OBJECTIVETo study the absorption kinetics of dehydrocavidine in rats' stomachs and intestines.

METHODThe absorption kinetics was investigated by the in situ perfusion in rats and the concentrations of drug perfusion solutions were determined by HPLC.

RESULTThe hourly absorption percentages of dehydrocavidine in stomach, small intestine were 8.88%, 2.08%, respectively. Although the absorption rate constants of dehydrocavidine in duodenum and jejunum are more than that in ileum and colon, there is no significance difference between them. The absorption rate constants kept at the same level when the concentrations of drug perfusion solution are at middle and high level. The increase of the pH of perfusion solution didnt significantly affect the absorption rate constants of the drug.

CONCLUSIONDehydrocavidine was absorbed poorly at stomach and all segments of intestine in rats, but the absorptions in stomach are better than intestine. Dehydrocavidine was absorbed mainly via passive transport mechanism between middle and high concentration levels.

Animals ; Berberine Alkaloids ; pharmacokinetics ; Colon ; metabolism ; Duodenum ; metabolism ; Hydrogen-Ion Concentration ; Ileum ; metabolism ; Intestines ; metabolism ; Jejunum ; metabolism ; Male ; Rats ; Rats, Sprague-Dawley ; Stomach ; metabolism

Objective To explore the value of blood inflammatory load in predicting overall survival of elderly patients with epithelial ovarian cancer(EOC).Methods Elderly patients with EOC were selected,and their clinical data and peripheral blood parameters were collected.We constructed an inflammation-related blood scoring system using univariate and multivariate Cox regression analysis.The Kaplan-Meier method was used for survival analysis.We used Cox proportional hazards analysis to identify the independent prognostic factors.A nomogram model was constructed based on independent prognostic factors,and the receiver operating characteristic curve,C-index,and calibration curve were used to evaluate the model.Results Patients with high blood inflammatory load had worse prognosis(P=0.002).Compared with the low inflammatory load group,patients with high inflammatory load had later clinical stages and larger ascites volume(P<0.05).Cox regression analysis showed that ACCI,CA125,residual lesions,and blood score were independent factors affecting overall survival(P<0.05).Conclusion The blood inflammatory load is the biomarker for the prognosis of elderly patients with EOC.Scoring the inflammatory load in the blood can assist in efficacy monitoring and treatment intervention of ovarian cancer patients.

Objective:To establish an animal model of acute systemic cold injury in mice.Methods:There were 98 C57BL/6 mice, half male and half female, with body weight of 22-27 g and age of 10 weeks. The mice were randomly divided into 7 groups ( n=14) according to the changes of anal temperature in cold environment, namely, group A (38.5 ± 1) ℃, group B (35 ± 1) ℃, group C (30 ± 1) ℃, group D (25 ± 1) ℃, group E (20 ± 1) ℃, group F (15 ± 1) ℃, and group G (10 ± 1) ℃, among which, group A was the blank control group, and the rest groups were the experimental group. The mice in the blank control group were placed in the normal environment (20 ± 5) ℃, and the mice in the experimental group were placed in the low temperature artificial climate box at - 20℃. The anal temperature of the mice was measured intermittently (as the core temperature), and the time required for the core temperature of the mice to drop to groups B, C, D, E, F and G was recorded. The righting reflex was used to evaluate the consciousness state, the action ability and the general state of each organ of mice were observed, and the blood routine and HE staining of each organ were detected. Results:The lower the core temperature of the experimental group, the longer the time required. The consciousness state, action ability, general state of organs, blood routine, and HE staining of organs in groups B, C, and D were basically the same as those in group A, and there was no acute systemic cold injury. Therefore, the blood routine, general observation of organs, and HE staining of organs in groups B, C, and D were no longer displayed compared with those in group A. Compared with group A, mice in group E began to suffer from disturbance of consciousness and action ability. With the decrease of core body temperature, the damage was aggravated, and mice in group G died. Compared with group A, the indices of blood routine test (WBC, RBC, HGB, PLT) of mice in group E began to decrease, and the univariate variance calculation showed that only WBC changes had statistical significance ( P<0.05). Compared with groups A and E, the indices of blood routine test (WBC, RBC, HGB, PLT) of mice in group F were further reduced, and the changes of each index in univariate variance calculation were statistically significant ( P<0.05). The general observation results showed that compared with group A, the lung, liver and spleen surfaces of mice in group E began to darken, and compared with groups A and E, the lung, liver, spleen, kidney and heart of mice in group F were further deepened and darkened, with irregular edges. HE staining results of various organs showed that compared with group A, the mice in group E began to have partial alveolar structure destruction and a small amount of inflammatory cell infiltration, the central vein of the liver was slightly congested, and the red and white pulp of the spleen were indistinct. Compared with groups A and E, the pathological structure damage of the lung, liver, spleen, kidney, heart and brain tissues of the mice in group F was further aggravated. Conclusions:Detection of consciousness state, action ability, general state of organs, blood routine and HE staining indices of organs in mice under low temperature can simulate the progress of clinical acute cold injury, and the animal model of acute systemic cold injury was successfully prepared.

The theory of "combination of five meridians" focuses on meridians and acupoints as well as compatibility and interrelationship of generation and restriction of five elements. By regulating corresponding meridians to diseased, the relationship of unbalancedis balanced, which can regulate body function and effectively treat diseases. Under the guide of theory "the combination of five meridians", according to etiology and pathogenesis of post-stroke urinary incontinence, wind, fire and phlegm, from three aspects of deficiency, excess and deficient root and excessive surface, under the treatment principle of "nourishing the mother if it is deficient, reducing the son if it is excessive", the original meridian, son meridian, mother meridian, conquering meridian and conquered meridian are selected while the methods of nourishing the mother, reducing the son, reinforcing the suppression and developing the weak are applied, so as to discuss the acupuncture treatment for post-stroke urinary incontinence, which can provide new clinical thoughts of acupuncture treatment for post-stroke urinary incontinence.

OBJECTIVE To investigate the effects of sacubitril/valsartan on renal function in patients with primary hypertension. METHODS A retrospective study was conducted among patients with primary hypertension who were admitted to PLA Strategic Support Force Characteristic Medical Center from January 2018 to June 2023. Based on their medication， they were divided into two groups： sacubitril/valsartan group and valsartan group. Propensity score matching was used to match baseline data between the two groups. Patients were treated with antihypertensive drugs based on improving their lifestyle. Sacubitril/valsartan group additionally received oral administration of 200 mg Sacubitril/valsartan tablets once daily， while valsartan group additionally received oral administration of 80 mg Valsartan capsules once daily. The increase amplitude of serum creatinine from baseline， the proportion of patients with elevated serum creatinine ＞30%-50% or ＞50%， and the proportion of patients with hyperkalemia （serum potassium ≥5.5 mmol/L） were compared between two groups at 2 months and 6 months after treatment. The trends of changes in serum creatinine， serum potassium and estimated glomerular filtration rate （eGFR） were compared between the two groups before treatment （at baseline）， 2 months and 6 months after treatment. RESULTS After propensity score matching， there were 62 patients in sacubitril/valsartan group and 61 patients in valsartan group； there were no significant differences in baseline characteristics between the two groups before treatment （P＞0.05）， indicating comparability. After 6 months of treatment， the increase of serum creatinine in the sacubitril/valsartan group was significantly lower than that in the valsartan group （P＝0.003）； the proportion of patients with elevated serum creatinine ＞30%-50% in the sacubitril/valsartan group was significantly lower than that in the valsartan group （P＝0.045）. None of the patients experienced hyperkalemia events after 2 months and 6 months of treatment. Repeated measures analysis of variance showed significantly statistical differences in serum creatinine and eGFR between the two groups within 6 months of treatment （P＜0.001）. Patients taking valsartan experienced a continuous increase in serum creatinine levels and a decrease in eGFR， while patients taking sacubitril/valsartan showed a first increase and then a decrease in serum creatinine levels， and a first decrease and then an increase in eGFR with a prolonged duration of medication. CONCLUSIONS Sacubitril/valsartan can delay or even reverse the decline in renal function levels， and limit the deterioration of renal function in patients with primary hypertension， without increasing the risk of hyperkalemia.

Deficient mismatch repair(dMMR)is currently recognized as a biomarker for predicting the efficacy of immune checkpoint inhib-itors(ICIs),and domestic and foreign guidelines recommend first-line immunotherapy for patients with solid dMMR tumors.For rectal can-cer,only 5%of patients are classified as dMMR/microsatellite instability-high(MSI-H),and most have"immune desert type"or mismatch re-pair proficient(pMMR)/microsatellite stabilization(MSS)diseases,which respond poorly to ICIs.Therefore,recently,the synergistic effect of immune drugs and neoadjuvant chemoradiotherapy has been the focus of basic and clinical research.An increasing number of clinical trials of phase Ⅱ/Ⅲ immuno-total neoadjuvant therapy(iTNT)have emerged,and the management of locally advanced rectal cancer(LARC)has begun to enter the non-operative treatment era.Furthermore,an increasing number of studies support the efficacy of neoadjuvant immun-otherapy in patients with dMMR/MSI-H LARC,which exempts such patients from surgery and chemoradiotherapy as follow-up treatment and results in a pivot in the treatment paradigm of a watch-and-wait strategy.Regarding the LARC with pMMR/MSS,the preliminary iTNT findings support ICIs as a shift from an initial posterior-line palliative scheme to a first-line selection strategy and the continuation of large-scale clinical trials.However,no definitive conclusion has been reached regarding the best iTNT application for LARC.Recent studies have shown that short-course radiotherapy and sequential neoadjuvant chemotherapy,combined with immunotherapy,can achieve good short-term outcomes.Finally,identifying other new biomarkers may facilitate the identification of patients with pMMR/MSS who are sensitive to immune drugs(especially for low rectal cancer).In the future,the treatment strategy of LARC should be combined with the stratification of clinical recurrence risk and patient willingness for organ retention to achieve stratified and accurate treatment.This article will review the re-lated research background,basic and clinical research progress and existing problems of iTNT in LARC.