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 analyze the results of the practice test and formal test of the annual professional proficiency test for residents in 2022, to investigate related influencing factors and the effectiveness of the practice test, and to propose the measures for improving the results of the annual professional proficiency test.Methods:The scores of the annual professional proficiency test were analyzed for 202 residents who participated in the test in 2022, and the data on sex, education background, type of personnel, whether they passed the medical licensing examination, and practice test scores were analyzed to investigate related influencing factors. SPSS 23.0 and GraphPad Prism 8 were used for the chi-square test, the t-test, the one-way of variance, and the Fisher's exact test. A multiple linear regression analysis was used to identify influencing factors, and a Pearson correlation analysis was also performed. Results:The scores of the annual professional proficiency test for 202 residents were normally distributed with the highest number of the residents with a score of 90-99 points and the lowest number of the residents with a score of <70 points. The residents who passed the medical licensing examination had a significantly higher score of the annual professional proficiency test than those who failed the examination ( t=2.87, P=0.005), and the residents who passed the three practice tests had a significantly higher score of the annual professional proficiency test than those who failed the practice tests ( P<0.05). The score of the second practice test, the score of the third practice test, and the passing of medical licensing examination were independent influencing factors for the score of annual professional proficiency test ( R2=0.236, R2=0.201, F=6.60, P<0.05). The correlation analysis showed that the scores of the three practice tests were positively correlated with the final score ( r=0.189, 0.373, and 0.311, P<0.05). Conclusions:Improving the passing rate of medical licensing examination and strengthening pre-examination practice tests can help to improve the score of annual professional proficiency test. At the same time, it is necessary to improve the quality of training through the measures such as strengthening the homogenization management of different types of students, improving the attention and enthusiasm of all levels, and accelerating the construction of question banks.

Objective:To investigate the risk factors for sepsis in patients severe trauma.Methods:A retrospective case-control study was conducted to analyze the clinical data of 149 patients with severe trauma admitted to General Hospital of Ningxia Medical University from January 2021 to June 2022, including 112 males and 37 females, aged 18-93 years [(50.6±16.3)years]. According to whether the patients developed sepsis, they were divided into sepsis group ( n=66) and non-sepsis group ( n=83). A comparison was made between the two groups in gender, age, measurements of body temperature, heart rate, respiration, systolic blood pressure, diastolic blood pressure, mean artery pressure (MAP), oxygen saturation (SPO 2), white blood cell (WBC), absolute neutrophil count (ANC), percentage of neutrophils (NEUT%), red blood cell count (RBC), hemoglobin (HGB), platelet count (PLT), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer level, level of lactic acid, level of blood glucose, quick sequential organ failure assessment (qSOFA), sequential organ failure assessment (SOFA), acute physiology and chronic health evaluation II (APACHE II) score, Glasgow coma scale (GCS), and injury severity score (ISS) within 24 hours of admission, causes of injury, injury sites, number of injury sites, hemorrhagic shock (HS), open injury, endotracheal intubation, length of ICU stay and total length of hospital stay. Univariate analysis and multivariate Logistic regression analysis were used to determine the independent risk factors for severe post-traumatic sepsis. Results:The results of univariate analysis showed that there were statistically significant differences in age, respiration, SPO 2, WBC and ANC, D-dimer level, blood glucose level, qSOFA, SOFA, APACHE II score, GCS, ISS, head and neck injury, open injury, tracheal intubation, length of ICU stay, and total length of hospital stay between the sepsis group and non-sepsis group ( P<0.05 or 0.01); whereas there were no significant differences in gender, underlying disease, body temperature, heart rate, systolic blood pressure, diastolic blood pressure, MAP, NEUT%, RBC, HGB, PLT, PT, APTT, lactic acid level, cause of injury, facial injury, chest injury, abdominal and pelvic injury, limb and pelvic injury, number of injury sites, and HS between the two groups ( P>0.05). Multivariate Logistic regression analysis showed that D-dimer level ( OR=0.97, 95% CI 0.96, 0.99, P<0.01) and tracheal intubation ( OR=15.80, 95% CI 2.14, 116.69, P<0.01) were significantly correlated with sepsis in patients with severe trauma. Conclusion:D-dimer level collected within 24 hours of admission and tracheal intubation are independent risk factors for sepsis in patients with severe trauma.

BACKGROUND: Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV). METHODS: We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development. RESULTS: We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron. CONCLUSION Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.
Child ; Humans ; Neurodevelopmental Disorders/epidemiology* ; Genetic Testing ; Phenotype ; Brain/pathology* ; Genetic Background ; SOX Transcription Factors/genetics*

Objective:To investigate the pathogen spectrum of acquired immunodeficiency syndrome (AIDS) patients with pulmonary opportunistic infections in the local area, and to evaluate the clinical application of metagenomic next-generation sequencing (mNGS) in these patients.Methods:From January to December 2021, AIDS patients with pulmonary infections admitted to Zhongnan Hospital of Wuhan University were enrolled. Their bronchoalveolar lavage fluid (BALF) was subjected to mNGS and coventional pathogen detection.Routine pathogen detection methods included smear, culture, polymerase chain reaction (PCR), and immunochromatographic colloidal gold. Fisher′s exact probability method was used for statistical analysis.Results:A total of 69 patients were included, and all of them were tested positive for mNGS. Among them, 53 cases (76.8%) were positive for fungi and viruses, 40 cases (58.0%) were positive for bacteria (excluding Mycobacterium tuberculosis (MTB) and nontuberculous mycobacteria (NTM)), six cases were positive for MTB, 11 cases were positive for NTM, and seven cases were positive for other pathogens. Mixed infections with two or more pathogens were found in 89.9%(62/69) of the patients. Among the conventional pathogen detections of BALF, 79.7%(55/69) of the patients were positive for pathogens, including 42 cases positive for Pneumocystis jirovecii PCR, 16 cases positive for BALF culture, nine cases positive for MTB PCR, and five cases positive for Cryptococcus antigen. The total detection rate of mNGS was 100.0%(69/69), which was higher than that of the conventional pathogen detection rate of 79.7%(55/69), and the difference was statistically significant (Fisher′s exact probability method, P<0.001). The specificity of mNGS detection was 88.4%. Combining clinical and two detection methods, the top five pathogens were Pneumocystis jirovecii (62.3%(43/69)), Candida (29.0%(20/69)), MTB (20.3%(14/69)), NTM and Talaromyces marneffei (15.9%(11/69), each). Fifty-three patients (76.8%) had co-infection with virus. Conclusions:The main cause of pulmonary infection in AIDS patients in this area is mixed infection, and Pneumocystis jirovecii is the most common pathogen. mNGS could significantly improve the pathogen detection rate in AIDS patients with pulmonary infections.

BACKGROUND: The HELIOS stent is a sirolimus-eluting stent with a biodegradable polymer and titanium oxide film as the tie-layer. The study aimed to evaluate the safety and efficacy of HELIOS stent in a real-world setting. METHODS: The HELIOS registry is a prospective, multicenter, cohort study conducted at 38 centers across China between November 2018 and December 2019. A total of 3060 consecutive patients were enrolled after application of minimal inclusion and exclusion criteria. The primary endpoint was target lesion failure (TLF), defined as a composite of cardiac death, non-fatal target vessel myocardial infarction (MI), and clinically indicated target lesion revascularization (TLR) at 1-year follow-up. Kaplan-Meier methods were used to estimate the cumulative incidence of clinical events and construct survival curves. RESULTS: A total of 2998 (98.0%) patients completed the 1-year follow-up. The 1-year incidence of TLF was 3.10% (94/2998, 95% closed interval: 2.54-3.78%). The rates of cardiac death, non-fatal target vessel MI and clinically indicated TLR were 2.33% (70/2998), 0.20% (6/2998), and 0.70% (21/2998), respectively. The rate of stent thrombosis was 0.33% (10/2998). Age ≥60 years, diabetes mellitus, family history of coronary artery disease, acute myocardial infarction at admission, and device success were independent predictors of TLF at 1 year. CONCLUSION: The 1-year incidence rates of TLF and stent thrombosis were 3.10% and 0.33%, respectively, in patients treated with HELIOS stents. Our results provide clinical evidence for interventional cardiologists and policymakers to evaluate HELIOS stent. CLINICAL TRIAL REGISTRATION ClinicalTrials.gov, NCT03916432.
Humans ; Middle Aged ; Sirolimus/therapeutic use* ; Drug-Eluting Stents/adverse effects* ; Prospective Studies ; Cohort Studies ; Treatment Outcome ; Risk Factors ; Time Factors ; Percutaneous Coronary Intervention/adverse effects* ; Cardiovascular Agents/therapeutic use* ; Coronary Artery Disease/therapy* ; Myocardial Infarction/etiology* ; Thrombosis/complications* ; Polymers ; Registries

Objective: To explore the effects and mechanism of water-soluble chitosan hydrogel on infected full-thickness skin defect wounds in diabetic mice. Methods: The experimental research method was adopted. The control hydrogel composed of polyvinyl alcohol and gelatin, and the water-soluble chitosan hydrogel composed of the aforementioned two materials and water-soluble chitosan were prepared by the cyclic freeze-thaw method. The fluidity of the two dressings in test tube before and after the first freeze-thawing was generally observed, and the difference in appearance of the final state of two dressings in 12-well plates were compared. According to random number table (the same grouping method below), the cell strains of L929 and HaCaT were both divided into water-soluble chitosan hydrogel group and control hydrogel group, respectively. After adding corresponding dressings and culturing for 24 h, the cell proliferation activity was measured using cell counting kit 8. Rabbit blood erythrocyte suspensions were divided into normal saline group, polyethylene glycol octyl phenyl ether (Triton X-100) group, water-soluble chitosan hydrogel group, and control hydrogel group, which were treated accordingly and incubated for 1 hour, and then the hemolysis degree of erythrocyte was detected by a microplate reader. Twenty-four female db/db mice aged 11-14 weeks were selected, and full-thickness skin defect wounds on their backs were inflicted and inoculated with the methicillin-resistant Staphylococcus aureus (MRSA), 72 h later, the mice were divided into blank control group, sulfadiazine silver hydrogel group, control hydrogel group, and water-soluble chitosan hydrogel group, which were treated accordingly. On post injury day (PID) 0 (immediately), 7, 14, and 21, the healing of the wound was observed. On PID 14 and 21, the wound healing rate was calculated. On PID 14, MRSA concentration in wounds was determined. On PID 21, the wounds were histologically analyzed by hematoxylin and eosin staining; the expression of CD31 in the wounds was detected by immunofluorescence method, and its positive percentage was calculated. Raw264.7 cells were taken and divided into interleukin-4 (IL-4) group, blank control group, control hydrogel group, and water-soluble chitosan hydrogel group, which were treated accordingly. At 48 h of culture, the percentages of CD206 positive cells were detected by flow cytometry. The number of samples was all 3. Data were statistically analyzed with independent sample t test, one-way analysis of variance, analysis of variance for repeated measurement, least significant difference test, and Dunnett T3 test. Results: Two dressings in test tube had certain fluidity before freeze-thawing and formed semi-solid gels after freeze-thawing for once. The final forms of two dressings in 12-well plates were basically stable and translucent sheets, with little difference in transparency. At 24 h of culture, the cell proliferation activities of L929 and HaCaT in water-soluble chitosan hydrogel group were significantly higher than those in control hydrogel group (with t values of 6.37 and 7.50, respectively, P<0.01). At 1 h of incubation, the hemolysis degree of erythrocyte in water-soluble chitosan hydrogel group was significantly lower than that in Triton X-100 group (P<0.01), but similar to that in normal saline group and control hydrogel group (P>0.05). On PID 0, the traumatic conditions of mice in the 4 groups were similar. On PID 7, more yellowish exudates were observed inside the wound in blank control group and control hydrogel group, while a small amount of exudates were observed in the wound in sulfadiazine silver hydrogel group and water-soluble chitosan hydrogel group. On PID 14, the wounds in blank control group and control hydrogel group were dry and crusted without obvious epithelial coverage; in sulfadiazine silver hydrogel group, the scabs fell off and purulent exudate was visible on the wound; in water-soluble chitosan hydrogel group, the base of wound was light red and obvious epithelial coverage could be observed on the wound. On PID 14, the wound healing rate in water-soluble chitosan hydrogel group was significantly higher than that in the other 3 groups (all P<0.01). On PID 21, the wound in water-soluble chitosan hydrogel group was completely closed, while the wounds in the other 3 groups were not completely healed; the wound healing rate in water-soluble chitosan hydrogel group was significantly higher than that in the other 3 groups (all P<0.01). On PID 14, the concentration of MRSA in the wound in water-soluble chitosan hydrogel group was significantly lower than that in blank control group (P<0.01), but similar to that in control hydrogel group and sulfadiazine silver hydrogel group (P>0.05). On PID 21, the new epidermis was severely damaged in blank control group; the epidermis on the wound in control hydrogel group also had a large area of defect; complete new epidermis had not yet being formed on the wound in sulfadiazine silver hydrogel group; the wound in water-soluble chitosan hydrogel group was not only completely covered by the new epidermis, the basal cells of the new epidermis were also regularly aligned. On PID 21, the percentage of CD31 positivity in the wound in water-soluble chitosan hydrogel group was (2.19±0.35)%, which was significantly higher than (0.18±0.05)% in blank control group, (0.23±0.06)% in control hydrogel group, and (0.62±0.25)% in sulfadiazine silver hydrogel group, all P<0.01. At 48 h of culture, the percentage of CD206 positive Raw264.7 cells in water-soluble chitosan hydrogel group was lower than that in IL-4 group (P>0.01) but significantly higher than that in blank control group and control hydrogel group (P<0.05 or P<0.01). Conclusions: The water-soluble chitosan hydrogel has good biosafety and can induce higher level of macrophage M2 polarization than control hydrogel without water-soluble chitosan, so it can enhance the repair effect of MRSA-infected full-thickness skin defect wounds in diabetic mice and promote rapid wound healing.
Mice ; Female ; Animals ; Rabbits ; Interleukin-4 ; Hydrogels/pharmacology* ; Wound Healing ; Chitosan/pharmacology* ; Diabetes Mellitus, Experimental ; Water ; Methicillin-Resistant Staphylococcus aureus ; Gelatin ; Polyvinyl Alcohol ; Hemolysis ; Saline Solution ; Eosine Yellowish-(YS) ; Hematoxylin ; Octoxynol ; Silver ; Phenyl Ethers ; Sulfadiazine

Objective:To evaluate the effects of exosomes derived from cardiac fibroblasts pretreated with sevoflurane on ventricular electrical conduction in isolated rat hearts subjected to hypothermic ischemia-reperfusion (I/R) using the multi-electrode array mapping technique.Methods:Primary cardiac fibroblasts were extracted by differential adhesion in SPF Sprague-Dawley rats of either sex.Cardiac fibroblasts of passage 2-4 were treated with 2.5% sevoflurane for 1 h, and then cultured for 24-48 h to extract exosome.SPF healthy male Sprague-Dawley rats, aged 2-3 months, weighing 280-320 g, were divided into 3 groups ( n=8 each) using a random number table method: control group (group C), I/R group and sevoflurane-pretreated cardiac fibroblast-derived exosome+ IR group (group S+ IR). Hearts were perfused for 110-min equilibration in group C. After 20 min of equilibration, the perfusion was suspended for 60 min (global ischemia) followed by 30 min of reperfusion in IR and S+ IR groups.Exosomes 1 ml (200 μg) derived from cardiac fibroblasts pretreated with sevoflurane were injected through the tail vein at 48 h before surgery in group S+ IR, and the equal volume of normal saline was injected instead in C and IR groups.The cardiac conduction velocity (CV), conduction absolute inhomogeneity (P 5-95) and inhomogeneity index (P 5-95/P 50) were obtained at 20 min of equilibration (T 0) and 15 and 30 min of reperfusion (T 1, 2) using the microelectrode array attaching to the left ventricular surface of the isolated heart. Results:Compared with group C, CV was significantly decreased and P 5-95 and P 5-95/P 50 were increased at T 1 ( P<0.05), and no significant change was found at T 2 in group S+ IR ( P>0.05), and CV was significantly decreased and P 5-95 and P 5-95/P 50 were increased at T 1, 2 in group IR ( P<0.05). Compared with group IR, CV was significantly increased and P 5-95 and P 5-95/P 50 were decreased at T 1, 2 in group S+ IR ( P<0.05). Conclusions:Exosomes derived from cardiac fibroblasts pretreated with sevoflurane can improve ventricular electrical conduction in isolated rat hearts subjected to hypothermic I/R.

Food allergy(FA)is a global health problem that affects a large population,and thus effective treatment is highly desirable.Oral immunotherapy(OIT)has been showing reasonable efficacy and favorable safety in most FA subjects.Dependable biomarkers are needed for treatment assessment and outcome prediction during OIT.Several immunological indicators have been used as biomarkers in OIT,such as skin prick tests,basophil and mast cell reactivity,T cell and B cell responses,allergen-specific antibody levels,and cytokines.Other novel indicators also could be potential biomarkers.In this review,we discuss and assess the application of various immunological indicators as biomarkers for OIT.