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%.

Objective To analyze the expression and role of the disulfidptosis-related gene PDZ and LIM domain protein 1(PDLIM1)in various tumors.Methods The expression of PDLIM1 mRNA was analyzed by Xiantao website.The diagnostic and prognostic capabilities of PDLIM1 in 33 types of tumors were explored using the Xiantao website and Sangerbox 3.0 data analysis platform.The correlation between PDLIM1 and clinical classification and its staging was analyzed by the TISIDB database.The correlation between PDLIM1 and tumor immunity was analyzed by Sangerbox 3.0 data analysis platform and Kaplan-Meier Plotter database.Protein-protein interaction networks(PPI)were constructed by STRING database and Cytoscape,and were enriched by Sangerbox 3.0 data analysis platform.Finally,the GSCA website was applied to acquire the expression of PDLIM1 mRNA and its sensitivity to drugs.Results There was heterogeneity in the expression of PDLIM1 mRNA among 33 tumors.PDLIM1 had good diagnostic ability in cholangiocarcinoma(CHOL),glioblastoma multiforme(GBM),kidney renal clear cell carcinoma(KIRC),lung adenocarcinoma(LUAD),ovarian cancer(OV),pancreatic cancer(PAAD),skin cutaneous melanoma(SKCM)and testicular germ cell tumor(TGCT).High expression of PDLIM1 mRNA in glioma,low-grade glioma(LGG),KIPAN,GBM,uveal melanoma(UVM),and adrenocortical carcinoma(ACC)suggested poor prognosis,while low expression in sarcoma suggested poor prognosis.PALIM1 mRNA expression was correlated with the classification of head and neck squamous cell carcinoma(HNSC),kidney renal papillary cell carcinoma(KIRP),uterine corpus endometrial carcinoma(UCEC),uterine carcinosarcomas(UCS),and UVM as well as the staging of cervical squamous cell carcinoma and endocervical adenocarcinoma(CESC),HNSC,UCEC,and LGG.PDLIM1 was significantly associated with immune infiltration of 36 tumors led by prostateadenocarcinoma(PRAD),and was found to have a relatively good prognosis after immunotherapy in patients with high PDLIM1 mRNA expression.PDLIM1 exerted effects on organisms mainly through its involvement in the regulation of actin cytoskeleton,cell adhesion,and cancer-related pathways,and was sensitive to various drugs led by Isoliquiritigenin.Conclusion PDLIM1 was closely related to the clinical prognosis and immune infiltration of a variety of tumors,and it is expected to be a cancer diagnostic and prognostic biomarker or therapeutic target.

Objective:To evaluate the performance of rural practitioners of endoscopic cleaning and disinfection participating in the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers and to analyze the influencing factors.Methods:The questionnaires for skill assessment were designed based on the skill scheme and clinical practice of the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers in rural China, and the App Early diagnosis, Early treatment was used as the examination platform. The practitioners in 539 county hospitals from 25 provinces participating in the program in 2019 were assessed for techniques and skills for endoscopic cleaning and disinfection and the excellence rate was calculated. Multivariate logistic regression model was used to analyze the influencing factors for the examination. Results:A total of 1 671 endoscopic cleaning and disinfection practitioners participated in the assessment with the score of 73.41±16.60. The passing rate was 85.82%, and the excellence rate was 44.94%. Among all questions, the correct rate of "opportunistic screening flow chart" was the highest (98.21%), and that of "the evaluation index for mass screening" was the lowest (57.89%). The multivariate logistic regression analysis showed that the excellence rate was high in practitioners who had a bachelor degree or above ( OR=1.627,95% CI:1.319-2.007, P<0.001), the career for 5 to <15 years (5 to <10 years: OR=1.329,95% CI:1.045-1.689, P=0.020; 10 to <15 years: OR=1.384,95% CI:1.026-1.867, P=0.033), working in eastern and central regions (eastern regions: OR=3.476,95% CI:2.368-5.103, P<0.001;central regions: OR=4.028,95% CI:2.679-6.057, P<0.001) and with full understanding of the screening scheme ( OR=1.547,95% CI:1.246-1.921, P<0.001) . Conclusion:Practitioners on the Early Diagnosis and Treatment Program for Upper Gastrointestinal Cancers in rural China have mastered the basic screening scheme and skills for endoscopic cleaning and disinfection. The education background, duration of the career, area and understanding of screening scheme are influencing factors for the excellence rate of endoscopic cleaning and disinfection.

Promoter is an important genetic tool for fine-tuning of gene expression and has been widely used for metabolic engineering. Corynebacterium glutamicum is an important chassis for industrial biotechnology. However, promoter libraries that are applicable to C. glutamicum have been rarely reported, except for a few developed based on synthetic sequences containing random mutations. In this study, we constructed a promoter library based on the native promoter of odhA gene by mutating the -10 region and the bystanders. Using a red fluorescent protein (RFP) as the reporter, 57 promoter mutants were screened by fluorescence imaging technology in a high-throughput manner. These mutants spanned a strength range between 2.4-fold and 19.6-fold improvements of the wild-type promoter. The strongest mutant exhibited a 2.3-fold higher strength than the widely used strong inducible promoter P_trc. Sequencing of all 57 mutants revealed that 55 mutants share a 1-4 bases shift (4 bases shift for 68% mutants) of the conserved -10 motif "TANNNT" to the 3' end of the promoter, compared to the wild-type promoter. Conserved T or G bases at different positions were observed for strong, moderate, and weak promoter mutants. Finally, five promoter mutants with different strength were employed to fine-tune the expression of γ-glutamyl kinase (ProB) for L-proline biosynthesis. Increased promoter strength led to enhanced L-proline production and the highest L-proline titer of 6.4 g/L was obtained when a promoter mutant with a 9.8-fold higher strength compared to the wild-type promoter was used for ProB expression. The use of stronger promoter variants did not further improve L-proline production. In conclusion, a promoter library was constructed based on a native C. glutamicum promoter P_odhA. The new promoter library should be useful for systems metabolic engineering of C. glutamicum. The strategy of mutating native promoter may also guide the construction of promoter libraries for other microorganisms.
Corynebacterium glutamicum/metabolism* ; Gene Library ; Metabolic Engineering ; Promoter Regions, Genetic/genetics*

Objective:To investigate the 30-day mortality risk in elderly patients with sepsis-induced myocardial dysfunction(SIMD), and to analyze its related risk factors.Methods:This was a multicenter retrospective case-control study.A total of 254 elderly patients with sepsis or septic shock admitted to the Second Hospital of Shanxi Medical University(117 cases), the First Hospital of Shanxi Medical University(89 cases)and Shanxi Provincial People's University(48 cases)from January 2015 to December 2019 were enrolled.According to whether or not combined with SIMD, patients were divided into the SIMD group(n=68)and the control group(n=186). All patients were followed for 30 day to evaluate the rate of mortality and the related factors.Results:Among 254 elderly patients, the incidence of SIMD was 26.8%.There were significant differences between the SIMD group and the control group in age, heart rate, E/A value, left ventricular ejection fraction(LVEF), procalcitonin, lactate, C-reactive protein, troponin, N-terminal pro-B-type natriuretic peptide(NT-proBNP)and sequential organ failure assessment(SOFA)score(all P<0.05). The significant differences were found between the SIMD group and the control group in the all-cause mortality risk, the duration of invasive mechanical ventilation, ICU hospitalization time and total hospitalization days(35.3% or 24 cases vs.22.6% or 42 cases, 7.0 d vs.4.8 d, 9.5 d vs.7.5 d and 18.8 d vs.15.1 d, P<0.05). Age ≥65 years( RR=1.867), diabetes( RR=2.661), procalcitonin ≥13.2 μg/L( RR=3.307), and lactate ≥3.65 mmol/L( RR=2.964)were risk factors for SIMD, and serum troponin ≥0.08 μg/L( HR=2.019), NT-proBNP ≥537.4 ng/L( HR=4.411), lactate ≥3.65 mmol/L( HR=3.934)and LVEF <50.0%( HR=3.761)were risk factors for the mortality(all P<0.05). Conclusions:Elderly patients with the sepsis-induced SIMD have severe infections, mainly involving the left ventricle, and have an increased risk of mortality and a longer duration of hospital stays.

In order to meet the social demand for ultrasound talents, a layered training system of ultrasound medical talents suitable for China's national conditions has been explored. The department of ultrasound of West China Hospital of Sichuan University has formulated and implemented a "three-layers" ultrasound education and training system in combination with its own reality. The first layer mainly refers mastering the basic ultrasound examination ability mainly through relevant ultrasound theoretical knowledge and basic operation skills training. The second layer is based on the first level to further master the ability of ultrasound diagnosis and differential diagnosis of common and frequently occurring diseases in various systems, and to be capable of engaging in basic ultrasound teaching and scientific research. The third layer means mastering the ability of ultrasound diagnosis, evaluation and interventional diagnosis and treatment of difficult and specialized diseases, grasping the latest development direction of the sub-specialty, and having the ability to engage in ultrasound teaching and clinical research. The results show that the "three-layers" ultrasound education and training system conforms to China's national conditions and is worthy of reference and promotion.

To evaluate the effects of resuscitation with normal saline and sodium potassium magnesium calcium and glucose injection on renal structure and function in septic rats. Rat model of sepsis was established by ligation and perforation of cecum. Male SD rats were divided into four groups: sham operation group, sepsis group, saline resuscitation group, sodium potassium magnesium calcium and glucose injection resuscitation group. Blood gas analysis was performed at the end of resuscitation. The rats were sacrificed 72 hours after resuscitation. Blood samples were taken to measure the plasma levels of blood urea nitrogen (BUN), creatinine, interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factorα (TNFα). Caspase-3 expression was detected by immunohistochemistry in kidney sections. The degree of renal injury was evaluated by regular HE staining and electron microscope. Compared with normal saline resuscitation, sodium potassium calcium magnesium glucose injection resuscitation could decrease the levels of BUN, serum creatinine, IL-1β, IL-6 and TNFα ( P<0.05) , reduce the expression of caspase-3 ( P<0.05) , and improve the renal injury score ( P<0.05) . Sodium potassium calcium magnesium glucose injection resuscitation can significantly improve the renal function of sepsis rats with less pathological damage of the kidney.

Objective:To study the clinical effect of the minimally invasive treatment of calcaneal fractures by closed reduction using calcaneal plastic reduction forceps combined with threaded-pin external fixation.Methods:Clinical data of 16 patients with unilateral calcaneal fractures admitted to Affiliated Zhongshan Hospital of Dalian University from January 2015 to December 2017, including 14 males and 2 females, with a unilateral calcaneal fracture were analyzed retrospectively. The Bohler angle, Gissane angle, and calcaneal width, height and length were measured before and after the operation. The ankle function was evaluated according to the AOFAS score at 6 and 12 months after the operation.Results:The Bohler angle, Gissane angle, width, height and length 3 d and 6 months after operation were significantly better than before operation: (28.82 ± 1.72)° and (25.84 ± 1.96)° vs. (16.71 ± 2.74)°, (120.92 ± 3.85)° and (119.65 ± 3.84)° vs. (103.63 ± 4.62)°, (35.23 ± 1.94) and (36.51 ± 2.01) mm vs. (39.52 ± 1.26) mm, (48.52 ± 2.16) and (48.86 ± 1.98) mm vs. (46.94 ± 2.48) mm, (71.23 ± 2.49) and (70.94 ± 2.36) mm vs. (67.53 ± 2.53) mm, there were statistical differences ( P<0.05); there were no statistical difference in those indexes before 6 months after operation and 3 d after operation ( P>0.05). The average AOFAS score 12 months after operation was significantly higher than 6 months after operation (80.6 scores vs. 60.1 scores), there was statistical difference ( P<0.01). At the final follow-up, the AOFAS score was excellent, good, moderate, and poor in 11 cases, 3 cases, 1 case and 1 case. The average AOFAS score was 60.1 at 6 months after the operation and 80.6 at 12 months after the operation, which was significantly higher than the average AOFAS score at 6 months after the operation ( P < 0.01). At the final follow-up, the AOFAS score was excellent, good, moderate, and poor in 11 cases, 3 cases, 1 case and 1 case, respectively. Conclusions:The application of closed reduction using calcaneal plastic reduction forceps combined with threaded-pin external fixation is effective for the treatment of displaced calcaneal fractures, with a simple procedure, minimal trauma, fewer skin and soft tissue complications, and satisfactory clinical results.

Objective:To understand the epidemiological characteristics and risk factors of fatal cases of hand, foot, and mouth disease (HFMD) in children under 5 years old in China from 2008 to 2018, and provide evidence for the development of targeted prevention and control measures and reduction of the incidence of fatal HFMD cases.Methods:The incidence data of reported HFMD cases in China during 2008-2018 were collected from the National Notifiable Disease Surveillance Reporting System of China for the analyses on the demographic characteristics, spatial distribution, diagnosis or reporting and pathogen spectrum of the HFMD cases. Then the risk factors causing deaths were analyzed by using logistic regression model.Results:From 2008 to 2018, a total of 3 646 fatal cases of HFMD in children under 5 years old were reported in China. There were more fatal HFMD cases in boys than in girls (1.82∶1), the death mainly occurred in age group 0 to 2 years (87.71%). Adjusted mortality rate of HFMD in children under 5 years old in China declined from 0.87 per 100 000 in 2010 to 0.11 per 100 000 in 2018 (APC=-23.20%). In the 2 523 laboratory-confirmed deaths, 2 323 (92.07%) were EV-A71 infections, but the constituents of CV-A16 and other enterovirus infections increased. The interval from onset to diagnosis M=2( P25-P75:2 -4)d. The interval from onset to death M=3( P25-P75:2 -4)d. Age between 0 and 1 years, EV-A71 infection, longer interval between onset and diagnosis, and living in rural area were the risk factors causing fatal HFMD cases. Conclusions:The number of the fatal cases, the rate of mortality and case fatality HFMD in China had shown downward trends since 2010. EV-A71 is still the main pathogen causing fatal cases, but we should pay more attention to gene pattern of the other enteroviruses except EV-A71 and CV-A16. To reduce the risk of the fatal cases we should strengthen the health education about the immunization of EV-A71 inactivated vaccines and reduce the interval from onset to diagnosis in young children in western provinces and rural areas.

A high performance liquid chromatography method based on amino column to uncover the glycosyls of aroma glycosides in Meili grape was established.Meili grapes were sampled from Yangling, Shaanxi province, China.Aroma glycosides in grape skins were extracted by extraction buffer (0.1 mol/L Na2HPO4/NaH2PO4, pH 7.0, 13% ethanol (V/V)), then enzymatically hydrolysed by AR2000 enzyme preparation in citrate-phosphate buffer (pH 5.0), and the glycosyls liberated were isolated by amino column, and determined by high performance liquid chromatography-refractive index detector (HPLC-RID).The HPLC-RID experimental conditions were developed as follows: amino column temperature 35℃, RID temperature 35℃, injection volume 20 μL, mobile phase acetonitrile/ethyl acetate/water=60∶25∶15 (V/V), flow rate 1 mL/min.The results showed that the reasonable linearity was achieved for rhamnose, xylose, arabinose, apiose and glucose (R2>0.996), with the detection limit (LOD) of 93-123 mg/L and quantitation limit (LOQ) of 309-409 mg/L.The relative standard deviation (RSD, n=10) of the peaks of each monosaccharide (5 g/L) was 2.3%-6.4%, and the recoveries ranged from 73.8% to 125.7%.The molar percentages of the aroma glycosides in Meili grape were 4.1%-6.1% for 6-O-α-L-rhamnopyranosyl-β-D-glucopyranoside, 2.3%-8.8% for 6-O-β-D-xylopyranosyl-β-D-glucopyranoside, 0.1%-3.9% for 6-O-α-L-arabinofuranosyl-β-D-glucopyranoside, 5.5%-9.8% for 6-O-α-L-apiofuranosyl-β-D-glucopyranoside, and 76.3%-86.8% for 6-O-β-D-glucopyranosyl-β-D-glucopyranoside.The contents of each aroma glycoside and the total glycosides in Meili grape didn′t show obvious relationship with berry maturity index during grape maturity.