Objective To investigate the effects of Simo decoction on duodenal microinflammation and NOD-like receptor thermal protein domain associated protein 3(NLRP3)/cysteinyl aspartate-specific proteinase-1(Caspase-1)/gasdermin D(GSDMD)signaling pathway in rats with functional dyspepsia(FD).Methods The FD model was established by multifactorial method.SD rats were randomly divided into normal group,model group(FD model),positive control group(gavage administration of 0.305 mg·kg-1 mosapride injection)and experimental-H,-M,-L groups(gavage administration of 5.62,2.81,1.40 g·kg-1 Simo decoction).Small intestinal advancement rate and gastric emptying rate was determined;the levels of interleukin(IL)-1 β and IL-18 in serum were determined by enzyme linked immunosorbent assay(ELISA);the protein expression of NLRP3 and GSDMD in duodenal tissue was detected by Western blotting.Results The gastric emptying rates of normal,model,positive control and experimental-H,-M,-Lgroupswere(58.34±5.72)％,(29.16±8.37)％,(48.77±6.10)％,(48.35±6.04)％,(48.20±3.49)％and(39.24±4.20)％;the small intestinal propulsion rates were(82.01±7.55)％,(41.95±9.53)％,(64.61±10.18)％,(75.04±9.76)％,(60.58±7.13)％and(45.89±7.40)％;serum IL-1 β expression were(12.86±0.88),(43.73±4.60),(18.84±0.86),(24.61±1.57),(19.14±0.77)and(29.04±0.72)pg·mL-1;IL-18 expressions were(95.00±3.74),(170.60±8.78),(108.50±3.05),(118.90±3.45),(99.90±8.70)and(141.00±3.71)pg·mL-1;the relative expression levels of NLRP3 proteins were 0.32±0.02,0.84±0.05,0.42±0.03,0.48±0.02,0.61±0.04 and 0.62±0.05;the relative expression levels of GSDMD proteins were 0.34±0.05,0.93±0.06,0.35±0.03,0.52±0.02,0.53±0.06 and 0.55±0.05,respectively.Compared with the normal group,the above indexes in the model group have statistical significance;compared with the model group,the above indexes in the experimental-H group and the positive control group also have statistical significance(P＜0.01 or P＜0.05).Conclusion Simo decoction can effectively improve the general condition and duodenal microinflammation in FD rats,and the mechanism may be related to the inhibition of duodenal NLRP3/Caspase-1/GSDMD signaling pathway.

Objective:To investigate the risk factors affecting the prognosis of penile cancer after surgery.Methods:We retrospectively analyzed the clinical data on 112 cases of penile cancer treated in Weifang People's Hospital from January 2013 to De-cember 2023.Using the Kaplan-Meier survival curve,χ2 test,Fisher's exact test,and univariate and multivariate Cox risk regression analyses,we compared the clinical characteristics among different groups,and determined the independent prognostic risk factors for cancer-specific survival(CSS)of the patients.Results:The 1-,3-and 5-year CSS rates of the penile cancer patients were 78.2%,66.1% and 63.7%,respectively.Kaplan-Meier analysis indicated a significant correlation of a higher neutrophil-to-lymphocyte ratio(NLR)with a lower CSS rate(P<0.001).Multivariate Cox regression analysis showed high NLR(HR=2.6;95% CI:1.031-6.558;P=0.043)to be an independent risk factor for CSS.Conclusion:Preoperative NLR is an independent risk factor for the prognosis of penile cancer.In addition,older age,farmer or worker occupation,lower education,preoperative lymphocyte-to-monocyte ratio(LMR)≤2.81,preoperative fibrinogen(FIB)≥3.41 g/L,advanced tumor stage and tumor differentiation are associated with the poor prognosis the malignancy.

ObjectiveTo explore the effect of Ganshuang granule on liver fibrosis （S1 and S2） in chronic hepatitis B （CHB） with liver depression spleen deficiency and blood stasis syndrome. MethodA total of 100 patients were classified into the control group （50 in total with 4 lost and 2 rejected， 44 finally included） and observation group （50 in total with 5 lost and 2 rejected， 43 finally included） with the random number table method. Both groups were given oral entecavir tablets （0.5 mg/time， once a day， 12 months）， and oral glutathione tablets was applied depending on the conditions of patients. In addition， the control group took the analog drug of Ganshuang granule （3 g/time， 3 times/day， 12 months） and the observation group received Ganshuang granules （3 g/time， 3 times/day， 12 months）， followed by histological examination of the liver by puncture biopsy. The two groups were compared in terms of inflammatory activity grade and fibrosis stage， as well as liver stiffness measure （LSM）， liver function， hepatitis B virus （HBV） DNA， liver depression and spleen deficiency syndrome score， aspartate aminotransferase （AST）-to-platelet ratio index （APRI）， and fibrosis index based on the four factors （FIB-4）. ResultAfter treatment， liver fibrosis in the observation group was milder than that in the control group （P<0.05） and the inflammatory activity grade in the observation group was lower than that in the control group （P<0.05）. The effective rate in down-regulating inflammatory activity grade in the observation group was 77.78% as compared with the 45.83% in the control group （χ²=5.546， P<0.05）. The effective rate in decreasing the fibrosis stage in the observation group was 59.26%， which was higher than that （16.67%） in the control group （χ²=9.669， P<0.01）. The LSM and score of the liver stagnation and spleen deficiency syndrome in the observation group were lower than those in the control group at the 6th months and 12th months of treatment （P<0.05，P<0.01）. The levels of alanine aminotransferase （ALT）， AST， and alkaline phosphatase （ALP） in the observation group were lower than those in the control group （P<0.01）. The APRI and FIB-4 in the observation group were lower than those in the control group （P<0.01）. ConclusionThe Ganshuang granule combined with entecavir can alleviate inflammation and liver fibrosis， delay and reverse liver fibrosis， protect liver， and improve the traditional Chinese medicine syndrome of liver fibrosis （S1 and S2） in CHB， which is worth of clinical use and further research.

Humans ; COVID-19 ; Consensus ; SARS-CoV-2 ; China

OBJECTIVE: To investigate the expression of programmed death receptor-1 (PD-1) and inducible costimulator (ICOS) on the surface of CD8⁺ T cells in peripheral blood of patients with primary immune thrombocytopenia (ITP), and explore the roles of PD-1 and ICOS in the occurrence and development of ITP. METHODS: A total of 28 ITP patients treated in Tianjin Medical University General Hospital from September to December 2020 were selected, including 13 patients with newly diagnosed ITP, 15 patients with chronic ITP, and 22 healthy volunteers were recruited as control group. Flow cytometry was used to detect the expression levels of PD-1 and ICOS, and evaluate their correlation with clinical indicators. RESULTS: The percentage of CD8 ⁺ T cells in ITP patients of chronic group was higher than that of the newly diagnosed group and the control group (P<0.05). The expression level of PD-1 on CD8⁺ T cells in ITP patients of newly diagnosed group and chronic group were significantly lower than that of the control group (P<0.05), while the expression level of ICOS were significantly higher (P<0.05). In ITP patients, PD-1 was negatively correlated with platelet count (r=-0.4942, P<0.01), but positively with ICOS (r=0.4342). PD-1 and ICOS were both negatively correlated with lymphocyte count (r_PD-1=-0.4374; r_ICOS=-0.4492). CONCLUSION In ITP patients, the unbalanced expression of PD-1 and ICOS may interfere with the immune homeostasis of the body, which can be used as a therapeutic target for ITP patients.
CD8-Positive T-Lymphocytes/metabolism* ; Flow Cytometry ; Humans ; Inducible T-Cell Co-Stimulator Protein/metabolism* ; Platelet Count ; Programmed Cell Death 1 Receptor/metabolism* ; Purpura, Thrombocytopenic, Idiopathic

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

OBJECTIVE: To evaluate whether the efficacy of Getong Tongluo Capsule (, GTC, consisted of total flavone of Radix Puerariae) on improving patients' quality of life and lowering blood pressure are superior to the extract of Ginkgo biloba (EGB) for patients with convalescent-phase ischemic stroke and primary hypertension. METHODS: This randomized, positive-drug- and placebo-controlled, double-blind trial was conducted from September 2015 to October 2017. Totally 477 eligible patients from 18 hospitals in China were randomly assigned in a 2:1:1 ratio to the following interventions, twice a day for 12 weeks: (1) GTC 250 mg plus EGB-matching placebo 40 mg (237 cases, GTC group), (2) EGB 40 mg plus GTC-matching placebo 250 mg (120 cases, EGB group) or (3) GTC-matching placebo 250 mg plus EGB-matching placebo 40 mg (120 cases, placebo group). Moreover, all patients were orally administered aspirin enteric-coated tablets 100 mg, once a day for 12 weeks. The primary outcome was the Barthel Index (BI). The secondary outcomes included the control rate of blood pressure and National Institutes of Health Stroke Scale (NIHSS) scores. The incidence and severity of adverse events (AEs) were calculated and assessed. RESULTS: The BI relative independence rates, the clinical recovery rates of NIHSS, and the total effective rates of NIHSS in the GTC and EGB groups were significantly higher than the placebo group at 12 weeks after treatment (P<0.05), and no statistical significance was found between the GTC and EGB groups (P>0.05). The control rate of blood pressure in the GTC group was significantly higher than the EGB and placebo groups at 12, 18 and 24 weeks after treatment (P<0.01). There were no statistically significant differences in the incidences of AEs, adverse drug reactions, or serious AEs among the 3 groups (P>0.05). CONCLUSION GTC exhibited significant efficacy in improving patients' quality of life as well as neurological function and controlling hypertension. (Registration No. ChiCTR1800016667).

Ulcerative colitis (UC) is a chronic refractory non-specific intestinal inflammatory disease that is difficult to be cured. The discovery of new ulcerative colitis-related metabolite biomarkers may help further understand UC and facilitate early diagnosis. It may also provide a basis for explaining the mechanism of drug action in the treatment of UC. Compound Sophorae Decoction (CSD) is an empirical formula used in the clinical treatment of UC. Although it is known to be efficacious, its mechanism of action in the treatment of UC is unclear. The purpose of this study was to investigate the changes in endogenous substances in UC rats and the effects of CSD on metabolic pathways using the metabonomics approach. Metabolomics studies in rats with UC and normal rats were performed using LC-MS/MS. Rats with UC induced using TNBS enema were used as the study models. Metabolic profiling and pathway analysis of biomarkers was performed using statistical and pathway enrichment analyses. 36 screened potential biomarkers were found to be significantly different between the UC and the normal groups; it was also found that CSD could modulate the levels of these potential biomarkers. CSD was found to be efficacious in UC by regulating multiple metabolic pathways.

Objective To examine if the variations at sea level would be able to predict subsequent susceptibility to acute altitude sickness in subjects upon a rapid ascent to high altitude. Methods One hundred and six Han nationality male individuals were recruited to this research. Dynamic electrocardiogram, treadmill exercise test, echocardiography, routine blood examination and biochemical analysis were performed when subjects at sea level and entering the plateau respectively. Then multiple regression analysis was performed to construct a multiple linear regression equation using the Lake Louise Score as dependent variable to predict the risk factors at sea level related to acute mountain sickness (AMS). Results Approximately 49.05% of the individuals developed AMS. The tricuspid annular plane systolic excursion (22.0±2.66 vs. 23.2±3.19 mm, t=1.998, P=0.048) was significantly lower in the AMS group at sea level, while count of eosinophil [(0.264±0.393)×10⁹/L vs. (0.126±0.084)×10⁹/L, t=-2.040, P=0.045], percentage of differences exceeding 50 ms between adjacent normal number of intervals (PNN50, 9.66%±5.40% vs. 6.98%±5.66%, t=-2.229, P=0.028) and heart rate variability triangle index (57.1±16.1 vs. 50.6±12.7, t=-2.271, P=0.025) were significantly higher. After acute exposure to high altitude, C-reactive protein (0.098±0.103 vs. 0.062±0.045 g/L, t=-2.132, P=0.037), aspartate aminotransferase (19.7±6.72 vs. 17.3±3.95 U/L, t=-2.231, P=0.028) and creatinine (85.1±12.9 vs. 77.7±11.2 mmol/L, t=-3.162, P=0.002) were significantly higher in the AMS group, while alkaline phosphatase (71.7±18.2 vs. 80.6±20.2 U/L, t=2.389, P=0.019), standard deviation of normal-to-normal RR intervals (126.5±35.9 vs. 143.3±36.4 ms, t=2.320, P=0.022), ejection time (276.9±50.8 vs. 313.8±48.9 ms, t=3.641, P=0.001) and heart rate variability triangle index (37.1±12.9 vs. 41.9±11.1, t=2.020, P=0.047) were significantly lower. Using the Lake Louise Score as the dependent variable, prediction equation were established to estimate AMS: Lake Louise Score=3.783+0.281×eosinophil-0.219×alkaline phosphatase+0.032×PNN50. Conclusions We elucidated the differences of physiological variables as well as noninvasive cardiovascular indicators for subjects after high altitude exposure compared with those at sea level. We also created an acute high altitude reaction early warning equation based on the physiological variables and noninvasive cardiovascular indicators at sea level.
Acute Disease ; Adolescent ; Adult ; Alkaline Phosphatase/blood* ; Altitude ; Altitude Sickness/physiopathology* ; Aspartate Aminotransferases/blood* ; Blood Pressure/physiology* ; C-Reactive Protein/analysis* ; Creatinine/blood* ; Electrocardiography/methods* ; Exercise Test/methods* ; Heart Rate/physiology* ; Humans ; Leukocyte Count ; Male ; Risk Factors ; Young Adult

Objective:To explore the effect of Paiteling on the proliferation，metastasis and invasion of HeLa cells and relevant proteins of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Method:① HeLa cells were divided into blank group and Paiteling concentration gradient groups (3.906，2.604，1.953，1.563，1.302，1.116，0.977 g·L^-1). After drug intervention for 24 h，the cell morphological changes were observed under microscope. The cell viability was measured by thiazole blue (MTT) colorimetry，and the half inhibitory concentration (IC₅₀) of Paiteling on HeLa cells was calculated. ② HeLa cells were divided into blank group，cisplatin group (0.01 g·L^-1)，Paiteling high-dose group (2.974 g·L^-1)，Paiteling medium-dose group (1.487 g·L^-1) and Paiteling low-dose group (0.991 g·L^-1). Cell proliferation and toxicity test (CCK-8) method was used to detect the effect of Paiteling on the proliferation ability of HeLa cells，scratch test was used to detect cell migration，and invasion test (Transwell) was used to detect changes in cell invasion ability. ③ Inhibitor LY294002 group (0.006 g·L^-1) was added. Western blot (WB) was used to detect the expressions of Paiteling on PI3K，Akt，recombinant human B-cell lymphoma factor-xl (Bcl-xl)，and B-cell lymphoma/leukemia associated D protein (Bad). Result:① Compared with the blank group，microscopic observation showed that the number of cells in the treatment group was significantly reduced, and the cell morphology was incomplete. MTT experiments showed that Paiteling has a significantly inhibitory effect on HeLa cell proliferation (P<0.01). The IC₅₀ of Paiteling on HeLa cells was calculated as 2.974 g·L^-1. ② The CCK-8 experiment showed that compared with the blank group，all the drug-treated groups had an inhibitory effect on HeLa cell proliferation at 24，36，48 h (P<0.01), compared with the cisplatin group，middle and low-dose Paiteling groups showed a reduced inhibitory effect on HeLa cell proliferation at each time point (P<0.01). The scratch test showed that，compared with the blank group，each drug-added group could inhibit the migration ability of HeLa cells (P<0.01)，and the cell migration rate of the high-dose Paiteling group was lower than that of the cisplatin group (P<0.05). Transwell experiments showed that compared with the blank group，the number of membranes permeated by HeLa cells in each drug-treated group was decreased (P<0.01)，and the number of membranes permeated in the middle and low-dose Paiteling groups was increased compared with the cisplatin group (P<0.01). ③ Western blot showed that compared with the blank group，the expression levels of PI3K，Bcl-xl，and Akt in the high，medium，and low-dose Paiteling groups and the LY294002 group decreased (P<0.05，P<0.01)，while the expression of Bad increased (P<0.01). Compared with the high-dose Paiteling group，the PI3K，Akt，and Bcl-xl protein expressions were increased in the low-dose Paiteling group (P<0.01)，whereas Bad expression was decreased (P<0.01). Conclusion:Paiteling can inhibit HeLa cell proliferation，metastasis and invasion ability in a dose-dependent and time-dependent manner，which may be related to its effect on the expressions of PI3K/Akt signaling pathway-related proteins.