OBJECTIVE To evaluate the cost-effectiveness of the first-line treatment using the combination therapy of sugemalimab and chemotherapy （hereinafter referred to as the “combination therapy”） for advanced esophageal squamous cell carcinoma （ESCC） with high programmed death-ligand 1 （PD-L1） expression from the perspective of the Chinese healthcare system. METHODS A partitioned survival model was constructed based on data from the GEMSTONE-304 study. The model cycle was set at 3 weeks， with a study duration of 10 years and a discount rate of 5%. The primary output parameters of the model included total costs， quality-adjusted life year （QALY）， incremental costs， and incremental cost-effectiveness ratio （ICER）. Cost- utility analysis was employed to assess the economic feasibility of the combination therapy compared to chemotherapy alone. The robustness of the base case analysis results was evaluated through univariate sensitivity analysis， probabilistic sensitivity analysis， and scenario analysis. RESULTS The ICER of the combination therapy compared to chemotherapy alone was 288 430.35 yuan/QALY， significantly exceeding the willingness-to-pay （WTP） threshold of 173 354.52 yuan/QALY which was set at 1.94 times the per capita gross domestic product （GDP） in 2023. The price of sugemalimab was the primary factor influencing the ICER. When the WTP threshold was set at 1.94 times the per capita GDP （173 354.52 yuan/QALY）， the probability of the combination therapy being cost-effective compared to chemotherapy alone was 0. The combination therapy only became cost-effective compared to chemotherapy alone when the price of the drug dropped to 6 107.41 yuan per box （600 mg）. CONCLUSIONS From the perspective of the Chinese healthcare system， the combination therapy for first-line treatment of advanced ESCC with high PD-L1 expression is not cost-effective； the combination therapy is cost-effective when the price of sugemalimab decreas by 50.65%.

Background::There is a need for effective and safe therapies for psoriasis that provide sustained benefits. The aim of this study was to assess the efficacy and safety of tildrakizumab, an anti-interleukin-23p19 monoclonal antibody, for treating moderate-to-severe plaque psoriasis in Chinese patients.Methods::In this multi-center, double-blind, phase III trial, patients with moderate-to-severe plaque psoriasis were enrolled and randomly assigned (1:1) to receive subcutaneous tildrakizumab 100 mg or placebo at weeks 0 and 4. Patients initially assigned to placebo were switched to receive tildrakizumab at weeks 12, 16, and every 12 weeks thereafter. Patients in the tildrakizumab group continued with tildrakizumab at week 16, and every 12 weeks until week 52. The primary endpoint was the Psoriasis Area and Severity Index (PASI 75) response rate at week 12.Results::At week 12, tildrakizumab demonstrated significantly higher PASI 75 response rates (66.4% [73/110] vs. 12.7% [14/110]; difference, 51.4% [95% confidence interval (CI), 40.72, 62.13]; P <0.001) and Physician’s Global Assessment (60.9% [67/110] vs. 10.0% [11/110]; difference, 49.1% [95% CI, 38.64, 59.62]; P <0.001) compared to placebo. PASI 75 response continued to improve over time in both tildrakizumab and placebo-switching to tildrakizumab groups, reaching maximal efficacy after 28 weeks (86.8% [92/106] vs. 82.4% [89/108]) and maintained up to 52 weeks (91.3% [95/104] vs. 87.4% [90/103]). Most treatment-emergent adverse events were mild and not related to tildrakizumab. Conclusion::Tildrakizumab demonstrated durable efficacy through week 52 and was well tolerated in Chinese patients with moderate-to-severe plaque psoriasis.Trial registration::ClinicalTrials.gov, NCT05108766.

Objective To compare the detection rates of X-ray,ultrasound,computed tomography(CT)and cone beam CT(CBCT)for submandibular gland calculi in different positions,and to explore the auxiliary value of 3-dimensional visualization technology in diagnosis and treatment of submandibular gland calculi.Methods The X-ray,ultrasound,CT and CBCT examination data of 113 patients with submandibular gland calculi at General Hospital of Ningxia Medical University from Nov.2014 to Mar.2021 were retrospectively analyzed.The detection rates and overall detection rates of the 4 imaging methods for calculi in different positions were compared.Mimics 19.0 software and CBCT data were used for 3D reconstruction imaging,visually displaying the location,size,morphology,and number of calculi from a visual perspective.Results There was no significant difference in the total detection rate of submandibular gland calculi between CBCT and CT(98.2％[111/113]vs 95.6％[108/113],P＞0.05),but both were significantly higher than that of X-ray(65.5％,74/113)and ultrasound(73.5％,83/113).The detection rates of ultrasound for calculi in the anterior and middle ducts were the lowest(63.6％[21/33]and 72.2％[26/36],respectively),which were significantly different from those of CBCT(97.0％[32/33]and 100.0％[36/36],respectively)and CT(93.9％[31/33]and 97.2％[35/36],respectively)(all P＜0.05).The detection rate of X-ray for calculi in the posterior duct was significantly lower than that of ultrasound,CBCT,and CT(40.9％[18/44]vs 81.8％[36/44],97.7％[43/44],and 95.5％[42/44],all P＜0.01).After CBCT data were imported into Mimics 19.0 software,submandibular gland calculi with different sizes,shapes,or numbers were successfully visualized and reconstructed.The reconstructed image was clear,and anatomical position relationship between the calculi and the mandible was visualized.Conclusion CBCT has good application value in the diagnosis of submandibular gland calculi and can replace traditional CT for the diagnosis of sialolithiasis.Clinically,CBCT examination can be directly performed for accurate diagnosis of calculi in the posterior duct which are not detected by double coincidence diagnosis but are indicated by ultrasound.For calculi in the anterior and middle ducts,X-ray and CBCT are preferred.Visualization technology helps clinical patient education and the development of personalized preoperative treatment plans.

Objective:The transjugular or transfemoral approach is used as a common method for hepatic venous pressure gradient (HVPG) measurement in current practice. This study aims to confirm the safety and effectiveness of measuring HVPG via the forearm venous approach.Methods:Prospective recruitment was conducted for patients with cirrhosis who underwent HVPG measurement via the forearm venous approach at six hospitals in China and Japan from September 2020 to December 2020. Patients' clinical baseline information and HVPG measurement data were collected. The right median cubital vein or basilic vein approach for all enrolled patients was selected. The HVPG standard process was used to measure pressure. Research data were analyzed using SPSS 22.0 statistical software. Quantitative data were used to represent medians (interquartile ranges), while qualitative data were used to represent frequency and rates. The correlation between two sets of data was analyzed using Pearson correlation analysis.Results:A total of 43 cases were enrolled in this study. Of these, 41 (95.3%) successfully underwent HVPG measurement via the forearm venous approach. None of the patients had any serious complications. The median operation time for HVPG detection via forearm vein was 18.0 minutes (12.3~38.8 minutes). This study confirmed that HVPG was positively closely related to Child-Pugh score ( r = 0.47, P = 0.002), albumin-bilirubin score ( r = 0.37, P = 0.001), Lok index ( r = 0.36, P = 0.02), liver stiffness ( r = 0.58, P = 0.01), and spleen stiffness ( r = 0.77, P = 0.01), while negatively correlated with albumin ( r = -0.42, P = 0.006). Conclusion:The results of this multi-centre retrospective study suggest that HVPG measurement via the forearm venous approach is safe and feasible.

Objective: To investigate the clinicopathological features and immunohistochemical phenotypes of gastric SMARCA4-deficient undifferentiated carcinoma, and to discuss the daily diagnostics of this entity and analyze its prognosis. Methods: The cases of gastric SMARCA4-deficient undifferentiated carcinoma diagnosed at the Department of Pathology, Peking University Cancer Hospital, China from January 2010 to August 2022 were collected. The histological sections were reviewed, the immunohistochemical results and clinicopathological features were analyzed, and relevant literature was reviewed. Results: Pure foci of undifferentiated carcinoma were seen in 7 cases, and 1 case was accompanied by a moderately differentiated tubular adenocarcinoma component. Undifferentiated carcinoma foci showed similar sheet-like or solid diffuse growth pattern, medium-sized tumor cells characterized by 1-2 nucleoli, and abundant cytoplasm and rhabdoid appearance. The average patient age was 65±8 years. Six patients were male and 2 were female. Immunohistochemical staining showed that undifferentiated carcinoma of all 8 tumors were negative for SMARCA4 (BRG1). Among 7 patients who underwent SMARCA2 (BRM) and SMARCB1 (INI1) staining, 4 cases showed loss of BRM expression, 2 cases showed weakly positive staining, and 1 case was diffusely positive, but all 7 cases were diffusely strong positive for INI1. The neuroendocrine marker, synaptophysin, was weakly positive in 5 cases, while CgA and CD56 were negative in 8 cases. Ki-67 index was more than 70%. Two cases were mismatch repair deficient and showed the loss of MLH1/PMS2 expression, while 1 case showed only MSH2 loss. PD-L1 staining showed that combined positive score (CPS)≥1 in 4 cases (CPS ranging from 1 to 55) and CPS<1 in the other 3 cases. Four patients had clinical stage Ⅳ disease. Two of them died within 3 months after diagnosis. Conclusions: Gastric SMARCA4-deficient undifferentiated carcinoma/rhabdoid carcinoma is a rare group of highly malignant tumors with a poor prognosis. Loss of the core subunit of SWI/SNF complex may be associated with the development of dedifferentiated histological pattern and aggressive tumor progression, which may be more frequently accompanied with mismatch repair deficiency.
Male ; Female ; Humans ; Carcinoma/pathology* ; Adenocarcinoma ; Colorectal Neoplasms ; Cell Differentiation ; Stomach Neoplasms ; Biomarkers, Tumor ; DNA Helicases ; Nuclear Proteins ; Transcription Factors

Objective:To characterize the injuries suffered by athletes in snow events other than alpine skiing in the Zhangjiakou Zone of the Olympic Winter Games Beijing 2022, in order to provide insights for prevention of sports injuries and preparation of large-scale winter sports events.Methods:The medical records were retrospectively collected of all athletes who had been treated at Beijing University Third Hospital Chongli within the closed loop of the Zhangjiakou Zone during the Winter Olympics and Paralympics (from November 21, 2021 to April 5, 2022). The incidence, severity and part of the injuries were analyzed, as well as the medical treatment process.Results:In the Zhangjiakou Zone, a total of 1,188 athletes participated in the Winter Olympic Games, with an injury incidence of 2.9% (34/1,188), while 420 ones participated in the Winter Paralympic Games, with an injury incidence of 1.7% (7/420). The average daily medical visits were the highest during the Winter Olympics phase (1.16 visits per day), and their emergency severity index (ESI) ranged from level 3 to level 4. The department of orthopedics was visited the most (92.7%, 38/41). Lower limb injuries accounted for the highest proportion (53.7%, 22/41), with the knee ones accounting for 36.6% (15/41) of all injuries. Most of the athletes with ESI level 3 received splint fixation (62.5%, 5/8), while those with ESI level 4 mostly received observation and follow-up (57.6%, 19/33). A total of 57 radiological examinations were performed in the 41 athletes. X-ray was used the most frequently on a single day (5.00 times) while magnetic resonance imaging was per day on average (0.16 times). The transfer time for the athletes injured was (27.4±8.8) min which was not influenced by the 4 weather conditions (cloudy, sunny, light snow, and cloudy) ( P=0.374). Conclusions:The incidence of injuries during the Beijing Winter Olympics in the Zhangjiakou Zone was lower than that in other areas of the Beijing Winter Olympics and in previous Winter Olympics. There were no serious life-threatening cases. The imaging examination resources and transfer speed in the Zhangjiakou Zone were able to meet the medical needs of athletes at all stages of the Beijing Winter Olympics and Paralympics. Athletes should pay attention to protection of their lower limbs during skiing competitions.

Objective:To comparae the accuracy of imaging examination in preoperative parathyroid localization, and the safety and effect of total parathyroidectomy on secondary hyperparathyroidism complicated by chronic renal failure.Method:A total of 257 patients with secondary hyperparathyroidism who underwent total parathyroidectomy at the Department of General Surgery , Zhongshan Hospital, Dalian University from Mar 2012 to Mar 2022 were analyzed retrospectively.Result:Six hundred fourty parathyroid glands were found by color Doppler ultrasound and 954 parathyroid glands were by enhanced CT before the operation. Among them, the number of patients with accurate location of all 4 parathyroid glands by color Doppler ultrasound was 54, while that by enhanced CT was 216. The parathyroid detection rate by enhanced CT was significantly higher than that of color Doppler ultrasound ( χ2=325.480, P<0.001), and the accuracy rate was significantly higher tnan that of color ultrasound ( χ2=215.146, P<0.001). The average values of iPTH before operation, on the day after operation, on the 1st day and 7th day after operation were (1 880±890), (137±82), (66±46) and (34±23) pg/ml, respectively. The clinical symptoms of all patients were significantly relieved. Conclusions:Enhanced CT is superior to color Doppler ultrasound in the overall detection rate and individual localization accuracy of preoperative parathyroid localization. Total parathyroidectomy is safe and reliable in the treatment of secondary hyperparathyroidism complicated by chronic renal failure.

Objective:To explore the risk factors associated with the clinical progression of COVID-19 infection in kidney transplant(KT)recipients during the spread of Omicron variant and evaluate the effectiveness of anti-RNA virus agents in blocking the clinical progression of COVID-19 in these recipients.Methods:Retrospective analysis was conducted for the clinical data on COVID-19 infection in 232 KT recipients followed up from December 4, 2022 to January 31, 2023 at Department of Renal Transplantation, Organ Transplantation Center, Beijing Tsinghua Changgung Hospital.Inclusion criteria were age ≥18 years and stable kidney function without renal replacement therapy.The follow-up time was 30 days after COVID-19 infection.Based upon whether or not there was an infection of COVID-19, KT recipients were divided into two groups of infection(181 cases)and non-infection(51 cases). In infection group, recipients were further assigned into two sub-groups of disease progression(n=23)and stable(158 cases)according to whether or not there was a progression to severe disease.Various factors such as gender, age, body mass index(BMI), time after transplantation, underlying diseases(history of hypertension, diabetes mellitus, coronary heart disease & chronic lung disease), smoking history and dosing of anti-RNA virus agents were collected.Pearson χ2 test or Fisher's exact probability method was utilized for examining enumeration data while Mann-Whitney U test for measurement data.Univariate Logistic regression analysis was conducted and variables with P<0.05 were included into multifactorial Logistic regression analysis to identify independent risk factors for clinical progression of COVID-19 infection in KT recipients. Results:Among 232 KT recipients, infection rate of COVID-19 was 78.0%(181/232). The clinical classification was mild(112 cases), moderate(46 cases), severe(21 cases)and critical(n=2 cases). The severe rate was 12.7%(23/181). After infection with COVID-19, the proportion of KT recipients aged ≥65 years progressing from mild/moderate to severe was higher than those aged<65 years[38.5%(5/13)vs 10.7%(18/168)]. The difference was statistically significant( P=0.014); The proportion of diabetic KT recipients progressing from mild/moderate to severe was higher than those without diabetes[19.1%(13/68)vs 8.8%(10/113)]. The difference was statistically significant( P=0.045). Univariate Logistic analysis showed similar results.Age≥65 years( OR=5.21, 95% CI: 1.54-17.64, P=0.008)or diabetes mellitus( OR=2.44, 95% CI: 1.003-5.911, P=0.049)were the risk factors for COVID-19 infection recipients progressing from mild/moderate to severe disease.Multivariate Logistic analysis revealed that age ≥65 years( OR=4.03, 95% CI: 1.14-14.34, P=0.031)was an independent risk factor for COVID-19 infection recipients progressing from mild/moderate to severe.Among 181 cases of COVID-19 mild/medium infected patients, 18 cases received nimativir/ritonavir and 10 cases had azvudine for anti-RNA virus treatment.However, none of them progressed to severe; 153 cases did not use anti-RNA virus drugs and 23 cases(15.0%)progressed to severe disease and the difference was statistically significant( P=0.028). Among 23 severe cases, 14 cases received nirmatrelvir/ritonavir and 2 cases had azivudine for anti-RNA virus treatment.The former did not progress to critical disease while 1 case in the latter progressed to critical illness and death; 1/7 recipients not using anti-RNA virus agents progressed to critical illness and died while another 6 cases did not progress to critical illness. Conclusions:KT recipients aged ≥65 years or diabetes mellitus have a greater risk of progression from mild/moderate to severe disease after COVID-19 infection.Among them, age ≥65 years is an independent risk factor for patients with COVID-19 infection to progress from mild/moderate to severe.Antiviral treatment with nirmatrelvir/ritonavir or azivudine in KT recipients during mild/moderate stage of COVID-19 infection can significantly reduce the rate of severe disease.Treatment with Nirmatrelvir/Ritonavir is still effective in the severe stage.

Background::The pharmacokinetic and clinical behaviors of many proton pump inhibitors (PPIs) in peptic ulcer treatment are altered by CYP2C19 genetic polymorphisms. This non-inferiority study evaluated the efficacy and safety of the novel PPI anaprazole compared with rabeprazole. We also explored the influence of Helicobacter pylori ( H. pylori) infection status and CYP2C19 polymorphism on anaprazole. Methods::In this multicenter, randomized, double-blind, double-dummy, positive-drug parallel-controlled, phase III study, Chinese patients with duodenal ulcers were randomized 1:1 to receive rabeprazole 10 mg + anaprazole placebo or rabeprazole placebo + anaprazole 20 mg once daily for 4 weeks. The primary efficacy endpoint was the 4-week ulcer healing rate assessed by blinded independent review. Secondary endpoints were the proportion of patients with improved overall and individual duodenal ulcer symptoms at 4 weeks. Furthermore, exploratory subgroup analysis of the primary endpoint by H. pylori status and CYP2C19 polymorphism was conducted. Adverse events were monitored for safety. Non-inferiority analysis was conducted for the primary endpoint. Results::The study enrolled 448 patients (anaprazole, n = 225; rabeprazole, n = 223). The 4-week healing rates were 90.9% and 93.7% for anaprazole and rabeprazole, respectively (difference, -2.8% [95% confidence interval, -7.7%, 2.2%]), demonstrating non-inferiority of anaprazole to rabeprazole. Overall duodenal ulcer symptoms improved in 90.9% and 92.5% of patients, respectively. Improvement rates of individual symptoms were similar between the groups. Healing rates did not significantly differ by H. pylori status or CYP2C19 genotype for either treatment group. The incidence of treatment-emergent adverse events was similar for anaprazole (72/220, 32.7%) and rabeprazole (84/219, 38.4%). Conclusions::The efficacy of anaprazole is non-inferior to that of rabeprazole in Chinese patients with duodenal ulcers.Registration::ClinicalTrials.gov, NCT04215653.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.