Network Meta-analysis was conducted to evaluate the efficacy and safety of different traditional Chinese medicine injections combined with conventional western medicine in treatment of cerebral small vessel disease(CSVD). Computerized searches were conducted in PubMed, Cochrane Library, Web of Science, EMbase, CNKI, Wanfang, VIP, and SinoMed for randomized controlled trial(RCT) published in Chinese or English using traditional Chinese medicine injections to treat CSVD. The search time is from the inception to July 15, 2024. Literature screening and statistical analysis were conducted with NoteExpress 3.0.3, RevMan 5.3.5, and Stata 15.1.6. A total of 45 articles were included, involving 3 717 patients, with 1 944 patients in the treatment group and 1 773 patients in the control group. A total of 15 kinds of traditional Chinese medicine injections were involved. Network Meta-analysis indicated that,(1) in terms of improving clinical total effective rate, the best intervention in SUCRA was Ciwujia Injection + conventional western medicine.(2) In terms of reducing NIHSS scores, the best intervention in SUCRA was Xueshuantong Injection + conventional western medicine.(3) In terms of improving ADL scores, the best intervention in SUCRA was Danshen Injection + conventional western medicine.(4) In terms of improving MMSE scores, the best intervention in SUCRA was Xueshauntong Injection + conventional western medicine.(5) In terms of improving MoCA scores, the best intervention in SUCRA was Salvianolate Injection + conventional western medicine.(6) In terms of reducing plasma viscosity(PV), the best intervention in SUCRA was Danhong Injection + conventional western medicine.(7) In terms of reducing the hematocrit, the best intervention in SUCRA was Xuesaitong Injection + conventional western medicine.(8) In terms of reducing fibrinogen, the best intervention in SUCRA was Xuesaitong Injection + conventional western medicine.(9) In terms of reducing erythrocyte sedimentation rate(ESR), the best intervention in SUCRA was Danshen Injection + conventional western medicine.(10) In terms of reducing total cholesterol(TC), triglycerides(TG), and low-density lipoprotein(LDL), the best intervention in SUCRA was Danshen Injection + conventional western medicine. The radar chart results indicated that the advantage of Salvianolate Injection lies in improving cognitive function, while the advantage of Xueshuantong Injection lies in improving neurological function. The advantage of Xuesaitong Injection lies in improving hemodynamic parameters, and the advantage of Danshen Injection lies in improving behavioral ability, hemodynamics, and blood lipid levels. In terms of safety, there was no significant difference in the incidence of adverse reactions between the traditional Chinese medicine injection treatment group and the conventional western medicine group, and no serious adverse reactions occurred. The results showed that the combination of traditional Chinese medicine injections and conventional western medicine can effectively improve the clinical total effective rate, the neurological and cognitive functions, hemodynamic parameters, and blood lipid levels of patients suffering from CSVD. In addition, more double-blind, multi-center, large-sample RCT is needed to verify these findings and to provide more high-quality evidence on the efficacy and safety of traditional Chinese medicine injections for CSVD.
Humans ; Cerebral Small Vessel Diseases/drug therapy* ; Drugs, Chinese Herbal/administration & dosage* ; Injections ; Randomized Controlled Trials as Topic

OBJECTIVE To study the toxicokinetics and tissue distribution characteristics of alpha-amanitin in rats.METHODS The tail venous blood was collected from SD rats before and 5,10,20,30 and 45 min,1,1.5,2.5,4 and 8 h after intraperitoneal injection of alpha-amanitin(1.5 mg·kg-1),and the concentration of alpha-amanitin in blood was determined by liquid chromatography-mass spectrometry(LC-MS/MS).DAS 2.0 software was used to analyze and plot the drug-time curve with toxicokinetic parame-ters.Based on the toxicokinetics results,18 SD rats were randomly divided into three groups.The rats were sacrificed,and left ventricular arterial(LVA)blood and 9 types of tissue samples involving the heart,liver,spleen,lung,kidney,whole brain,small intestine,stomach wall and testis were collected 15 min,40 min and 2.5 h after dosing,and the concentrations of alpha-amanitin were measured by LC-MS/MS to obtain the tissue distribution results of alpha-amanitin in SD rats.RESULTS Toxicokinetics studies revealed that the peak blood concentration(Cmax)was(633±121)μg·L-1,the elimination half-life(T1/2)was(0.72±0.37)h,and the peak time(Tmax)was(0.52±0.16)h.The total clearance rate(CLz)was(1.62±0.26)L·h·kg-1,the area under the curve(AUC0-t)was(946±183)μg·h·L-1,and the mean reten-tion time(MRT0-t)was(1.18±0.17)h.The apparent volume of distribution(Vz)was(1.65±0.86)L·kg-1.The results of tissue distribution study showed that alpha-amanitin was widely distributed in SD rats with the highest concentration in the kidney,followed by the lung,small intestines,stomach wall,LVA blood and liver,but was low in the heart,spleen,testicles and other tissues,and very low in the brain.Alpha-amanitin was absorbed and eliminated quickly,peaked at 40 min in each tissue,and the concen-tration was minimized after 2.5 h.CONCLUSION The absorption and elimination of alpha-amanitin by intraperitoneal injection are rapid in SD rats,and the blood concentration reaches the peak about 31 min after administration,but can not be detected 4 h later.Alpha-amanitin is mainly distributed in the kidney,followed by the tissues and metabolic organs with rich blood flow,such as the lung,small intestines,stomach wall,LVA blood and liver.The content of alpha-amanitin is low in the heart,spleen,testicles and other tissues,and very low in the brain.It is speculated that it may have toxic targeting effect on the kidney and low blood-brain barrier permeability.

The present study aimed to explore the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma in the treatment of gastric ulcer by network pharmacology and animal experiments. UPLC-Q-TOF-MS/MS was employed to chara-cterize the chemical components of non-polysaccharide fraction of Bletillae Rhizoma, and the common targets of Bletillae Rhizoma and gastric ulcer were screened out by network pharmacology. The "drug-component-target-disease" network was constructed. Protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analyses were performed based on Matescape database to predict the therapeutic effect and mechanism of Bletillae Rhizoma. Finally, the gastric ulcer model was induced in mice by alcohol to verify the therapeutic effect and mechanism of non-polysaccharide fraction of Bletillae Rhizoma on gastric ulcer. Forty-seven chemical components were identified from non-polysaccharide fraction of Bletillae Rhizoma, among which gymnoside Ⅰ, gymnoside Ⅱ, militarine, bletilloside A, and shancigusin I might be the main active components of non-polysaccharide fraction of Bletillae Rhizoma against gastric ulcer. PPI network analysis revealed core targets such as albumin(ALB), serine/threonine kinase 1(AKT1), tumor necrosis factor(TNF), and epidermal growth factor receptor(EGFR). The KEGG enrichment analysis showed that non-polysaccharide fraction of Bletillae Rhizoma mainly exerted the therapeutic effect by regulating the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT) signaling pathway, mitogen-activated protein kinase(MAPK) signaling pathway, and Ras signaling pathway. The results of animal experiments showed that non-polysaccharide fraction of Bletillae Rhizoma could significantly improve alcohol-induced ulceration in mice to increase ulcer inhibition rate, decrease the levels of TNF-α, interleukin(IL)-1β, IL-6, vasoactive intestinal peptide(VIP), and thromboxane B2(TXB2), elevated the le-vels of IL-10, prostaglandin E2(PGE2), epidermal growth factor(EGF), and vascular endothelial growth factor(VEGF), down-re-gulate the protein levels of PI3K and AKT, and up-regulate the protein levels of p-PI3K and p-AKT. This study indicates that Bletillae Rhizoma may play a role in the treatment of gastric ulcer through multiple components, targets, and pathways and verifies partial prediction results of network pharmacology. The findings of this study provide a scientific and experimental basis for clinical application.
Animals ; Mice ; Stomach Ulcer/drug therapy* ; Proto-Oncogene Proteins c-akt ; Animal Experimentation ; Network Pharmacology ; Phosphatidylinositol 3-Kinases ; Tandem Mass Spectrometry ; Vascular Endothelial Growth Factor A ; Tumor Necrosis Factor-alpha ; Molecular Docking Simulation ; Drugs, Chinese Herbal/pharmacology*

Simiao Yong'an Decoction is a classic prescription for treating gangrene. Modern medical evidence has proven that Si-miao Yong'an Decoction has therapeutic effects on atherosclerosis(AS), vascular occlusion angeitides, and hypertension, while its pharmacodynamic mechanism remains unclear. The evidence of network pharmacology, molecular docking, literature review, and our previous study suggests that luteolin and kaempferol are two major flavonoids in Simiao Yong'an Decoction and can inhibit macrophage inflammation and exert anti-AS effects. However, due to lack of the metabolism studies in vivo, little is known about the metabolic characteristics of luteolin and kaempferol. This study employed ultra-performance liquid chromatography coupled with linear ion trap-Orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS/MS) and relevant software to identify the metabolites and metabolic pathways of luteolin and kaempferol in rat plasma, urine, and feces, after oral administration of luteolin and kaempferol, respectively. After the administration of luteolin, 10, 11, and 3 metabolites of luteolin were detected in the plasma, urine, and feces, respectively. After the administration of kaempferol, 9, 3, and 1 metabolites of kaempferol were detected in the plasma, urine, and feces, respectively. The metabolic pathways mainly involved methylation, glucuronidation, and sulfation. This study enriches the knowledge about the pharmacological mechanism of luteolin and kaempferol and supplies a reference for revealing the metabolic process of other flavonoids in Simiao Yong'an Decoction, which is of great significance for elucidating the pharmacological effects and effective substances of this decoction in vivo.
Rats ; Animals ; Tandem Mass Spectrometry/methods* ; Luteolin/analysis* ; Drugs, Chinese Herbal/chemistry* ; Kaempferols/analysis* ; Chromatography, High Pressure Liquid/methods* ; Molecular Docking Simulation

Humans ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Herpesvirus 4, Human/genetics* ; Mutation ; Epstein-Barr Virus Infections/pathology* ; Hepatitis A Virus Cellular Receptor 2/genetics*

OBJECTIVE: To observe the effects of catgut embedding and polyglycolic acid/poly-lactic acid (PGLA) embedding at "Zusanli" (ST 36) on the activation of local skin mast cells (MC), and expression of substance P (SP) and histamine (HA), and to explore the mechanism of the temporal stimulation effect of acupoint catgut embedding and provide a foundation for further research on the initiation mechanism of acupoint catgut embedding. METHODS: One hundred and sixty male SPF-grade SD rats were randomly divided into a blank group (10 rats), a sham-embedding group (50 rats), a catgut group (50 rats), and a PGLA group (50 rats). Each intervention group was further randomly divided into five subgroups according to the time points after intervention: 8 hours, 3 days, 7 days, 14 days, and 21 days, with 10 rats in each subgroup. One-time sham-embedding, catgut embedding and PGLA embedding was given at left "Zusanli" (ST 36) in each intervention group, respectively. The skin and subcutaneous connective tissue of the left "Zusanli" (ST 36) were collected at the corresponding time points after intervention, except for the blank group (only one day before intervention). Toluidine blue staining was used to detect MC count and degranulation, and immunohistochemical staining was used to detect the expression of SP and HA positive cells. RESULTS: There was no significant difference in MC count between the subgroups of each intervention group and the blank group (P>0.05). There was no significant difference in MC count between the subgroups of the catgut group and the PGLA group (P>0.05). The MC count in the 8-hour subgroup of PGLA group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the MC count in the 21-day subgroup of PGLA group was lower than that in the 21-day subgroup of catgut group (P<0.05). Compared with the blank group, the degranulation rates of MC were increased in the 8-hour and 3-day subgroups of sham-embedding group, 8-hour, 3-day, and 7-day subgroups of catgut group, and 8-hour, 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.01, P<0.05, P<0.001). There was no significant difference in the degranulation rate of MC between the subgroups of the catgut group and the PGLA group (P>0.05), and no significant difference in the degranulation rate of MC between the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of SP positive cells was increased in the 8-hour subgroup of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 3-day, 7-day, and 14-day subgroups of PGLA group (P<0.001, P<0.05). The expression of SP positive cells in the 7-day subgroup of catgut group was higher than that in the 8-hour subgroup of catgut group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.001). The expression of SP positive cells in the 7-day subgroup of PGLA group was higher than that in the 3-day subgroup of PGLA group (P<0.05), while the expression of SP positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.01). There was no significant difference in the expression of SP positive cells between the subgroups of the two embedding groups at the same time point (P>0.05). Compared with the blank group, the expression of HA positive cells was increased in the 8-hour, 3-day subgroups of sham-embedding group, 8-hour, 3-day, 7-day, and 14-day subgroups of catgut group, and 8-hour, 3-day, 7-day, 14-day, and 21-day subgroups of PGLA group (P<0.001, P<0.01, P<0.05). The expression of HA positive cells in the 14-day subgroup of catgut group was lower than that in the 7-day subgroup of catgut group (P<0.05), while the expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 8-hour subgroup of PGLA group (P<0.05), and the expression of HA positive cells in the 14-day subgroup of PGLA group was lower than that in the 7-day subgroup of PGLA group (P<0.05). The expression of HA positive cells in the 3-day subgroup of PGLA group was higher than that in the 3-day subgroup of catgut group (P<0.05). CONCLUSION Catgut and PGLA embedding at "Zusanli" (ST 36) in healthy rats could induce changes in local skin MC, SP, and HA, which may be one of the mechanisms of the temporal stimulation effect after acupoint embedding. There are certain differences between different suture materials. A moderate inflammatory response in the acupoint area, mediated by MC and involving SP and HA, may be one of the initiating factors for the effect of acupoint catgut embedding.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Mast Cells ; Histamine ; Substance P/genetics* ; Catgut ; Acupuncture Points

Aim To develop a ultra-high performance liquid chromatography electrospray-ionization tandem mass spectrometry ( UPLC-MS/MS ) method for the simultaneous determination of salidroside derivative pOBz in rat plasma and brain tissue, and to study the pharmacokinetic profile and penetration of the blood-brain barrier in rats after a single dose intravenous administration of pOBz. Methods SD rats were administered pOBz at a dose of 50 mg • kg

Aim To investigate the neuroprotective effect of prophylactic administration of salidroside (Sal) on MCAO rats. Methods A total of 52 SD adult male rats were randomly divided into sham operation group (Sham), model group (MCAO) and salidroside pre-administration group (MCAO + Sal). The dose of Sal was 50 mg·kg

Objective:To explore the therapeutic efficacy and factors influencing the sequential combination of nucleos(t)ide analogues (NAs) with pegylated interferon alpha (Peg-IFN-α) in the treatment of patients with chronic hepatitis B (CHB).Methods:144 CHB cases with NAs treatment for more than 1 year, HBV DNA < 20 IU/ml, hepatitis B surface antigen (HBsAg) quantification < 3 000 IU/ml, treated with a sequential combination of Peg-IFN-α treatment for 48 to 96 weeks, and followed up were selected from the Fifth Medical Center of the PLA General Hospital between May 2018 and May 2020. Intention-to-treat analysis was used to measure the HBsAg clearance rate at 96 weeks. The Kaplan-Meier method was used to compute the cumulative HBsAg clearance rate at 96 weeks. Univariate and multivariate logistic regression were used to analyze the factors influencing HBsAg clearance at 48 weeks of sequential combination therapy. Univariate and multifactorial COX proportional hazard models were used to analyze the factors influencing HBsAg clearance following 96 weeks of prolonged PEG-IFN-α treatment. The receiver operating characteristic curve was used to assess the predictive value of factors influencing HBsAg clearance. A Mann-Whitney U test was used to compare the measurement data between groups. The count data was compared using the χ2 test between groups. Results:41 (28.47%) cases achieved HBsAg clearance at 48 weeks of sequential combination therapy. The HBsAg clearance rate at 96 weeks was 40.28% (58/144) by intention-to-treat analysis. The Kaplan-Meier method computed that the cumulative HBsAg clearance rate at 96 weeks was 68.90%. Multivariate logistic regression analysis showed that HBsAg quantification at baseline ( OR = 0.090, 95% CI: 0.034-0.240, P < 0.001) and a 24-week drop in HBsAg level ( OR = 7.788, 95% CI: 3.408-17.798, P < 0.001) were independent predictors of HBsAg clearance in CHB patients treated sequentially in combination with NAs and Peg-IFN-α for 48 weeks. Receiver operating characteristic curve analysis showed that the baseline HBsAg quantification [area under the receiver operating characteristic curve (AUC), 0.911, 95% CI: 0.852-0.952)] and 24-week drop in HBsAg level (AUC = 0.881, 95% CI: 0.814-0.930) had equally good predictive value for 48-week HBsAg clearance, but there was no statistically significant difference between the two ( Z = 0.638, P = 0.523). The value of the combination of baseline HBsAg quantification and 24-week drop in HBsAg level (AUC = 0.981, 95% CI: 0.941-0.997) was superior to that of single baseline HBsAg quantification ( Z = 3.017, P = 0.003) and 24-week drop in HBsAg level ( Z = 3.214, P = 0.001) in predicting HBsAg clearance rate at 48 weeks. Multivariate COX proportional hazards model analysis showed that HBsAg quantification at 48 weeks ( HR = 0.364, 95% CI: 0.176-0.752, P = 0.006) was an independent predictor of HBsAg clearance with a prolonged course to 96 weeks of Peg-IFN-α treatment. Conclusion:The HBsAg clearance rate can be accurately predicted with baseline HBsAg quantification combined with a 24-week drop in HBsAg level in patients with CHB who are treated with a sequential combination of NAs and Peg-IFN-α therapy for 48 weeks. Prolonging the course of Peg-IFN-α treatment can enhance the HBsAg clearance rate's capability. An independent predictor of HBsAg clearance is HBsAg quantification at 48 weeks of sequential combination therapy with a prolonged course of 96 weeks of Peg-IFN-α treatment.

Aim To study the neuroprotective effect of p-benzoyl salidroside (pOBz), a derivative of salidroside, on MCAO model rats.Methods ( 1 ) Thirty healthy adult male SD rats were randomly divided into Sham group, MCAO group and MCAO + pOBz group (25, 50, 1(X) mg • kg"1).MCAO model was made by suture-embolus method.The rats were scored for neurological function impairment and weighed every day.pOBz was intraperitoneally injected and administered continuously for two days after preparation of MCAO model.The cerebral infarction volume of rats was detected by MRI.( 2 ) Twenty-four healthy adult male SD rats were randomly divided into Sham group, MCAO group, MCAO + pOBz group (50 mg • kg"1 ) and MCAO + Sal group (50 mg • kg 1 ).The model was made by the suture-embolus method.pOBz was in-traperitoneally injected and administered continuously for one day.Western blot was used to detect the ex pression of NeuN, EGR1 , Bcl-2 and Bax.(3) Eighteen healthy adult male SD rats were randomly divided j j into Sham group, MCAO group and MCAO + pOBz group ( 50 mg • kg 1 ).Administration continued for 2 days.Immunofluorescence staining was used to detect the expression of NeuN.Results Intraperitoneal injection of pOBz for 2 days could reduce the cerebral infarction volume of MCAO rats, improve neurological impairment and increase the expression of NeuN and EGR1 , and the effect was better than that of Sal.pOBz improved Bcl-2/Bax in brain tissues of MCAO rats to the same extent as Sal did.Conclusions pOBz can reduce the volume of cerebral infarction in MCAO rats and has better neuroprotective effect than that of salidroside.