Objective The results of ASTRUM-007 reveal the clinical benefits of PD-L1-positive esophageal squamous cell carcinoma(ESCC)patients.This study aims to analyze the economics of first-line treatment of PD-L1-positive ESCC with brucella combined with chemotherapy from the perspective of China's health system.Methods A three-state partitioned survival model(PSM)including progression-free survival(PFS),disease progression(PD),and death(D)was established to evaluate the economy of serplulimab combined with chemotherapy,the first-line treatment for PD-L1 positive advanced ESCC,compared with the placebo combination chemotherapy.The cycle period was two weeks,the horizon of the simulation was a lifetime,and the annual discount rate was set to 5%.The main outcome parameters are total cost,quality-adjusted life year(QALY),and incremental cost-effectiveness ratio(ICER).One-way sensitivity analysis(OWSA),probability sensitivity analysis(PSA),and scenario analysis were used to evaluate the impact of the change of important parameters in the model on ICER.Results The basic results showed that the incremental effect and incremental cost of the serplulimab combined with chemotherapy compared with the placebo combination chemotherapy were 1.281 QALYs and 266 573.26 yuan,respectively,and the ICER was 208 166.24 yuan/QALY.OWSA showed that the price of serplulimab was the most sensitive parameter to ICER;PSA showed that when the WTP threshold was three times China's per capita GDP in 2022,Serplulimab combined with chemotherapy was significantly more economical than the placebo combination chemotherapy;scenario analysis revealed that according to the ASTRUM-007 study in the Central Asian group and the charitable drug donation program of serplulimab:in patients with PD-L1 1≤CPS<10,ICER was 205 056.83 yuan/QALY;with 218 022.59/QALY in patients with PD-L1 CPS≥10,and the mean value of ICER was lower than three times of China's per capita GDP.The ICER of all patients was 59 046.65 yuan/QALY,with 68 294.42 yuan/QALY of patients with PD-L1 1≤CPS<10,44 744.02 yuan/QALY of patients with PD-L1 CPS≥10.The ICER value was lower than China's per capita GDP.Conclusion Serplulimab combined with chemotherapy is more economical than placebo combined with chemotherapy in the treatment of PD-L1-positive ESCC patients.

Objective To investigate the feasibility and clinical effect of the treatment of Neer Ⅱ b distal clavicular fracture with locking plate under arthroscopy.Methods Between June 2018 and September 2022,the medical records of 15 patients with Neer Ⅱ b distal clavicular fracture treated with locking plate under arthroscope were retrospectively analyzed,including 9 males and 6 females,aged from 25 to 57 years old with an average of(42.50±7.75)years old,5 left shoulder,10 right shoul-der,and duration of the disease ranged from 4 to 7 days with an average of(5.16±0.98)d.Visual analog score(VAS),Con-stant-Murley shoulder joint score scale and Neer standard score were used before operation,1 month after operation and the last follow-up.Results All patients successfully completed the treatment of Neer Ⅱ b distal clavicular fracture with locking plate under arthroscopy,with the operation time ranging from 0.3 to 1.0 h with an average of(0.55±0.24)h.All patients were healed at stage Ⅰ.The follow-up time ranged from 6 to 15 months with an average of(9.2±2.8)months.The preoperative VAS score was 7.23±0.67,the Constant-Murley shoulder joint score was(19.57±0.91),and the Neer standard score was(11.27±1.12);The VAS score was(1.56±0.81),the Constant-Murley shoulder joint score was(52.62±1.54),and the Neer standard score was(61.98±2.99)in the first month after operation;At the last follow-up,the VAS was(0.42±0.54),the Constant-Murley shoulder joint score was(91.24±1.97),and the Neer standard score was(93.24±3.38).The difference between VAS,Con-stant-Murley shoulder joint score and Neer standard score was statistically significant at one month postoperative and preoper-ative(P＜0.05),and the difference between the last follow-up visit and one month postoperative was statistically significant(P＜0.05).Conclusion The treatment of Neer Ⅱ b distal clavicular fracture with locking plate under arthroscope can restore the function of shoulder joint,with definite curative effect and feasibility.

Objective:To explore the difference of inflammatory factor imbalance between adolescent and adult patients with depression.Methods:A total of 30 adolescent and 30 adult patients with depression, and 30 adolescent and 30 adult healthy controls were included from January 2022 to August 2023. Interleukin-6 (IL-6), interleukin-17 (IL-17), transforming growth factor-beta1(TGF-β1), interleukin-10(IL-10) and Maresin-1(MaR1) level were detected by enzyme-linked immunosorbent assay. 24-item Hamilton depression scale (HAMD-24) was used to assess the severity of depression in all depressed patients. SPSS 26.0 statistical software was used for t-test, covariance analysis, Spearman analysis and multivariate binary logistic regression, and the predictive value of selected inflammatory factors in depression was evaluated by receiver operating characteristic(ROC) curve. Results:(1)In adolescent group, the levels of IL-6 ((64.000±38.632) pg/mL), IL-17((239.132±49.757) pg/mL), and TGF-β1((737.267±328.447)pg/mL) in patients with depression were higher than those in control group((32.396±16.330)pg/mL, (214.954±42.326)pg/mL, (454.542±297.194)pg/mL, all P<0.05), while the level of MaR1((21 381.301±3 946.011)pg/mL) was significantly lower than that in control group((30 130.138±10 278.999)pg/mL)( P<0.001). The level of IL-17 was positively correlated with the total score of HAMD-24 ( r=0.429) and the course of disease ( r=0.571), the level of IL-10 was negatively correlated with body weight factor score ( r=-0.384), and the levels of TGF-β1 was negatively correlated with anxiety/somatization factor score ( r=-0.449)(all P<0.05) in adolescent patients with depression.MaR1( B=0.000 1, OR=0.999 8, AUC=0.794, P<0.05) was an independent risk factor for adolescents depression.(2)In adult depression group, the levels of IL-6, IL-17, IL-10, TGF-β1 and MaR1 were higher than those in adult control group(all P<0.05). The level of TGF-β1 in adult depression group was negatively correlated with the total score of HAMD-24 ( r=-0.427), the score of anxiety/somatization factor ( r=-0.368), the score of blocking factor ( r=-0.405), and the score of hopelessness factor ( r=-0.398).The level of MaR1 was positively correlated with the age of onset of disease ( r=0.425)(all P<0.05) in adult patients with depression.MaR1( B=0.000 4, OR=1.000 3, AUC=0.874, P<0.001) and IL-6( B=0.040, OR=1.040 7, AUC=0.779, P<0.05) were independent risk factors for adult depression.The AUC of IL-6 combined with MaR1 was 0.938. Conclusion:There are differences in the underlying mechanism of immune imbalance between adolescent and adult patients with depression.MaR1 may be a diagnostic biomarker for depression in adolescents and adults.

The canonical transient receptor potential channel(TRPC)proteins form Ca2+-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1-/-mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6-/-mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1-/-cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factor-kappa B(NF-κB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-κB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-κB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca2+influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-κB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.

This paper aims to investigate the effects and mechanisms of adipose-derived stem cells-exosomes(ADSCs-exos) toge-ther with aucubin in protecting human-derived nucleus pulposus cells(NPCs) from inflammatory injury, senescence, and apoptosis. The tert-butyl hydroperoxide(TBHP)-induced NPCs were assigned into normal, model, aucubin, ADSCs-exos, and aucubin+ADSCs-exos groups. The cell viability was examined by cell counting kit-8(CCK-8), cell proliferation by EdU staining, cell senescence by senescence-associated-β-galactosidase(SA-β-Gal), and cell cycle and apoptosis by flow cytometry. Enzyme-linked immunosorbent assay was employed to examine the expression of interleukin-1β(IL-1β), IL-10, and tumor necrosis factor-α(TNF-α). Real-time fluorescence quantitative PCR and Western blot were employed to determine the mRNA and protein levels of aggregated proteoglycan(aggrecan), type Ⅱ collagen alpha 1(COL2A1), Toll-like receptor 4(TLR4), and nuclear factor-kappa B(NF-κB). The results showed that compared with the model group, the aucubin or ADSCs-exos group showed enhanced viability and proliferation of NPCs, decreased proportion of G_0/G_1 phase cells, increased proportion of S phase cells, reduced apoptosis and proportion of cells in senescence, lowered IL-1β and TNF-α levels, elevated IL-10 level, down-regulated mRNA and protein levels of TLR4 and NF-κB, and up-regulated mRNA and protein levels of aggrecan and COL2A1. Compared with the aucubin or ADSCs-exos group, the aucubin+ADSCs-exos combination further increased the viability and proliferation of NPCs, decreased the proportion of G_0/G_1 phase cells, increased the proportion of S phase cells, reduced the apoptosis and proportion of cells in senescence, lowered the IL-1β and TNF-α levels, elevated the IL-10 level, down-regulated the mRNA and protein levels of TLR4 and NF-κB, and up-regulated the mRNA and protein levels of aggrecan and COL2A1. In summary, both aucubin and ADSCs-exos could exert protective effects by inhibiting inflammatory responses, reducing apoptosis and senescence of NPCs, improving cell viability and proliferation as well as extracellular matrix synthesis, which may be associated with the inhibition of TLR4/NF-κB signaling pathway activation. The combination of both plays a synergistic role in the protective effects.
Humans ; NF-kappa B/metabolism* ; Interleukin-10 ; Nucleus Pulposus/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Aggrecans/metabolism* ; Toll-Like Receptor 4/metabolism* ; RNA, Messenger/metabolism*

Human-animal parasitic diseases caused by medical helminths are hazardous to human health. Genetic polymorphism studies on medical helminth populations can not only understand the biological characteristics and genetic structure of their populations, but also help reveal how they adapt to their parasitic environment, thus contributing to deepen our understanding of the epidemiological patterns of parasitic diseases and improve our understanding of accurate prevention and control of parasitic diseases. With the development of molecular biology, molecular markers such as DNA barcodes, simple sequence repeats, and single nucleotide polymorphism markers have been widely used to study the genetic relationships among parasite populations and individuals, and to reveal the genetic variation of parasite populations and the evolution of species origins. In this paper, we systematically review the application of three molecular markers commonly used in the study of genetic polymorphism in medical helminths, with a view to laying the foundation for related research.

Objective: Compare and analyze the results of the domestic Lanyi AH600 glycated hemoglobin analyzer and other different detection systems to understand the comparability of the detection results of different detectors, and establish the best cut point of Lanyi AH600 determination of haemoglobin A1c (HbA1c) in the diagnosis of diabetes. Methods: Multi center cohort study was adopted. The clinical laboratory departments of 18 medical institutions independently collected test samples from their respective hospitals from March to April 2022, and independently completed comparative analysis of the evaluated instrument (Lanyi AH600) and the reference instrument HbA1c. The reference instruments include four different brands of glycosylated hemoglobin meters, including Arkray, Bio-Rad, DOSOH, and Huizhong. Scatter plot was used to calculate the correlation between the results of different detection systems, and the regression equation was calculated. The consistency analysis between the results of different detection systems was evaluated by Bland Altman method. Consistency judgment principles: (1) When the 95% limits of agreement (95% LoA) of the measurement difference was within 0.4% HbA1c and the measurement score was≥80 points, the comparison consistency was good; (2) When the measurement difference of 95% LoA exceeded 0.4% HbA1c, and the measurement score was≥80 points, the comparison consistency was relatively good; (3) The measurement score was less than 80 points, the comparison consistency was poor. The difference between the results of different detection systems was tested by paired sample T test or Wilcoxon paired sign rank sum test; The best cut-off point of diabetes was analyzed by receiver operating characteristic curve (ROC). Results: The correlation coefficient R² of results between Lanyi AH600 and the reference instrument in 16 hospitals is≥0.99; The Bland Altman consistency analysis showed that the difference of 95% LoA in Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180) was -0.486%-0.325%, and the measurement score was 94.6 points (473/500); The difference of 95% LoA in the Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant II) was -0.727%-0.612%, and the measurement score was 89.8 points; The difference of 95% LoA in the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT) was -0.231%-0.461%, and the measurement score was 96.6 points; The difference of 95% LoA in the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT) was -0.469%-0.479%, and the measurement score was 91.9 points. The other 14 hospitals, Lanyi AH600, were compared with 4 reference instrument brands, the difference of 95% LoA was less than 0.4% HbA1c, and the scores were all greater than 95 points. The results of paired sample T test or Wilcoxon paired sign rank sum test showed that there was no statistically significant difference between Lanyi AH600 and the reference instrument Arkray HA8180 (Z=1.665,P=0.096), with no statistical difference. The mean difference between the measured values of the two instruments was 0.004%. The comparison data of Lanyi AH600 and the reference instrument of all other institutions had significant differences (all P<0.001), however, it was necessary to consider whether it was within the clinical acceptable range in combination with the results of the Bland-Altman consistency analysis. The ROC curve of HbA1c detected by Lanyi AH600 in 985 patients with diabetes and 3 423 patients with non-diabetes was analyzed, the area under curve (AUC) was 0.877, the standard error was 0.007, and the 95% confidence interval 95%CI was (0.864, 0.891), which was statistically significant (P<0.001). The maximum value of Youden index was 0.634, and the corresponding HbA1c cut point was 6.235%. The sensitivity and specificity of diabetes diagnosis were 76.2% and 87.2%, respectively. Conclusion: Among the hospitals and instruments currently included in this study, among these four hospitals included Nanjing Maternity and Child Health Care Hospital in Jiangsu Province (reference instrument: Arkray HA8180), Tibetan Traditional Medical Hospital of TAR (reference instrument: Bio-Rad Variant Ⅱ), the People's Hospital of Chongqing Liang Jiang New Area (reference instrument: Huizhong MQ-2000PT), and the Taihe Hospital of traditional Chinese Medicine in Anhui Province (reference instrument: Huizhong MQ-2000PT), the comparison between Lanyi AH600 and the reference instruments showed relatively good consistency, while the other 14 hospitals involved four different brands of reference instruments: Arkray, Bio-Rad, DOSOH, and Huizhong, Lanyi AH600 had good consistency with its comparison. The best cut point of the domestic Lanyi AH600 for detecting HbA1c in the diagnosis of diabetes is 6.235%.
Pregnancy ; Child ; Humans ; Female ; Glycated Hemoglobin ; Cohort Studies ; Diabetes Mellitus/diagnosis* ; Sensitivity and Specificity ; ROC Curve

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Humans ; Methylenetetrahydrofolate Reductase (NADPH2)/metabolism* ; Genotype ; CRISPR-Cas Systems ; Polymorphism, Genetic ; Genetic Predisposition to Disease ; Polymorphism, Single Nucleotide ; Gene Frequency

OBJECTIVE: To explore the mechanism of proteasome inhibitor MG132 in improving osteoporosis. METHODS: Total of 32 female SD rats, weighing 220 to 250 g and 8 weeks old, were selected. They were randomly divided into 4 groups(n=8). Rats of group A and group B were cut off ovaris on both sides to make model of osteoporosis, and then they were given proteasome inhibitors MG132 and dimethyl sufoxide (DMSO) respectively. Group C was a sham group and rats were given MG132. Group D was a normal group and rats were given MG132 too. The rats were killed in batches at 6 and 12 weeks after administration, and the femoral neck tissues were obtained. Relevant data were analyzed, such as pathomorphological observation, micro-CT analysis, detection of 20S proteasome activity in tissues, and expression of Wnt and β-catenin. RESULTS: Morphological observation showed that the trabecular were slightly thinner, reticulated, and occasionally interrupted in group A, while the trabecular were obviously thinner and discontinuous in group B. And the trabecular were intact and arranged reticulated in group C and D. The analysis results of bone mineral density(BMD), bone surface(BS), bone volume/total volume(BV/TV) and trabecular thickness(Tb.Th) showed that group B was worse than other groups in all parameters at different time points(P<0.05), and group A was worse than group C and group D in BS(P<0.05), there was no significant difference in all parameters between group C and group D. RFU value of 20S proteasome in group B was significantly higher than that in other groups(P<0.05). According to the results of Western blot, the gray values of Wnt protein and β-catenin protein in group A were significantly higher than those in other groups (P<0.05). CONCLUSION MG-132, a ubiquitin proteasome inhibitor, can regulate Wnt/β-catenin signaling pathway by inhibiting the degradation of β-catenin protein, and delaying the occurrence and development of osteoporosis.
Animals ; Bone Density ; Female ; Leupeptins ; Osteoporosis/drug therapy* ; Proteasome Inhibitors/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Wnt Signaling Pathway ; beta Catenin/metabolism*