Effect of Tongluo Juanbi Granules on Inflammatory Injury and Apoptosis of Osteoarthritis Based on TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Tongluo Juanbi granules on chondrocyte apoptosis and Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway of rabbits with knee osteoarthritis （KOA） and study the mechanism of Tongluo Juanbi granules in the prevention and treatment of KOA. MethodThirty New Zealand rabbits were randomly assigned to the following five groups （n=6）： sham group， model group， low-dose and high-dose groups of Tongluo Juanbi granules （4.1 and 8.2 g·kg-1·d-1）， and celecoxib group （10.9 mg·kg-1·d-1）. The KOA model was established by destabilization of the medial meniscus （DMM） for six weeks. Six weeks after the modeling， the drug was given once a day for eight weeks. The pathological changes of cartilago articularis were observed by hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was performed to detect chondrocyte apoptosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in synovial fluid. The mRNA and protein expression levels of genes related to the TLR4/MyD88/NF-κB signaling pathway were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the sham group， the cartilago articularis of the model group significantly degenerated. Mankin's score was increased （P<0.01）， and the contents of IL-1β and TNF-α in synovial fluid were increased （P<0.01）. The number of apoptosis of chondrocytes was increased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were up-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were down-regulated （P<0.01）. Compared with the model group， chondrocyte degeneration in both low-dose and high-dose groups of Tongluo Juanbi granules was improved， and Mankin's score was decreased （P<0.01）. The contents of IL-1β and TNF-α were decreased （P<0.01）， and the number of apoptosis of chondrocytes was decreased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were down-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were up-regulated （P<0.01）. In addition， in the above observation indicators， the high-dose group of Tongluo Juanbi granules was significantly superior to the low-dose group of Tongluo Juanbi granules. ConclusionTongluo Juanbi granules could inhibit chondrocyte apoptosis in rabbits with KOA and improve cartilage degeneration， which may be related to inhibiting inflammatory responses mediated by TLR4/MyD88/NF-κB signaling pathway.

Experimental study on pharmacodynamics of Su Bei Zhi Ke granules (SBZKG) for acute tracheobronchitis / 中国临床药理学与治疗学

AIM: To observe the effect of Su Bei Zhi Ke granules (SBZKG) on acute tracheobronchitis (Syndrome of Wind-cold Attacking Lung). METHODS: Mouse ear swelling experiment and mouse abdominal capillary permeability experiment was used to observe its anti-inflammatory effect. Cough test in mice induced by ammonia water, and phlegm test in rats were used to observe the expectorant and antitussive effects of phenol red test in mice. We used the mortality rate experiment of infected mice to observe its antibacterial and antiviral effects. RESULTS: Compared with the contral group, the large and medium dose groups of SBZKG both reduced mouse auricle swelling (P<0.05) and increased swelling inhibition rate, reducing mouse abdominal capillary permeability (P<0.05, P<0.01). SBZKG can increase the phenol red sputum output in the respiratory tract of mice (P<0.01), prolong the cough incubation period of mice, reduce the number of coughs in mice (P<0.05, P<0.01), and increase the sputum output in rats (P<0.05, P<0.01). SBZKG can reduce the mortality rate of mice infected with bacteria and viruses. CONCLUSION: SBZKG has certain anti-inflammatory, antitussive, expectorant, antibacterial and antiviral effects, and has certain therapeutic effects on acute tracheobronchitis.

Effect of Qingshen granules on miR-23b and PINKl/Parkin pathway in rat NRK-52E cell transdifferentiation model / 中国药理学通报

Aim To investigate the targeting mechanism of miR-23b on PINKl/Parkin pathway in transdifferentiation of NRK-52E cellsinduced by TGF-β1, and to elucidate the intervention mechanism of Qingshen granules drug-containing serum on NRK-52E cell transdifferentiation. Methods Ultra-high performance liquid chromatography ( UPLC ) fingerprinting method was used to analyze Qingshen granules. The NRK-52E transdifferentiation model induced by TGF-β1 was constructed. The NRK-52E cells were divided into simulated no-load control group, miR-23b-5p simulated group, inhibitor no-load control group, and miR-23b-5p inhibitor group, after transfection with siRNA, and the effect of miR-23b-5p on PINK1 expression was ob-served. The NRK-52E cells were then divided into normal group, TGF-(31 group, Qingshen granule group, miR-23 b-mimic group, miR-23 b-mimic group, and miR-23b-mimic + Qingshen granule group. Western blot was used to detect the expression of Pinkl, Parkin, LC3 n, Beclin-1, P62 and a-SMA proteins, and RT- PCR was used to detect the expression of miR-23 b-5p, Pinkl, Parkin, Beclin-1 and a-SMA mRNA in NRK- 52E cells. Dual-Luciferase Reporter gene experiment was used to detect the targeting relationship between miR-23b-5p and PINKL Results UPLC fingerprinting method found 11 active components in Qingshen granules. After overexpression of miR-23b-5p, the expression of PINkl mRNA significantly increased (P 0. 05 ). The experimental results showed that the expressions of miR- 23b-5p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 II/ I ratio in TGF-β1 group were significantly lower than those in normal group, but the expressions of P62 and a-SMA were significantly higher than those in normal group ( P <0.05). The expressions of miR-23 b-5 p, Pinkl, Parkin, Beclin-1, LC3 II and LC3 11/ I ratio in Qingshen granule group and miR-23 b-mimic group were significantly higher than those in TGF-β1 group, and the expressions of P62 and a-SMA were significantly lower than those in TGF-β1 group (P < 0. 05 ). The performance of miR-23 b-mimic + Qingshen granule group was better than that of miR-23 b-mimic group (P < 0. 05 ). Conclusions Qingshen granules can up- regulate the expression of miR-23b-5p in NRK-52E cellsand inhibit the transdifferentiation process of NRK- 52E cells by enhancing the mitochondrial autophagy activity mediated by PINKl/Parkin pathway.

Mechanism and experimental validation of Zukamu granules in treatment of bronchial asthma based on network pharmacology and molecular docking / 中国药理学通报

Aim To anticipate the mechanism of zuka- mu granules (ZKMG) in the treatment of bronchial asthma, and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology. Methods The database was examined for ZKMG targets, active substances, and prospective targets for bronchial asthma. The protein protein interaction network diagram (PPI) and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma. The Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene ontology (GO) were used for enrichment analysis, and network pharmacology findings were used for molecular docking, ovalbumin (OVA) intraperitoneal injection was used to create a bronchial asthma model, and in vivo tests were used to confirm how ZKMG affected bronchial asthma. Results There were 176 key targets for ZKMG's treatment of bronchial asthma, most of which involved biological processes like signal transduction, negative regulation of apoptotic processes, and angiogenesis. ZKMG contained 194 potentially active components, including quercetin, kaempferol, luteolin, and other important components. Via signaling pathways such TNF, vascular endothelial growth factor A (VEGFA), cancer pathway, and MAPK, they had therapeutic effects on bronchial asthma. Conclusion Key components had strong binding activity with appropriate targets, according to molecular docking data. In vivo tests showed that ZKMG could reduce p-p38, p-ERKl/2, and p-I

Effect of Qihuang Jianpi Zishen Granules on STAT3/mTOR Signaling Pathway in Patients with Systemic Lupus Erythematosus / 中国实验方剂学杂志

ObjectiveTo investigate the clinical efficacy of Qihuang Jianpi Zishen Granules in the treatment of systemic lupus erythematosus （SLE） and its effect on the signal transducer and activator of tranSCription 3/mammalian target of rapamycin （STAT3/mTOR） signaling pathway， and to decipher the possible mechanism. MethodSixty female SLE patients who met the criteria in the First Affiliated Hospital of Anhui University of Chinese Medicine from May 2022 to May 2023 were selected and randomized into a control group and an observation group （30 cases in each group）. The control group was treated with prednisone acetate + hydroxychloroquine sulfate orally， and the observation group was additionally treated with Qihuang Jianpi Zishen granules. The treatment lasted for 8 weeks. The SLE disease activity （SLEDAI）， TCM syndrome score， erythrocyte sedimentation rate （ESR）， hypersensitive C-reactive protein （hs-CRP）， immune indexes ［immunoglobulin G （IgG）， C3， C4， CD4+， and CD8+］， interleukin （IL）-17， IL-23， interferon （IFN）-γ， 24 h urinary protein （24 h PRO）， serum creatinine （SCr）， and expression of proteins ［STAT3， phosphorylated （p）-STAT3， mTOR protein and STAT3，mTOR mRNA］ in the STAT3/mTOR signaling pathway were determined before and after treatment. In addition， the adverse reactions were recorded. ResultAfter 8 weeks of treatment， the total response rate in the observation group was 93.33% （28/30）， which was higher than that （70.00%， 21/30） in the control group （χ2=4.007， P<0.05）. After treatment， both groups showed declined SLEDAI， TCM syndrome score， ESR， hs-CRP， IgG， CD8+， IL-17， IL-23， IFN-γ， 24 h PRO， SCr， and expression of proteins in the STAT3/mTOR pathway （P<0.01） and elevated levels of C3， C4， and CD4+ （P<0.01）. Moreover， the observation group had lower SLEDAI， TCM syndrome score， ESR， hs-CRP， IgG， CD8+， IL-17， IL-23， IFN-γ， 24 h PRO， SCr， and expression of proteins in the STAT3/mTOR pathway （P<0.05， P<0.01） and higher levels of C3， C4， and CD4+ （P<0.05， P<0.01） than the control group after treatment. Neither group showed serious adverse reactions during the treatment period. ConclusionQihuang Jianpi Zishen Granules can ameliorate the inflammatory response， reduce the disease activity， and mitigate the kidney injury in SLE by inhibiting the STAT3/mTOR signaling pathway to regulate the immune function.

Study on the treatment of cerebral infarction with Chinese medicine Shenmajingfu granule by network pharmacology / 药学实践杂志

Objective To explore the material basis and mechanism of the Chinese medicine Shenmajingfu granules in the treatment of cerebral infarction. Methods The potential active ingredients and targets of Shenmajingfu granules were retrieved through TCMSP, ETCM database and TCM Database. The related target genes of cerebral infarction were searched from OMIM database. The common targets of Shenmajingfu granules and cerebral infarction were obtained by the intersection method. Cytoscape was used to construct active components of Shenmajingfu granules-targets network. Protein-protein interaction network was constructed by STRING software. DAVID database was used for GO and KEGG enrichment analysis. Results The 183 potential active ingredients of Shenmajingfu granules were screened out. 1785 potential targets were screened in the TCMSP database, including 30 targets related to cerebral infarction. These target genes were mainly involved in the inflammatory response and apoptosis process, involving the TNF signaling pathway, HIF-1 signaling pathway and NF-κB signaling pathway. Conclusion The therapeutic effect of Shenmajingfu granules on cerebral infarction may be related to the regulation of inflammatory response, improvement of impaired neurological function and protection of cerebral ischemia-reperfusion injury.

Inhibition of Oxidative Stress of Sciatic Nerve in Diabetic Rats by Tangbikang Granules Regulating AMPK/PGC-1α/SIRT3 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effect of Tangbikang granules on oxidative stress of sciatic nerve in diabetic rats by regulating adenylate activated protein kinase/peroxisome proliferator-activated receptor γ coactivator-1α/mitochondrial Sirtuins 3 （AMPK/PGC-1α/SIRT3） signaling pathway. MethodThe spontaneous obesity type 2 diabetes model was established using ZDF rats. After modeling， they were randomly divided into high， medium， and low dose Tangbikang granule groups （2.5， 1.25， 0.625 g·kg-1·d-1） and lipoic acid group （0.026 8 g·kg-1·d-1）， and the normal group was set up. The rats were administered continuously for 12 weeks after modeling. The blood glucose of rats was detected before intervention and at 4， 8， 12 weeks after intervention. At the 12th week， motor nerve conduction velocity （MNCV）， sensory nerve conduction velocity （SNCV）， nerve blood flow velocity， mechanical pain threshold， and thermal pain threshold were detected. The sciatic nerve was taken for hematoxylin-eosin （HE） staining to observe the tissue morphology. The ultrastructure of the sciatic nerve was observed by transmission electron microscope. The expression levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in sciatic nerve were determined by enzyme-related immunosorbent assay （ELISA）. The mRNA expressions of AMPKα， AMPKβ， PGC-1α， and SIRT3 in sciatic nerve were determined by real-time polymerase chain reaction （Real-time PCR）. ResultCompared with the normal group， fasting blood glucose in the model group was increased at each time point （P<0.01）. The mechanical pain threshold was decreased （P<0.05）， and the incubation time of the hot plate was extended （P<0.01）. MNCV， SNCV， and nerve blood flow velocity decreased （P<0.05）. The expression level of SOD was decreased （P<0.01）. The expression levels of MDA， IL-1β， and TNF-α were increased （P<0.01）. The mRNA expression levels of AMPKα， AMPKβ， PGC-1α， and SIRT3 were decreased （P<0.01）. The structure of sciatic nerve fibers in the model group was loose， and the arrangement was disordered. The demyelination change was obvious. Compared with the model group， the fasting blood glucose of rats in the high dose Tangbikang granule group was decreased after the intervention of eight weeks and 12 weeks （P<0.01）. The mechanical pain threshold increased （P<0.05）. The incubation time of the hot plate was shortened （P<0.01）. MNCV， SNCV， and Flux increased （P<0.05）. The expression level of SOD was increased （P<0.01）. The expression levels of MDA， IL-1β， and TNF-α were decreased （P<0.01）. The mRNA expression levels of AMPKα， AMPKβ， PGC-1α， and SIRT3 were increased （P<0.01）. The sciatic nerve fibers in the high-dose Tangbikang granule group were tighter and more neatly arranged， with only a few demyelinating changes. The high， medium， and low dose Tangbikang granule groups showed a significant dose-effect trend. ConclusionTangbikang granules may improve sciatic nerve function in diabetic rats by regulating AMPK/PGC-1α/SIRT3 signaling pathway partly to inhibit oxidative stress.

Study on metabolites derived from Zhideke granules in rats in vivo / 中国药房

OBJECTIVE To analyze the metabolites of Zhideke granules and speculate its metabolic pathway in rats in vivo. METHODS Male SD rats were randomly divided into blank group and administration group （Zhideke granules， 9.45 g/kg）； they were given ultrapure water or relevant medicine， twice a day， every 6-8 h， for 3 consecutive days. Serum， urine and feces samples of rats were collected， and their metabolites were identified by UPLC-Q-Exactive-MS technique after intragastric administration of Zhideke granules； their metabolic pathways were speculated. RESULTS After intragastric administration of Zhideke granules， 16 prototype components （i.g. irisflorentin， baicalin， chlorogenic acid） and 11 metabolites （i.g. hydration products of kaempferol or luteolin， methylation products of chlorogenic acid， and hydroxylation products of baicalin） were identified in serum， urine and feces of rats. Among them， 8 prototype components and 4 metabolites were identified in serum samples； 10 prototype components and 7 metabolites were identified in urine samples； 8 prototype components and 5 metabolites were identified in the fecal samples. CONCLUSIONS The metabolites of Zhideke granules in rats mainly include baicalin， irisflorentin，chlorogenic acid， and the main metabolic pathways included methylation， hydroxylation， glucuronidation.

Improvement effects of Runchang granules on the constipation in mice and its mechanism / 中国药房

OBJECTIVE To investigate the improvement effects of Runchang granules on the constipation in mice and its potential mechanism. METHODS The mice were randomly divided into normal control group， model group， Runchang granules low-dose and high-dose groups （5， 10 g/kg）， mosapride group （0.003 g/kg， positive control）， with 6 mice in each group. The latter 4 groups were given loperamide intragastrically （0.004 g/kg）， twice a day， for 3 consecutive days. Normal control group and model group were given purified water intragastrically， and administration groups were given relevant medicine intragastrically for 7 consecutive days. After the last medication， fecal moisture content and intestinal motility of mice were determined， while the structures of colon and ileum， and the secretion of colonic mucus were observed. Protein expressions of tyrosine kinase receptor （c-kit）， mucin 2 （MUC2） and stem cell factor （SCF） were determined in colon； meanwhile， the mRNA expression levels of inflammatory factors [tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6）， IL-1β， inducible nitric oxide synthase （iNOS）] as well as factors related to promoting intestinal motility [neuronal nitric oxide synthase （nNOS）， smooth muscle myosin light chain kinase （smMLCK）， 5-hydroxytryptamine 4 receptor （5-HT4R）， MUC2， SCF， c-kit] were determined. RESULTS Compared with model group， the fecal water content， intestinal propulsion rate， protein expression of c-kit in colon， relative expressions of MUC2 and SCF protein， and mRNA expressions of factors related to promoting intestinal motility （except for nNOS and SCF in Runchang granules low-dose group） were all increased significantly in Runchang granules low-dose and high-dose groups， and mosapride group （P＜0.05 or P＜0.01）. mRNA expression levels of inflammatory factors were decreased significantly（P＜0.05 or P＜0.01）. Both colon and ileum injuries improved， and the secretion of colon mucus was increased significantly in Runchang granules high-dose group （P＜0.01）. CONCLUSIONS Runchang granules have laxative effect and can improve constipation in mice， and its mechanism may be related to the promotion of the secretion of colon mucus and MUC2 expression， and the activation of SCF/c-kit signaling pathway.

Identification of chemical components and components migrating to the blood of Jianpi huazhuo tiaozhi granules / 中国药房

OBJECTIVE To analyze the chemical components and components migrating to the blood of Jianpi huazhuo tiaozhi granules （JHTG）. METHODS SD rats were divided into a control group and a medication group， with 6 rats in each group. The medication group was given JHTG 3 mL. Sixty minutes after medication， the serum samples of the 2 groups were collected， and the chemical components and components migrating to the blood of JHTG were separated by ultra-high performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） and mass spectrometry data were collected. Combined with the overall scheme of UNIFI natural products， based on the 6400 natural product theory mass spectrometry database， the structure was analyzed and confirmed by literature review and reference substance comparison. RESULTS & CONCLUSIONS A total of 130 components were identified from JHTG， including 3 in Codonopsis Radix， 13 in Nelumbinis Folium， 15 in Poria， 5 in Atractylodis Macrocephalae Rhizoma， 9 in Citri Reticulatae Pericarpium， 1 in Coicis Semen， 19 in Alisma Rhizoma， 24 in Salviae Miltiorrhizae Radix et Rhizoma， 7 in Hordei Fructus Germinatus， 24 in Crataegi Fructus， 2 in Amomi Fructus， and 3 in Aucklandiae Radix. In addition， quercetin and quercetin-3-O-β-D-glucopyranoside， kaempferol and citric acid may originate from Nelumbinis Folium or Crataegi Fructus， while oleanolic acid may originate from Poria or Crataegi Fructus. By comparing the reference substances， 8 components were finally determined （pachymic acid， atractylenolide Ⅱ， alisol A， alisol B， alantolactone， bornyl acetate， salvianolic acid A， salvianolic acid C）. A total of 72 prototype components such as quercetin and kaempferol were identified， mainly including flavonoids， terpenoids， lignans and phenolic acids. A total of 11 metabolites such as （NATCM’s Project of High- dehydroanonaine and 16-O-acetylpachymic acid were level Construction of Key TCM Disciplines）identified， mainly terpenoids. Metabolic pathways include phase Ⅰ metabolic reactions such as dehydrogenation and dehydroxylation， and phase Ⅱ metabolic reactions such as methylation and acetylation.

Identification of Scolopendra Dispensing Granules by Allele-specific PCR / 中国实验方剂学杂志

ObjectiveTo establish an allele-specific polymerase chain reaction （PCR） method for identifying Scolopendra dispensing granules， so as to ensure the quality and therapeutic effects of Scolopendra and its preparations. MethodThe primer interval suitable for the PCR was selected based on the cytochrome c oxidase subunit 3（COX-3） gene sequence of Scolopendra， and the single nucleotide polymorphism （SNP） loci of Scolopendra and its adulterants were mined from the interval for the design of specific primers. The samples of Scolopendra and its adulterants were collected. The PCR system was established and optimized regarding the annealing temperature， cycles， Taq enzymes， DNA template amount， PCR instruments， and primer concentrations， and the specificity and applicability of this method were evaluated. ResultThe PCR system was composed of 12.5 μL 2×M5 PCR Mix， 0.4 μL forward primer （10 μmol·L-1）， 0.4 μL reverse primer （10 μmol·L-1）， 2.5 μL DNA template， and 9.2 μL sterile double distilled water. PCR parameters： Pre-denaturation at 94 ℃ for 3 min， 30 cycles （94 ℃ for 20 s， 62 ℃ for 20 s， 72 ℃ for 45 s）， and extension at 72 ℃ for 5 min. After PCR amplification with the system and parameters above， the electrophoresis revealed a bright band at about 135 bp for Scolopendra and no band for the adulterants. ConclusionThe established allele-specific PCR method can accurately identify the medicinal materials， decoction pieces， and standard decoction freeze-dried powder of Scolopendra， as well as the intermediates and final products of Scolopendra dispensing granules， which is of great significance for ensuring the quality and clinical efficacy of Scolopendra and its preparations.

Optimization of water extraction technology of Xiangqin jiere granules by orthogonal design based on G1-entropy weight compared with BP neural network / 中国药房

OBJECTIVE Optimizing the water extraction technology of Xiangqin jiere granules. METHODS The orthogonal test of 3 factors and 3 levels was designed， and comprehensive scoring was conducted for the above indexes by using G1-entropy weight to obtain the optimized water extraction technology of Xiangqin jiere granules with water addition ratio， extraction time and extraction times as factors， using the contents of forsythoside A， baicalin， phillyrin， oroxylin A-7-O-β-D-glycoside， wogonoside， baicalein and wogonin， and extraction rate as evaluation indexes. BP neural network modeling was used to optimize the network model and water extraction process using the results of 9 groups of orthogonal tests as test and training data， the water addition multiple， decocting time and extraction times as input nodes， and the comprehensive score as output nodes. Then the two analysis methods were compared by verification test to find the best water extraction process parameters. RESULTS The water extraction technology optimized by the orthogonal test was 8-fold water， extracting 3 times， extracting for 1 h each time. Comprehensive score was 96.84 （RSD＝0.90%）. The optimal water extraction technology obtained by BP neural network modeling included 12-fold water， extracting 4 times， extracting for 0.5 h each time. The comprehensive score was 92.72 （RSD＝0.77%）， which was slightly lower than that of the orthogonal test. CONCLUSIONS The water extraction technology of Xiangqin jiere granules is optimized successfully in the study， which includes adding 8-fold water， extracting 3 times， and extracting for 1 hour each time.

Safety Evaluation of Tianzhi Granules in Treating Mild-to-moderate Vascular Dementia / 中国实验方剂学杂志

ObjectiveTo systematically evaluate the safety of Tianzhi granules used in the treatment of mild-to-moderate vascular dementia. MethodA randomized， double-blind， double-simulated， positive drug/placebo parallel controlled multi-center phase Ⅳ clinical trial and an open multi-center phase Ⅳ clinical trial of Tianzhi granules in the treatment of mild-to-moderate vascular dementia were conducted. Safety data of 1 492 patients were included and analyzed according to inclusion and exclusion criteria. The main evaluation measures were the incidence rate of adverse events/adverse reactions， laboratory indicators， vital signs， and electrocardiogram （ECG） results. ResultA total of six adverse events possibly related to the test drug occurred in 520 patients of the double-blind trial， and the symptoms were all mild and recovered. The incidence of adverse events was not statistically different among Tianzhi granules， donepezil， and placebo groups. Nine adverse events possibly related to the test drug were observed in 972 patients of the open trial， and the symptoms were mild and recovered. Laboratory tests （blood routine， urine routine， liver function， kidney function， and coagulation） and vital signs were compared before treatment （baseline） and after treatment of 12 and 24 weeks， respectively. There was no statistical significance in the main indicators before and after treatment. In the double-blinded trial， there was no significant difference in safety indicators between different groups before and after treatment. The most frequent adverse reaction was gastrointestinal discomfort， with an incidence rate of 6.64‰. ConclusionAdverse reactions occasionally occur in patients using Tianzhi granules， and it is safe to use Tianzhi granules to treat mild-to-moderate vascular dementia clinically.

Altered Chief Cell Morphology in the Gastric Gland of Streptozotocin-Diabetic Rats

SUMMARY: Diabetes mellitus (DM) is a metabolic disorder with rising incidences worldwide. Gastric symptoms of DM have been reported, including nausea, vomiting, bloating, and epigastric pain. Moreover, acute to chronic gastritis and atrophic gastritis occur in DM can affect the chief cells of the gastric gland. Chief cells are vital because of their ability to digest and separate vitamin B12 from protein. Lack of vitamin B12 leads to impaired DNA synthesis and abnormal metabolism in red blood cells, and eventually leading to pernicious anemia. Furthermore, decreased vibratory and positional senses, numbness, ataxia with subacute combined degeneration, and dementia are present in pernicious anemic patients. Twenty-four male adult Sprague-Dawley rats were used in this study. The rats were divided into control (n = 12) and diabetic (n = 12) groups. The rats were further separated into two categories: short-term (4 weeks) and long-term (24 weeks) groups. DM model was induced by manually injecting intraperitoneally with streptozotocin in citrate buffer at a dose of 60 mg/kg body weight. The same amount of buffer was injected into the control group. After sacrifice, three regions of the stomach (the cardia, body, and pylorus) were dissected. Histopathology was performed by staining with toluidine blue. Image analysis was used to quantify the zymogen granule accumulation in chief cells. The data were compared between the control and DM rats in each period using Student's t-test. In addition, transmission electron microscopy (TEM) was also used to examine the ultrastructures. There was a significant decrease in the percentage of zymogen granules in DM rats. Under TEM, the destructions of mitochondria, rough endoplasmic reticulum, and Golgi apparatus in the DM rat were observed in the chief cells. In rats with uncontrolled diabetes, there is damage to the chief cells all over the area of the stomach, affecting digestion and malabsorption of vitamin B12. Therefore, this result helps clinicians recognize that diabetic patients with gastric symptoms may have hidden pernicious anemia.

La diabetes mellitus (DM) es un trastorno metabólico con incidencia creciente a nivel mundial. Se han informado síntomas gástricos de DM, que incluyen náuseas, vómitos, distensión abdominal y dolor epigástrico. Además, la gastritis aguda a crónica y la gastritis atrófica que ocurren en la DM pueden afectar las células principales de la glándula gástrica. Las células principales son vitales debido a su capacidad para digerir y separar la vitamina B12 de las proteínas. La falta de vitamina B12 conduce a una síntesis de ADN deteriorada y un metabolismo anormal en los glóbulos rojos, lo que eventualmente conduce a una anemia perniciosa. Además, los pacientes con anemia perniciosa presentan disminución de los sentidos vibratorio y posicional, entumecimiento, ataxia con degeneración combinada subaguda y demencia. En este estudio se usaron 24 ratas Sprague-Dawley macho adultas. Las ratas se dividieron en grupos control (n = 12) y diabéticas (n = 12). Las ratas se separaron además en dos categorías: grupos a corto plazo (4 semanas) y a largo plazo (24 semanas). El modelo de DM se indujo inyectando manualmente por vía intraperitoneal estreptozotocina en tampón de citrato a una dosis de 60 mg/kg de peso corporal. Se inyectó la misma cantidad de tampón en el grupo control. Después del sacrificio, se disecaron tres regiones del estómago (cardias, cuerpo y píloro). La histopatología se realizó mediante tinción con azul de toluidina. El análisis de imágenes se utilizó para cuantificar la acumulación de gránulos de zimógeno en las células principales. Los datos se compararon entre las ratas control y DM en cada período utilizando la prueba t de Student. Además, se utilizó microscopía electrónica de transmisión (TEM) para examinar la ultraestructura celular. Hubo una disminución significativa en el porcentaje de gránulos de zimógeno en ratas DM. Bajo TEM, se observaron en las células principales las destrucción de las mitocondrias, del retículo endoplásmico rugoso y del complejo golgiense en la rata DM. En ratas con diabetes no controlada, hay daño en las células principales de toda el área del estómago, lo que afecta la digestión y la malabsorción de vitamina B12. Por lo tanto, este resultado ayuda a los médicos a reconocer que los pacientes diabéticos con síntomas gástricos pueden tener una anemia perniciosa oculta.

Sustancia Cromatofílica: Una Propuesta de Cambio a la Terminologia Histologica y Terminologia Neuroanatomica / Chromatophilic Substance: a Proposal to Change the Terminologia Histologica and Terminologia Neuroanatomica

En Terminologia Histologica y Terminologia Neuroanatomica está registrado el término Substantia chromatophilica de origen grecolatino, con los códigos H2.00.06.1.00009 y 78, respectivamente. Dicho término ha sido empleado para referirse a un conglomerado de estructuras que en unión fungen como maquinaria de síntesis proteica y que son característicos de las células nerviosas. Teniendo en cuenta los lineamientos de la Federative International Programme for Anatomical Terminology (FIPAT) referentes a la denominación de nombres estructurales con un valor descriptivo e informativo, creemos que el término en cuestión no es el más adecuado. Por lo anterior, el objetivo del presente estudio fue analizar y evaluar la concordancia de las raíces grecolatinas que componen el término. Para ello, se llevó a cabo una búsqueda en el Diccionario de la lengua española, Diccionario de Términos Médicos, diccionario VOX Griego-Español y el diccionario VOX Ilustrado Latino-Español Español-Latino. Los resultados obtenidos indican que la palabra chromatophilica no presenta registro en español, sin embargo, sus sinónimos hacen referencia a material biológico afín por los colorantes. En base a lo anterior, proponemos el término Ribocumulus corponeuralis en función de su estructura y ubicación, en reemplazo de Substantia chromatophilica.

SUMMARY: In Terminologia Histologica and Terminologia Neuroanatomica the term Substantia chromatophilica of Greco-Latin origin is registered with the codes H2.00.06.1.00009 and 78, respectively. This term has been used to refer to a conglomerate of structures that together function as protein synthesis machinery and are characteristic of nerve cells. Considering the guidelines of the Federative International Programme for Anatomical Terminology (FIPAT) regarding the denomination of structural names with a descriptive and informative value, we believe that the term in question is not the most appropriate. Therefore, this study aimed to analyze and evaluate the concordance of the Greco-Latin roots that compose the term. For this purpose, a search was conducted in the Diccionario de la Lengua Española, Diccionario de Términos Médicos, Diccionario VOX Griego-Español and the Diccionario VOX Ilustrado Latino-Español Español-Latino. The results obtained indicate that the word chromatophilica is not registered in Spanish, however, its synonyms refer to biological material related to dyes. Based on the aforementioned, we propose the term Ribocumulus corponeuralis based on its structure and location, as a replacement for Substantia chromatophilica.

Analysis of Formulation and Characteristics of Provincial Standards for Traditional Chinese Medicine Dispensing Granules / 中国实验方剂学杂志

In order to standardize the quality control of traditional Chinese medicine（TCM） dispensing granules， the Chinese Pharmacopoeia Commission has promulgated and implemented 200 national drug standards for TCM dispensing granules， but there are still varieties of TCM dispensing granules without unified standards. Many provinces have actively invested in the formulation of provincial standards for TCM dispensing granules to make up for the gaps in standards for varieties of traditional Chinese medicine dispensing granules other than the national standards. By the end of July 2022， 29 provincial-level administrative regions have successively promulgated and implemented a total of 5 602 provincial standards for TCM dispensing granules， involving more than 400 varieties. In order to better understand the formulation and characteristics of provincial standards， this study took 105 provincial standards that have been promulgated and implemented in Henan province as an example， and comprehensively analyzed the formulation and characteristics through quality control indicators such as dry extract rate of raw materials， contents of index components and their transfer rates， specifications and so on. The formulation and characteristics of the same TCM dispensing granules in the provincial standards of different provinces were further analyzed， in order to provide reference for the formulation of provincial standards of TCM dispensing granules and the implementation of national standards.

Analysis on Quality Standard of Fraxini Cortex（Fraxinus chinensis） Dispensing Granules Based on Standard Decoction / 中国实验方剂学杂志

ObjectiveTo establish the quality standard for Fraxini Cortex（Fraxinus chinensis） dispensing granules based on standard decoction， and to provide a basis for the quality control of this dispensing granules. MethodHigh performance liquid chromatography（HPLC） specific chromatograms of 15 batches of Fraxini Cortex（F. chinensis） standard decoctions and 3 batches of Fraxini Cortex（F. chinensis） dispensing granules were established with the mobile phase of 0.1% phosphoric acid aqueous solution（A）-acetonitrile（B） for gradient elution（0-10 min， 12%-15%B； 10-30 min， 15%-32%B） and the detection wavelength of 220 nm. And similarity evaluation， cluster analysis and principal component analysis（PCA） were also carried out. HPLC quantitative analysis of multi-components by single marker（QAMS） was established to determine the contents of the main components in the standard decoctions and dispensing granules. The contents of the corresponding components in Fraxini Cortex（F. chinensis） decoction pieces were also detected， and the transfer rates from decoction pieces to standard decoctions and dispensing granules were calculated. ResultThe similarities between specific chromatograms of 15 batches of Fraxini Cortex（F. chinensis） standard decoctions and 3 batches of Fraxini Cortex（F. chinensis） dispensing granules were all>0.9， and 7 common peaks were identified. The results of cluster analysis and PCA showed that there was some differences in the composition of different batches of standard decoctions， but did not show aggregation of origin. As the standard decoctions， the extract rate was 6.18%-11.62%， the contents of esculin， syringin， fraxin， esculetin， fraxetin， calceolarioside B were 44.92-103.51， 1.36-11.87， 33.26-90.73， 4.63-29.75， 2.40-16.86， 2.49-17.35 mg·g-1， and the transfer rates from decoction pieces to standard decoction were 25.21%-42.54%， 52.57%-88.84%， 43.43%-79.45%， 49.15%-88.27%， 49.22%-72.69%， 27.66%-47.67%， respectively. The extract rates of Fraxini Cortex（F. chinensis） dispensing granules were 10.4%-10.7%， the transfer rates of the above six components from decoction pieces to dispensing granules were 42.76%-43.17%， 80.01%-80.90%， 59.59%-59.88%， 51.35%-52.67%， 60.50%-60.93%， 37.98%-38.37%， respectively， which were generally consistent with the transfer rates from decoction pieces to standard decoctions. ConclusionThe established quality control standard of Fraxini Cortex（F. chinensis） dispensing granules based on standard decoctions is reasonable and reliable， which can provide reference for the quality control and process research of this dispensing granules.

Investigation on the mechanism of Compound zaoren granules in improving insomnia based on serum meta-bonomics / 中国药房

OBJECTIVE To study the mechanism of Compound zaoren granule in improving insomnia. METHODS Forty-nine mice were divided into blank group， model group， positive control group 1 （Estazolam tablets 0.5 mg/kg），control group 2 （Shumian capsule 0.6 g/kg）， Compound zaoren granule low-dose， medium-dose and high-dose groups （2.5， 5， 10 g/kg）， with 7 mice in each group. The insomnia model was established by chronic unpredictable mild stress combined with 4-chloro-DL- phenylacetic acid. The behavioral changes of mice were investigated through open field test and pentobarbital sodium synergistic hypnosis experiment， as well as the pathomorphology of mice hypothalamus tissue was observed by HE staining. The metabonomics analysis and multivariate statistical analysis of serum in mice were performed by UHPLC-Q-TOF-MS/MS， and the differential metabolites were screened out； the metabolic pathway analysis was conducted based on MetaboAnalyst 5.0 database. RESULTS Compared with blank group， the total travelling distance， the number of entering the central region and the moving distance in the central region of the model group were significantly reduced （P＜0.05）， the proportion of total rest time was significantly increased （P＜0.05）， the sleep duration of mice was significantly shortened （P＜0.05）， and hypothalamic nerve cells damaged and severely vacuolated. Compared with model group， the total travelling distance of Compound zaoren granule low-dose and medium-dose groups were increased significantly and the proportions of total rest time of those groups were decreased significantly （P＜0.05）， and the sleep duration of mice in Compound zaoren granule high-dose group was prolonged significantly （P＜0.05）； the hypothalamic nerve cells of mice in each administration group recovered to varying degrees， and the hypothalamus histiocytes of mice in the Compound zaoren granules high-dose group were closer to those in the blank group. A total of 18 differential metabolites （such as phenylalanine， taurine， norvaline， methionine） and 4 important amino acid metabolic pathways （L-phenylalanine， tyrosine and tryptophan biosynthesis； taurine and hypotaurine metabolism； L-phenylalanine metabolism； cysteine and methionine metabolism） were identified through metabolomics analysis. CONCLUSIONS Compound zaoren granules can normalize the disordered metabolism in vivo by regulating differential metabolites such as phenylalanine， taurine， and four amino acid metabolic pathways， so as to improve insomnia.

Comprehensive chemical profiling and quantitative analysis of ethnicYi medicine Miao-Fu-Zhi-Tong granules using UHPLC-MS/MS / 中国天然药物

Developing analytical methods for the chemical components of natural medicines remains a challenge due to its diversity and complexity. Miao-Fu-Zhi-Tong (MFZT) granules, an ethnic Yi herbal prescription, comprises 10 herbs and has been clinically applied for gouty arthritis (GA) therapy. Herein, a series of chemical profiling strategies including in-house library matching, molecular networking and MS/MS fragmentation behavior validation based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) were developed for qualitative analysis of MFZT granules. A total of 207 compounds were identified or characterized in which several rare guanidines were discovered and profiled into alkyl substituted or cyclic subtypes. Moreover, network pharmacology analysis indicated that MFZT's anti-gout mechanism was mostly associated with the nuclear factor kappa-B (NF-κB) signaling, nucleotide oligomerization domain (NOD)-like signaling and rheumatoid arthritis pathways, along with the synergistic effect of 84 potential active compounds. In addition, a quantitative analytical method was developed to simultaneously determine the 29 potential effective components. Among them, berberine, pellodendrine, 3-feruloylquinic acid, neoastilbin, isoacteoside and chlorogenic acid derivatives at higher concentrations were considered as the chemical markers for quality control. These findings provide a holistic chemical basis for MFZT granules and will support the development of effective analytical methods for the herbal formulas of natural medicines.

Three oral Chinese patent medicines for children with tic disorder: a rapid health technology assessment / 中国中药杂志

This study aims to comprehensively evaluate the clinical value of Shaoma Zhijing Granules(SZG), Changma Xifeng Tablets(CXT), and Jiuwei Xifeng Granules(JXG) in the treatment of children with tic disorder with the method of rapid health technology assessment(RHTA), which is expected to serve as a reference for medical and health decision-making and clinical rational use of drugs in children. To be specific, relevant articles were retrieved from eight databases and three clinical trial registry platforms. After the quality evaluation, rapid assessment was carried out from the dimensions of disease burden and unmet needs, technical characteristics, safety, efficacy and economy, and the results were analyzed and presented descriptively. A total of 22 articles(1 in English, 21 in Chinese) were screened out: 18 randomized controlled trials(RCTs) and 4 clinical controlled trials(CCTs). Among them, 5 were about the SZG(all RCTs) and 9 were on CXT(6 RCTs and 3 CCTs). The rest 8 focused on JXG(7 RCTs and 1 CCT). Moreover, the overall risk of bias for 94.40% RCTs was evaluated as "some concerns" and only one(5.60%) had high risk of bias. In terms of quality, the 4 CCTs scored 5-6 points(<7 points), suggesting low quality. SZG alone or in combination with tiapride has obvious advantages in improving traditional Chinese medicine syndromes and tic symptoms compared with tiapride alone, with the average daily cost of CNY 79.44-119.16. Compared with conventional western medicine or placebo, CXT alone or in combination with conventional western medicine can improve the total effective rate and alleviate tic symptoms, and the average daily cost is CNY 22.50-67.50. JXG alone or in combination with conventional western medicine can effectively relieve tic symptoms compared with conventio-nal western medicine or placebo, with the average daily cost of CNY 82.42-164.85. The adverse events related to the three Chinese patent medicines mainly occurred in the digestive, respiratory, and nervous systems, all of which were mild. In general, SZG, CXT, and JXG are effective for children with tic disorder. They have been approved to be used in this field, of which SZG was approved in 2019, with the most up-to-date research evidence and high-quality RCT in Q1 journals. However, the comparative analysis of the three was affected by many factors, which should be further clarified. Based on the large sample data available in multiple dimensions, a comprehensive comparative evaluation of the three Chinese patent medicines should be carried out, thereby highlighting the advantages and disadvantages of them and serving a reference for rational clinical use and drug supervision.