ObjectiveTo explore the effects of modified Danggui Beimu Kushen pills on tumor growth and T-cell subsets in H22 hepatocellular carcinoma-bearing mice and to provide an experimental basis for the treatment of hepatocellular carcinoma with modified Danggui Beimu Kushen pills combined with immune checkpoint antibodies. MethodA H22 hepatocellular carcinoma-bearing mouse model was established. The modeled mice were randomized into model， cisplatin， low- （4 g·kg^-1·d^-1）， medium- （8 g·kg^-1·d^-1）， and high-dose （16 g·kg^-1·d^-1） modified Danggui Beimu Kushen pills groups. After continuous administration for 14 days， the mice were sacrificed on day 15. The tumor volume was measured on days 0， 4， 8， 12， 15 of drug administration. Tumors were weighed and thymus index and spleen index were calculated. Spleen lymphocytes were co-cultured with H22 hepatoma cells， and the tumor cell-killing rate was detected by the cell counting kit-8 （CCK-8）. Real-time polymerase chain reaction was carried to determine the mRNA levels of programmed cell death protein-1 （PD-1） and lymphocyte activation gene-3 （LAG-3） in spleen and tumor tissues. The number of CD4⁺ and CD8⁺ T cells and the expression of PD-1 and LAG-3 were detected by immunohistochemistry （IHC）. ResultOn day 8 of drug administration， tumor volumes in all treatment groups decreased compared with that in the model group. On day 15， both tumor volume and tumor weight were significantly lower in the treatment groups than in the model group （P<0.01）， with the cisplatin group showing the most pronounced reduction. Compared with the model and cisplatin groups， medium- and high-dose modified Danggui Beimu Kushen pills increased the thymus index （P<0.01）. Compared with the model group， all treatment groups showed increased spleen index （P<0.05， P<0.01）， with the cisplatin group showing the most significant increase. Compared with the model and cisplatin groups， all the groups of modified Danggui Beimu Kushen pills demonstrated increased number of CD4⁺ and CD8⁺ T cells and tumor cell-killing rate in the spleen and tumor tissues （P<0.01） and down-regulated mRNA and protein levels of LAG-3 （P<0.05， P<0.01）. The high-dose group of modified Danggui Beimu Kushen pills had lower mRNA level of PD-1 in the tumor tissue than the model and cisplatin groups （P<0.01）. ConclusionModified Danggui Beimu Kushen pills may promote the proliferation and tumor microenvironment infiltration of CD4⁺ and CD8⁺ T cells in H22 tumor-bearing mice by down-regulating LAG-3 expression， thereby improving T-cell immune activity and inhibiting tumor growth. This study provides an experimental basis for the combination of modified Danggui Beimu Kushen pills and immune checkpoint antibodies in the treatment of hepatocellular carcinoma.

Objective To investigate the clinical characteristics and risk factors of thyroid dysfunction(TD)in malignant tumor patients treated with immune checkpoint inhibitors(ICIs).Methods A total of 157 cancer patients who were hospitalized and received ICIs treatment in the First People's Hospital of Yunnan Province from January 2019 to June 2022 were collected and divided into the normal thyroid function group and abnormal thyroid function group based on whether TD had occurred.Fifty-eight patients with the normal thyroid function and 58 patients with the abnormal thyroid function were selected,and 58 healthy adults who underwent the physical examination in our hospital were randomly selected as the control group.The baseline data on the gender,age,tumor and ICIs type,history of surgery before medication,history of radiotherapy and chemotherapy,and the related indicators of liver and kidney function,blood lipids,thyroid hormone levels and so on were collected.The relevant indicators of the three groups were statistically analyzed,and the normal thyroid function group and abnormal thyroid function group were compared to evaluate the clinical characteristics and related risk factors of TD caused by ICIs.Results 1.Among 157 patients treated with ICIs,58 cases(36.9%)had thyroid dysfunction,including 39 cases of hypothyroidism(including subclinical hypothyroidism),9 cases of hyperthyroidism(including subclinical hyperthyroidism),and 10 cases of pure related antibody abnormality.2.The analysis of the data of the normal thyroid function group,the abnormal thyroid function group and the control group showed that the age,thyroid stimulating hormone(TSH),and thyroid function of the three groups were significantly different.TSH)baseline level,free triiodothyronine(FT3)baseline level and aspartate transaminase(AST)baseline level were statistically different(P<0.05).There were significant differences in TSH baseline and radiotherapy history between the normal thyroid function group and the abnormal thyroid function group(P<0.05);Multivariate analysis showed that the radiotherapy history(OR=7.291,95% CI= 1.579-33.663,P<.05),baseline TSH level(OR=3.917,95% CI= 1.697-9.038,P<0.05)were the independent risk factors for thyroid dysfunction in cancer patients after ICIs treatment.Conclusion Hypothyroidism is the most common type of TD caused by ICIs in cancer patients.The baseline TSH level and the history of radiotherapy are the independent risk factors for thyroid dysfunction.

Objective To evaluate the effects of high-fat diet on the pharmacokinetics of metronidazole in Chinese healthy adult subjects.Methods This program is designed according to a single-center,randomized,open,single-dose trial.Forty-seven healthy subjects were assigned to receive single dose of metronidazole tablets 200 mg in either fasting and high-fat diet state,and blood samples were taken at different time points,respectively.The concentrations of metronidazole in plasma were determined by high performance liquid chromatography-mass spectromentry.Results The main pharmacokinetic parameters of metronidazole in fasting state and high-fat diet state were as follows:Cmax were(4 799.13±1 195.32)and(4 044.17±773.98)ng·mL-1;tmax were 1.00 and 2.25 h;t1/2 were(9.11±1.73)and(9.37±1.79)h;AUC0_t were(5.59±1.19)x 104 and(5.51±1.18)x 104 ng·mL-1·h;AUC0_∞ were(5.79±1.33)x 104 and(5.74±1.32)× 104 ng·mL-1·h.Compared to the fasting state,the tmaxof the drug taken after a high fat diet was delayed by 1.25 h(P＜0.01),Cmax,AUC0_t,AUC0-∞ were less or decreased in different degrees,but the effects were small(all P＞0.05).Conclusion High-fat diet has little effects on the pharmacokinetic parameters of metronidazole,which does not significantly change the degree of drug absorption,but can significantly delay the time to peak.

Objective The purpose of this study was to investigate the bacterial communities of biting midges and ticks collected from three sites in the Poyang Lake area,namely,Qunlu Practice Base,Peach Blossom Garden,and Huangtong Animal Husbandry,and whether vectors carry any bacterial pathogens that may cause diseases to humans,to provide scientific basis for prospective pathogen discovery and disease prevention and control. Methods Using a metataxonomics approach in concert with full-length 16S rRNA gene sequencing and operational phylogenetic unit(OPU)analysis,we characterized the species-level microbial community structure of two important vector species,biting midges and ticks,including 33 arthropod samples comprising 3,885 individuals,collected around Poyang Lake. Results A total of 662 OPUs were classified in biting midges,including 195 known species and 373 potentially new species,and 618 OPUs were classified in ticks,including 217 known species and 326 potentially new species.Surprisingly,OPUs with potentially pathogenicity were detected in both arthropod vectors,with 66 known species of biting midges reported to carry potential pathogens,including Asaia lannensis and Rickettsia bellii,compared to 50 in ticks,such as Acinetobacter lwoffii and Staphylococcus sciuri.We found that Proteobacteria was the most dominant group in both midges and ticks.Furthermore,the outcomes demonstrated that the microbiota of midges and ticks tend to be governed by a few highly abundant bacteria.Pantoea sp7 was predominant in biting midges,while Coxiella sp1 was enriched in ticks.Meanwhile,Coxiella spp.,which may be essential for the survival of Haemaphysalis longicornis Neumann,were detected in all tick samples.The identification of dominant species and pathogens of biting midges and ticks in this study serves to broaden our knowledge associated to microbes of arthropod vectors. Conclusion Biting midges and ticks carry large numbers of known and potentially novel bacteria,and carry a wide range of potentially pathogenic bacteria,which may pose a risk of infection to humans and animals.The microbial communities of midges and ticks tend to be dominated by a few highly abundant bacteria.

Objective:To explore the incidence and mortality of digestive system cancers, and the trend of the disease burden attributed to different risk factors in population in China.Methods:Data were obtained from the GLOBOCAN 2020 and the Global Burden of Disease Study in 2019 databases and only the data from the Chinese population were included. Using Excel 2019 and R 4.2.1 software, indicators including age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), age-standardized disability-adjusted life year (DALY) rate and its rate of change were used to illustrate the disease burden of digestive system cancers attributed to different factors and their trends.Results:In 2020, the ASIR of digestive system cancers in China was 83.00/100 000, and the ASMR was 63.80/100 000. The numbers of digestive system cancer cases and deaths increased with age, and more cases and deaths occurred in men than in women in all age groups. The age-standardized DALY rate of esophageal cancer, gastric cancer and liver cancers showed decreasing trends in China from 1990 to 2019 (rate of change: -45.26%, -46.87%, and -65.63%, respectively), whereas the age-standardized DALY rate of pancreatic cancer, colorectal cancer and gallbladder and biliary tract cancer showed increasing trends (rate of change: 67.61%, 30.52%, and 7.21%, respectively). The trend of the mortality rate was consistent with the DALY rate. Compared with the age-standardized DALY rate attributed to behavioral factors, the annual proportion of the age-standardized DALY rate attributed to metabolic factors to the total age-standardized DALY rate of esophageal cancer, liver cancer, pancreatic cancer, and colorectal cancer increased from 1990 to 2019. There was no significant change in the rank of age-standardized DALY rate of gastric cancer, liver cancer, pancreatic cancer, and gallbladder and biliary tract cancer attributed to different risk factors in China from 1990 to 2019, but the rank of certain attributed risk factors for the age-standardized DALY rate of esophageal cancer and colorectal cancer moved ahead (esophageal cancer: high BMI; colorectal cancer: low milk intake, and low whole-grain intake).Conclusions:The incidence and mortality of digestive system cancers was serious in China in 2020, and the annual proportion of the disease burden of digestive system cancers attributed to metabolic factors increased from 1990 to 2019. The rank of attributed risk factors for several digestive system cancers changed significantly.

Objective To investigate the hemodynamic effects of enhanced external counterpulsation(EECP)on cerebral arteries with different stenoses.Methods Zero-dimensional/three-dimensional multiscale hemodynamic models of cerebral arteries with different stenoses were constructed.Numerical simulations of the EECP hemodynamics were performed under different counterpulsation modes to quantify several hemodynamic indicators of the cerebral arteries.Among them,the mean time-averaged wall shear stress(TAWSS)downstream of the stenosis was in the range of 4-7 Pa,a low percentage of TAWSS risk area,and high narrow branch flow were considered to inhibit the development of atherosclerosis and create a good hemodynamic environment.Results For cerebral arteries with 50%,60%,70%,and 80%stenosis,the hemodynamic environment was optimal in counterpulsation mode when the moment of cuff deflation was 0.5,0.6,0.7,and 0.7 s within the cardiac cycle.Conclusions For 50%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.5 s should be selected.For 60%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.6 s should be selected.For 70%or 80%stenotic cerebral arteries,the counterpulsation mode with a deflation moment of 0.7 s should be selected.As stenosis of the cerebral arteries increases,the pressure duration should be prolonged.This study provides a theoretical reference for the EECP treatment strategy for patients with ischemic stroke with different stenoses.

Objective To design a pressure reading system for splinting distal radius fractures to enable real-time monitoring of splint fixation pressure.Methods A pressure reading system for splinting distal radius fractures was developed with the components of a main contrl unit,a pressure and temperature acquisition unit and a power management unit.The main control unit had a STC15 series SCM as the main control chip,and the pressure and temperature acquisition unit was realized with a FSR400 thin film pressure sensor and a DS18B20 digital temperature measurement chip.The software of the system was developed with C language.The system developed was used to test the magnitude and distribution of the pressure on the splints by applying loads on the fixation straps at 90°,60° and 30° directions to the willow splint and 3D printing splint,respectively,with the total mass of the loads increased from 600 g to 1 200 g and each test repeated by 6 times.Results The system developed was capable of collecting the pressure values at real time and showed them on the display screen.The maximum pressure always occurred at the the connection between the fixation straps and the edge of the splints and the middle parts of the splints were subject to relatively low pressure in case of different loads,when the fixation straps were 90°,60° and 30° to the willow splint and 3D printing splint respectively.The maximum pressure on the willow splint was(239.17±4.49)g when the fixation strap was 90° to the splint and loaded with 1 200 g;the minimum pressure on the willow splint was(89.83±17.38)g when the fixation strap was 60° to the splint and loaded with 600 g.The maximum pressure on the 3D printing splint was(177.67±21.77)g when the fixation strap was 90° to the splint and loaded with 1 100 g;the minimum pressure was(66.50±3.02)g for the 3D printing splint when the fixation strap was 30° to the splint and loaded with 600 g.Conclusion The ssystem developed can read pressure values of the splint under different loads and angles,and the 3D printing splint behaves better than the willow splint in the evenness of pressure distribution.Theoretical references are provided for quantitative clinical treatment with splint fixation.[Chinese Medical Equipment Journal,2024,45(8):44-50]

Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective To investigate the correlation of the distribution patterns of stem-branch circuit qi at birth and at conception of children with the predisposition to pediatric epilepsy.Methods A case-control study was conducted in 1 113 children with epilepsy(case group)and 2 346 non-epilepsy children(control group)who sought medical consultation in the Pediatric Outpatient Department of the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine at the same period.Chi-square test and binary logistic regression were used to analyze the circuit qi endowment of children between the two groups at conception and at birth.Results(1)The analysis of the circuit qi distribution at birth showed that there was a statistically significant difference in the distribution of dominant qi between the case group and the control group at birth(P＜0.05).The initial qi(the first circuit qi in the theory of six climatic factors)accounted for the most(215 cases,19.30％)and the sixth qi accounted for the least(145 cases,13.0％).There was no significant difference in the distribution of suiyun(yearly evolutive phase),dominant circuit(regular yearly evolutive phase),guest circuit(alterable yearly evolutive phase),guest qi(alterable yearly circuit qi)and sitian(the first half of the alterable yearly circuit qi)at birth(P＞0.05).The results of binary logistic regression analysis showed that the risk of predisposition to epilepsy in the children was increased when the children were born in the Chinese lunar year of Ren(OR=1.444,95％CI:1.055-1.975),at the initial qi(OR=1.363,95％CI:1.057-1.757)and at the fifth qi(OR=1.378,95％CI:1.065-1.783).(2)The analysis on the distribution of circuit qi at conception showed that there was no significant difference in the distribution of suiyun and sitian-zaiquan semiannual circuit qi between the case group and the control group(P＞0.05).Binary logistic regression analysis showed that the risk of predisposition to epilepsy in the children was increased when pregnancy in the suiyun of taimu-taimu(OR=1.866,95％CI:1.142-3.048)and at sitian semiannual circuit qi of shaoyang minister fire and zaiquan semiannual circuit qi of jueyin wind-wood(OR=1.672,95％CI:1.004-2.786).Conclusion There is a certain correlation between circuit qi endowment and the prevalence of pediatric epilepsy.

Objective To campare biomechanical effects of different postural compression techniques on three-dimensional model of lumbar disc herniation(LDH)by finite element analysis.Methods Lumbar CT image of a 48-year-old female patient with LDH(heighted 163 cm,weighted 53 kg)was collected.Mimics 20.0,Geomagic Studio,Solidwords and other software were used to establish three-dimensional finite element model of LDH on L4,5 segments.Compression techniques under horizon-tal position,30° forward bending and 10° backward extension were simulated respectively.After applying the pressure,the ef-fects of compression techniques under different positions on stress,strain and displacement of various tissues of intervertebral disc and nerve root were observed.Results L4,5 segment finite element model was successfully established,and the model was validated.When compression manipulation was performed on the horizontal position,30° flexion and 10° extension,the annular stress were 0.732,5.929,1.286 MPa,the nucleus pulposus stress were 0.190,1.527,0.295 MPa,and the annular strain were 0.097,0.922 and 0.424,the strain sizes of nucleus pulposus were 0.153,1.222 and 0.282,respectively.The overall displace-ment distance of intervertebral disc on Y direction were-3.707,-18.990,-4.171 mm,and displacement distance of nerve root on Y direction were+7.836,+5.341,+3.859 mm,respectively.The relative displacement distances of nerve root and interverte-bral disc on Y direction were 11.543,24.331 and 8.030 mm,respectively.Conclusion Compression manipulation could make herniated intervertebral disc produce contraction and retraction trend,by increasing the distance between herniated interverte-bral disc and nerve root,to reduce symptoms of nerve compression,to achieve purpose of treatment for patients with LDH,in which the compression manipulation is more effective when the forward flexion is 30°.