Minimum wage standard adjustment and employment: Heterogeneity effects on the human capital investment.

Considerable debate has arisen around the potential effects of increasing the minimum wage on employment. This study aims to analyze the impact of changes in China's minimum wage standard on employment. The research utilises the canonical model method and constructs a regression model based on standard labor economics theory. The analysis is conducted using sample data from Chinese industrial enterprises between 2000 and 2007. Regression analysis is performed by categorizing enterprises based on their level of human capital investment. The findings indicate that minimum wage increases have a non-linear impact on employment, when seen from the standpoint of human capital investment. When the level of human capital investment is low, an increase in the minimum wage standard leads to a decrease in employment; when the level of human capital investment is high, an increase in the minimum wage standard leads to an increase in employment. According to the findings, the reason for this is that, investments in human capital can improve business profitability, increase worker marginal productivity, and increase labor demand. Similarly, the employment effect of a change in the minimum wage is positive in regions with high levels of human capital investment due to the externality effect of human capital. Adjustments to the minimum wage have a negative impact on employment in areas of the country with low levels of human capital investment. This demonstrates that changing the minimum wage does not result in a simple increase or decrease in total employment. The level of investment in human capital within the organization and the region is an important factor in determining the type and magnitude of the impact.

Values of different DIC scoring systems in early diagnosis and prognosis prediction of coagulation dysfunc-tion in sepsis patients / 实用医学杂志

Objective To evaluate five types of DIC scoring systems based on sepsis patients,to explore the values of different DIC scoring systems in the occurrence and prognosis of DIC in sepsis patients,and to compare the applicability of different DIC scoring systems for sepsis complicated with DIC.Methods Laboratory indexes and clinical data from sepsis patients who had been hospitalized in Gansu Provincial People's Hospital from December 1,2019 to December 31,2021 were retrospectively analyzed within 24 hours.Five types of DIC scoring systems were used to score,and the difference of diagnostic rate and discharge outcome in sepsis patients with different severity was compared.The ROC curves of five DIC scoring systems were established to evaluate the accu-racy of DIC in sepsis patients.Results The fatality rate of sepsis increased with the severity of sepsis(P<0.05).There were statistically significant differences in discharge outcomes between DIC and non-DIC in the five scoring systems(P<0.05).JMHW,CDSS and part of ISTH were detected in JAAM cases,while ISTH was detected in non-dominant ISTH cases.ISTH,JAAM,JMHW,CDSS,and non-dominant ISTH5 scoring systems were used to diagnose DIC,and absence of full health restoration and death were 3.0,3.8,4.2,3.9,and 3.0 times higher than non-DIC cases,respectively.Conclusion JAAM scoring system has higher diagnostic rate and sensitivity for adult sepsis.CDSS and JMHW scoring systems are more accurate in predicting the prognosis of sepsis patients.

Overview of the Research on the Characteristics of the Eldon-Uriel Formula of Mongolian Medicine and the Treatment of Atherosclerosis / 医药导报

Atherosclerosis(AS)is the common pathological basis of ischemic cardiovascular diseases,and its formation mechanism is complex.Western medical treatment has problems such as a long cycle and a high relapse rate.Ethnic medicine is an important part of traditional medicine,which has unique efficacy in treating cardiovascular diseases.Studies have shown that the Mongolian medicine Eldon-Uriel regulates blood lipids and improves blood rheology in the treatment of AS.This paper aims to pro-vide new ideas for the prevention and treatment of AS by collecting,organizing,and summarizing the relevant literature on Eldon-Uriel and introducing its unique concept,mechanism of action,and clinical studies in the treatment of AS.

Efficacy of electroacupunture at Zusanli (ST36) on jumping-injured muscle based on transcriptome sequencing and genes analysis.

OBJECTIVE: To reveal the efficacy and possible mechanism of electroacupuncture at Zusanli (ST36) on injured skeletal muscle induced by jumping load. METHODS: In the present study, female Sprague-Dawley rats were randomly divided into four groups with 6 of each, including normal control group (NC), jumping-induced muscle injury model group (JI), JI with electroacupuncture stimulation treatment group (EA), and JI with non-electroacupuncture stimulation group (NEA). Transmission electron microscopy, transcriptome sequencing and analysis, prediction of protein interaction networks, real-time polymerase chain reaction verification, and Western blotting were performed on the gastrocnemius muscle of ipsilateral lower limbs. RESULTS: The structural repair of injured gastrocnemius myofibers following jumping training in EA rats was better than that of NEA rats. A total of 136 genes were differentially expressed in EA rats relative to JI rats, with 55 genes upregulated and 81 genes downregulated. According to results of transcriptome analysis, and prediction of protein mutual interaction by the online STRING database, Heat shock protein beta-7 (Hspb7) and myozenin2 (Myoz2) genes were targeted. Expressions of Hspb7 and Myoz2 mRNAs were increased in EA rats relative to JI rats (0.05). The expression of Hspb7 protein was upregulated in EA rats relative to that in NC, JI, and NEA rats (0.01, 0.05, and0.05, respectively). The expression of Myoz2 protein was upregulated in EA rats relative to that in NC and JI rats (both 0.01respectively). CONCLUSIONS: The present results suggest that electroacupuncture stimulation at Zusanli (ST36) could improve muscle healing following jumping-induced muscle injury, owing to the upregulation of Hspb7 and Myoz2 proteins.

Correlation between intestinal flora characteristics and hepatic and renal impairments in HIV-infected heterosexual men / 上海预防医学

ObjectiveTo explore the relationship between the intestinal flora and the impairment of liver and kidney in HIV-infected men who have heterosexual sex with healthy women. MethodsFecal samples from 41 HIV-infected heterosexual men who have sex with women （PMSW） and 43 age- and BMI-matched healthy heterosexual men who have sex with women （NMSW） were collected and subjected to 16S rDNA sequencing. The blood levels of AST， ALT， TBIL， UREA， Cr， UA， β2-MG and other liver and kidney function indicators were measured. Bioinformatics methods were used to analyze the characteristics of the intestinal flora of the patients in these two groups， to compare the differential bacteria strains， and to analyze their correlation with liver and kidney function indicators. ResultsIn comparison with NMSW， the alpha diversity of intestinal flora was decreased in PMSW， and the beta diversity analysis showed significant differences in flora characteristics between the two groups （P<0.05）. The abundance of Clostridium， Phylum thick-walled， Trichosporon， and Clostridium tumefaciens decreased but Fusobacteriota increased （LDA score >4）. The comparison of liver and kidney function indexes revealed that AST， β2-MG levels were higher in PMSW than in NMSW， while TBIL was lower in PMSW than in NMSW. The number of patients with abnormal β2-MG was much higher in PMSW than in NMSW， and the difference was statistically significant （P<0.001）. It was also found that AST was negatively correlated with Clostridium （P<0.05）； TBIL was negatively correlated with Clostridium and positively correlated with Phylum thick-walled and Trichosporon （P<0.05）. β2-MG was negatively correlated with Phylum thick-walled， Clostridium， Trichosporon and Rumenococcus （P<0.05） and positively correlated with Clostridium （P<0.05）. ConclusionIn PMSW group， the alpha diversity of the flora is decreased. AST and β2-MG levels are increased， and TBIL level is decreased. These changes were significantly correlated with different strains of bacteria in the intestinal flora.

Establishment of prediction model for severe acute pancreatitis complicated with abdominal hypertension / 中华胰腺病杂志

Objective:To construct the prediction model of SAP complicated with intra-abdominal hypertension (IAH), and evaluate the prediction efficiency of the model.Methods:The clinical data of 322 SAP patients admitted to the emergency department of Cangzhou Hospital of Integrated Chinese and Western Medicine in Hebei Province from January 2017 to December 2021 were retrospectively analyzed. They were divided into IAH group ( n=153) and control group ( n=169) according to whether they had IAH complications or not. The clinical characteristics and laboratory test results of the two groups were compared. Multifactor logistic step-up regression was used to analyze the risk factors of SAP patients complicated with IAH. A nomogram model for predicting SAP complicated with IAH was established by using R software. The receiver operating characteristic curve (ROC) of the model was plotted, and the area under the curve (AUC) was calculated to evaluate its prediction efficiency. Calibration chart, Hosmer-Lemesshow test and decision curve analysis were used to evaluate the prediction accuracy and clinical application value of the model. The Bootstrap method was applied to verify the model internally. Results:In IAH group, cases with body mass index, CRP, procalcitonin (PCT), WBC, acute physiological and chronic health assessmentⅡ (APACHEⅡ) score, modified CT Severity Index score (MCTSI), incidence of complications (abdominal effusion, abdominal infection, gastrointestinal dysfunction, shock, multiple organ dysfunction syndrome), mechanical ventilation, the number of high-volume fluid reactivation (24 h≥4 L) were more than those in control group; serum albumin and serum calcium in IAH group were lower than those in control group, and the differences were statistically significant (all P value <0.05). Multivariate logistic regression analysis showed that serum albumin ( OR=0.815, 95% CI 0.710-0.937), CRP ( OR=1.005, 95% CI 1.002-1.008), MCTSI ( OR=2.043, 95% CI 1.695-2.463), complication of gastrointestinal dysfunction ( OR=4.179, 95% CI 2.170-8.049), and high-volume fluid resuscitation ( OR=4.265, 95% CI 2.269-8.015) were independent risk factors for IAH in SAP.The Nomogram prediction model was established using the five factors above as parameters, and the AUC value for predicting IAH complication was 0.886. The Hosmer-Lemesshow test showed a high consistency between the prediction results and the actual clinical observation results ( P=0.189). The results of decision curve analysis showed that the prediction probability of the model was between 10% and 85%, which could bring more benefits to patients. Conclusions:The early prediction model of SAP with concurrent IAH is successfully established, which can better predict the risk of SAP with concurrent IAH.

Diagnostic value of neutrophil CD64 index in disseminated nontuberculous mycobacteria infection / 中华传染病杂志

Objective:To investigate the diagnostic value of neutrophil CD64 index (nCD64) in disseminated nontuberculous mycobacteria (NTM) infection.Methods:Thirty-six patients with NTM infection from January 2020 to June 2021 in Huashan Hospital, Fudan University were included. Patients were classified into groups of disseminated infection and focal infection according to their medical history and discharge diagnosis. The expressions of nCD64 in patients with focal infection and disseminated infection before treatment were collected and analyzed. Statistical analysis was performed using the Mann-Whitney U test, and the diagnostic value of nCD64 for disseminated NTM infection was analyzed using the receiver operator characteristic curve (ROC curve). Results:Among the 36 patients with NTM infection, 18 cases were focal infection (due to the low white blood cell count of the patient with myelodysplastic syndrome, the detection results were biased, which were excluded from the subsequent analysis) and 18 cases were disseminated infection. The expression of nCD64 in focal infection was 0.72(0.50, 1.55), and that in disseminated infection was 13.63(6.77, 32.31). The difference was statistically significant ( U=15.50, P<0.001). Using focal infection as a control, the area under the ROC curve for the operational characteristics of the subjects was 0.949 3 for disseminated NTM infection. The diagnostic cut-off value of nCD64 was 3.06, with the sensitivity and specificity of the disseminated NTM infection were 88.89% and 100.00%, respectively. Conclusions:In patients with NTM infection before effective treatment, the diagnostic cut-off value of nCD64 of 3.06 has high sensitivity and specificity, which is useful for the aided diagnosis of disseminated NTM infection.

Clinical application of LinaTech linear accelerator VenusX to hippocampal protection in whole-brain radiotherapy / 中华放射医学与防护杂志

Objective:To compare the dosimetric differences between the VenusX accelerator with an orthogonal dual-layer multi-leaf collimator (MLC) and the Varian′s CLINAC IX and EDGE accelerators with a single-layer MLC for hippocampus protection in the whole-brain radiotherapy (WBRT).Methods:Forty patients with multiple brain metastases admitted to the Radiotherapy Department of the Shanghai General Hospital from June 2021 to February 2023 were selected in this study. Three whole-brain treatment plans were designed based on the above three accelerators for each patient. Under the same prescription dose, radiation field, and plan constraints, the three plans were compared in terms of the dosimetric differences in target volumes, hippocampi, and adjacent organs at risk (OARs), as well as the execution efficiency.Results:For the planning target volume (PTV), there were statistically significant differences in approximate maximum dose ( D2) between the VenusX and IX plans ( t = 4.94, P < 0.05), in approximate minimum dose ( D98) between the VenusX and EDGE plans ( t = 5.98, P < 0.05), in the target conformity indices (CIs) between VenusX plan and EDGE plans, and between the VenusX and IX plans ( t = -6.84, -14.30; P < 0.05), and dose homogeneity indices (HIs) between the VenusX and IX plans ( t = 3.48, P < 0.05). For OARs, the maximum doses ( Dmax) and average doses ( Dmean) to bilateral hippocampi of the VenusX plan were lower than those of the EDGE and IX plans ( t = 8.59-17.11, P < 0.05); the maximum doses ( Dmax) to bilateral lenses, bilateral optic nerves, and optic chiasma of the VenusX plan were lower than those of the other two plans ( t = 2.10-20.80, P < 0.05); and the differences between the maximum doses ( Dmax) to the brain stem of the VenusX and EDGE plans were statistically significant ( t = 3.86, P < 0.05). In terms of plan execution efficiency, the number of machine jumps (MU) and the treatment time of the VenusX plan were higher than those of the EDGE and IX plans, with statistically significant differences ( t = -56.48, -56.90, P < 0.05). Conclusions:The doses to target volumes of the three treatment plans all meet the prescription requirements, and the VenusX plan outperforms the EDGE and IX plans in the protection of OARs. Despite the reduced execution efficiency, the VenusX plan shortens the actual treatment time by improving the dosage rate, thus meeting the clinical requirements.

Analysis of Animal Models of Ovarian Cancer Based on the Clinical Characteristics of Traditional Chinese and Western Medicine / 世界科学技术-中医药现代化

Ovarian cancer is a heterogeneous malignant tumor,one of the most common causes of cancer death in women worldwide,and there is currently no effective treatment available for its treatment,which seriously affects women's life and health.In order to deeply explore the pathogenesis of ovarian cancer and study the specific therapeutic drugs and methods,this paper summarizes,summarizes,assigns and evaluates the clinical characteristics of traditional Chinese and Western medicine for ovarian cancer,and screens out a more complete animal model.Through CNKI,Wanfang,Pubmed and other databases,the relevant content of ovarian cancer animal models was collected and sorted,and the model diagnostic indicators were assigned and the consistency was evaluated.In the evaluation of the model,it is found that the animal model of spontaneous ovarian cancer can simulate the pathogenesis process of human natural ovarian cancer,and the model has high modulus rate,high similarity,and high consistency with the clinical characteristics of traditional Chinese and Western medicine.The subcutaneous tumor graft type model and the blood stasis type model were in good clinical agreement with traditional Chinese medicine,a high degree of similarity,and a longer survival time.At present,animal models of ovarian cancer are mainly based on Western medicine models,and research on animal models consistent with traditional Chinese medicine syndromes is rare.Therefore,the improvement direction of ovarian cancer animal models and the necessity of improving the evaluation system are proposed,so as to make the animal models of ovarian cancer more clinical,and provide a theoretical basis for the determination of the efficacy of traditional Chinese medicine and the discussion of pharmacological effects of ovarian cancer,and provide a theoretical basis for the subsequent research on the pathogenesis and treatment measures of ovarian cancer,in order to improve the model of combining ovarian cancer symptoms in line with the clinical characteristics of traditional Chinese medicine and Western medicine.

Influence of 4D CT-based respiratory signal acquisition methods on delineation of moving tumor targets / 中国辐射卫生

@#<b>Objective</b> To compare the effects of different respiratory signal acquisition methods on the delineation of moving tumor targets. <b>Methods</b> A cube phantom containing a sphere was placed on a motion platform to simulate respiratory movement by setting motion period, frequency, and direction. Respiratory signal was acquired by real-time position management (RPM) method and GE method independently. Target delineation was conducted using the maximum intensity projection (MIP) sequence. The difference between the reconstructed volume and the theoretical moving volume was compared under the two respiratory signal acquisition methods for cube and sphere targets. <b>Results</b> Under the same respiratory signal acquisition method, the same respiratory amplitude, and different respiratory frequencies, reconstructed volume changes were relatively small. For the sphere target, the deviation between the reconstructed volume and the theoretical moving volume was −1.5% to 5.7% with the RPM method and −1.3% to −13.8% with the GE method (both <i>P</i> < 0.05). For the cube target, the deviation between the reconstructed volume and the theoretical moving volume was 0.2% to 0.9% with the RPM method and −2.6% to 0.9% with the GE method, with no statistical significance. <b>Conclusion</b> For small-volume sphere targets, the target volumes obtained from MIP images by the two respiratory signal acquisition methods are both smaller than the actual moving volume. For large-volume cube targets, there is no significant difference between the reconstructed and theoretical results with any respiratory signal acquisition method. The RPM method produces smaller deviation and better image quality when reconstructing small-volume targets.

Advances in the diagnosis of primary solid small bowel tumors by contrast-enhanced multislice spiral CT / 中国辐射卫生

@#Primary small bowel tumors have low incidence and contain predominantly solid components, and the lesions are similar and difficult to be detected and distinguished with multislice spiral CT (MSCT) plain scans. In this article we describe contrast-enhanced MSCT technique and imaging characteristics for solid small bowel tumors or small bowel tumors containing predominantly solid components, including the type and use of contrast agents. In contrast-enhanced MSCT, small bowel imaging with CT has the advantages of determining the true extent of intestinal wall lesions, the possible extent of wall penetration, the degree of mesenteric involvement, and distant metastases, as well as easiness to detect and identify the blood supply vessels of small bowel tumors and assessment of the corresponding complications. Contrast-enhanced MSCT has become the best noninvasive imaging technique for the diagnosis, evaluation, and staging of solid small bowel tumors or small bowel tumors containing predominantly solid components. CT texture analysis (CTTA) is a new research hotspot and can be useful for the correct diagnosis of primary small bowel tumors containing predominantly solid components.

Starting effect of highly active antiretroviral therapy on the incidence of anemia in HIV-infected patients / 上海预防医学

ObjectiveTo investigate the risk factors of anemia in HIV-infected patients receiving highly active antiretroviral therapy （HAART） in the Pudong New Area. MethodsA retrospective cohort study was conducted among HIV-infected patients who started HAART from 2005 to 2020 in Pudong New Area. Cox proportional hazards model was used to analyze the risk factors of anemia， moderate or severe anemia， and chronic anemia. The piecewise linear mixed-effect model was used to analyze the association between initial HAART classes and hemoglobin change in the follow-up. ResultsA total of 2 403 HIV-infected patients were included in the analysis. Among them， there were 357 cases of new onset anemia， 86 cases of chronic anemia and 102 cases of moderate or severe anemia， with the incidence density of 4.41/100 person years， 0.89/100 person years and 0.96/100 person years respectively. Multifactorial Cox regression analysis results showed that female， age >45 years， baseline CD4+ T lymphocyte count （CD4） <200 cells‧μL-1， opportunistic infections， glomerular filtration rate （eGFR） <60 mL‧min-1‧（1.73 m2）-1， and zidovudine （AZT） or protease inhibitor （PIs） based regimens were associated factors for the development of anemia. Female， age >45 years， CD4 <200 cells‧μL-1， opportunistic infections， and AZT-based regimens were associated with the development of chronic anemia. Mild anemia at baseline and AZT-based regimens were associated with the development of moderate or severe anemia. Linear mixed-effects model showed that the use of AZT （-7.87 g‧L-1， 95%CI： -9.42 to -6.32） or PIs （-3.43 g‧L-1， 95%CI： -5.57 to -1.30） was associated with lower Hb at follow-up. ConclusionInitial use of AZT and PIs is associated with progression to anemia and a lower follow-up hemoglobin level. Increased hemoglobin monitoring in users of AZT and PIs may be beneficial， especially during the first 6 months after initiation of HAART.

The Effects and Regulatory Mechanism of Flavonoids from Stems and Leaves of Scutellaria baicalensis Georgi in Promoting Neurogenesis and Improving Memory Impairment Mediated by the BDNF-ERK-CREB Signaling Pathway in Rats.

BACKGROUND: It is well known that Alzheimer's Disease (AD) is a neurodegenerative disease accompanied by memory impairment and major pathological changes of the extracellular Senile Plaque (SP) and intracellular Neurofibrillary Tangles (NFTs). However, many pieces of evidence indicate that neurogenesis disorders are also regarded as a new opinion in AD. OBJECTIVE: This study aims to investigate the effects and regulatory mechanism of flavonoids from the stems and leaves of Scutellaria baicalensis Georgi in promoting neurogenesis and improving memory impairment mediated by BDNF-ERK-CREB signaling pathway in rats. METHODS: Male Wistar rats were intracerebroventricularly injected with amyloid-beta protein 25-35 (Aß25-35) in combination with Aluminum Trichloride (Alcl3) and recombinant human transforming growth factor-ß1 (RHTGF-ß1) (composited Aß), to establish an AD model. Morris water maze was used to screen AD model rats and measure the learning and memory ability of model rats. The expression of Ki67 protein, which is involved in cell neurogenesis, in the hippocampal gyrus of rats was detected by the immunohistochemical method. The mRNA and protein expression levels of Grb2, SOS1, Ras, ERK, and BDNF, in the BDNF-ERK-CREB signaling pathway, in the hippocampus and cerebral cortex regions of rats were assayed by the Quantitative real-time PCR (qPCR) and Western blotting methods, respectively. RESULTS: Intracerebroventricular injection of composited Aß could induce rats' memory impairment, decrease the protein expression of Ki67 in the hippocampal gyrus, and increase the mRNA and protein expression levels of Grb2, SOS1, Ras, ERK, and BDNF in the hippocampus and cerebral cortex. However, SSF could significantly ameliorate rats' memory impairment induced by composited Aß, lower the Ki67 protein expression in the hippocampal gyrus, and regulate the abnormal mRNA and protein expression levels of Grb2, SOS1, Ras, ERK and BDNF in the hippocampus and cerebral cortex regions of rat brains. CONCLUSION: Composited Aß induced memory impairment, decreased neurogenesis and initiated the abnormal mRNA and protein expressions of Grb2, SOS1, Ras, ERK, and BDNF in the BDNF- ERK-CREB signaling pathway. The effects of SSF in promoting neurogenesis and improving memory impairment may be related to the regulation of the abnormal expressions of Grb2, SOS1, Ras, ERK, and BDNF molecules in the BDNF-ERK-CREB signaling pathway.

Erratum to: Verticillin A inhibits colon cancer cell migration and invasion by targeting c-Met / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The online version of the original article can be found at https://doi.org/10.1631/jzus.B2000190 Erratum to: J Zhejiang Univ-Sci B (Biomed & Biotechnol) 2020 21(10):779-795 https://doi.org/10.1631/jzus.B2000190.

Preliminary study on the role of glycoprotein A repetitions predominant in regulating tuberculosis pathogenesis through regulatory T cells / 中华传染病杂志

Objective:To investigate the role of glycoprotein A repetitions predominant (GARP) in the pathogenesis of tuberculosis through regulatory T cell (Treg), in order to provide new targets for the treatment of tuberculosis.Methods:Sixty patients with active pulmonary tuberculosis (ATB) admitted to Huashan Hospital, Fudan University and Wuxi Fifth People′s Hospital from January to September 2021 were included. And six individuals with latent tuberculosis infection (LTBI), and 16 healthy controls (HC) were recruited during the same period. Flow cytometry was performed to detect the proportion of Treg in the peripheral blood, and the expressions of GARP and transforming growth factor-β1 (TGF-β1) on Treg in different groups. Mann-Whitney U test was used for statistical analysis. Results:Among the 60 patients with ATB, 23 patients did not receive anti-tuberculosis drug therapy, 17 patients were treated for less than three months, ten patients were treated for three to less than six months, and ten patients were treated for greater than or equal to six months. The percentage of CD4 + CD25 + forkhead box protein 3 (Foxp3) + Treg in untreated ATB patients was 7.50%(5.67%, 9.00%), which was higher than that in HC (5.57%(5.03%, 6.09%)), and the difference was statistically significant ( U=95.00, P=0.010). The percentage of GARP expressing in CD4 + CD25 + Foxp3 + Treg in untreated ATB patients was 10.37%(7.79%, 12.90%), which was higher than that in LTBI (7.02%(5.15%, 8.81%)) and HC (5.33%(4.26%, 6.67%)), respectively, and the differences were both statistically significant ( U=31.00, P=0.040; U=36.00, P<0.001, respectively), while there was no significant difference between LTBI and HC ( U=25.00, P=0.095). The percentage of CD4 + CD25 + Foxp3 + Treg expressing TGF-β1 in untreated ATB patients was 7.13%(4.25%, 8.89%), which was higher than that in HC (3.59%(2.10%, 5.17%)), and the difference was statistically significant ( U=71.00, P=0.001). The expressions of GARP in CD4 + CD8 -CD25 + Foxp3 + Treg in patients with ATB treated for less than three months group, three to less than six months group and greater than or equal to six months group were 7.82%(3.94%, 13.17%), 6.92%(5.61%, 9.47%) and 7.26%(5.82%, 9.64%), respectively. The expressions of TGF-β1 in CD4 + CD8 -CD25 + Foxp3 + Treg in the above three treatment groups were 11.16%(7.91%, 15.23%), 8.66%(5.43%, 12.54%) and 7.82%(6.01%, 9.53%), respectively, and the expression of TGF-β1 in CD4 + CD8 -CD25 + Foxp3 + Treg in the patients with ATB treated for less than three months group was higher than that in the greater than or equal to six months group, the difference was statistically significant ( U=37.50, P=0.024). Conclusions:Foxp3/GARP/TGF-β1 pathway may be involved in the immune mechanism of Treg regulating the pathogenesis of tuberculosis, and GARP may be a new target for anti-tuberculosis therapy.

CD8 + T cell exhaustion statuses in patients with human immunodeficiency virus infection, Mycobacterium tuberculosis infection and co-infection / 中华传染病杂志

Objective:To analyze the statuses of CD8 + T cell exhaustion in patients with human immunodeficiency virus (HIV) infection, Mycobacterium tuberculosis (MTB) infection and co-infection. Methods:A total of 87 patients infected with HIV and/or MTB in Wuxi Fifth People′s Hospital and Taicang First People′s Hospital from August 2019 to January 2020 were enrolled, including 18 cases of HIV infection, 34 cases of active tuberculosis (ATB), 19 cases of latent tuberculosis infection (LTB), seven cases of HIV coinfected with ATB, and nine cases of HIV coinfected with LTB. Another 11 healthy controls were also included. The peripheral blood of all subjects was collected for cell surface staining and intracellular cytokine staining, and flow cytometry was used to detect the expressions of activation molecules including CD62 ligand, CD44 and CD127, the transcription factor like eomesodermin (EOMES), T cell factor 1 (TCF-1), T-box expressed in T cells (T-bet), B lymphocyte-induced maturation protein 1 (Blimp-1), inhibitory receptors including programmed death-1 (PD-1) and T-cell immunoglobulin and mucin domain 3 (Tim-3) on CD8 + T cells. Mann-Whitney U test was used for statistical analysis. Results:The mean fluorescence intensities (MFIs) of the activation molecules CD62 ligand and CD44 in the HIV group were lower than those in the healthy control group, while the inhibitory receptor Tim-3 was higher than that in the healthy control group. The differences were all statistically significant ( U=31.00, 1.00 and 0.00, respectively, all P<0.010). The MFIs of CD62 ligand and CD44 in HIV coinfected with LTB group were lower than those in LTB group, while PD-1 and Tim-3 were higher than those in LTB group. The differences were all statistically significant ( U=4.00, 26.00, 6.00 and 3.00, respectively, all P<0.010). The MFIs of CD62 ligand, CD44 and CD127 in HIV coinfected with ATB group were lower than those in ATB group, while PD-1 and Tim-3 were higher than those in ATB group. The differences were all statistically significant ( U=9.00, 40.00, 45.50, 28.00 and 7.00, respectively, all P<0.010). The proportion of terminal effector CD8 + T cells in the HIV group was higher than that in the healthy control group, while the proportion of central memory CD8 + T cells was lower than that in the healthy control group. The differences were both statistically significant ( U=15.00 and 33.00, respectively, both P<0.010). The proportion of terminal effector CD8 + T cells in the HIV coinfected with LTB group was higher than the LTB group, while the proportion of central memory CD8 + T cells was lower than that in the LTB group. The differences were both statistically significant ( U=7.00 and 20.00, respectively, both P<0.010). The proportion of terminal effector CD8 + T cells in the HIV coinfected with ATB group was higher than that in ATB group, while the proportion of central memory CD8 + T cells was lower than that in ATB group. The differences were statistically significant (both U=7.00, P<0.001). The expression level of PD-1 + Tim-3 + T cells in HIV group was higher than that in healthy control group, that in HIV coinfected with LTB group was higher than that in LTB group, and that in HIV coinfected with ATB group was higher than that in ATB group. The differences were all statistically significant ( U=21.00, 6.00 and 5.50, respectively, all P<0.001). The MFI of transcription factors EOMES and TCF-1 in HIV coinfected with LTB group were lower than those in HIV group, while the MFI of T-bet was higher than that in HIV group. The differences were all statistically significant ( U=3.00, 4.00 and 9.00, respectively, all P<0.001). The MFI of EOMES and TCF-1 in HIV coinfected with ATB group were lower than those in HIV group, while the MFI of T-bet and Blimp-1 were higher than those in the HIV group. The differences were all statistically significant ( U=11.00, 14.00, 7.00 and 22.00, respectively, all P<0.050). Conclusions:MTB co-infected with HIV patients present lower immune function and a higher degree of CD8 + T cell exhaustion. In addition, HIV patients co-infected with LTB and ATB have a higher degree of CD8 + T cell exhaustion than HIV infected patients.

Variability in reference for serum metabolomics profiles among healthy Han people in different regions of China / 中华内分泌代谢杂志

Objective:To establish the reference for serum metabolomics profiles among healthy Han adults in China, and explore the variation on metabolomics profiles by geographic regions, sex, and age.Methods:Cross-sectional data and serum samples were obtained from the China National Health Survey. A total of 1 039 male and 1 032 female healthy adults(≥30 years) were included in this study. Serum metabolomics analyses were conducted with ultra-performance liquid chromatography-mass spectrometry(UPLC-MS). Orthogonal partial least squares discriminant analysis(OPLS-DA) was performed to compare the differences of metabolomics among different region, sex, and age.Results:Significant differences on metabolomics profiles were identified among region, sex, and age. A total of 114 region-related metabolites were spotted, including 53 metabolites that involved in human metabolic pathways, mainly peptides(20 metabolites) and glycerophospholipid metabolism-related(14 metabolites). Fifty-nine metabolites were pinned down to be sex-related, among which cotinine was significant in all 7 provinces. Age-related metabolites were only found in Shaanxi and Hainan, with 22 metabolites were recognized.Conclusion:Serum metabolomics varies by geographic regions, sex, and age. When metabolomics is applied for diagnosis or biomarker screening in various studies, it shall take into consideration of setting tailored references.

Targeting macrophagic SHP2 for ameliorating osteoarthritis via TLR signaling

Osteoarthritis (OA), in which M1 macrophage polarization in the synovium exacerbates disease progression, is a major cause of cartilage degeneration and functional disabilities. Therapeutic strategies of OA designed to interfere with the polarization of macrophages have rarely been reported. Here, we report that SHP099, as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2 (SHP2), attenuated osteoarthritis progression by inhibiting M1 macrophage polarization. We demonstrated that M1 macrophage polarization was accompanied by the overexpression of SHP2 in the synovial tissues of OA patients and OA model mice. Compared to wild-type (WT) mice, myeloid lineage conditional Shp2 knockout (cKO) mice showed decreased M1 macrophage polarization and attenuated severity of synovitis, an elevated expression of cartilage phenotype protein collagen II (COL2), and a decreased expression of cartilage degradation markers collagen X (COL10) and matrix metalloproteinase 3 (MMP3) in OA cartilage. Further mechanistic analysis showed thatSHP099 inhibited lipopolysaccharide (LPS)-induced Toll-like receptor (TLR) signaling mediated by nuclear factor kappa B (NF-κB) and PI3K-AKT signaling. Moreover, intra-articular injection of SHP099 also significantly attenuated OA progression, including joint synovitis and cartilage damage. These results indicated that allosteric inhibition of SHP2 might be a promising therapeutic strategy for the treatment of OA.

Association between serum total bilirubin and fundus arteriosclerosis in different genders / 中华检验医学杂志

Objective:To assess the relationship between serum total bilirubin and fundus arteriosclerosis in different genders.Methods:The physical examination data of Huadong Sanatorium in 2018 were analyzed, and a total of 26 275 people were included in this retrospective cross-sectional study. The age of this study was 18-86 (47.7±11.1) years old. Among them, there were 15 244 males (58.02%) and 11 031 females (41.98%). Participants were divided into 4 groups according to total bilirubin quartile values: Q1<11.50 μmol/L, Q2∶11.50-13.93 μmol/L, Q3∶13.94-17.14 μmol/L and Q4>17.14 μmol/L. The relationship between total serum bilirubin and fundus arteriosclerosis is determined using univariate and multivariate logistic regression analysis methods. The restricted cubic spline method was used to detect the dose-response relationship between total bilirubin and fundus arteriosclerosis. Results:In males, univariate analysis showed that high level of total bilirubin was a protective factor for fundus arteriosclerosis ( OR=0.87, 95% CI 0.78-0.97, P=0.012). After adjusting for other confounding factors, multivariate analysis showed that high level of total bilirubin remained as an independent protective factor for fundus arteriosclerosis ( OR=0.86, 95% CI 0.74-0.99, P=0.047). There was a linear dose-response relationship between total bilirubin level and fundus arteriosclerosis ( P=0.012). In females, univariate analysis showed that there were no statistically significant association between high level of total bilirubin and fundus arteriosclerosis ( OR=0.96, 95% CI 0.80-1.17, P=0.709). After adjusting for other confounding factors, multivariate analysis showed no statistically significant association between high level of total bilirubin and fundus arteriosclerosis ( OR=0.98, 95% CI 0.76-1.27, P=0.888). No linear dose-response relationship between total bilirubin level and fundus arteriosclerosis was found in females ( P=0.253). Conclusion:There are gender differences in the relationship between total bilirubin and fundus arteriosclerosis in this cohort. Elevated levels of total bilirubin are associated with fundus arteriosclerosis in males but not in females.

Dual role of interleukin-33 in tumors / 中南大学学报(医学版)

Interleukin-33 (IL-33) is a new member of the IL-1 cytokine family which plays roles in the nucleus as a nuclear factor and is released by damaged or necrotic cells to act as a cytokine. It can be released via damaged or necrotic cells and functions as a cytokine. The released IL-33 activates the downstream NF-κB and MAPKs signaling pathways through the isomers of the specific receptor ST2 and the interleukin-1 receptor accessory protein (IL-1RAcP), resulting in danger signals and the activated multiple immune responses. IL-33 is abnormally expressed in various tumors and involves in tumorigenesis, development, and metastasis. Moreover, IL-33 can play both pro-tumor and anti-tumor roles in the same type of tumor.