As a hot spot in clinical research today, immune checkpoint inhibitor has been recommended by guidelines in the first- and second-line treatments of advanced cervical cancer as immune monotherapy or combination therapy. It has also achieved good efficacy in clinical practice. In locally advanced cervical cancer, immune checkpoint inhibitors have been included in the guidelines for adjuvant therapy, and good tumor regression effects have been achieved in clinical practice. Based on the results of existing trials, immune checkpoint inhibitors have also shown good clinical potential as neoadjuvant therapy. Furthermore, the issue of immunotherapy rechallenge has increasingly captured clinicians’ attention, offering a potential new therapeutic strategy for cervical cancer patients with prior immunotherapy exposure. In this article, the clinical application and research progress of immune checkpoint inhibitors in the treatment of cervical cancer in recent years are summarized to provide valuable ideas and directions for clinical treatment.

Objective:This study investigated the awareness and consumption of Trogia venenata among populations in regions affected by Yunnan unexplained sudden death (YUSD). The findings aim to support etiological research on YUSD and contribute to the formulation of preventive measures against Trogia venenata poisoning. Methods:This study was a case-control study. From 2018 to 2021, surveys were conducted in 90 villages across 25 counties within YUSD-affected areas in Yunnan Province. Households with YUSD cases were designated as case households, whereas households without YUSD cases served as controls, ande were selected through convenience sampling at a 3:1 ratio. An enhanced questionnaire was designed to collect information on the consumption of Trogia venenata, and symptoms following consumption. Frequency data were presented as percentages, and group comparisons were conducted using χ 2 tests or Fisher’s exact tests. Results:A total of 711 questionnaires were collected (response rate: 100%), comprising 175 case households and 536 control households. Trogia venenata was present in 80.82% of the villages surveyed. Among the 711 households, 15.89% reported consuming Trogia venenata, primarily through stir-frying (53.10%), followed by boiling (29.20%), boiling and stir-frying (15.93%), and steaming (1.77%). Most households (94.69%) consumed fresh fruiting bodies, with 69.02% consuming them fewer than three times annually. The consumption rates were higher among the case households than among the control households. Of the 113 households with a history of Trogia venenata consumption, 35.40% reported symptoms such as nausea, vomiting, and limb soreness. The proportions of affected families in each group were compared according to their source, cooking method, fruiting body status and consumption frequency. The proportion of affected families with high consumption frequency (≥3 times/year) was higher than that with low consumption frequency (<3 times/year). Among 421 YUSD cases, 63 cases (14.96%) had a history of Trogia venenata consumption before death, with 43 cases showing symptoms within the longest known latency period (14 d) for poisoning by this mushroom. Conclusions:Trogia venenata is prevalent in 80.82% of YUSD-affected regions, with 16.67% of the population reporting its consumption, predominantly as fresh fruiting bodies prepared by stir-frying or boiling. Confirmed Trogia venenata consumption was identified in 14.96% of YUSD cases, suggesting that mushroom poisoning is a significant risk factor for YUSD. Ongoing health education and interventions are critical for mitigating the risk of Trogia venenata poisoning.

Objective:To analyze the infection status of Coxsackievirus B group (CVB) in regions affected by sudden unexplained death in Yunnan (referred to as sudden death in Yunnan), and to provide a scientific basis for formulating effective prevention and control strategies.Methods:A cross-sectional survey method was employed. The population from 16 counties (cities, districts, referred to as counties) affected by sudden death in Yunnan Province from 2002 to 2022 and the population from one non-affected county in 2021 and 2022 (control population) were classified into cases of sudden death in Yunnan (7 cases), co-occurring cases (29 cases), high-risk population (1 303 cases), and control population (270 cases). Blood samples were collected from these populations. By using enzyme-linked immunosorbent assay (ELISA), CVB immunoglobulin M (CVB-IgM) antibodies in the acute-phase serum samples of the population in the affected areas were detected, and CVB immunoglobulin G (CVB-IgG) antibodies in the convalescent-phase serum samples were detected. Both types of detections were carried out on the control population, and the test results were analyzed.Results:A total of 1 609 serum samples were tested, including 1 339 samples from the population in the affected areas (923 acute-phase samples and 416 convalescent-phase samples) and 270 samples from the control population. Among the 16 affected counties, positive CVB-IgM antibody results were detected in 9 counties. The overall positive rate of the population in the affected areas was higher than that of the control population [7.80% (72/923) vs. 4.44% (12/270), χ 2 = 40.78, P < 0.001]. The positive rates of the high-risk population in Dayao County and Lufeng City were both higher than that of the control population [(22.22% (22/99), 10.92% (25/229) vs. 4.44% (12/270), χ 2 = 27.37, 7.56, P < 0.05]. Positive CVB-IgG antibody results were detected in 7 counties. The overall positive rate of the population in the affected areas was higher than that of the control population [(4.09% (17/416) vs. 0.74% (2/270), χ 2 = 6.81, P = 0.009]. The positive rates of CVB-IgM and CVB-IgG antibodies in the population of the affected areas in Dayao County [22.22% (22/99), 9.80% (5/51)] were both higher than those of the control population ( P < 0.05). Among the five affected villages in Dayao County, the positive rates of CVB-IgM and CVB-IgG antibodies in the population of Aji Ju Village were the highest [25.49% (13/51), 3/13]. Conclusions:The positive rates of both CVB-IgM and CVB-IgG antibodies in the population of the areas affected by sudden death in Yunnan were higher than those of the control population, indicating that CVB infection occurred during the sudden death events in the above-mentioned affected areas.

Objective:To study the etiological relationship between Yunnan sudden unexplained death (hereinafter referred to as YNSUD) and the desmosomal protein gene mutation of arrhythmogenic right ventricular cardiomyopathy (ARVC).Methods:From September 2019 to August 2020, a cross-sectional survey method was used to select 9 key counties (cities) of YNSUD in Yunnan Province as survey sites. Autopsy cardiac blood samples of YNSUD cases ( n = 11) were collected, and peripheral venous blood samples of co-occurring case ( n = 1), case relatives ( n = 128), and control population ( n = 60) were collected. Genomic DNA from blood was extracted. After PCR amplification, 97 exons of 5 ARVC desmosomal protein genes, including plakophilin-2 (PKP2), desmoglein-2 (DSG2), desmocollin-2 (DSC2), desmoplakin (DSP), and junction plakoglobin (JUP) were sequenced by Sanger method, and the gene mutation was analyzed. Results:Compared with the control population, YNSUD cases, co-occurring case and case relatives carried 52 gene mutation sites in 36 exons of the ARVC desmosomal protein gene, with a total mutation rate of 37.11% (36/97). Among them, there were 21 in DSP gene, 10 in DSG2 gene, 8 in PKP2 gene, 8 in DSC2 gene, and 5 in JUP gene. YNSUD cases, co-occurring case and case relatives carried two same gene mutation sites: DSG2 gene exon 15 c.3321 T>C synonymous mutation and JUP gene exon 3 c.213 T>C synonymous mutation.Conclusions:The mutation rate of ARVC desmosomal protein gene is relatively high in the population of YNSUD. The two same gene mutation sites (DSG2 gene c.3321 T>C and JUP gene c.213 T>C) carried by YNSUD cases, co-occurring case and case relatives may be associated with the pathogenesis of YNSUD.

Objective:To explore the anesthetic effect of butorphanol combined with ropivacaine iliac fascia space block and femoral nerve combined with lateral femoral cutaneous nerve block in tibiofibular fracture surgery.Methods:A total of 86 patients with tibiofibular fractures admitted to the Sun Simiao Hospital of Beijing University of Chinese Medicine and Tongchuan Mining Bureau Central Hospital from December 2022 to December 2023 were selected and divided into observation group and control group by random number table method, with 42 cases in each group. The control group was given femoral nerve combined with lateral femoral cutaneous nerve block anesthesia, and the observation group was given iliac fascia space block anesthesia. The changes of heart rate (HR) and peripheral capillary oxygen saturation (SpO 2) at different time points during operation (before nerve block, 15 min after nerve block, 5 min before the end of operation) were compared between the two groups. The Visual Analogue Scale (VAS) was used to evaluate the pain degree at 6 h and 24 h after operation. The serum levels of prostaglandin E 2 (PGE 2), catalase (CAT) and superoxide dismutase (SOD) were compared between the two groups before operation and 24 h after operation. The duration of sensory block and motor nerve block after operation were recorded. The occurrence of postoperative complications was recorded. Results:There were no significant differences in HR and SpO 2 between the two groups at different time points during operation (all P>0.05). The VAS scores at 24 h after operation in both groups were lower than those at 6 h after operation (all P<0.05). At 6 h and 24 h after operation, the VAS scores of pain in the observation group were lower than those in the control group (all P<0.05). The serum CAT and SOD levels at 24 h after operation in both groups were lower than those before operation, and the serum PGE 2 levels were higher than those before operation, the serum CAT and SOD levels at 24 h after operation in the observation group were higher than those in the control group (all P<0.05), and the serum PGE 2 in the observation group was lower than that in the control group ( P<0.05). The motor nerve block time in the observation group was shorter than that in the control group, and the sensory block duration was longer than that in the control group (all P<0.05). There were 3 cases of nausea and 1 case of vomiting in the observation group, and 4 cases of nausea, 1 case of vomiting and 1 case of delirium in the control group. There was no significant difference in the incidence of complications between the two groups [9.52%(4/42) vs 14.29%(6/42), P>0.05]. Conclusions:Compared with femoral nerve combined with lateral femoral cutaneous nerve block, the iliac fascia space block anesthesia applied in the anesthetic management of tibiofibular fracture surgery has more stable intraoperative analgesic and sedative effects, helps to reduce the degree of postoperative pain, and has good safety.

Objective:To analyze the infection status of Coxsackievirus B group (CVB) in regions affected by sudden unexplained death in Yunnan (referred to as sudden death in Yunnan), and to provide a scientific basis for formulating effective prevention and control strategies.Methods:A cross-sectional survey method was employed. The population from 16 counties (cities, districts, referred to as counties) affected by sudden death in Yunnan Province from 2002 to 2022 and the population from one non-affected county in 2021 and 2022 (control population) were classified into cases of sudden death in Yunnan (7 cases), co-occurring cases (29 cases), high-risk population (1 303 cases), and control population (270 cases). Blood samples were collected from these populations. By using enzyme-linked immunosorbent assay (ELISA), CVB immunoglobulin M (CVB-IgM) antibodies in the acute-phase serum samples of the population in the affected areas were detected, and CVB immunoglobulin G (CVB-IgG) antibodies in the convalescent-phase serum samples were detected. Both types of detections were carried out on the control population, and the test results were analyzed.Results:A total of 1 609 serum samples were tested, including 1 339 samples from the population in the affected areas (923 acute-phase samples and 416 convalescent-phase samples) and 270 samples from the control population. Among the 16 affected counties, positive CVB-IgM antibody results were detected in 9 counties. The overall positive rate of the population in the affected areas was higher than that of the control population [7.80% (72/923) vs. 4.44% (12/270), χ 2 = 40.78, P < 0.001]. The positive rates of the high-risk population in Dayao County and Lufeng City were both higher than that of the control population [(22.22% (22/99), 10.92% (25/229) vs. 4.44% (12/270), χ 2 = 27.37, 7.56, P < 0.05]. Positive CVB-IgG antibody results were detected in 7 counties. The overall positive rate of the population in the affected areas was higher than that of the control population [(4.09% (17/416) vs. 0.74% (2/270), χ 2 = 6.81, P = 0.009]. The positive rates of CVB-IgM and CVB-IgG antibodies in the population of the affected areas in Dayao County [22.22% (22/99), 9.80% (5/51)] were both higher than those of the control population ( P < 0.05). Among the five affected villages in Dayao County, the positive rates of CVB-IgM and CVB-IgG antibodies in the population of Aji Ju Village were the highest [25.49% (13/51), 3/13]. Conclusions:The positive rates of both CVB-IgM and CVB-IgG antibodies in the population of the areas affected by sudden death in Yunnan were higher than those of the control population, indicating that CVB infection occurred during the sudden death events in the above-mentioned affected areas.

Objective:To explore the anesthetic effect of butorphanol combined with ropivacaine iliac fascia space block and femoral nerve combined with lateral femoral cutaneous nerve block in tibiofibular fracture surgery.Methods:A total of 86 patients with tibiofibular fractures admitted to the Sun Simiao Hospital of Beijing University of Chinese Medicine and Tongchuan Mining Bureau Central Hospital from December 2022 to December 2023 were selected and divided into observation group and control group by random number table method, with 42 cases in each group. The control group was given femoral nerve combined with lateral femoral cutaneous nerve block anesthesia, and the observation group was given iliac fascia space block anesthesia. The changes of heart rate (HR) and peripheral capillary oxygen saturation (SpO 2) at different time points during operation (before nerve block, 15 min after nerve block, 5 min before the end of operation) were compared between the two groups. The Visual Analogue Scale (VAS) was used to evaluate the pain degree at 6 h and 24 h after operation. The serum levels of prostaglandin E 2 (PGE 2), catalase (CAT) and superoxide dismutase (SOD) were compared between the two groups before operation and 24 h after operation. The duration of sensory block and motor nerve block after operation were recorded. The occurrence of postoperative complications was recorded. Results:There were no significant differences in HR and SpO 2 between the two groups at different time points during operation (all P>0.05). The VAS scores at 24 h after operation in both groups were lower than those at 6 h after operation (all P<0.05). At 6 h and 24 h after operation, the VAS scores of pain in the observation group were lower than those in the control group (all P<0.05). The serum CAT and SOD levels at 24 h after operation in both groups were lower than those before operation, and the serum PGE 2 levels were higher than those before operation, the serum CAT and SOD levels at 24 h after operation in the observation group were higher than those in the control group (all P<0.05), and the serum PGE 2 in the observation group was lower than that in the control group ( P<0.05). The motor nerve block time in the observation group was shorter than that in the control group, and the sensory block duration was longer than that in the control group (all P<0.05). There were 3 cases of nausea and 1 case of vomiting in the observation group, and 4 cases of nausea, 1 case of vomiting and 1 case of delirium in the control group. There was no significant difference in the incidence of complications between the two groups [9.52%(4/42) vs 14.29%(6/42), P>0.05]. Conclusions:Compared with femoral nerve combined with lateral femoral cutaneous nerve block, the iliac fascia space block anesthesia applied in the anesthetic management of tibiofibular fracture surgery has more stable intraoperative analgesic and sedative effects, helps to reduce the degree of postoperative pain, and has good safety.

Objective:To study the etiological relationship between Yunnan sudden unexplained death (hereinafter referred to as YNSUD) and the desmosomal protein gene mutation of arrhythmogenic right ventricular cardiomyopathy (ARVC).Methods:From September 2019 to August 2020, a cross-sectional survey method was used to select 9 key counties (cities) of YNSUD in Yunnan Province as survey sites. Autopsy cardiac blood samples of YNSUD cases ( n = 11) were collected, and peripheral venous blood samples of co-occurring case ( n = 1), case relatives ( n = 128), and control population ( n = 60) were collected. Genomic DNA from blood was extracted. After PCR amplification, 97 exons of 5 ARVC desmosomal protein genes, including plakophilin-2 (PKP2), desmoglein-2 (DSG2), desmocollin-2 (DSC2), desmoplakin (DSP), and junction plakoglobin (JUP) were sequenced by Sanger method, and the gene mutation was analyzed. Results:Compared with the control population, YNSUD cases, co-occurring case and case relatives carried 52 gene mutation sites in 36 exons of the ARVC desmosomal protein gene, with a total mutation rate of 37.11% (36/97). Among them, there were 21 in DSP gene, 10 in DSG2 gene, 8 in PKP2 gene, 8 in DSC2 gene, and 5 in JUP gene. YNSUD cases, co-occurring case and case relatives carried two same gene mutation sites: DSG2 gene exon 15 c.3321 T>C synonymous mutation and JUP gene exon 3 c.213 T>C synonymous mutation.Conclusions:The mutation rate of ARVC desmosomal protein gene is relatively high in the population of YNSUD. The two same gene mutation sites (DSG2 gene c.3321 T>C and JUP gene c.213 T>C) carried by YNSUD cases, co-occurring case and case relatives may be associated with the pathogenesis of YNSUD.

Objective:To understand the electrocardiogram and echocardiography examination results of population in key areas of unexplained sudden death in Yunnan Province (referred to as Yunnan sudden death).Methods:From 2014 to 2022, electrocardiogram examination was performed on population (including same incident cases, relatives of the cases, villagers of the affected villages, and control individuals) in key areas of Yunnan sudden death from May to October each year. Echocardiography examination was performed on relatives of the cases and villagers of the affected villages, and the types of electrocardiogram and echocardiography changes were sorted out and analyzed.Results:Electrocardiogram examination was conducted on 1 same incident case, 241 relatives of the cases, 464 villagers of the affected villages, and 99 control individuals, respectively. The types of electrocardiogram changes in the same incident case were Q-T interval prolongation and sinus tachycardia. A total of 17 types of electrocardiogram changes were detected in the relatives of the cases, mainly including sinus arrhythmia (12.45%, 30/241), sinus bradycardia (11.20%, 27/241), and left axis deviation (8.30%, 20/241). A total of 21 types of electrocardiogram changes were detected in the villagers of the affected villages, mainly including left axis deviation (9.48%, 44/464), sinus bradycardia (8.19%, 38/464), and T-wave abnormalities (7.76%, 36/464). A total of 10 types of electrocardiogram changes were detected in the control individuals, mainly including sinus arrhythmia (12.12%, 12/99), T-wave abnormalities (9.09%, 9/99), and sinus bradycardia (7.07%, 7/99). Echocardiography examination was conducted on 49 relatives of the cases and 365 villagers of the affected villages, respectively. A total of 12 types of echocardiography changes were detected in the relatives of the cases, mainly including tricuspid regurgitation (18.37%, 9/49), decreased right ventricular diastolic function (8.16%, 4/49), aortic regurgitation (6.12%, 3/49), and atrial septal defect (6.12%, 3/49). A total of 15 types of echocardiography changes were detected in the villagers of the affected villages, mainly including tricuspid regurgitation (8.77%, 32/365), aortic regurgitation (6.85%, 25/365), and decreased left ventricular diastolic function (6.58%, 24/365).Conclusion:There are many types of changes in electrocardiogram and echocardiography in the population of key areas of Yunnan sudden death.

Objective:To analyze the biochemical failure rate and its predictive factors after radical prostatectomy (RP) in patients with high-risk localized prostate cancer.Methods:The data of 166 patients with high-risk localized prostate cancer who underwent RP surgery in Peking university cancer hospital from January 2015 to November 2021 were retrospectively reviewed. The average age was 65.4±6.2 years old, and the average body mass index (BMI) was 24.86±3.23 kg/m 2. The median prostate-specific antigen (PSA) was 19.84 (10.98, 44.47) ng/ml, PSA density was 0.68 (0.34, 1.32)ng/ml 2, and prostate volume was 31.20 (25.58, 40.23) ml. Biopsy pathology Gleason score according to the International society of Urological Pathology(ISUP) grade group: 18 cases of group 1, 33 cases of group 2, 30 cases of group 3, 51 cases of group 4, and 33 cases of group 5, 1 case was unknown. The percentage of puncture positive needles was (55.4±25.7)%, and the largest linear length of positive lesions was 80.0% (60.0%, 90.0%). Preoperative clinical stage : 14 cases in ≤T 2b stage, 117 cases in T 2c stage, 13 cases in T 3a stage and 22 cases in ≥T 3b stage; 157 cases in N 0 stage, 9 cases in N 1 stage. One hundred and three patients (62.0%) were assessed by traditional imaging and 63(38.0%) were assessed by PSMA PET-CT. The patients underwent laparoscopic radical prostatectomy. 64 patients (38.6%) received neoadjuvant therapy, including 37 received neoadjuvant therapy for 1-3 months, 23 for 4-6 months and 4 for over 6 months. The postoperative pathological characteristics, treatment and prognosis of the patients were analyzed. The primary endpoint was biochemical failure, including biochemical persistence(BCP, defined as PSA≥0.1ng/ml at 4-6 weeks after operation, and confirmed by re-examination at least 1 week interval) and biochemical recurrence(BCR, PSA falling below 0.1ng/ml after operation and then rising ≥0.2 ng/ml without adjuvant therapy or after the end of adjuvant treatment). Results:Compared with preoperative clinicopathological characteristics, 48(28.9%) cases had postoperative pathological ISUP upgrade, 98 (59.0%)cases had T stage upgrade, and 13 (7.8%) cases had N stage upgrade. The rate of positive margins was 53%, and apex margin was the most common positive site (65.9%). The postoperative PSA in 114 patients (68.7%) decreased to less than 0.1ng/ml, of which 74 patients didn't receive the therapy and 40 patients received adjuvant therapy. 52 patients (31.3%) had postoperative PSA more than 0.1ng/ml and among them, 51 cases received salvage treatment. 5 patients (3.0%) underwent PSA progression during adjuvant or salvage endocrine therapy and were considered to have castration resistance. After a median follow-up time of 25.5 (12.0, 40.0) months, 78 patients (48.4%, 78/161) experienced biochemical failure, including 49 BCP and 29 BCR, the median time of biochemical failure was 30.0 (95% CI 14.5-45.5) months. Adjuvant therapy could reduce the rate of BCR (31.1% and 15.8%, P=0.08). Baseline PSA, PSA density, proportion of pathological ISUP ≥4, proportion of pathological T stage ≥T 3a, adjuvant therapy, and positive surgical margins were significantly associated with biochemical failure ( P=0.034, 0.002, 0.004, 0.025, <0.001and 0.047). Multivariate Cox regression analysis showed that adjuvant therapy ( P<0.001, OR=0.12), PSA density ( P=0.03, OR=1.19) and positive surgical margins ( P=0.034, OR=1.80) were independent factors for biochemical failure. Conclusions:Patients with high-risk localized prostate cancer have a high rate of biochemical failure after RP and need to receive RP-based multimodal therapy. Adjuvant therapy, PSA density and positive surgical margins are independent factors associated with postoperative biochemical failure.