OBJECTIVES: To investigate the effect of Scleromitrion diffusum on gastric mucosal epithelial-mesenchymal transition (EMT) in rats with gastric precancerous lesion. METHODS: Fifty SD rats were randomly divided into blank control group (n=11), model control group (n=13), Scleromitrion diffusum (SD) group (n=13) and vitase group (n=13). Gastric precancerous lesion animal model was prepared by 1-methyl-3-nitro-1-nitrosoguanidine complex polyfactor method, and the drugs were administrated by gavage once a day for 6 weeks. The pathological changes of gastric mucosa were observed with hematoxylin and eosin staining, the expression of EMT marker proteins were detected with immunohistochemical staining and Western blotting. RESULTS: Compared with the model control group, the gastric mucosal injury was significantly attenuated in the Scleromitrion diffusum group, the mucosal tissue structure gradually recovered, the saccular expansion area was reduced, and the inflammatory infiltration was ameliorated. The expression of epithelial cadherin was higher, and the expression of neural cadherin and vimentin in the Scleromitrion diffusum group were lower than those of model control group (all P<0.05). CONCLUSIONS Scleromitrion diffusum can ameliorate gastric mucosal injury in rats with gastric precancerous lesion by reversing the EMT.
Animals ; Rats ; Rats, Sprague-Dawley ; Epithelial-Mesenchymal Transition/drug effects* ; Precancerous Conditions/metabolism* ; Gastric Mucosa/metabolism* ; Stomach Neoplasms/drug therapy* ; Male ; Cadherins/metabolism*

The nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome plays a crucial role in the prognosis of subarachnoid hemorrhage (SAH). WNK1 kinase negatively regulates NLRP3 in various inflammatory conditions, but its role in early brain injury (EBI) after SAH remains unclear. In this study, we used an in vivo SAH model in rats/mice and AAV-WNK1 intraventricular injection to investigate its neuroprotective mechanisms. WNK1 expression was significantly reduced in SAH patient blood and SAH model brain tissue, correlating negatively with microglial activation. AAV-WNK1 alleviated brain edema, neuronal necrosis, behavioral deficits, and inflammation by inhibiting NLRP3 inflammasome activation. In hemin-stimulated BV-2 cells, WNK1 overexpression reduced NLRP3 activation and inflammatory cytokines. Chloride counteracted WNK1's inhibitory effects, and WNK1 suppressed P2X7R-induced NLRP3 activation. Mechanistically, WNK1 functioned via the OXSR1/STK39 pathway. These findings highlight WNK1 as a key regulator of intracellular chloride balance and neuroinflammation, presenting a potential therapeutic target for SAH treatment.
Animals ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Subarachnoid Hemorrhage/complications* ; Inflammasomes/metabolism* ; Rats ; Mice ; Neuroinflammatory Diseases/metabolism* ; WNK Lysine-Deficient Protein Kinase 1/genetics* ; Male ; Humans ; Chlorides/metabolism* ; Mice, Inbred C57BL ; Rats, Sprague-Dawley ; Brain Injuries/metabolism* ; Microglia/metabolism* ; Protein Serine-Threonine Kinases

Objective: To analyze the current status of latent tuberculosis infection (LTBI) among freshmen in boarding middle schools in Longgang District, Shenzhen, so as to provide reference for formulating tuberculosis prevention and control strategies in the next stage. Methods: Data for tuberculosis health examination conducted among primary and secondary school students in Longgang District of Shenzhen in September 2022 to May 2023 were utilized to analyze the latent tuberculosis infection rate, and to explore the differences in latent tuberculosis infection rate among different grades, school nature, school categories and school levels. Results: The latent tuberculosis infection rate among freshmen in boarding secondary schools in Longgang District, Shenzhen in 2022 was 2.45%. The infection rate among full middle school (6.45%) and high school (3.37%) were higher than that in boarding junior high school (0.28%), nine year education school (0) and twelve year education school (1.00%) ( P <0.01). Moreover, the infection rate of high school freshmen (2.68%) was higher than that of bording junior high school (0.33%), and the rate of public schools (2.87%) and municipal schools (3.24%) were higher than those of private schools (1.78%) and distric-level schools (2.13%) respectively, with statistical significance observed for all differences( χ 2=43.58, 25.15, 22.69, P <0.01). Conclusions The latent tuberculosis infection rate among new boarding secondary students is relatively low in Longgang District of Shenzhen. However, the infection rate is higher in high school, public and municipal school. School should fully guarantee sports participation of students, enhance students awareness of tuberculosis through health knowledge lectures, and reduce the incidence of tuberculosis among students.

Objective:To observe the effects of Huatan Quyu Decoction on the protein expressions of β-catenin and GSK-3 β and the expression of anticardiolipin antibody and β-amyloid protein related to cognitive function in rats with vascular dementia based on Wnt/β-catenin signal pathway.Methods:A total of 96 male SD rats were divided into blank group, model group, Donepezil hydrochloride group and Huatan Quyu Decoction low-, midium-, high-dosage group according to random number table method, with 16 rats in each group. Except for the blank group, the rat model of vascular dementia was prepared by modified 2-VO method. Huatan Quyu Decoction low-, medium- and high-dosage groups were administrated with Huatan Quyu Decoction 6.1, 12.1 and 24.2 g/kg, respectively; the Western medicine group was administrated with Donepezil hydrochloride 0.5 mg/kg; the blank group and the model group were administrated with the same amount of normal saline for 28 consecutive days. On the 1st, 7th, 14th and 28th day after administration, the learning and memory ability of rats was evaluated by Morris water maze test, the levels of ACA and Aβ in serum were measured by enzyme linked immunosorbent assay (ELISA), and the expressions of β-catenin and GSK-3β proteins related to Wnt/β-catenin signal pathway in hippocampus were measured by Western blot.Results:Compared with model group, the escape latency was shortened in the Huatan Quyu Decoction high-dosage group and Donepezil group on 7 and 14 days of administration ( P<0.05), and the times of crossing the platform increased in Huatan Quyu Decoction high-dosage group on 1 and 28 days of administration ( P<0.05). Compared with model group, the serum ACA level in Donepezil group, Huatan Quyu Decoction medium- and high-dosage groups decreased at day 1, 7, 14 and 28 after administration ( P<0.05). The serum Aβ level in Donepezil group, Huatan Quyu Decoction medium- and high-dosage groups decreased at 7, 14 and 28 days after administration ( P<0.05); On the 14th and 28th days after administration, the levels of ACA and Aβ in TCM low-dosage group decreased ( P<0.05). Compared with model group, the expression of β-catenin protein in hippocampus of Donepezil group and Huatan Quyu Decoction medium- and high-dosage groups increased ( P<0.05), while the expression of GSK-3β in hippocampus of Donepezil group and Huatan Quyu Decoction low-, medium- and high-dosage groups decreased ( P<0.01). Conclusion:Huatan Quyu Decoction can activate the Wnt/β-catenin signaling pathway, up-regulate the expression of β-catenin protein in hippocampal tissue of rats, inhibit the expression of GSK-3β, reduce the levels of ACA and Aβ in serum of rats, and improve the cognitive function of rats with vascular dementia.

ObjectiveTo evaluate the effect and safety of Jiuxin Pill （救心丸） on exercise tolerance and quality of life in patients with stable angina pectoris （SAP）. MethodsA randomised， double-blind， placebo-controlled， multicentre study design was used to enroll 170 patients of SAP from nine centres， which were divided into 85 patients each in the trial group and control group with 1∶1 ratio. Both groups maintained the original western medicine treatment plan， and added Jiuxin Pill or placebo respectively， 2 pills （0.05 g） each time twicely for 28 days. The main outcomes were total exercise time （TED） in the exercise treadmill test and Seattle Angina Questionnaire （SAQ） scores including physical limitation （PL）， angina stability （AS）， angina frequency （AF）， treatment satisfaction （TS）， and disease perception （DP）. The secondary outcomes were exercise treadmill test indicators including heart rate recovery in 1 min （HRR1）， metabolic equivalents （METs）， maximum magnitude of ST-segment depression， and the Borg rating of perceived exertion scale， the average number of angina attacks per week， withdrawal and reduction rate of nitroglycerin， traditional Chinese medicine syndrome scores， incidence of major adverse cardiovascular events. Safety indicators were evaluated and the occurrence of adverse events during the trial was recorded. Data was collected before treatment， day 28±2 in treatment period， and follow-up at day 56 which is 28±2 days after treatment period finished. ResultsEighty-four and eighty-five patients respectively from trial group and control group were included to the full analysis set （FAS） and safety analysis set （SS）. Compared with the group before treatment and with the control group after treatment， the trial group had higher TED， HRR1， and METs， and lower maximum magnitude of ST-segment depression and Borg rating of perceived exertion scores after treatment （P＜0.01）. Compared with the group before treatment and with the control group after treatment and at follow-up， the total SAQ score and scores of AS， AF， TS and DP of the trial group after treatment and at follow-up elevated， while the average number of angina attacks per week and traditional Chinese medicine syndrome scores reduced （P＜0.01）. There was no statistically significant difference in the withdrawal and reduction rate of nitroglycerin between groups （P＞0.05）. Major adverse cardiovascular events occurred in 1 case （1/84， 1.19%） in the trial group and 1 case （1/85， 1.18%） in the control group， and the difference between groups was not statistically significant （P＞0.05）. A total of 3 cases of adverse events occurred in the trial group （3/84， 3.57%）， and a total of 6 cases of adverse events occurred in the control group （6/85， 7.06%）， and there was no statistically significant difference in the incidence of adverse events between groups （P＞0.05）. ConclusionIn the treatment of SAP， Jiuxin Pill combined with conventional western medicine can further enhance exercise tolerance， improve quality of life， and demonstrate great safety.

The objective of this study was to examine the effects of electroacupuncture on the expression of ATP-binding cassette transporter A1(ABCA1),ATP-binding cassette transporter G1(ABCG1),and class B type Ⅰ scavenger receptor(SR-B Ⅰ)genes and proteins in peritoneal macrophages of atherosclerotic rabbits.The study aimed to explore the mechanism underlying the treatment of atherosclerosis(AS)with electroacupuncture.Methods Twenty-six male New Zealand rabbits were randomly divided into the negative control group(n=7)and the modeling group(n=19)using a random number table method.The negative control group rabbits were fed a regular diet,while the modeling group was induced with a combination of high-fat feed and common carotid artery balloon injury surgery to create an AS model.After successful modeling,the rabbits in the modeling group were further divided into the model group,the electroacupuncture group,and the atorvastatin group,with 6 rabbits in each group.The rabbits in the electroacupuncture group received electroacupuncture at"'Neiguan'(PC6)","'Zusanli'(ST36)",and"'Guanyuan'(ST25)"acupoints,using a density wave,a current of 1 mA,and a frequency of 4 Hz/20 Hz,once a day.The needle was retained for 20 minutes each time,and a total of 4 courses of treatment were conducted,with 6 days per course.The rabbits in the atorvastatin group were administered atorvastatin calcium tablet suspension(1 mg/kg)orally once a day,for 6 days per course,with a total of 4 courses.After the interventions,HE staining was performed to observe the morphological changes in the common carotid artery tissue of the rabbits.Peritoneal macrophages were collected from the rabbits,and the mRNA expression levels of ABCA1,ABCG1,and SR-B Ⅰ were measured using real-time fluorescence PCR.The protein expression levels of ABCA1,ABCG1,and SR-B Ⅰ were detected using Western blotting.Results The negative control group exhibited smooth intima of common carotid artery in rabbits,while the model group displayed damaged intima of common carotid artery,thickened artery walls,and the formation of atherosclerotic plaques.The electroacupuncture group and atorvastatin group showed significant improvements in wall thickening and a reduction in plaque area.Compared with the negative control group,the mRNA and protein expressions of ABCA1,ABCG1,and SR-B Ⅰ in peritoneal macrophages of rabbits in the model group were reduced(P＜0.01).Compared with the model group,the electroacupuncture group and atorvastatin group exhibited increased mRNA and protein expressions of ABCA1,ABCG1,and SR-B Ⅰ in abdominal macrophages of rabbits(P＜0.01).Furthermore,the atorvastatin group demonstrated increased mRNA levels of ABCG1 and SR-B Ⅰ,as well as increased protein expressions of ABCA1,ABCG1,and SR-B Ⅰ in peritoneal macrophages of rabbits,in comparison to the electroacupuncture group(P＜0.01).Conclusion Electroacupuncture can enhance the expressions of ABCA1,ABCG1,and SR-B Ⅰ mRNA and protein in abdominal macrophages of AS rabbits,thereby promoting the process of cholesterol reverse transport.This may be one of the mechanisms underlying the effectiveness of acupuncture in the treatment of AS.

Objective:To explore the predictive value of pulmonary effective arterial elastance (Ea) in patients with heart failure (HF).Methods:This is a retrospective cohort study, which retrospectively included 284 patients with HF who underwent right heart catheterization at Heart Failure Center in Fuwai Hospital between September 2013 and February 2022. Data regarding baseline clinical characteristics, hemodynamic profiles, and prognosis were collected. Ea was calculated as mean pulmonary arterial pressure/stroke volume. Patients were divided into Ea<0.555 group and Ea≥0.555 group according to the median value of Ea (0.555 mmHg/ml, 1 mmHg=0.133 kPa). The primary outcome was the primary clinical event, set as the first occurrence of a series of composite events, including all-cause death, heart transplantation, left ventricular assist device implantation, and HF rehospitalization. Event-free survival was defined as the absence of primary clinical events. Spearman correlation analysis was used to calculate the correlation coefficient between Ea and parameters reflective of right heart function. The Kaplan-Meier analysis was used to compare the different groups for the estimation of outcomes with the log-rank test. We used Cox proportional-hazards regression models to estimate hazard ratios ( HR) for primary clinical event. Subgroup analysis was performed based on the age, gender, New York Heart Association (NYHA) functional class, left ventricular ejection fraction, presence of pulmonary hypertension, and serum N-terminal pro-B-type natriuretic peptide (NT-proBNP) values. We used receiver operating characteristic (ROC) curve to calculate the area under the curve ( AUC) of Ea for predicting event-free survival in patients with HF. Results:The median age was 51 years, and 206 (72.5%) patients were male. Ea and pulmonary vascular resistance (PVR) were significantly correlated ( r=0.698, P<0.001). The correlation between Ea and pulmonary arterial elastance (PAC) were even more significant ( r=-0.888, P<0.001). Compared with Ea<0.555 group, Ea≥0.555 group presented with higher serum NT-proBNP values (4 443 (1 792, 8 554) ng/L vs. 1 721 (480, 4 528)ng/L, P<0.001), higher PVR (3.4 (2.5, 4.7) Wood vs. 1.4 (0.9, 2.2) Wood, P<0.001), lower cardiac output (3.0 (2.3, 3.9) L/min vs. 4.3 (3.8, 4.9) L/min, P<0.001), and lower PAC (1.6 (1.3, 2.0) ml/mmHg vs. 4.0 (3.0, 6.0) ml/mmHg, P<0.001). The median follow-up time was 392 (166, 811) days. The Kaplan-Meier survival curve demonstrated a lower event-free survival rate in the Ea≥0.555 group compared to the Ea<0.555 group ( Plog-rank<0.001). After multivariate adjustment, Ea ( HR=1.734, P<0.001) remained significantly associated with the primary outcome. Subgroup analysis indicated that Ea was associated with the primary outcome across all subgroups. The AUC was 0.724 ( P<0.001) for Ea to predict event-free survival calculated from ROC analysis. Conclusions:Ea is closely related to parameters reflective of right ventricular afterload. Increased Ea is an independent predictor of adverse outcomes in patients with HF.

Biological hydroxyapatite(BHA)is widely used in the treatment of clinical bone defects due to its good biocompatibility and osteoconductivity.The clinical application of mateiral size is based on the principle of bone defect area adaptation,which contributes to diversity of BHA sizes.However,different sizes correspond to different hierarchi-cal levels of bone biomimicry.As the size changes,the bone biomimicry hierarchy evolves accordingly and influences the process of bone repair and regeneration through osteo-coagulo-immunomodulation,leading to unstable bone graft outcomes.Therefore,this paper reviews the size effect of clinical BHA,analyzes the multilevel structure of natural bone,proposes the evolution of bone biomimetic hierarchy triggered by the size of BHA,and further analyzes the size-media-ted osteo-coagulo-immunomodulation.Based on the hierarchical levels of bone and its osteo-coagulo-immunomodula-tion effect,we provide a new understanding of the biolog-ical principle of the size effect of biomaterials and a theo-retical basis for the basic research and clinical application of different size BHA materials.

Host cell residue DNA is one of the most common impurity which can affect the safety of biological products,therefore,domestic and international regulatory agencies have required the limit for host cell residue DNA in different biological products,either at the final product qualification or the appropriate intermediate control stage.The removal effect is verified by monitoring the residue DNA of products in different production stages,which is beneficial for assuring the scientificity and stability of the production process.In order to strengthen the understanding of control strategy about host cell residual DNA,the paper reviews progress in host cell residual DNA in biological products by authors'work experience and other's research,which provides reference for future work.

Objective:To investigate the effect of thrombin in preventing endoleaks and promoting sac regression after endovascular repair of abdominal aortic aneurysm.Methods:Retrospective study was performed on patients with abdominal aortic aneurysm (AAA) who were admitted to Peking University Third Hospital for endovascular repair (EVAR) from May 2018 to May 2023. Thrombin injection was performed during EVAR in patients with high risk of endoleaks, and the success rate of the operation, perioperative mortality (30 d), incidence of endoleak, thrombin-related allergic reactions and ectopic embolism were observed.Results:In 83 patients, the technical success rate was 100% (83/83). The average operation time was (89.9±17.1) min. The average hospitalization was (5.8±1.3) days. There were no thrombin-related allergic reactions and ectopic embolism in peri-operation. The median follow-up time was 36 months. Five patients lost follow-up. During the follow-up period, 3 patients died, of which 2 died of acute myocardial infarction at 16 and 24 months, respectively, and 1 died of lung cancer at 34 months. The remaining 75 patients survived, with an overall survival rate of 96.2% (75/78). Type Ⅱ internal leakage occurred in 3 of the 75 patients, with an incidence of 4.0%. The maximum diameter and volume of the sac did not increase significantly during follow-up, and conservative treatment was performed. The mean maximum sac diameter of 75 patients was (43.8±7.4) mm, which was significantly lower than that of (61.4±14.4) mm before EVAR ( P<0.001). The sac volume was also significantly decreased [(125.5±54.1) cm 3vs. (239.3±145.1) cm 3, P<0.01]. Conclusions:The use of thrombin in the prevention and treatment of endoleak during EVAR is safe and effective after mid-term follow-up. In the follow-up of EVAR, attention should be paid to the change of sac volume.