Esophageal carcinoma is a malignant disease with a high incidence rate and poor prognosis. The mitochondrial apoptosis pathway plays a pivotal role in the regulation of cell death and has become a focal point in current cancer therapeutics research. Various active components from traditional Chinese medicine （TCM） can target the mitochondrial apoptosis pathway to inhibit esophageal carcinoma， presenting as potential therapeutic agents for this disease. This paper summarizes relevant research on the inhibition of esophageal carcinoma by active components in TCM via targeting the mitochondrial apoptosis pathway. It has been found that flavonoids （casticin， icariin， luteolin， kaempferol， hesperetin， deguelin， etc.）， terpenoids （oridonin， Jaridonin， artesunate， ethyl acetate fraction of pleurotus ferulatus triterpenoid， etc.）， alkaloids （matrine， swainsonine， etc.）， polyphenols （curcumin， epigallocatechin-3-gallate， corilagin， etc.）， steroids （α-hederin， polyphyllin Ⅵ， etc.）， phenols （optimized scorpion venom peptide CT-K3K7， gecko active polypeptide， etc.）， volatile oils （cinnamaldehyde， α -asarone， etc.） and other active components from TCM can target the intrinsic mitochondrial apoptosis pathway， induce apoptosis in esophageal carcinoma cells， and inhibit their proliferation， invasion and migration by regulating oxidative stress， blocking the cell cycle， regulating signaling pathways such as PI3K/Akt and MAPK.

Objective To study the pharmacokinetics of dihydralazine sulfate,triamterene,hydrochlorothiazide and reserpine in compound reserpine and triamterene in rats.Methods SD rats were randomly divided into three groups.Compound reserpine and triamterene was given at dose of 3.6,10.8 and 32.4 mg·kg-1 by single oral gavage,respectively.HPLC-MS was used to measure the blood concentrations of dihydralazine sulfate,triamterene,hydrochlorothiazide,and reserpine at various time points.DAS software was used to compute the pharmacokinetic parameters.Results After a single oral gavage of 3.6,10.8 and 32.4 mg·kg-1 of compound reserpine tablets triamterene,the tmax of dihydralazine sulfate in rat plasma were 1.50,1.33,and 1.42 h,and the Cmax of dihydralazine sulfate were 12.30,38.31 and 120.52 μg·L-1,respectively.The tmax of triamterene were 1.33,1.33,and 1.42 h,and the Cmax of triamterene were 20.93,67.36,and 168.64 μg·L-1,respectively.The tmax of hydrochlorothiazide were 2.00,2.00,and 1.75 h,and the Cmax of hydrochlorothiazide were 19.89,57.58,and 160.78 μg·L-1,respectively.Risperdal was found at very low levels in rat plasma,and only trace amounts were detected at 1.00 and 1.50 h of 32.4 mg·kg-1 administration.Conclusions Dihydralazine sulfate,triamterene,and hydrochlorothiazide can be eliminated quickly after compound reserpine and triamterene was given orally to rats,and their oral absorption is basically linear.The greater the dosage,the better the absorption of effective components.

Objective To explore the impact of integrated traditional Chinese and Western medicine on the overall survival(OS)of patients with biliary tract carcinoma(BTC),and to analyze the related factors affecting the OS of patients with BTC,so as to provide accurate prognosis assessment for clinical diagnosis and treatment.Methods The medical records of 198 patients with BTC in Henan Provincial Hospital of Traditional Chinese Medicine from February 2018 to October 2023 were retrospectively analyzed.The Cox proportional hazards model was utilized to analyze the independent prognostic factors affecting the OS of BTC patients.Survival curves were constructed using the Kaplan-Meier method,and the Log-rank test was employed to compare median OS differences among various groups.Results A total of 116 patients with BTC were included.There were 59 cases(50.86％)in the Western medicine group,with a median OS of(14±2.77)months,and the 1-,2-and 3-year OS rates were 81.36％,61.02％and 46.11％,respectively.There were 57 cases(49.14％)in the integrated traditional Chinese and Western medicine group,with a median OS of(29±3.91)months,and the 1-,2-and 3-year OS rates were 82.32％,67.64％and 58.00％,respectively.There was a statistically significant difference in survival time between the two groups(P=0.038).Univariate analysis indicated that age,clinical stage,surgical treatment,chemotherapy,targeted therapy,local therapy and integrated traditional Chinese and Western medicine were significantly correlated with OS in BTC patients(all P＜0.05).Multivariate analysis revealed that age,clinical stage,surgical treatment,chemotherapy,targeted therapy,local therapy,and integrated traditional Chinese and Western medicine had significant effects on the OS of patients with BTC(all P＜0.05).Conclusion The median OS of the traditional Chinese and Western medicine groups was significantly longer than that of the Western medicine group,and the long-term OS rate of the patients was significantly better than that of the Western medicine group.Age,clinical stage,surgery,chemotherapy,targeted therapy,local therapy,and integrated traditional Chinese and Western medicine are independent prognostic factors affecting OS in patients with BTC.

Objective To explore the impact of integrated traditional Chinese and Western medicine on the overall survival(OS)of patients with biliary tract carcinoma(BTC),and to analyze the related factors affecting the OS of patients with BTC,so as to provide accurate prognosis assessment for clinical diagnosis and treatment.Methods The medical records of 198 patients with BTC in Henan Provincial Hospital of Traditional Chinese Medicine from February 2018 to October 2023 were retrospectively analyzed.The Cox proportional hazards model was utilized to analyze the independent prognostic factors affecting the OS of BTC patients.Survival curves were constructed using the Kaplan-Meier method,and the Log-rank test was employed to compare median OS differences among various groups.Results A total of 116 patients with BTC were included.There were 59 cases(50.86％)in the Western medicine group,with a median OS of(14±2.77)months,and the 1-,2-and 3-year OS rates were 81.36％,61.02％and 46.11％,respectively.There were 57 cases(49.14％)in the integrated traditional Chinese and Western medicine group,with a median OS of(29±3.91)months,and the 1-,2-and 3-year OS rates were 82.32％,67.64％and 58.00％,respectively.There was a statistically significant difference in survival time between the two groups(P=0.038).Univariate analysis indicated that age,clinical stage,surgical treatment,chemotherapy,targeted therapy,local therapy and integrated traditional Chinese and Western medicine were significantly correlated with OS in BTC patients(all P＜0.05).Multivariate analysis revealed that age,clinical stage,surgical treatment,chemotherapy,targeted therapy,local therapy,and integrated traditional Chinese and Western medicine had significant effects on the OS of patients with BTC(all P＜0.05).Conclusion The median OS of the traditional Chinese and Western medicine groups was significantly longer than that of the Western medicine group,and the long-term OS rate of the patients was significantly better than that of the Western medicine group.Age,clinical stage,surgery,chemotherapy,targeted therapy,local therapy,and integrated traditional Chinese and Western medicine are independent prognostic factors affecting OS in patients with BTC.

Objective To study the pharmacokinetics of dihydralazine sulfate,triamterene,hydrochlorothiazide and reserpine in compound reserpine and triamterene in rats.Methods SD rats were randomly divided into three groups.Compound reserpine and triamterene was given at dose of 3.6,10.8 and 32.4 mg·kg-1 by single oral gavage,respectively.HPLC-MS was used to measure the blood concentrations of dihydralazine sulfate,triamterene,hydrochlorothiazide,and reserpine at various time points.DAS software was used to compute the pharmacokinetic parameters.Results After a single oral gavage of 3.6,10.8 and 32.4 mg·kg-1 of compound reserpine tablets triamterene,the tmax of dihydralazine sulfate in rat plasma were 1.50,1.33,and 1.42 h,and the Cmax of dihydralazine sulfate were 12.30,38.31 and 120.52 μg·L-1,respectively.The tmax of triamterene were 1.33,1.33,and 1.42 h,and the Cmax of triamterene were 20.93,67.36,and 168.64 μg·L-1,respectively.The tmax of hydrochlorothiazide were 2.00,2.00,and 1.75 h,and the Cmax of hydrochlorothiazide were 19.89,57.58,and 160.78 μg·L-1,respectively.Risperdal was found at very low levels in rat plasma,and only trace amounts were detected at 1.00 and 1.50 h of 32.4 mg·kg-1 administration.Conclusions Dihydralazine sulfate,triamterene,and hydrochlorothiazide can be eliminated quickly after compound reserpine and triamterene was given orally to rats,and their oral absorption is basically linear.The greater the dosage,the better the absorption of effective components.

Objective To analyze the epidemiological characteristics of visceral leishmaniasis in Gansu Province from 2017 to 2023, so as to provide insights into formulation of the visceral leishmaniasis control strategy in the province. Methods All epidemiological features of confirmed and clinically diagnosed cases of visceral leishmaniasis reported in Gansu Province from January 1, 2017 to December 31, 2023 were retrieved from the Chinese Disease Prevention and Control Information System, and the epidemiological characteristics of visceral leishmaniasis cases were analyzed descriptively. Results A total of 280 visceral leishmaniasis cases were reported in 39 counties (cities and districts) of Gansu Province from 2017 to 2023, including 258 local cases reported in 21 endemic counties (districts) and 22 imported cases reported in 18 non-endemic areas. Of the 280 cases, there were 262 cases with mountain type zoonotic visceral leishmaniasis (MT-ZVL), 12 cases with desert-type zoonotic visceral leishmaniasis (DT-ZVL), and 6 cases with unknown type. Re-emerging MT-ZVL occurred in Maiji District, Qinzhou District, Lixian County, Kangxian County, Zhenyuan County, Qin’an County and Yongjing County, and re-emerging DT-ZVL occurred in Dunhuang City, while emerging DT-ZVL occurred in Yumen City. The five counties (districts) reporting the highest number of visceral leishmaniasis cases included Wudu District, Wenxian County, Tanchang County, Zhouqu County and Diebu County, and a total of 220 cases were reported in these five counties, accounting for 78.57% of all visceral leishmaniasis cases in the province. Visceral leishmaniasis cases were reported each month throughout the year, with the peak in July. All reported visceral leishmaniasis cases had ages of 6 months to 81 years, including 50.71% (142/280) under 15 years of age, 49.29% (138/280) at ages of 15 years and older, and of all cases under 15 years of age, children at ages of 0 to 3 years were the most commonly affected (27.14%, 76/280). Among 280 visceral leishmaniasis cases, there were 173 males and 107 females with a male to female ratio of 1.62∶1, and farmer was the most common occupation (40.36%), followed by diaspora children (37.86%). Conclusions The prevalence of visceral leishmaniasis appeared an overall tendency towards a decline in Gansu Province from 2017 to 2023; however, there are still multiple challenges for visceral leishmaniasis control in the province. Reinforced dog monitoring and management, intensified human health education and improved capability building among professionals are recommended to manage the rebounding and spread of visceral leishmaniasis.

Objective To investigate the effect of fibulin-3 on the senescence of intervertebral disc nucleus pulposus cells(NPCs)through the regulation of tissue inhibitor of metalloproteinases 3(TIMP-3)expression and to elucidate the molecular mechanisms involved.Methods 1).The nucleus pulposus tissues and imaging data of 37 patients who had undergone intervertebral disc surgery were collected.The degree of degeneration of the intervertebral discs were classified according to the Pfirrmann grading system.The senescence degree of NPCs was determined using senescence-associated β-galactosidase(SA-β-gal)staining.Fibulin-3 expression levels were determined using Western blot and ELISA.The relationship between fibulin-3 and disc degeneration and NPCs senescence was investigated.2).Human intervertebral disc NPCs were cultured in vitro.The proliferation and senescence of NPC across continuous passage were observed via CCK-8 assay and SA-β-gal staining,respectively.Fibulin-3 expression levels and the expression of inflammatory cytokines and matrix metalloproteinases were assessed.Exogenous fibulin-3 was added to verify its effect on the proliferation and senescence of NPCs.3).The effect of fibulin-3 on the apoptosis and proliferation of NPCs was verified through gene overexpression,which was used in combination with an apoptosis inhibitor for bidirectional verification.4).Bioinformatics analysis was performed to explore the relationship between fibulin-3 and the TIMP family.Experiments overexpressing fibulin-3 and silencing the TIMP-3 gene were performed to verify their role in NPCs senescence.Results 1).The intervertebral disc degeneration samples from 37 patients were classified according to the Pfirrmann grading system.The higher the degeneration grade,the lower fibulin-3 expression.Spearman correlation analysis showed that the disc grade was negatively correlated with the NPC senescence grade(r=-0.87,P＜0.001)and fibulin-3 expression(r=-0.79,P＜0.001).2).As the passage number of NPCs increased,fibulin-3 expression gradually decreased,cell proliferation ability weakened,and the expression of inflammatory cytokines and matrix metalloproteinases increased.After exogenous fibulin-3 was added,cell morphology and growth status were maintained,cell senescence was significantly inhibited,and the expression of inflammatory cytokines and matrix metalloproteinases was markedly reduced.3).Gene overexpression experiments showed that fibulin-3 reduced NPC apoptosis and promoted cell proliferation,thereby inhibiting NPC senescence.4).Bioinformatics analysis revealed a significant association between fibulin-3 and TIMP-3 of the TIMP family.Further experiments confirmed that overexpressing fibulin-3 enhanced TIMP-3 expression,while silencing the TIMP-3 gene significantly weakened the inhibitory effect of fibulin-3 on NPCs senescence.This indicates that,through regulating TIMP-3,fibulin-3 inhibits the activity of matrix metalloproteinases,affects the synthesis and degradation of the extracellular matrix,and ultimately inhibits NPCs senescence.Conclusion This study demonstrates that fibulin-3 plays a crucial role in inhibiting the senescence of intervertebral disc NPCs by regulating TIMP-3.The specific mechanisms involved are as follows,fibulin-3 upregulates TIMP-3 expression,inhibits matrix metalloproteinase activity,and reduces extracellular matrix degradation,thereby promoting extracellular matrix synthesis.Additionally,fibulin-3 inhibits NPCs senescence by reducing apoptosis and promoting cell proliferation.Therefore,fibulin-3 and TIMP-3 have potential therapeutic significance in maintaining intervertebral disc health and delaying degeneration.

[This corrects the article DOI: 10.1016/j.apsb.2022.06.009.].

Objective:To study the main blood parameters of Leishmania-infected dogs with different clinical symptoms in the high incidence area of visceral leishmaniasis in Gansu Province, and to provide scientific basis for early diagnosis and monitoring of canine leishmaniasis. Methods:In May 2019, Wenxian County of Longnan City and Diebu County of Gannan Tibetan Autonomous Prefecture, the historical endemic areas of visceral leishmaniasis in Gansu Province, were selected as the investigation sites, and 40 dogs with positive Leishmania DNA were investigated. According to their clinical symptoms, they were divided into three groups: asymptomatic ( n = 17), minimally symptomatic ( n = 12) and symptomatic ( n = 11). At the same time, 10 healthy dogs were selected as controls. Major blood indexes were detected by an automatic animal blood five-classification cell analyzer. Results:Compared with the control group, the number of red blood cells, hemoglobin content, hematocrit, and the number of lymphocytes, monocytes and eosinophils in the asymptomatic, minimally symptomatic and symptomatic groups were decreased ( P < 0.05), while the number of white blood cells and neutrophils in minimally symptomatic and symptomatic groups were decreased ( P < 0.05). The above blood indexes were lower in the symptomatic group than those in the asymptomatic group. The number of red blood cells (control group vs symptomatic group) decreased from (6.82 ± 0.05) × 10 12/L to (4.19 ± 0.08) × 10 12/L, hemoglobin content decreased from (15.84 ± 0.74) g/L to (9.65 ± 0.18) g/L, hematocrit decreased from (46.41 ± 0.95)% to (27.86 ± 0.42)%, the number of white blood cells decreased from (14.90 ± 0.22) × 10 9/L to (10.23 ± 0.24) × 10 9/L, the number of neutrophils decreased from (7.25 ± 0.18) × 10 9/L to (6.18 ± 0.11) × 10 9/L, the number of lymphocytes decreased from (2.80 ± 0.07) × 10 9/L to (1.64 ± 0.06) × 10 9/L, the number of monocytes decreased from (1.13 ± 0.01) × 10 9/L to (0.53 ± 0.02) × 10 9/L, and the number of eosinophils decreased from (1.70 ± 0.06) × 10 9/L to (0.71 ± 0.03) × 10 9/L. Conclusion:Different clinical symptoms of Leishmania-infected dogs have different blood test results.

Objective:To investigate the value of gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced MRI in predicting the pathological grade and early recurrence rate of hepatocellular carcinoma.Methods:The imaging data, pathological data, and follow-up data of 90 patients with hepatocellular carcinoma who underwent Gd-EOB-DTPA-enhanced MRI examination and surgical treatment in People's Hospital of Baise from January 2016 to October 2017 were retrospectively analyzed. The correlation between the signal intensity of contrast-enhanced MRI and postoperative pathological grade was analyzed. Kaplan-Meier survival analysis was performed to investigate the effects of the signal characteristics of hepatobiliary lesions on the early recurrence rate of hepatocellular carcinoma.Results:A total of 59 (65.56%) patients showed low-intensity signals and 31 (34.44%) patients showed mixed-intensity signals. High-intensity signal was not found in any patients. The signal intensity of the hepatobiliary phase was significantly correlated with the pathological grade of the tumor ( χ2 = 2.26, P = 0.040) and tumor size ( t = 3.10, P = 0.033). The early recurrence rate of hepatocellular carcinoma was significantly higher in patients exhibiting mixed-intensity signals than that in patients exhibiting low-intensity signals ( χ2 = 2.25, P = 0.041). Conclusion:Gd-EOB-DTPA-enhanced MRI in the hepatobiliary phase with different signal intensities has the potential to predict the pathological grade and early recurrence rate of hepatocellular carcinoma.