Objective To observe the clinical efficacy of thumb-tack needling for subcutaeous embedding combined with joint mobilization in the treatment of post-stroke shoulder-hand syndrome.Methods A total of 80 patients with post-stroke shoulder-hand syndrome were randomly divided into a treatment group and a control group,with 40 patients in each group.Both groups were given arthrocentesis,the control group was given ordinary acupuncture on the basis of arthrocentesis,and the treatment group was combined with thumb-tack needling for subcutaeous embedding.One course of treatment was 4 weeks and a total of 4 weeks of treatment was given.After 1 month of treatment,the clinical efficacy of the two groups was evaluated.The changes of Visual Analogue Scale(VAS)of pain scores and simplified Fugl-Meyer Assessment(FMA)scores,as well as the pain-free passive forward flexion and abduction of the shoulder joint of the affected limb were observed before and after treatment.The Simple Quality of Life Scale(SF-36)scores of the patients in the two groups were compared after treatment.The safety and the occurrence of adverse reactions in the two groups were also evaluated.Results(1)The total effective rate was 95.00%(38/40)in the treatment group and 80.00%(32/40)in the control group.The efficacy of the treatment group was superior to that of the control group,and the difference was statistically significant(P＜0.05).(2)After treatment,the VAS scores and upper extremity FMA scores of the patients in the two groups were significantly improved(P＜0.05),and the treatment group was significantly superior to the control group in improving the VAS scores and upper extremity FMA scores,and the differences were statistically significant(P＜0.05).(3)After treatment,the joint mobility of patients in the two groups were significantly improved(P＜0.05),and the improvement of shoulder joint movement in the treatment group was superior to that in the control group,and the difference was statistically significant(P＜0.05).(4)After treatment,the SF-36 Quality of Life Scale scores of the treatment group were significantly superior to those of the control group in terms of physical function,psychological function,emotional health,and social function levels,and the difference was statistically significant(P＜0.05).(5)There was no significant difference in the incidence of adverse reactions between the treatment group and the control group(P＞0.05).Conclusion Thumb-tack needling for subcutaeous embedding combined with joint mobilization exert certain effect in the treatment of post-stroke shoulder-hand syndrome.It can significantly improve the pain symptoms of patients,thus improving their quality of life,and the clinical effect is remarkable.

In cardiovascular disorders, neurological diseases, and chronic metabolic diseases, the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is essential for maintaining cell homeostasis. According to studies, boosting Nrf2 expression can be used to cure or prevent chronic diseases that are characterized by oxidative stress, inflammation, and mitochondrial dysfunction. Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease characterized by hepatic steatosis brought on by a number of causes other than alcohol. In recent years, its incidence has gradually risen across the globe. According to relevant studies, NAFLD and the Nrf2 signaling pathway are tightly connected. Inhibiting lipid production and metabolism-related enzymes, repairing impaired liver metabolism, and lowering hepatic lipid storage are all possible with Nrf2 activation. Exercise is a powerful tool for treating and preventing NAFLD. However, exercise type, exercise intensity, environment, and exhaustion all have an impact on the Nrf2 signaling pathway. By activating Nrf2, exercise can lessen liver inflammation, oxidative stress, endoplasmic reticulum stress, and insulin resistance, and ameliorate liver damage to improve NAFLD. The activation of Nrf2 signaling pathway, its associated mechanism of controlling antioxidation, and the impact of exercise on the Nrf2 signaling pathway are all explained in this work. Based on the pathogenesis of NAFLD, this article examines the connection between exercise, Nrf2, and NAFLD, and the current state of knowledge regarding Nrf2’s role in the amelioration of NAFLD through exercise. It offers a theoretical frame of reference for future research into how Nrf2 might be used to improve NAFLD.

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 To evaluate the bioequivalence of metronidazole tablet and reference formulation in Chinese healthy subjects.Methods A single-dose,two-cycle,randomized,open,self-crossover trial was designed with 48 healthy subjects randomly assigned to fasting or postprandial group.For each group,a single oral dose of metronidazole tablet(200 mg)or a reference preparation(200 mg)per cycle were enrolled.The concentration of metronidazole in plasma was measured by high performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS).The non-compartmental model was applied to calculate the pharmacokinetic parameters for bioequivalence analysis via SAS 9.3 software.Results The main pharmacokinetic parameters of test and reference metronidazole tablets in the fasting group were as follows,the Cmax were(4 855.00±1 383.97)and(4 799.13±1 195.32)ng·h·mL-1;the AUC0-t were(54 834.68±12 697.88)and(55 931.35±11 935.28)ng·h·mL-1;the AUC0-∞ were(56 778.09±13 937.76)and(57 922.83±13 260.54)ng·h·mL-1;the Tmax were respectively 1.17 and 1.00 h;t1/2 were(8.99±1.76)and(9.11±1.73)h,respectively.The ratio of the geometric mean and its 90％confidence intervals(CI)of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.As for postprandial conditions,the main pharmacokinetic parameters of test and reference metronidazole tablets were as follows,the Cmax were(4 057.08±655.08)and(4 044.17±773.98)ng·h·mL-1;the AUC0-t were(55 956.42±12 228.12)and(55 121.04±11 784.55)ng·h·mL-1;the AUC0-∞ were(58 212.83±13 820.00)and(57 350.38±13 229.46)ng·h·mL-1;the Tmax were 2.50 and 2.25 h;the t1/2 were(9.37±1.68)and(9.37±1.79)h,respectively.The ratio of the geometric mean and 90％CI of Cmax,AUC0-t and AUC0-∞ were all within the equivalent interval of 80.00％-125.00％.Conclusion The two preparations were bioequivalent to Chinese healthy adult volunteers under both fasting and fed conditions.

Objective To investigate the effect of dapagliflozin-mediated miR-98-5p on high glucose-induced damage in human renal tubular epithelial cells.Methods Blood samples from patients with diabetic nephropathy(DN)and healthy individuals were collected.The expression of serum miR-98-5p was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR),and kidney injury-related indicators were measured using a biochemical immunoassay analyzer.HK-2 cells were cultured in vitro and randomly divided into control group(5 mmol·L-1 glucose),HG group(30 mmol·L-1 glucose),experimental-L group(30 mmol·L-1 glucose+20 μmol·L-1 dapagliflozin),experimental-H group(30 mmol·L-1 glucose+40 μmol·L-1 dapagliflozin),anti-miR-NC group(transfected with anti-miR-NC+30 mmol·L-1 glucose+40 μmol·L-1 dapagliflozin),and anti-miR-98-5p group(transfected with anti-miR-98-5p+30 mmol·L-1 glucose+40 μmol·L-1 dapagliflozin).Cell viability was evaluated using the cell counting kit 8(CCK-8)assay 24 hours after drug treatment;miR-98-5p expression in cells was detected by RT-qPCR;cell apoptosis rate was measured by flow cytometry,apoptosis-related protein expression was detected by Western blot;and inflammatory cytokine expression was measured by enzyme-linked immunosorbent assay.Results The expression levels of miR-98-5p in the serum of DN patients and healthy individuals were 1.00±0.25 and 0.39±0.05,respectively,showing a significant difference between the two groups(P＜0.05).The expression levels of miR-98-5p in the control group,HG group,experimental-H group,anti-miR-NC group,and anti-miR-98-5p group were 1.00±0.09,0.31±0.04,0.72±0.06,0.75±0.07 and 0.22±0.03;the cell survival rates were(100.00±3.36)％,(51.63±5.89)％,(79.46±9.90)％,(82.88±5.71)％and(59.69±7.43)％;apoptosis rates were(3.52±0.20)％,(35.80±3.67)％,(16.43±1.57)％,(15.71±1.42)％and(29.37±2.18)％;tumor necrosis factor-α(TNF-α)levels were(22.46±1.67),(68.37±6.05),(34.45±2.47),(35.11±2.84)and(60.46±3.56)pg·mL-1,respectively.The differences among these indicators were all statistically significant when comparing the HG group to the control group,the experimental-H group to the HG group,and the anti-miR-98-5p group to the anti-miR-NC group(all P＜0.05).Conclusion Dapagliflozin can alleviate high glucose-induced HK-2 cell damage by upregulating the expression of miR-98-5p,inhibiting inflammation,and reducing cell apoptosis.

Objective To evaluate the bioequivalence and safety of ezetimibe tablets in healthy Chinese subjects.Methods The study was designed as a single-center,randomized,open-label,two-period,two-way crossover,single-dose trail.Subjects who met the enrollment criteria were randomized into fasting administration group and postprandial administration group and received a single oral dose of 10 mg of the subject presparation of ezetimibe tablets or the reference presparation per cycle.The blood concentrations of ezetimibe and ezetimibe-glucuronide conjugate were measured by high-performance liquid chromatography-tandem mass spectrometry(HPLC-MS/MS),and the bioequivalence of the 2 preparations was evaluated using the WinNonlin 7.0 software.Pharmacokinetic parameters were calculated to evaluate the bioequivalence of the 2 preparations.The occurrence of all adverse events was also recorded to evaluate the safety.Results The main pharmacokinetic parameters of total ezetimibe in the plasma of the test and the reference after a single fasted administration:Cmax were(118.79±35.30)and(180.79±51.78)nmol·mL-1;tmax were 1.40 and 1.04 h;t1/2 were(15.33±5.57)and(17.38±7.24)h;AUC0-t were(1 523.90±371.21)and(1 690.99±553.40)nmol·mL-1·h;AUC0-∞ were(1 608.70±441.28),(1 807.15±630.00)nmol·mL-1·h.The main pharmacokinetic parameters of total ezetimibe in plasma of test and reference after a single meal:Cmax were(269.18±82.94)and(273.93±87.78)nmol·mL-1;Tmax were 1.15 and 1.08 h;t1/2 were(22.53±16.33)and(16.02±5.84)h;AUC0_twere(1 463.37±366.03),(1 263.96±271.01)nmol·mL-1·h;AUC0-∞ were(1 639.01±466.53),(1 349.97±281.39)nmol·mL-1·h.The main pharmacokinetic parameters Cmax,AUC0-tand AUC0-∞ of the two preparations were analyzed by variance analysis after logarithmic transformation.In the fasting administration group,the 90％CI of the log-transformed geometric mean ratios were within the bioequivalent range for the remaining parameters in the fasting dosing group,except for the Cmax of ezetimibe and total ezetimibe,which were below the lower bioequivalent range.The Cmax of ezetimibe,ezetimibe-glucuronide,and total ezetimibe in the postprandial dosing group was within the equivalence range,and the 90％CI of the remaining parameters were not within the equivalence range for bioequivalence.Conclusion This test can not determine whether the test preparation and the reference preparation of ezetimibe tablets have bioequivalence,and further clinical trials are needed to verify it.

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 This study aimed to comprehensively analyze and compare the clinicopathological features and prognosis of Chinese patients with human epidermal growth factor receptor 2(HER2)-low early breast cancer(BC)and HER2-IHC0 BC. Methods Patients diagnosed with HER2-negative BC(N=999)at our institution between January 2011 and December 2015 formed our study population.Clinicopathological characteristics,association between estrogen receptor(ER)expression and HER2-low,and evolution of HER2 immunohistochemical(IHC)score were assessed.Kaplan-Meier method and log-rank test were used to compare the long-term survival outcomes(5-year follow-up)between the HER2-IHC0 and HER2-low groups. Results HER2-low BC group tended to demonstrate high expression of ER and more progesterone receptor(PgR)positivity than HER2-IHC0 BC group(P<0.001).The rate of HER2-low status increased with increasing ER expression levels(Mantel-Haenszel χ2 test,P<0.001,Pearson's R=0.159,P<0.001).Survival analysis revealed a significantly longer overall survival(OS)in HER2-low BC group than in HER2-IHC0 group(P=0.007)in the whole cohort and the hormone receptor(HR)-negative group.There were no significant differences between the two groups in terms of disease-free survival(DFS).The discordance rate of HER2 IHC scores between primary and metastatic sites was 36.84%. Conclusion HER2-low BC may not be regarded as a unique BC group in this population-based study due to similar clinicopathological features and prognostic roles.

Objective:To meet people's increasing needs for essential public health services in different regions of China,and to adjust the needs of essential public health services according to local conditions,including demographic characteristics,disease burden,economic development level,etc.Methods:The selection and evaluation framework of extended essential public health services was developed through a literature review,based on the Multi-criteria decision analysis theory,and the operational selection process and subsidy standard of extended essential public health services were explored through conducting case simulation for public health intervention programs.Results:The study initially constructed a selection and evaluation framework containing three dimensions and eight indicators,and formed the process and steps for selecting and adjusting the provincial essential public health services programs.Conclusions:The study provides an evidence-based reference for the governments'decision-making on adjusting the connotation of the local essential public health services system.

Objective:To explore the predictive value of admission serum homocysteine levels and quantitative electroencephalogram (qEEG) indicators for adverse outcomes in patients with cerebral hemorrhage.Methods:A retrospective study was conducted on 89 patients, who were collected as the study objects with hemorrhagic stroke treated in the neurology intensive care unit at Kailuan General Hospital from January 2017 to December 2022. Patients were categorized into two groups based on modified Rankin Scale (mRS) scores at discharge: a good prognosis group (mRS≤2) and a poor prognosis group (mRS 3-6). Clinical data and qEEG monitoring of various brain regions were collected. The impact factors of hemorrhagic prognosis were analyzed using multifactorial logistic regression. ROC curve analysis was performed to assess the predictive value of qEEG and admission homocysteine levels for adverse outcomes in hemorrhagic stroke patients.Results:(1) The age of the poor prognosis group was higher than that of the good prognosis group((66.51+13.64) to (60.53+11.69), t=2.15, P=0.034) and admission serum homocysteine levels were significantly higher in the poor prognosis group than in the good prognosis group (17.28(15.52,24.72)mmol/L to 14.50(10.28,16.00)mmol/L, Z=4.14, P<0.001). (2) In the poor prognosis group, power values of δ brain waves in leads Fp1-2, F4, C4, P4, F8, and T4 were higher than those in the good prognosis group (87.99(41.57,196.69) to 50.67(26.64,54.75), Z=2.76, P=0.006); (79.17(40.71,200.00) to 45.06(20.22,61.00), Z=2.10, P=0.036); (72.64(34.97,219.78) to 34.42(19.81,63.4), Z=2.03, P=0.043); (65.06(33.36,177.45) to 28.12(15.88,63.36), Z=2.08, P=0.038); (52.92(25.64,187.91) to 23.61(11.67,43.26), Z=2.21, P=0.027); (66.67(32.56,180.76) to 36.31(17.2,53.78), Z=2.46, P=0.014); (57.30(25.24,127.04) to 29.57(11.91,41.89), Z=2.26, P=0.024). Power values of θ brain waves in leads Fp1-2, F3, F4, C3, C4, P3-4, O1, F7-8, and T3-4 were higher in the poor prognosis group(77.45(47.63,138.72)比35.88(20.92,44.81), Z=3.50, P<0.001); (77.05(35.16,120.22) to 38.74(19.86,58.09), Z=2.27, P=0.023); (85.24(52.53,147.90) to 35.42(14.7,52.59), Z=2.61, P=0.009); (75.81(37.90,124.97) to 36.85(17.92,55.43), Z=2.30, P=0.021); (72.00(43.92,123.54) to 28.37(14.02,51.9), Z=2.22, P=0.027); (67.08(32.01,104.05) to 31.32(17.98,45.28), Z=2.10, P=0.035); (55.33(32.29,94.30) to 25.64(11.87,34.01), Z=2.24, P=0.025); (48.84(20.64,96.28) to 19.85(9.83,28.58), Z=2.30, P=0.022);(48.46(25.06,81.78) to 23.95(8.80,29.16), Z=2.51, P=0.012); (64.46(39.38,112.44) to 26.85(15.74,39.58), Z=2.80, P=0.005); (65.68(31.78,102.00) to 31.09(15.98,46.96), Z=2.38, P=0.017); (45.26(28.34,73.14) to 21.45(10.57,36.59), Z=2.04, P=0.042); (43.50(22.58,78.67) to 25.45(11.91,32.26), Z=2.22, P=0.027). Power values of slow-wave index in leads Fp1-2, F3-4, C3-4, P4, F7-8, and T4, as well as the overall brain average, were higher in the poor prognosis group (6.64(2.98,10.42) to 3.65(2.31,4.30), Z=2.65, P=0.01); (6.53(3.96,11.65) to 3.53(2.56,4.51), Z=2.30, P=0.022); (7.38(4.62,13.12) to 3.83(1.70,4.71), Z=2.38, P=0.017); (5.88(4.02,12.15) to 3.18(2.21,4.46), Z=2.29, P=0.022); (6.13(3.83,11.22) to 2.97(1.53,4.58), Z=2.01, P=0.044); (6.07(3.53,9.39) to 2.74(2.00,3.81), Z=2.40, P=0.016);(4.11(2.51,9.23) to 2.18(1.37,2.82), Z=2.25, P=0.024); (5.71(3.81,10.44) to 3.22(1.86,4.04), Z=2.28, P=0.023); (6.00(3.65,10.37) to 3.04(2.00,4.00), Z=2.39, P=0.017); (4.08(2.56,8.33) to 2.08(1.60,3.14), Z=2.50, P=0.013), with significant statistical differences noted (5.45(3.31,10.08) to 3.17(2.02,4.88), Z=3.62, P=0.005). (3) Logistic regression results showed that admission homocysteine levels ( OR 1.311,95% CI 1.008-1.705, P=0.044), admission NIHSS scores ( OR 1.588,95% CI 1.074-2.349, P=0.020), and overall brain average slow-wave index were influencing factors for poor prognosis in cerebral hemorrhage ( OR 8.596,95% CI 1.088-67.889, P=0.041). (4) ROC curve analysis revealed that the AUC for predicting adverse outcomes in cerebral hemorrhage was 0.768 (95% CI (0.665, 0.872)) for admission homocysteine levels, 0.743 (95% CI (0.634, 0.852)) for the overall brain average slow-wave index, and 0.896 (95% CI (0.827, 0.965)) for admission NIHSS. The cutoff values were 15.67, 3.62, and 8.5, respectively. Sensitivity was 77.8%, 71.1%, and 68.9%, and specificity was 59.4%, 68.7%, and 100%, respectively. The Youden indices were 0.372, 0.398, and 0.689. Conclusion:In the acute phase of cerebral hemorrhage, electroencephalographic physiological changes manifest shows an increase in the δ, θ, and slow-wave index throughout the entire brain. Higher admission homocysteine levels suggest a worse prognosis in patients with cerebral hemorrhage. Admission homocysteine levels and overall brain average slow-wave index have certain predictive value for adverse outcomes in acute cerebral hemorrhage.