Objective To investigate the effects of total flavones from Oxytropis falcata Bunge on hepatic fibrosis(HF)induced by carbon tetrachloride and liver transforming growth factor(TGF-β)/Smad signaling pathway.Methods Forty-eight male rats were randomly divided into normal group(intraperitoneal injection of peanut oil,intragastric administration of 0.9％NaCl),model group(intraperitoneal injection of 40％CC14 peanut oil solution induced HF model,intragastric administration of 0.9％NaCl),positive control group(modeling,intragastric administration of 0.2 mg·kg-1 of colchicine),experimental-L,-M,-H groups(modeling,intragastric administration of 100,200 and 400 mg·kg-1 of total flavonoid extract of Oxytropis falcata Bunge),8 individuals in each group,for 4 consecutive weeks.The histopathological changes were observed by hematoxylin-eosin and Masson staining.Serum liver function and liver fibrosis were measured;erum inflammatory factors were detected;fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to determine gene expression in liver.Results The pathological injury of liver tissue in the model group was serious,and a large number of inflammatory factors and collagen fibers were accumulated,while the rest of the treatment groups had different degrees of remission.In normal group,model group,positive control group,experimental-L,-M,-H groups,glutamic-pyruvic transaminase levels were(49.28±12.44),(5 885.42±948.37),(4 454.60±489.27),(4 650.47±843.53),(3 761.75±887.30)and(3 544.90±1 066.75)μg·L-1;glutamic-oxaloacetic transaminase levels were(186.90±46.89),(5 936.23±793.81),(3 971.37±780.28),(4 360.30±863.35),(3 943.10±439.47)and(3 971.38±631.08)μg·L-1;hyaluronic acid levels were(45.08±17.16),(104.32±36.06),(66.83±20.09),(70.30±21.07),(60.00±9.68)and(59.02±10.73)μg·L-1;laminin levels were(23.13±3.89),(60.85±13.66),(35.67±9.92),(39.98±9.39),(36.55±12.21)and(34.68±24.83)μg·L-1;type Ⅲ procollagen level were(24.98±5.34),(82.58±30.14),(40.70±16.14),(51.08±23.21),(43.60±12.48)and(44.20±11.66)p±g·L-1;interleukin(IL)-1β levels were(37.63±1.24),(46.10±3.23),(39.22±2.36),(41.33±0.93),(40.25±2.04)and(39.18±2.23)pg·mL-1;tumor necrosis factor-α levels were(314.58±20.56),(383.71±16.97),(349.00±7.93),(348.88±25.11),(325.75±27.84)and(335.07±21.33)pg·mL-1;TGF-β1 mRNA expression of relative quantity respectively were 1.00±0.00,60.99±15.70,9.61±1.59,7.37±1.09,6.41±0.64,6.87±1.09;Smad7 mRNA relative expression were 1.00±0.00,0.34±0.05,0.21±0.03,0.35±0.02,0.38±0.02,0.42±0.03.The above indexes in the model group were compared with the normal group,and the above indexes in the experimental-M,-H groups were compared with the model group,and the differences were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion Total flavonoids of Oxytropis falcata Bunge have protective effects on CC14-induced liver fibrosis in rats,and the mechanism may be related to the regulation of TGF-β/Smad pathway.

Interventions for endometriosis(EMs)include surgical excision of lesions and hormonal therapy,which usually have limited efficacy and adverse drug reactions.Traditional Chinese medicine(TCM)has the multi-component and multi-target characteristics,which can help patients achieve good clinical benefits by intervening in different parts of the disease.In this paper,we briefly discuss the modern pharmacology of Sanlang and Curcuma longa,and deeply summarize the possible mechanisms of action of TCM monomer and classical compound extracts and their active ingredients through signal pathways in inflammation,immune system,angiogenesis,hormone regulation,etc.,so as to provide theoretical bases for the clinical use of TCM monomers,drug-to-drug groups and compounds in the treatment of EMs.

Objective Viral encephalitis is an infectious disease severely affecting human health.It is caused by a wide variety of viral pathogens,including herpes viruses,flaviviruses,enteroviruses,and other viruses.The laboratory diagnosis of viral encephalitis is a worldwide challenge.Recently,high-throughput sequencing technology has provided new tools for diagnosing central nervous system infections.Thus,In this study,we established a multipathogen detection platform for viral encephalitis based on amplicon sequencing. Methods We designed nine pairs of specific polymerase chain reaction(PCR)primers for the 12 viruses by reviewing the relevant literature.The detection ability of the primers was verified by software simulation and the detection of known positive samples.Amplicon sequencing was used to validate the samples,and consistency was compared with Sanger sequencing. Results The results showed that the target sequences of various pathogens were obtained at a coverage depth level greater than 20×,and the sequence lengths were consistent with the sizes of the predicted amplicons.The sequences were verified using the National Center for Biotechnology Information BLAST,and all results were consistent with the results of Sanger sequencing. Conclusion Amplicon-based high-throughput sequencing technology is feasible as a supplementary method for the pathogenic detection of viral encephalitis.It is also a useful tool for the high-volume screening of clinical samples.

Protein-protein interactions (PPIs) are fundamental to many biological processes that play an important role in the occurrence and development of a variety of diseases. Targeting the interaction between tumour-related proteins with emerging small molecule drugs has become an attractive approach for treatment of human diseases, especially tumours. Encouragingly, selective PPI-based therapeutic agents have been rapidly advancing over the past decade, providing promising perspectives for novel therapies for patients with cancer. In this review we comprehensively clarify the discovery and development of small molecule modulators of PPIs from multiple aspects, focusing on PPIs in disease, drug design and discovery strategies, structure-activity relationships, inherent dilemmas, and future directions.

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Hard capsules of traditional Chinese medicine(TCM) have different degrees of hygroscopicity, which affects the stability and efficacy of drugs. In this paper, 30 kinds of commercially available TCM capsules were used as the research object. The hygroscopicity curves of capsule contents, capsule shells, and capsules were tested respectively, and the first-order kinetic equation was used for fitting. The results show that during the 24 h hygroscopicity process, the capsule shell can reduce the weight gain caused by the hygroscopicity of the contents by 0.80%-53.0% and the hygroscopicity rate of the capsule contents by 1.74%-91.3%, indicating that the capsule shell has a strong delay effect on the hygroscopicity of the contents of the TCM capsules. Seven physical parameters of the contents of 30 kinds of TCM capsules were determined, and 14 prescription process-related parameters were sorted out. A partial least squares model for predicting the hygroscopicity rate of the contents of TCM capsules(with shell) for 24 h was established. It is found that the hygroscopicity rate of the capsule shell is positively correlated with the hygroscopicity of the contents of TCM capsules(with shell), suggesting that the capsule shell with a low hygroscopicity rate is helpful for moisture prevention. In addition, the pre-treatment process route of the preparation and the type of molding raw materials affect the hygroscopicity. A larger proportion of the extract in the capsule content and a smaller proportion of the fine powder of the decoction pieces indicate stronger hygroscopicity of the capsule content. The 24 h hygroscopicity rate of 15% was used as the classification node of hygroscopicity strength, and the hygroscopicity rate constant of 0.58 was used as the classification node of hygroscopicity speed. The classification system of hygroscopicity behaviors of TCM capsules was established: the varieties with strong and fast hygroscopicity accounted for about 6.67%, while those with strong and slow hygroscopicity accounted for about 33.3%; the varieties with weak and fast hygroscopicity accounted for about 26.7%, while those with weak and slow hygroscopicity accounted for about 33.3%. The classification system is helpful to quantify and compare the hygroscopicity behavior of different TCM capsules and provides a reference for the quality improvement, moisture prevention technologies, and material research of TCM capsules.
Medicine, Chinese Traditional ; Wettability ; Capsules ; Powders ; Technology ; Drugs, Chinese Herbal

Objectives: To investigated the safety and efficacy of treating patients with acute non-ST-segment elevation myocardial infarction (NSTEMI) and elevated levels of N-terminal pro-hormone B-type natriuretic peptide (NT-proBNP) with levosimendan within 24 hours of first medical contact (FMC). Methods: This multicenter, open-label, block-randomized controlled trial (NCT03189901) investigated the safety and efficacy of levosimendan as an early management strategy of acute heart failure (EMS-AHF) for patients with NSTEMI and high NT-proBNP levels. This study included 255 patients with NSTEMI and elevated NT-proBNP levels, including 142 males and 113 females with a median age of 65 (58-70) years, and were admitted in the emergency or outpatient departments at 14 medical centers in China between October 2017 and October 2021. The patients were randomly divided into a levosimendan group (n=129) and a control group (n=126). The primary outcome measure was NT-proBNP levels on day 3 of treatment and changes in the NT-proBNP levels from baseline on day 5 after randomization. The secondary outcome measures included the proportion of patients with more than 30% reduction in NT-proBNP levels from baseline, major adverse cardiovascular events (MACE) during hospitalization and at 6 months after hospitalization, safety during the treatment, and health economics indices. The measurement data parameters between groups were compared using the t-test or the non-parametric test. The count data parameters were compared between groups using the χ² test. Results: On day 3, the NT-proBNP levels in the levosimendan group were lower than the control group but were statistically insignificant [866 (455, 1 960) vs. 1 118 (459, 2 417) ng/L, Z=-1.25,P=0.21]. However, on day 5, changes in the NT-proBNP levels from baseline in the levosimendan group were significantly higher than the control group [67.6% (33.8%,82.5%)vs.54.8% (7.3%,77.9%), Z=-2.14, P=0.03]. There were no significant differences in the proportion of patients with more than 30% reduction in the NT-proBNP levels on day 5 between the levosimendan and the control groups [77.5% (100/129) vs. 69.0% (87/126), χ²=2.34, P=0.13]. Furthermore, incidences of MACE did not show any significant differences between the two groups during hospitalization [4.7% (6/129) vs. 7.1% (9/126), χ²=0.72, P=0.40] and at 6 months [14.7% (19/129) vs. 12.7% (16/126), χ²=0.22, P=0.64]. Four cardiac deaths were reported in the control group during hospitalization [0 (0/129) vs. 3.2% (4/126), P=0.06]. However, 6-month survival rates were comparable between the two groups (log-rank test, P=0.18). Moreover, adverse events or serious adverse events such as shock, ventricular fibrillation, and ventricular tachycardia were not reported in both the groups during levosimendan treatment (days 0-1). The total cost of hospitalization [34 591.00(15 527.46,59 324.80) vs. 37 144.65(16 066.90,63 919.00)yuan, Z=-0.26, P=0.80] and the total length of hospitalization [9 (8, 12) vs. 10 (7, 13) days, Z=0.72, P=0.72] were lower for patients in the levosimendan group compared to those in the control group, but did not show statistically significant differences. Conclusions: Early administration of levosimendan reduced NT-proBNP levels in NSTEMI patients with elevated NT-proBNP and did not increase the total cost and length of hospitalization, but did not significantly improve MACE during hospitalization or at 6 months.
Male ; Female ; Humans ; Aged ; Natriuretic Peptide, Brain ; Simendan/therapeutic use* ; Non-ST Elevated Myocardial Infarction ; Heart Failure/drug therapy* ; Peptide Fragments ; Arrhythmias, Cardiac ; Biomarkers ; Prognosis

Cannulated Screw is a common internal fixation for the treatment of femoral neck fractures. However, the traditional implantation method has disadvantages such as inaccuracy and large radiation exposure. Based on the anatomical characteristics of the femoral neck and geometric principles, we develop a novel guide device for cannulated screws insertion. The cadaver experiment showed that it can improve the accuracy of cannulated screws implantation, reduce puncture attempts and the radiation exposure of doctors and patients.
Bone Screws ; Femoral Neck Fractures/surgery* ; Fracture Fixation, Internal ; Humans ; Robotic Surgical Procedures

Objective: To investigate the incidence and treatment of perioperative anemia in patients with gastrointestinal neoplasms in Hubei Province. Methods: The clinicopathological data of 7 474 patients with gastrointestinal neoplasms in 62 hospitals in 15 cities (state) of Hubei Province in 2019 were collected in the form of network database. There were 4 749 males and 2 725 females. The median age of the patients was 62 years (range: 17 to 96 years). The hemoglobin value of the first time in hospital and the first day after operation was used as the criterion of preoperative anemia and postoperative anemia. Anemia was defined as male hemoglobin <120 g/L and female hemoglobin <110.0 g/L, mild anemia as 90 to normal, moderate anemia as 60 to <90 g/L, severe anemia as <60 g/L. The t test and χ² test were used for inter-group comparison. Results: The overall incidence of preoperative anemia was 38.60%(2 885/7 474), and the incidences of mild anemia, moderate anemia and severe anemia were 25.09%(1 875/7 474), 11.37%(850/7 474) and 2.14%(160/7 474), respectively. The overall incidence of postoperative anemia was 61.40%(4 589/7 474). The incidence of mild anemia, moderate anemia and severe anemia were 48.73%(3 642/7 474), 12.20%(912/7 474) and 0.47%(35/7 474), respectively. The proportion of preoperative anemia patients receiving treatment was 26.86% (775/2 885), and the proportion of postoperative anemia patients receiving treatment was 14.93% (685/4 589). The proportions of preoperative anemia patients in grade ⅢA, grade ⅢB, and grade ⅡA hospitals receiving treatment were 26.12% (649/2 485), 32.32% (85/263), and 29.93% (41/137), and the proportions of postoperative anemia patients receiving treatment were 14.61% (592/4 052), 22.05% (73/331), and 9.71% (20/206). The proportion of intraoperative blood transfusion (16.74% (483/2 885) vs. 3.05% (140/4 589), χ²=434.555, P<0.01) and the incidence of postoperative complications (17.78% (513/2 885) vs. 14.08% (646/4 589), χ²=18.553, P<0.01) in the preoperative anemia group were higher than those in the non-anemia group, and the postoperative hospital stay in the preoperative anemia group was longer than that in the non-anemia group ((14.1±7.3) days vs. (13.3±6.2) days, t=5.202, P<0.01). Conclusions: The incidence of perioperative anemia in patients with gastrointestinal neoplasms is high. Preoperative anemia can increase the demand for intraoperative blood transfusion and affect the short-term prognosis of patients. At present, the concept of standardized treatment of perioperative anemia among gastrointestinal surgeons in Hubei Province needs to be improved.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anemia/epidemiology* ; Blood Transfusion ; Female ; Gastrointestinal Neoplasms/surgery* ; Humans ; Length of Stay ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Objective: To investigate the effects of continuous goal-directed analgesia on fluid resuscitation during shock stage in patients with massive burns, providing a basis for rational optimization of analgesia protocols in patients with burn shock. Methods: A retrospective case series study was conducted. One hundred and thirty-six patients with massive burns who met the inclusion criteria were admitted to Zhengzhou First People's Hospital from January 2015 to December 2020, and the patients were divided into continuous analgesia (CA) group (68 cases,with average age of 44 years old) and intermittent analgesia (IA) group (68 cases,with average age of 45 years old) according to whether sufentanil injection was continuously used for intravenous analgesia during the shock stage. The patients in the 2 groups were predominantly male. Before and at 72 h of treatment, the severity of disease and trauma pain of patients in the 2 groups were scored by the acute physiology and chronic health evaluation Ⅱ (APACHE Ⅱ) and the visual analogue scale (VAS). Hematocrit, heart rate, mean arterial pressure (MAP), central venous pressure (CVP), oxygen saturation in central venous blood (ScvO₂), rehydration coefficient, blood lactate value, hourly urine output, and the adverse reactions such as hypotension, nausea, vomiting, dizziness, skeletal muscle tonicity, respiratory depression, bradycardia, pruritus, and drug addiction of patients in the 2 groups during the treatment were recorded at the 1^st, 2^nd, and 3^rd 24 h post-injury. Data were statistically analyzed with analysis of variance for repeated measurement, paired or independent sample t test, Bonferroni correction,chi-square test and Mann-Whitney U test. Results: Before treatment, APACHE Ⅱ and VAS scores of patients in the 2 groups were close (with t values of -0.67 and 0.32, respectively, P>0.05); At 72 h of treatment, APACHE Ⅱ and VAS scores of patients in CA group were 8.5±2.2 and 2.5±1.6, both of which were significantly lower than (15.2±3.0) and (7.9±2.0) of patients in IA group, respectively (with t values of -14.94 and -17.46, respectively, P<0.01). Compared with the pre-treatment period, the APACHE Ⅱ and VAS scores of patients in IA group decreased significantly at 72 h of treatment (with t values of 11.35 and 30.59, respectively, P<0.01); the changes in APACHE Ⅱ and VAS scores of patients at 72 h of treatment in comparison with those of patients before treatment in CA group were all similar to those of patients in IA group (with t values of 4.00 and 4.82, respectively, P<0.01). Compared with those of patients in IA group, there were no significant changes in CVP, hematocrit, heart rate, ScvO₂, and MAP of patients in CA group at all three 24 h post-injury (with t values of <0.01, 0.12, 2.10, 1.55, 0.03; 0.13, 0.22, <0.01, 0.17, 0.49; 0.63, 0.06, 0.04, 2.79, and 2.33, respectively, P>0.05). Compared with those of patients in IA group at the 1^st 24 h post-injury, CVP, ScvO₂ and MAP of patients were significantly higher at the 2^nd and 3^rd 24 h post-injury (with t values of -10.10, -9.31, -8.89; -10.81, -4.65, and -9.43, respectively, P<0.01), and the heart rate of patients was significantly lower at the 2^nd and 3^rd 24 h post-injury (with t values of 7.53 and 7.78, respectively, P<0.01), and the hematocrit of patients decreased significantly only at the 3^rd 24 h post-injury (t=15.55, P<0.01); the changes of CVP, ScvO₂, MAP and heart rate of patients at the 2^nd and the 3^rd 24 h post-injury, and HCT of patients at the 3^rd 24 h post-injury, in comparison with those of patients at the 1^st 24 h post-injury in CA group were similar to those of patients in IA group (with t values of -12.25, -10.24, -8.99, 9.42, -8.83, -7.53, -11.57, 10.44, and 12.91, respectively, P<0.01). Compared with those of patients in IA group, the rehydration coefficient of patients in CA group was significantly higher only at the 3^rd 24 h post-injury (t=5.60, P<0.05), blood lactate value of patients in CA group was significantly lower at the 1^st and 2^nd 24 h post-injury (with t values of 4.32 and 14.52, respectively, P<0.05 or P<0.01), the hourly urine output of patients in CA group increased significantly at the 1^st, 2^nd, and 3^rd 24 h post-injury (with t values of 24.65, 13.12, and 5.63, respectively, P<0.05 or P<0.01). Compared with the those of patients at the 1^st 24 h post-injury, the rehydration coefficient of patients in IA group decreased significantly at the 2^nd and the 3^rd 24 h post-injury (with t values of 33.98 and 36.91, respectively, P<0.01), the blood lactate values of patients in IA group decreased significantly at the 2^nd and the 3^rd 24 h post-injury (with t values of 8.20 and 11.68, respectively, P<0.01), and the hourly urine output of patients in IA group was significantly increased at the 2^nd and the 3^rd 24 h post-injury (with t values of -3.52 and -5.92, respectively, P<0.01); the changes of rehydration coefficients and blood lactate values of patients at the 2^nd and the 3^rd 24 h post-injury in comparison with those of patients at the 1^st 24 h post-injury in CA group were similar to those of patients in IA group (with t values of 35.64, 33.64, 9.86, and 12.56, respectively, P<0.01), but hourly urine output of patients in CA group increased significantly only at the 3^rd 24 h compared with that of patients at the 1^st 24 h post-injury (t=-3.07, P<0.01). Adverse reactions such as hypotension, nausea, vomiting, dizziness, bradycardia, and pruritus occurred rarely in patients of the 2 groups, and none of the patients had skeletal muscle tonicity, respiratory depression, or drug addiction. The incidence of adverse reactions of patients in CA group was similar to that in IA group (χ²=0.08, P>0.05). Conclusions: Continuous goal-directed analgesia can effectively relieve pain and improve vital signs of patients with large burns. Meanwhile it has little impact on volume load, which can assist in correcting ischemia and hypoxia during the shock period and help patients get through the shock period smoothly.
Adult ; Analgesia ; Burns/therapy* ; Fluid Therapy ; Goals ; Humans ; Male ; Middle Aged ; Pain ; Resuscitation ; Retrospective Studies ; Shock/therapy*