ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveTo explore the possible mechanism of Tongbian Decoction （通便汤， TD） in treating slow transit constipation （STC）. MethodsTwenty-four SD rats were randomly divided into normal group， model group， TD group， and mosapride group， with 6 rats per group. Except for the normal group， STC models were established by intragastric administration of loperamide hydrochloride combined with normal saline. On the day following successful model establishment， rats in the TD group received 18.63 g·kg⁻¹ of TD by gavage， while those in the mosapride group received 1.605 mg·d⁻¹ of mosapride， and those in the normal group and the model group received 10 ml·kg⁻¹ of normal saline by gavage. All treatments were administered once daily for 7 consecutive days. Twenty-four hours after the last administration， fecal pellet number and fecal water content were measured. After intragastric administration of a 10% activated charcoal suspension， the small intestinal transit rate was calculated 30 minutes later. Serum levels of gastrin （GAS） and motilin （MTL） were measured by ELISA. Colonic histopathology was observed by HE staining， and mucus secretion by Alcian blue-periodic acid-Schiff （AB-PAS） staining. Ultrastructure of colon tissue was examined using transmission electron microscopy. Protein expression levels of C-kit， stem cell factor （SCF）， autophagy-related protein 5 （ATG5）， Beclin1， vesicle-associated membrane protein B （VAPB）， and protein tyrosine phosphatase interacting protein 51 （VAPB-PTPIP51） were measured by Western Blot， and the mRNA levels were detected by real-time PCR. Immunohistochemistry was used to detect SCF， C-kit， Beclin1， and ATG5 expression. The calcium content in colon tissue was determined by ELISA. ResultsCompared to the normal group， rats in the model group showed significantly reduced fecal pellet number， fecal water content， small intestinal transit rate， and serum GAS and MTL levels （P＜0.01）； the number of goblet cells decreased， and the mucosal and muscular layers of the colon became thinner； mRNA and protein expression levels of ATG5 and Beclin1 in colon tissue significantly increased， while calcium content decreased （P＜0.05 or P＜0.01）； and electron microscopy revealed vacuolar degeneration and increased autophagosomes in colonic cells. Compared to the model group， both TD group and mosapride group showed increased fecal pellet number， fecal water content， small intestinal transit rate， serum GAS and MTL levels， and colonic calcium content， along with decreased Beclin1 and ATG5 protein levels （P＜0.05 or P＜0.01）； the mucosal thickness and goblet cell number increased significantly， and autophagosomes decreased； in the TD group， ATG5 and Beclin1 mRNA levels decreased； in the mosapride group， SCF， VAPB， and PTPIP51 mRNA levels increased， while Beclin1 mRNA decreased （P＜0.05 or P＜0.01）. Compared to the mosapride group， the TD group showed higher fecal pellet number， fecal water content， serum GAS levels， colonic calcium content， and C-kit expression， along with lower ATG5 and Beclin1 levels （P＜0.05 or P＜0.01）. ConclusionTD may improve constipation symptoms by upregulating the VAPB-PTPIP51 complex during mitochondria-endoplasmic reticulum interactions， reducing autophagy of interstitial cells of Cajal， and promoting intestinal motility.

ObjectiveThis paper aims to observe the syndrome improvement and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome）. MethodsThrough a multi-center randomized controlled methodology design，confirmed influenza cases were collected from October 2022 to April 2023 in the pediatrics department of eight hospitals，such as Dongfang Hospital of Beijing University of Chinese Medicine. A total of 180 children with influenza and heat accumulation in the lung and stomach syndrome conforming to the standard were recruited through the clinic. The sick children meeting the inclusion criteria were randomly divided into groups by a block-randomized method. The children in the experimental group were treated with Qingxuan Daozhi formula for five days，and those in the control group were treated with Oseltamivir Phosphate Granules for five days. The primary efficacy indicator was the negative conversion rate of influenza antigen detection. Secondary efficacy indicators were the Canadian acute respiratory illness and flu scale （CARIFS） and the incidence of complications，severe cases， and critical cases. Follow-up observation was conducted on the day of enrollment，48 hours after medication，72 hours after medication， and （6+1） d after medication. ResultsOne hundred and eighty participants were randomly assigned to the experimental group （90 cases） or the control group （90 cases）. All participants were followed up during the study. Comparison of influenza antigen detection results in the primary efficacy indicators showed that the average time of negative influenza antigen conversion in the experimental group was （5.29±1.25） d，and that in the control group was （5.40±1.68） d，without a statistically significant difference. After five days of intervention，52 cases in the experimental group and 51 cases in the control group converted to negative，without a statistically significant difference. CARIFS score results in the secondary efficacy indicators showed that during 72 hours after intervention，there were statistically significant differences between the experimental group and the control group in three dimensions， including headache，muscle soreness， and the need for extra care （P<0.05）. On the （6+1） days after the intervention，the differences in both the experimental group and the control group were statistically significant in 10 dimensions， including sore throat，bad sleep，uncomfortable feeling，poor spirit and fatigue，crying more than usual，the need for extra care，symptom，function，influence on parents，and total score （P<0.05）. The comparison results within the group in the dimensional scores of symptom， function， and influence on parents，as well as the CARIFS total score showed that with the delay of follow-up time，scores of both groups decreased significantly，with a statistically significant difference （P<0.01）. Inter-group comparison results showed that the mean score of the experimental group was higher than that of the control group at the time of enrollment. With the progress of intervention，the score of the experimental group was significantly decreased compared with that of the control group. At the end of follow-up，the mean score of the experimental group was lower than that of the control group，with no statistically significant difference. In terms of the incidence of complications，severe cases， and critical cases， there were no complications，severe cases， and critical cases in the two groups，without a statistically significant difference. ConclusionThe symptom improvement effect and negative antigen conversion rate of Qingxuan Daozhi formula in the treatment of influenza in children （heat accumulation in the lung and stomach syndrome） are not inferior to Oseltamivir Phosphate granules， and children's acceptance is better. It can be more widely used in clinical treatment of influenza in children （heat accumulation in the lung and stomach syndrome）.

SPECT myocardial perfusion imaging (MPI) can obtain many parameters such as myocardial perfusion, morphology, function and mechanical synchronization in one stop, which has become an essential non-invasive examination technique in the diagnosis and treatment of various cardiovascular diseases (CVD). With the continuous development of cardiac SPECT instrument, imaging scheme and image reconstruction algorithm, its application in the diagnosis and treatment of CVD is expanding. This paper reviews the research progress of qualitative, semi-quantitative and quantitative parameters of SPECT MPI in recent years, and expounds the threshold, influencing factors and application value of various parameters.

Objective:To develop a rapid, sensitive, and quantitative method for detecting Klebsiella pneumoniae using digital loop-mediated isothermal amplification(LAMP)-CRISPR/Cas12b. Methods:Five LAMP primers targeting the Kp-1 gene of Klebsiella pneumoniae and guide RNA (gRNA) for Cas12b were designed. The digital LAMP-CRISPR/Cas12b reaction mixture included 1×WarmStart ? LAMP master mix, 1×LAMP primers, 250 nmol/L Cas12b, 250 nmol/L gRNA, 3 μmol/L ssDNA reporter, 1 000 U/ml RNase inhibitor, 4 mmol/L Mg 2+, and DEPC water. After preparing the digital chip, it was incubated at 60℃ for one hour. Fluorescence distribution was then detected using a biochip analyzer to calculate the input DNA concentration. The specificity of the method was tested using genomic DNA from seven pathogenic microorganisms. The quantitative performance was assessed using serial dilutions of Klebsiella pneumoniae DNA ranging from 5-500 000 copies/μl. Clinical sputum samples were collected for comparison of quantitative performance with qPCR and qualitative performance with culture methods. Results:The digital LAMP-CRISPR/Cas12b method showed high specificity, yielding negative results for all six non-target pathogens. Quantitative performance tests indicated a sensitivity as low as 5 copies/μl, with a linear dynamic range of 5-50 000 copies/μl ( R2=0.927 4). Clinical sample quantitative testing showed that the correlation coefficient between digital LAMP-CRISPR/Cas12b and qPCR quantification was 0.917 0. Compared with the culture results of 72 samples, this method had a sensitivity of 100% and detected two additional samples with negative culture result, with a specificity of 91%; Compared with the culture method, qPCR had a sensitivity of 96% and a specificity of 83%. These results indicated that the digital LAMP-CRISPR/Cas12b method had good quantitative and qualitative detection performance for clinical sputum samples. Conclusions:This method offers advantages over qPCR, including rapidity, simplicity, and high precision. The digital LAMP-CRISPR/Cas12b method enables absolute quantification of Klebsiella pneumoniae in sputum samples, enhancing the accuracy of early screening for Klebsiella pneumoniae infections. These advantages make digital LAMP-CRISPR/Cas12b technology highly promising for the precise diagnosis of pathogenic microorganisms in field detection, primary healthcare, and resource-limited environments.

Diabetes of the exocrine pancreas(DEP) refers to a complication of diseases of the exocrine pancreas, associated with an increased risk of pancreatic cancer. Recent evidence has indicated that DEP, after type 2 diabetes, has become the second most common type of adults-onset diabetes, with a higher prevalence than type 1 diabetes. DEP is not a single condition but encompasses various exocrine pancreatic disorders that lead to hyperglycemia through different mechanisms, creating significant diagnostic and therapeutic challenges. This review examines the latest research on the risk factors and pathogenesis of DEP, aiming to provide insights to improve its clinical management strategies.

Objective:To analyze the prevalence trends and epidemiological characteristics of cardiometabolic multimorbidity(CMM) in Beijing from 2005 to 2022.Methods:A series of representative cross-sectional surveys were conducted in Beijing between 2005 and 2022 using a stratified multistage cluster random sampling method. A total of 110 496 permanent residents aged 18-79 years participated in face-to-face interviews, physical examinations, and laboratory testing. Complex sampling logistic regression models were employed to identify factors associated with CMM, and Joinpoint regression was used to assess temporal trends in prevalence. Results:The prevalence of CMM was 22.3% in 2005 and 24.3% in 2022, with an average annual percent change of 0.1%(95% CI -1.3%-1.3%, P>0.05). In rural areas, the prevalence increased by 1.3% per year(95% CI 0.2%-2.6%, P<0.05), while among obese individuals, it decreased by 1.0% annually( P<0.05). The most common CMM patterns were hypertension combined with dyslipidemia(13.2%), hypertension combined with diabetes(7.0%), and diabetes combined with dyslipidemia(5.8%). The prevalence of hypertension and dyslipidemia comorbidity showed a long-term decline among females, those aged 60-79 and obese individuals( P<0.05). In contrast, the prevalence of hypertension and diabetes comorbidity increased over time in rural residents and individuals with normal body weight( P<0.05). Furthermore, diabetes and dyslipidemia comorbidity rates increased significantly among males, adults aged 18-59 years, those with a college education or above, rural residents and individuals with normal body weight( P<0.05). Multivariable logistic regression indicated that male, older age, overweight, obese, and lower education level were independently associated with a higher risk of CMM( P<0.05). Conclusion:From 2005 to 2022, the prevalence of CMM remained high among adults in Beijing. While prevalence decreased among obese individuals, it increased significantly in rural areas. Hypertension combined with dyslipidemia was the most common multimorbidity pattern throughout the study period.

Objective To investigate the impact of inhibiting GATA binding protein 4(GATA4)on the susceptibility to atrial fibrillation in elderly individuals and to elucidate the underlying mecha-nisms.Methods Fifteen 3-month-old young SD rats and 45 18-month-old SD rats were selected.According to the age and the injection of adeno-associated virus,the rats were divided into young group,elderly group,negative control group and interfering GATA4 group,with 15 rats in each group.Based on age and AAV injection,the rats were categorized into four groups:young group,elderly group,negative control group,and GATA4 interference group,with 15 rats in each group.Left atrial anteroposterior diameter was assessed via echocardiography.The extent of atrial fibro-sis was evaluated using Masson staining.Western blot analysis was employed to examine the ex-pression levels of GATA4,calcium cycling-related proteins,and NOD-like receptor pyrin domain-containing protein 3(NLRP3).Mouse atrial myocytes(HL-1 cells)were divided into five groups according to viral infection:control group,knockdown negative control group,GATA4 knock-down group,overexpression negative control group,and GATA4 overexpression group.The expression of GATA4 and NLRP3 was analyzed using Western blotting.Results The incidence of atrial fibrillation in the elderly group was significantly higher than that in the young group(80.0％vs 11.1％,P＜0.01).Compared with the negative control group,the induction rate of atrial fibrillation in the GATA4 interference group was significantly decreased(22.2％vs 80.0％,P＜0.05).Compared with the young group,the left atrial diameter,percentage of collagen vol-ume,activation time,absolute value of conduction dispersion,and expression of NLPR3 in the aged group were significantly increased,and the expression of calcium cycling protein was disor-dered(P＜0.05,P＜0.01).Compared with the negative control group,the left atrial diameter,per-centage of collagen volume,activation time,absolute value of conduction dispersion,and expres-sion of NLPR3 in the GATA4 interference group were significantly decreased,and the disturbance of calcium circulation was alleviated(P＜0.05,P＜0.01).Compared with the negative group of knockdown and overexpression,the expression of GATA4 and NLRP3 in HL1 cells in GATA4 knockdown group was significantly decreased,and the expression of GATA4 and NLPR3 in HL-1 cells in GATA4 overexpression group was significantly increased(P＜0.01).Conclusion GATA4 inhibition decreases the susceptibility to atrial fibrillation and mitigates age-related structural remodeling,electrical remodeling,and inflammation in the atrium by regulating calcium cycling disorders and myocardial cell senescence via the NLRP3 pathway.

ABSTRCT AIM:To verify the effect of polygona-tum polysaccharide(PSP)combined with TGF-β3 in inducing the differentiation of rat tendon-derived stem cells(TDSCs)into chondrocytes by activating the TGF-β3/Smad2 pathway.METHODS:TDSCs were extracted from rat tail tendons using enzyme digestion,purified,passaged,and identified via flow cytometry.TDSCs were treated with different concentrations of PSP,and the optimal growth con-centration was determined using the CCK-8 assay.TDSCs were divided into four groups:PSP,TGF-β3,PSP+TGF-β3,and Control for differentiation induc-tion.Chondrogenic differentiation was evaluated using morphological observations,toluidine blue staining,immunofluorescence staining,and West-ern blot analysis to detect COLⅡ,SOX9,and AGG.Western blot was also used to measure the expres-sion levels of Smad2 and p-Smad2 to evaluate the activation of the TGF-β3/Smad2 pathway after chondrogenic induction.RESULTS:Flow cytometry analysis showed that TDSCs highly expressed CD90 and CD29,while CD11b and CD45 expression was low.The CCK-8 assay indicated that 5 μmol/L PSP was the optimal intervention dose.Toluidine blue staining revealed that the blue staining area in the PSP,PSP+TGF-β3,and TGF-β3 groups was larger compared to the Control group.Immunofluores-cence analysis demonstrated that COLⅡ expression was significantly increased in the PSP,TGF-β3,and PSP+TGF-β3 groups,with the highest expression in the PSP+TGF-β3 group(P＜0.05).Western blot analy-sis showed that the levels of p-Smad2/Smad2,COLⅡ,SOX9,and AGG were elevated in the PSP,TGF-β3,and PSP+TGF-β3 groups,with the highest ex-pression in the PSP+TGF-β3 group(P＜0.05).Compared to the Control group,the TGF-β3 and PSP groups also showed significantly increased expression(P＜0.05).CONCLUSION:PSP promotes the proliferation and chondrogenic differentiation of TDSCs,possibly by activating the TGF-β3/Smad2 pathway.

Objective To investigate the value of adjusting antiplatelet treatment regimens guided by thromboelastography(TEG)in predicting cerebral ischemic events after stent-assisted embolization of intracranial aneurysms.Methods This study retrospectively and consecutively enrolled patients with intracranial aneurysms who underwent stent-assisted coil embolization admitted to the Department of Neurosurgery of the General Hospital of Eastern Theater Command,from March 2022 to May 2024.Baseline and clinical data of the patients,including gender,age,hypertension,diabetes,dyslipidemia,smoking history,drinking history,and intraoperative use of tirofiban were collected.Antiplatelet therapy(conventional dose aspirin[100 mg once daily]+clopidogrel[75 mg once daily])was initiated immediately after the diagnosis of intracranial aneurysm,and TEG was performed 3 days later.According to the platelet inhibition rate in TEG parameters(platelet inhibition rate induced by arachidonic acid[AA]pathway[AA inhibition rate]or adenosine diphosphate[ADP]pathway[ADP inhibition rate],AA inhibition rate ≥ 50％indicated aspirin effectiveness,AA inhibition rate＜50％indicated aspirin resistance;ADP inhibition rate ≥ 30％indicated clopidogrel effectiveness,ADP inhibition rate＜30％indicated clopidogrel resistance),the patients were divided into the control group(TEG test results met the criteria,i.e.,AA inhibition rate ≥ 50％and ADP inhibition rate ≥ 30％),the conventional dual antiplatelet therapy group(TEG test results did not meet the criteria but were not adjusted for antiplatelet therapy,i.e.,AA inhibition rate＜50％and/or ADP inhibition rate＜30％,but with complex aneurysm morphology[such as irregular shape,daughter sac formation]or high bleeding risk,continuing conventional dual antiplatelet therapy),and the intensified group(TEG test results did not meet the criteria and the antiplatelet therapy regimen was adjusted,i.e.,AA inhibition rate＜50％and/or ADP inhibition rate＜30％,adjusting the antiplatelet therapy regimen).All patients underwent stent-assisted coil embolization after TEG testing.From 0 to 3 months after the operation,all three groups maintained the above antiplatelet therapy.At 3 months after the operation,routine head MRI,CT and other examinations were performed.If no cerebral ischemic events occurred and the imaging results were satisfactory(good stent position,no aneurysm occlusion residual or slight residual at the neck[neck width of the aneurysm 2mm]),the treatment could be adjusted to single antiplatelet therapy(aspirin 100 mg once daily).If a patient experienced a cerebral ischemic event during the follow-up period,regardless of the stage after the operation,dual antiplatelet therapy(aspirin[100mg once daily]+clopidogrel[75 mg once daily])was immediately restarted or maintained and continued for at least 6 months.The primary endpoint was intraoperative and 6-months postoperative cerebral ischemic events(including DSA-confirmed intraoperative acute thrombosis and infarction foci confirmed by head CT or MRI).Baseline and clinical data of the three groups were compared.All patients were divided into groups with ischemic stroke event and without according to the primary endpoint,univariate Logistic regression analysis was then performed on both groups.Variables with P＜0.1 in the univariate Logistic regression analysis were included in the multivariate Logistic regression analysis to explore the influencing factors of cerebral ischemic events after stent-assisted coil embolization for intracranial aneurysms.Results A total of 499 patients were included,including 178 males and 321 females,with a median age of 59(53,68)years.Among them,there were 341 patients in the control group,42 in the conventional dual antiplatelet therapy group,and 116 in the intensified group.There were 47 cases of cerebral ischemic events and 452 cases without cerebral ischemic events.There was a statistically significant difference in the intraoperative use rate of tirofiban across the control group,the conventional dual antiplatelet therapy group,and the intensified group(20.2％[69/341]vs.26.2％[11/42]vs.42.2％[49/116],P＜0.01);no statistically significant differences were observed among the three groups in terms of age,gender composition,the proportion of patients with hypertension,diabetes,dyslipidemia,smoking history,drinking history,and the incidence of cerebral ischemic events(all P＞0.05).The results of multivariate Logistic regression analysis showed that hypertension(OR,2.924,95％CI 1.416-6.037,P=0.004)and intraoperative use of tirofiban(OR,3.638,95％CI 1.892-6.996,P＜0.01)were independent risk factors for intraoperative and 6-months postoperative cerebral ischemic events after stent-assisted coil embolization in patients with intracranial aneurysms.In comparison with the control group,the intensified group has reduced the risk of cerebral ischemic events(OR,0.238,95％CI 0.088-0.646,P=0.005),while there was no statistically significant difference between the conventional dual antiplatelet therapy group and the control group(OR,0.521,95％CI 0.149-1.826,P=0.308).Conclusions This study demonstrates that adjusting the antiplatelet therapy regimens in patients with intracranial aneurysms who did not meet the platelet inhibition rate based on TEG results can significantly reduce the risk of intraoperative and 6-months postoperative cerebral ischemic events.These finding may require validation through further,large-scaled,prospective studies.