of 1 891 subjects were finally included in the study, with 45.52±6.99 for the SSRS total score, an abnormal rate of 43.68% (826/1 891) for the SCD-Q9 score and an abnormal rate of 60.02% (1 135/1 891) for the MoCA-B score. The SSRS total score, subjective support score, objective support score and support utilization score were negatively correlated with SCD-Q9 scores and positively correlated with MoCA-B scores (all P<0.05). An increase in SSRS total score ( β=-0.034, 95% CI: -0.051--0.017, P<0.001) and objective support score ( β=-0.074, 95% CI: -0.121--0.027, P=0.002) can lower SCD-Q9 scores. Compared to those who had only 1 source of financial support or help with practical problems when experiencing an acute situation, those with 2-4 ( OR=0.53, 95% CI: 0.34-0.82), 5 ( OR=0.46, 95% CI: 0.27-0.79), or 6-7 ( OR=0.42, 95% CI: 0.22-0.81) sources of help were more likely to have normal SCD-Q9 scores. Compared to individuals with ≤2 close friends who provided support and help, those with 3-5 ( OR=0.67, 95% CI: 0.50-0.91) or ≥6 friends ( OR=0.72, 95% CI: 0.54-0.97) were more likely to have normal MoCA-B scores. Moreover, compared to individuals who never participated in group activities, those who actively participated ( OR=0.59, 95% CI: 0.42-0.81) were more likely to have normal MoCA-B scores. Conclusions:Social support has protective effects on subjective and objective cognitive functions, and various social support conditions have different protective effects on subjective and objective cognitive functions among middle-aged and older people. Improving social support conditions for middle-aged and elderly individuals may delay the process of cognitive decline.

As the application of immune checkpoint inhibitors(ICIs)in the perioperative treatment of melanoma is increasingly introduced at earlier stages,it presents a critical opportunity for the development and clinical translation of neoadjuvant therapy.The results of phaseⅠ/Ⅱ clinical trials on neoadjuvant ICI therapy for melanoma demonstrate that neoadjuvant ICIs effectively improve the pathologic re-sponse rate in melanoma patients.Recent studies have shown that combining ICIs with other treatment modalities,including radiotherapy,chemotherapy,and targeted therapies,can enhance antitumor efficacy of neoadjuvant treatment for patients with melanoma.Optimizing treatment regimens,managing adverse events,identifying and addressing pseudoprogression,and handling cases of oligoprogression have become key areas of research in incorporating ICI regimens into neoadjuvant treatment for patients with melanoma.The search for bio-markers to monitor immunotherapy efficacy is expected to become a major focus of future research.This article provides a review of the re-search progress,controversies,and challenges in the application of ICIs in the neoadjuvant treatment of melanoma,and discusses future re-search directions,aiming to offer insights into the clinical application and development of ICIs in melanoma neoadjuvant therapy.

Objective To investigate the changes of blood lipid and glycosylated hemoglobin (HbA1c) levels in obese type 2 diabetes (T2DM) patients and their relationship with insulin resistance (Homa-IR). Methods A total of 120 cases of T2DM newly diagnosed in Motuo County, Tibet from February to October 2022 were selected as the observation group. According to BMI, the patients were divided into diabetes normal weight group (46 cases), overweight group (43 cases) and obesity group (31 cases); 145 healthy subjects were selected as the control group. The levels of HbA1c, fasting blood glucose (FPG), fasting insulin (FINS), serum total cholesterol (TC), triglycerides (TG), high-density lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) were detected in the study subjects, and Homa-IR and Homa-β indices were calculated. The height, weight, and abdominal circumference were measured. The differences in the levels of the above indicators between the observation group patients and the control group, as well as among various subgroups within the observation group were compared. The influencing factors of Homa-IR in obese T2DM patients were analyzed. Results Compared with the control group, a significant increase in BMI, abdominal circumference, blood pressure, HbA1c, FBG, FINS, TC, TG, LDL-C, UA, visceral fat area, and the levels of Home-IR and Home-β was found in the observation group (all P<0.05). There were significant differences in BMI, abdominal circumference, and the levels of FINS, Homa IR, Homa-β, and HbA1c in diabetes patients with different BMI (all P<0.05). Correlation analysis showed that TG levels in obese T2DM patients in the observation group were significantly correlated with HbA1c (r=0.396, P=0.027), Homa-IR (r=0.405, P=0.024), and Home-β (r=-0.401, P=0.025); LDL-C was significantly correlated with Homa-IR (r=0.411, P=0.022) and Homa-β (r=-0.412, P=0.021); HbA1c was significantly positively correlated with BMI (r=0.371, P=0.040). Conclusion Insulin resistance is closely related to TG, LDL-C, and BMI in obese T2DM patients from the Motuo ethnic minority of Tibet, suggesting that these factors may play a role in the occurrence of T2DM.

Objective: To determine the impact and mechanism of HIV derived microRNA99 (miRNA99) on macrophages pyroptosis. Methods: THP-1 cells were stimulated by phorbol ester (PMA) and then were cultured and differentiated into sidewall attached macrophages; the morphology and phenotype of CD11b were measured by microscopy and flow cytometry. TLR8 RNAi plasmid was transfected to macrophages and were detected by confocal fluorescence microscopy. The levels of IL-18 and IL-1β released by macrophages were measured by ELISA. Western blot(WB) was employed to examine TLR8 and cleaved caspase-1 protein expression in macrophages. Results: THP-1 cells that were challenged with PMA (100 ng/ml) for 24 h became smooth and adherent. In addition, the expression of CD11b in macrophages was up to 99%. TLR8 protein expression in macrophages transfected with TLR8 plasmids was significantly lower than that in macrophages transfected with control plasmids. Levels of IL-18 and IL-1β secreted by macrophages were elevated in LPS+ ATP group, miRNA99 group and control plasmid group, but not in control group and TLR8 RNAi plasmid group. Cleaved caspase-1 protein from macrophages of miRNA99 experimental group/ LPS+ ATP group and control plasmid group was significantly higher than that of control group and TLR8 RNAi plasmid group. Conclusions The present study demonstrates that HIV-derived miRNA99 could induce pyroptosis of macrophages via TLR8-dependent pathway.

Objective To study an accurate prediction algorithm for irregular respiratory movements,effectively compensate for the time delay of radiotherapy systems,so as to improve the target accuracy of imageguided tracking or gated radiotherapy for thoracic and abdominal tumors.Methods A prediction algorithm based on an adaptive neuro-fuzzy inference system (ANFIS) was proposed to precisely predict irregular respiratory motion.The ANFIS model structure adopted the position and velocity of respiratory motion as input parameters to construct an N×N fuzzy set that combines position and velocity,and to establish a training set through historical data.In the prediction,if the position or velocity in the latest input signal was out of the range of the training set,the position or velocity would be adjusted accordingly and treated as the input parameter of the ANFIS model for prediction.The ANFIS was evaluated using 20 cases of irregular respiratory clinical data from CyberKnife-treated thoracic and abdominal tumors patients.The accuracy of the four typical prediction algorithms,including ANFIS,neural network (NN),support vector machine (SVM),and CyberKnife Synchrony,was compared by retrospective offline analysis.Results The ANFIS algorithm showed better performance than NN,SVM and Synchrony in normalized root mean square error (nRMSE),the maximum error (Max),and the number of errors greater than 1 mm.Conclusions The accuracy and robustness of the ANFIS algorithm are superior to NN,SVM and CyberKnife Synchrony.The ANFIS can better predict irregular respiratory signals.

Objective To compare the effectiveness and safety of ultramini percutaneous nephrolithotomy (UMP) and retrograde intrarenal surgery (RIRS) in treatment of moderate-sized (about 1-2 cm) renal lower caliceal calculi.Methods From March 2015 to December 2016,patients in our hospital scheduled for surgery due to renal lower caliceal calculi with the greatest diameter of 10-22 mm were prospectively analyzed.Patients were randomized into two groups according to the random number table.Group UMP's operational channel was only F14 and the nephroscope's diameter was 1 mm.200 μm holmium laser lithotripsy was used to break the stones which was rushed out by eddy cuurent.In Group RIRS,all patients needed placing a F6 double J stent preoperatively for two weeks.A flexible ureteroscope sheath required imbedding intraoperatively.The stones were smashed by 200 μm holmium laser lithotripsy through the WOLF flexible ureteroscope.The intraoperative and postoperative datas including stone-free status and the complications were compared.Results 100 patients were enrolled in the study 50 patients in Group UMP,28 were male and 22 were female,mean age was 43.4 ± 7.9 years old.Mean stone size was 14.5 ±3.0 mm(range 10-22 mm).Among them,18 cases were complicated with mild and moderate hydronephrosis.The other 50 cases were allocated to Group RIRS,including 31 males and 19 females.Their mean age was 44.5 ± 8.3 years old and mean stone size was 13.7 ± 3.1 mm (range 10-21 mm).Among them,16 cases were complicated with mild and moderate hydronephrosis.No statistically significant difference were seen between the two groups (P ＞ 0.05).After three months' follow-up,one-time stone free rate(SFR) of UMP group was 94.0％ (47/50),which was significantly more superior than the 72.0％ (36/50) of the RIRS group(P ＜ 0.05).The intraoperative decrease in hemoglobin were (7.8 ± 3.3) g/L vs.(3.1 ± 3.4) g/L,and operating time(26.5 ± 6.1) min vs.(43.3 ± 6.3) min.Significant differences were also seen between the two groups(P ＜0.05).There was more blood loss and less operating time in the group of UMP.The hospital stay,delayed hemorrhage and postoperative fever between the UMP and RIRS groups were (4.3±1.3)d vs.(3.24 ± 1.21)d,8.0％ (4/50)vs.0(0/50),16.0％ (8/50)vs.12.0％ (6/50) respectively.No significant differences were seen (P ＞ 0.05).Conclusions Both UMP and RIRS procedures are effective and safe in the treatment of moderate-sized renal lower caliceal calculi.Compared with RIRS,UMP may be more effective and has less operating time,however wtih more intraoperative blood loss.

OBJECTIVE: To evaluate the safety and efficacy of percutaneous closure of the single secundum atrial septal defects (ASD) guided by transthoracic echocardiography (TTE) and/or transesophageal echocardiography (TEE).
 METHODS: From January, 2014 to December, 2014, thirty-two patients with single secundum ASD from Department of Cardiovascular Surgery, Union Hospital, Fujian Medical University, were treated with percutaneous closure of ASD guided by TTE or TEE.
 RESULTS: Thirty-two patients underwent ASD closure successfully, except one patient showed trivial residual shunts, which disappeared one month later. The remaining 31 patients were subjected to TTE. At once or at the 1st or 3rd month after the procedure, no ASD migration or residual shunts were observed.
 CONCLUSION Percutaneous closure of ASD guided by TTE or TEE is a safe and effective surgery method with minimal invasion and can avoid the chest incision and radioscopy.
Echocardiography ; Echocardiography, Transesophageal ; Heart Septal Defects, Atrial ; surgery ; Humans ; Septal Occluder Device