[Research progress on pathogenic mechanism of sepsis-induced liver injury and treatment with traditional Chinese medicine and its active components].

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.

Intervention effect of Cigu Xiaozhi prescription on ceramide lipoapoptosis in non-alcoholic fatty liver disease.

OBJECTIVE: To explore the mechanism of the Chinese medicine Cigu Xiaozhi prescription (, CGXZ) in the treatment of the non-alcoholic fatty liver disease (NAFLD) by detoxification and phlegm-reducing, the effect of CGXZ prescription on ceramide-mediated lipid apoptosis in Hep G2 cells with NAFLD. METHODS: The experiment was randomly divided into 6 groups: normal control group, model group, CGXZ prescription medicated serum high, medium, and low dose groups, and pioglitazone positive control group. Using 500 µmol/L free fatty acid (FFA) mixture to induce Hep G2 cells to establish NAFLD cell model, respectively, with 2%, 4%, and 6% concentration of CGXZ prescription medicated serum intervention for 24 h. The changes in organelles and lipid droplet accumulation were observed under the electron microscope. Furthermore, TdT-mediated dUTP Nick-End Labeling method was used to assay hepatocyte apoptosis; Biochemical determination of glutamic-pyruvic transaminase, glutamic oxalacetic transaminase, triglycerides, and FFA levels in Hep G2 cells; the content of ceramide was determined by high-performance thin-layer chromatography. Finally, Western Blot and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine the protein and gene expression levels, such as inducible nitric oxide synthase (iNOS), nuclear factor κB (NF-κB), B cell lymphoma 2 (Bcl-2) and Bcl-2-associated X (Bax). RESULTS: Under the electron microscope, the cells in the model group showed moderate-to-severe steatosis, and apoptotic bodies could be seen. The model group had greater improvements in the apoptosis rate (P < 0.01), and the levels of ceramide C2 and FFA in the cytoplasm (P < 0.01) than the normal control group. The protein expressions of NF-κB, iNOS, and Bax were significantly up-regulated (P < 0.05), while the Bcl-2 had no significant change (P > 0.05). Compared with the model group, the levels of ceramide C2 and FFA (P < 0.01), the protein expressions of NF-κB, iNOS, and Bax (P < 0.05) in the CGXZ prescription treatment group and pioglitazone positive control group were significantly decreased; Only the Bcl-2 protein was significantly up-regulated in the high-dose Chinese medicine group (P < 0.05). The down-regulation of Bax mRNA expression in each Chinese medicine treatment group was significantly better than in the pioglitazone positive control group (P < 0.01). CONCLUSIONS: The CGXZ prescription, formulated with the method of detoxification and phlegm, can inhibit lipoapoptosis in the NAFLD cell model by down-regulating the levels of ceramide C2 and FFA, which may be achieved by regulating ceramide/iNOS/NF-κB signaling pathway.

Perspective of Calcium Imaging Technology Applied to Acupuncture Research.

Acupuncture, a therapeutic treatment defined as the insertion of needles into the body at specific points (ie, acupoints), has growing in popularity world-wide to treat various diseases effectively, especially acute and chronic pain. In parallel, interest in the physiological mechanisms underlying acupuncture analgesia, particularly the neural mechanisms have been increasing. Over the past decades, our understanding of how the central nervous system and peripheral nervous system process signals induced by acupuncture has developed rapidly by using electrophysiological methods. However, with the development of neuroscience, electrophysiology is being challenged by calcium imaging in view field, neuron population and visualization in vivo. Owing to the outstanding spatial resolution, the novel imaging approaches provide opportunities to enrich our knowledge about the neurophysiological mechanisms of acupuncture analgesia at subcellular, cellular, and circuit levels in combination with new labeling, genetic and circuit tracing techniques. Therefore, this review will introduce the principle and the method of calcium imaging applied to acupuncture research. We will also review the current findings in pain research using calcium imaging from in vitro to in vivo experiments and discuss the potential methodological considerations in studying acupuncture analgesia.

Single-cell transcriptomics reveals ferrimagnetic vortex iron oxide nanoring-mediated mild magnetic hyperthermia exerts antitumor effects by alleviating macrophage suppression in breast cancer.

The potential of Ferrimagnetic vortex iron oxide nanoring-mediated mild magnetic hyperthermia (FVIO-MHT) in solid tumor therapy has been demonstrated. However, the impact of FVIO-MHT on the tumor microenvironment (TME) remains unclear. This study utilized single-cell transcriptome sequencing to examine the alterations in the TME in response to FVIO-MHT in breast cancer. The results revealed the cellular composition within the tumor microenvironment (TME) was primarily modified due to a decrease in tumor cells and an increased infiltration of myeloid cells. Subsequently, an enhancement in active oxygen (ROS) metabolism was observed, indicating oxidative damage to tumor cells. Interestingly, FVIO-MHT reprogrammed the macrophages' phenotypes, as evidenced by alterations in the transcriptome characteristics associated with both classic and alternative activated phenotypes. And an elevated level of ROS generation and oxidative phosphorylation suggested that activated phagocytosis and inflammation occurred in macrophages. Additionally, cell-cell communication analysis revealed that FVIO-MHT attenuated the suppression between tumor cells and macrophages by inhibiting phagocytic checkpoint and macrophage migration inhibitory factor signaling pathways. Inhibition of B2m, an anti-phagocytosis checkpoint, could promote macrophage-mediated phagocytosis and significantly inhibit tumor growth. These data emphasize FVIO-MHT may promote the antitumor capabilities of macrophages by alleviating the suppression between tumor cells and macrophages.

Analysis of Vitamin D in Children with Henoch-Schonlein Purpura / 昆明医科大学学报

Objective To analyze the changes of vitamin D in children with Henoch-Schonlein purpura(HSP).Methods 130 children with HSP from Kunming Children's Hospital between July 2022-July 2023 were selected as the study subjects and 100 healthy children were selected during the same period as the control group.The blood samples were collected from the children with HSP and the healthy children.The content of vitamin D was measured by Kunming Kingmed Institute for Clinical Laboratory.Results The content of 25(OH)D in children with HSP was lower than that in healthy children,and the difference was statistically significant(P<0.01).The proportion of vitamin D insufficiency in children with HSP was higher than that in healthy children,and the difference was statistically significant(P<0.01).Conclusion The children with HSP are prone to vitamin D insufficiency.Vitamin D supplementation may provide a new method for the treatment of HSP.

Electroacupuncture at Sensitized Acupoints Relieves Somatic Referred Pain in Colitis Rats by Inhibiting Sympathetic-Sensory Coupling to Interfere with 5-HT Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate whether electroacupuncture (EA) at sensitized acupoints could reduce sympathetic-sensory coupling (SSC) and neurogenic inflammatory response by interfering with 5-hydroxytryptamine (5-HT)ergic neural pathways to relieve colitis and somatic referred pain, and explore the underlying mechanisms.@*METHODS@#Rats were treated with 5% dextran sodium sulfate (DSS) solution for 7 days to establish a colitis model. Twelve rats were randomly divided into the control and model groups according to a random number table (n=6). According to the "Research on Rat Acupoint Atlas", sensitized acupoints and non-sensitized acupoints were determined. Rats were randomly divided into the control, model, Zusanli-EA (ST 36), Dachangshu-EA (BL 25), and Xinshu (BL 15) groups (n=6), as well as the control, model, EA, and EA + GR113808 (a 5-HT inhibitor) groups (n=6). The rats in the control group received no treatment. Acupuncture was administered on 2 days after modeling using the stimulation pavameters: 1 mA, 2 Hz, for 30 min, with sparse and dense waves, for 14 consecutive days. GR113808 was injected into the tail vein at 5 mg/kg before EA for 10 min for 7 consecutive days. Mechanical sensitivity was assessed with von Frey filaments. Body weight and disease activity index (DAI) scores of rats were determined. Hematoxylin and eosin staining was performed to observe colon histopathology. SSC was analyzed by immunofluorescence staining. Immunohistochemical staining was performed to detect 5-HT and substance P (SP) expressions. The calcitonin gene-related peptide (CGRP) in skin tissue and tyrosine hydroxylase (TH) protein levels in DRG were detected by Western blot. The levels of hyaluronic acid (HA), bradykinin (BK), prostaglandin I2 (PGI2) in skin tissue, 5-HT, tryptophan hydroxylase 1 (TPH1), serotonin transporters (SERT), 5-HT 3 receptor (5-HT3R), and 5-HT 4 receptor (5-HT4R) in colon tissue were measured by enzyme-linked immunosorbent assay (ELISA).@*RESULTS@#BL 25 and ST 36 acupoints were determined as sensitized acupoints, and BL 15 acupoint was used as a non-sensitized acupoint. EA at sensitized acupoints improved the DAI score, increased mechanical withdrawal thresholds, and alleviated colonic pathological damage of rats. EA at sensitized acupoints reduced SSC structures and decreased TH and CGRP expression levels (P<0.05). Furthermore, EA at sensitized acupoints reduced BK, PGI2, 5-HT, 5-HT3R and TPH1 levels, and increased HA, 5-HT4R and SERT levels in colitis rats (P<0.05). GR113808 treatment diminished the protective effect of EA at sensitized acupoints in colitis rats (P<0.05).@*CONCLUSION@#EA at sensitized acupoints alleviated DSS-induced somatic referred pain in colitis rats by interfering with 5-HTergic neural pathway, and reducing SSC inflammatory response.

Novel Nitric Oxide Donor-Azole Conjugation Strategy for Efficient Treatment of Cryptococcus neoformans Infections.

Invasive fungal infections (IFIs) such as cryptococcal meningitis (CM) remain a serious health issue worldwide due to drug resistance closely related to biofilm formation. Unfortunately, available antifungal drugs with ideal safety and promising potency are still lacking; thus, the research of new candidate and therapeutic approach is urgently needed. As an important gas messenger molecule, nitric oxide (NO) shows vital inhibition on various microorganism biofilms. Hence, three series of novel NO-donating azole derivatives were designed and synthesized, and the in vitro antifungal activity as well as the mechanism of action was investigated. Among them, 3a and 3e displayed excellent antifungal activity against Cryptococcus neoformans and biofilm depending on the release of NO. Moreover, a more stable analogue 3h of 3a demonstrated markedly anti-CM effects via intranasal dropping, avoiding the first-pass effects and possessing a better brain permeability bypass blood-brain barrier. These results present a promising antifungal candidate and intranasal dropping approach for the treatment of CM, warranting further studies.

Solanum nigrum Linn.: Advances in anti-cancer activity and mechanism in digestive system tumors.

Cancer has currently become a serious public health issue in many countries worldwide, and tumors of the digestive system have attracted an increasing number of researchers' due to their numerous types, high proportion and wide area of occurrence. While tumors of the digestive system suffer from high mortality rates, leading to untimely diagnosis and a poor prognosis, making it necessary to update current treatment approaches such as surgery, radiation therapy, and chemotherapy. This highlights the importance of exploring novel therapeutic ideas and targets. Traditional Chinese medicine has a long history of clinical use due to its low toxicity and multi-factor targeting of multiple pathways. As a kind of traditional Chinese herb, S. nigrum Linn. is highly regarded for its proven antitumor activity. The aim of this study was to comprehensively recapitulate and analyze the anti-cancer effects and molecular mechanisms of treatment of gastrointestinal tumors with S. nigrum Linn. extracts and related compounds, including classical signaling pathways mediated by them as well as noncoding RNA pathways associated with tumor suppression. Components that have been found to be responsible for the anti-cancer activity of S. nigrum Linn. include solanine, solasonine, solamargine, a-L-rhhamnopyranose, uttroside B, degalactotigonin, glycoprotein, and other compounds. The underlying mechanisms of anti-cancer activity reflected in this study include apoptosis, cell cycle arrest, autophagy, anti-angiogenesis, suppression of metastasis and invasion, immune escape, and increased sensitivity to radiotherapy. S. nigrum Linn. has great potential in the treatment of tumors of the digestive system, and through further clinical trials and pharmacological mechanisms it has the potential to become a uniform and standardized anti-tumor drug.

[Molecular mechanism of ligustilide attenuating OGD/R injury in PC12 cells by inhibiting ferroptosis].

The aim of this study is to explore the mechanism of ligustilide, the main active constituent of essential oils of traditional Chinese medicine Angelicae Sinensis Radix, on alleviating oxygen-glucose deprivation/reperfusion(OGD/R) injury in PC12 cells from the perspective of ferroptosis. OGD/R was induced in vitro, and 12 h after ligustilide addition during reperfusion, cell viability was detected by cell counting kit-8(CCK-8) assay. DCFH-DA staining was used to detect the level of intracellular reactive oxygen species(ROS). Western blot was employed to detect the expression of ferroptosis-related proteins, glutathione peroxidase 4(GPX4), transferrin receptor 1(TFR1), and solute carrier family 7 member 11(SLC7A11), and ferritinophagy-related proteins, nuclear receptor coactivator 4(NCOA4), ferritin heavy chain 1(FTH1), and microtubule-associated protein 1 light chain 3(LC3). The fluorescence intensity of LC3 protein was analyzed by immunofluorescence staining. The content of glutathione(GSH), malondialdehyde(MDA), and Fe was detected by chemiluminescent immunoassay. The effect of ligustilide on ferroptosis was observed by overexpression of NCOA4 gene. The results showed that ligustilide increased the viability of PC12 cells damaged by OGD/R, inhibited the release of ROS, reduced the content of Fe and MDA and the expression of TFR1, NCOA4, and LC3, and improved the content of GSH and the expression of GPX4, SLC7A11, and FTH1 compared with OGD/R group. After overexpression of the key protein NCOA4 in ferritinophagy, the inhibitory effect of ligustilide on ferroptosis was partially reversed, indicating that ligustilide may alleviate OGD/R injury of PC12 cells by blocking ferritinophagy and then inhibiting ferroptosis. The mechanism by which ligustilide reduced OGD/R injury in PC12 cells is that it suppressed the ferroptosis involved in ferritinophagy.

Fixating lead in coal gangue with phosphate using phosphate-dissolving bacteria: Phosphorus dissolving characteristics of bacteria and adsorption mechanism of extracellular polymer.

Controlling and preventing lead pollution is currently the focus of environmental remediation. Coal gangue contains large quantities of lead, and its environmental impact cannot be ignored. This study investigated the tolerance of Stenotrophomonas maltophilia (YZ-1 train) to lead ion and its fixation effect on lead in coal gangue. The fixation mechanism of lead ions by using the YZ-1 train was studied with CaHPO4 and Ca3(PO4)2. The tolerance mechanism and fixation characteristics of the three bacterial extracellular polymers and cell components to lead were analyzed. The results show that the YZ-1 train had a strong resistance to lead ions. The amount of lead released from coal gangue can be reduced by up to 91.1% upon treatment with the YZ-1 train, which can dissolve phosphate minerals to form stable hydroxyapatite (Pb5(PO4)3(OH)) and pyromorphite (Pb5(PO4)3Cl) with lead ions. Tryptophan and tyrosine from cellular components and extracellular polymers with loosely and tightly bound proteins are the main participants in the fixation of lead ions. The by-products of soluble microbes affect the fixation of lead ions in soluble extracellular polymers. The carboxylic acids and carboxylates secreted by bacteria are involved in the adsorption and fixation of lead ions.

[Involvement of sympathetic nerve activation in acupoint application induced improvement of gastric ulcer and motility in rats with gastric ulcer].

OBJECTIVE: To observe the effect of mustard oil application at "Liangmen" (ST21) on gastric ulcer (GU) and gastric motility and its association with the sympathetic nerve activity in rats with GU, so as to provide experimental basis for improvement of GU by acupoint application. METHODS: Thirty-nine male SD rats were randomly divided into control (n=7), model, acupoint application (AA), medication (guanethidine, an adrenergic sympathetic antagonist) and AA+medication groups (n=8 in each of the latter 4 groups). The GU model was made by applying acetic acid-immersed filter paper onto the gastric antrum. For rats of the AA and AA+medication groups, 50% mustard oil was applied to left ST21 for 10 min, once a day, for 9 consecutive days. Rats of the medication and AA+medication groups received intraperitoneal injection of guanethidine solution (40 mg/kg) beginning from the modeling day on, once a day for 10 consecutive days. The rat's body weight of each group was recorded on the 0th, 1st, 3rd, 7th and 9th day. The intragastric peristaltic wave frequency and the myoelectrical activity (frequency of slow waves, and integration of fast waves) of the gastric smooth muscle were recorded by using PowerLab data acquisition system. The gastric ulcer area was measured after the rats were executed, and histopathological changes of gastric antrum tissues (histopathological score including epithelial cell injury, submucosal edema, hemorrhagic injury, inflammatory cell infiltration score) were observed after H.E. staining. RESULTS: Compared with the control group, the body weight ratio, frequency of gastric peristaltic waves and slow wave frequency of gastric smooth muscle were significantly decreased (P<0.001, P<0.05), while the ulcer area, total histopathological score, epithelial cell injury score, submucosal edema score, hemorrhagic injury score and inflammatory cell infiltration score were significantly increased in the model group (P<0.05, P<0.001). Relevant to the model group, the AA group had a significant increase in the body weight ratio, frequency of gastric peristaltic waves, slow wave frequency, integration of fast waves (P<0.05, P<0.001), and a considerable decrease in the ulcer area, total histopathological score, epithelial cell injury score, submucosal edema score, hemorrhagic injury score and inflammatory cell infiltration score (P<0.05, P<0.001), and the medication group has a significantly decrease in the frequency of gastric peristaltic waves (P<0.05). In comparison with the AA group, the body weight ratio, frequency of gastric peristaltic waves and slow wave frequency of gastric smooth muscle in both medication and AA+medication groups, and the integration of fast waves in the medication group were obviously lower (P<0.05, P<0.001, P<0.01), whereas the levels of ulcer area, total pathological score, submucosal edema score, hemorrhagic injury score and inflammatory cell infiltration score in both medication and AA+medication groups, and the epithelial cell injury score in medication group were significantly higher (P<0.05, P<0.001). CONCLUSION: Application of mustard oil at acupoint ST21 can effectively remit GU caused by acetic acid and regulate gastric rhythmic contraction, which was mediated by sympathetic nerve.

Postprogression treatment of lenvatinib plus PD-1 inhibitor in advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy.

PURPOSE: This study compares the efficacy and safety of lenvatinib and programmed cell death protein (PD)-1 versus lenvatinib alone for advanced hepatocellular carcinoma (Ad-HCC) refractory to hepatic arterial infusion chemotherapy (HAIC). METHODS: From April 2016 to September 2021, 145 patients with Ad-HCC refractory to HAIC based on modified Response Evaluation Criteria in Solid Tumors criteria were enrolled by two radiologists and classified into the HAIC-lenvatinib group (H-L, n = 87) and HAIC-lenvatinib-PD-1 group (H-L-P, n = 58). A propensity score-matching method was used to reduce selective bias. The overall survival (OS) and postprogression-free survival (PPS) rates were compared using the Kaplan-Meier method with log-rank test. Multivariable analyses of independent prognostic factors were evaluated by means of the forward stepwise Cox regression model. RESULTS: After propensity score matching 1:1, the median OS was 43.6 months in the H-L-P group and was significantly longer than that (18.9 months) of the H-L group (p = .009). The median PPS was 35.6 months in the H-L-P group and was significantly longer than that (9.4 months) of the H-L group (p = .009). Multivariate analyses showed that the factors that significantly affected the OS were α-fetoprotein (hazard ratio [HR], 2.14; 95% CI, 1.26-3.98; p = .006), early response to HAIC (HR, 0.44; 95% CI, 1.20-3.85; p = .009), and H-L treatment (HR, 0.52; 95% CI, 0.30-0.86; p = .012). Modified albumin-bilirubin grade (HR, 1.32; 95% CI, 1.03-1.70; p = .026), early response to HAIC (HR, 0.44; 95% CI, 0.25-0.77; p = .004), and H-L (HR, 0.47 ; 95% CI, 0.28-0.78; p = .003) significantly affected the PPS. CONCLUSIONS: This combination therapy of PD-1 inhibitors plus lenvatinib has promising survival benefits in the management of patients with Ad-HCC refractory to HAIC. PLAIN LANGUAGE SUMMARY: Lenvatinib plus programmed death 1 inhibitor is an effective and safe postprogression treatment and improved significantly overall survival and postprogression-free survival compared with lenvatinib alone in patients with advanced hepatocellular carcinoma refractory to hepatic arterial infusion chemotherapy.

Microbial community structure of different tongue fur types in patients with chronic gastritis.

OBJECTIVE: To explore the correlation between tongue and oral microbiota, we studied the microbial community structure of different tongue coating types in patients with chronic gastritis. METHODS: 16S rDNA gene sequencing and bioinformatics analysis were used to study the dynamic changes and correlation of microbial flora in patients with chronic gastritis, healthy people, and patients with different tongue fur. In addition, it was also discussed between the severity of gastritis and the microflora of tongue fur. RESULTS: The microbial diversity of tongue fur in patients with chronic gastritis was significantly different from healthy controls. There were significant changes in bacterial communities' diversity and relative abundance between extra tongue fur in patients but not in healthy people. Oral bacteria with relative abundance > 1% and < 0.05 among different tongue fur flora were dominant bacteria, including 12 phyla such as and , and 256 genera such as and . CONCLUSIONS: The changes in oral flora in patients with chronic gastritis were related to tongue fur. Therefore, the significant microbiota might enlighten further study on the correlation between tongue inspection and oral microbiota in patients with chronic gastritis.

Guanxin Danshen Dripping Pills Improve Quality of Life and Cardiovascular Prognoses of CHD Patients after PCI with Anxiety or Depression (GLAD Study): A Randomized Double-Blind Placebo-Controlled Study / 中国结合医学杂志

OBJECTIVE@#To assess the efficacy and safety of Guanxin Danshen Dripping Pills (GXDS) in the treatment of depression or anxiety in patients with coronary heart disease (CHD) after percutaneous coronary intervention (PCI).@*METHODS@#From September 2017 to June 2019, 200 CHD patients after PCI with depression and anxiety were included and randomly divided into GXDS (100 cases) and placebo control groups (100 cases) by block randomization and a random number table. Patients in the GXDS and control groups were given GXDS and placebo, respectively, 0.4 g each time, 3 times daily for 12 weeks. The primary outcomes were scores of Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Scale (GAD-7) and the Seattle Angina Pectoris Scale (SAQ). The secondary outcomes included 12 Health Survey Summary Form (SF-12) scores and the first onset time and incidence of major adverse cardiovascular events (MACEs). Other indices including blood pressure, blood lipids, microcirculation and inflammatory-related indices, etc. were monitored at baseline, week 4, and week 12.@*RESULTS@#In the full analysis set (200 cases), after treatment, the PHQ-9 and GAD-7 scores in the GXDS group were considerably lower than those in the control group (P<0.05). Compared with the baseline, the total PHQ-9 scores of the experimental and control groups decreased by 3.97 and 1.18, respectively. The corrected mean difference between the two groups was -2.78 (95% CI: -3.47, -2.10; P<0.001). The total GAD-7 score in the GXDS group decreased by 3.48% compared with the baseline level, while that of the placebo group decreased by 1.13%. The corrected mean difference between the two groups was -2.35 (95% CI: -2.95, -1.76; P<0.001). The degree of improvement in SAQ score, SF-12 score, endothelin and high-sensitive C-reactive protein levels in the GXDS group were substantially superior than those in the placebo group, and the differences between the two groups were statistically significant (P<0.05). Similar results were obtained in the per protocol population analysis of 177 patients. Three cases of MACES were reported in this study (1 in the GXDS group and 2 in the placebo group), and no serious adverse events occurred.@*CONCLUSIONS@#GXDS can significantly alleviate depression and anxiety, relieve symptoms of angina, and improve quality of life in patients with CHD after PCI. (Registration No. ChiCTR1800014291).

Pharmacokinetic effects of metformin hydrochloride, food and alcohol on Ramulus Mori (Sangzhi) alkaloids / 药学学报

Ramulus Mori (Sangzhi) alkaloids (SZ-A) are a group of polyhydroxy alkaloids extracted and isolated from the traditional Chinese medicine mulberry twig, which is mainly used for the treatment of type 2 diabetes mellitus (T2DM). In addition to acting as a glycosidase inhibitor in the small intestine after oral administration, SZ-A can also be absorbed into blood and widely distributed to target organs related to diabetes, exerting multiple pharmacological effects. It is important to elucidate the possible pharmacokinetic influences of SZ-A for its clinical rational applications, such as drug interactions, the effects of food and alcohol on the absorption of SZ-A. However, studies in this area are limited. Therefore, the pharmacokinetic interactions between orally administrated SZ-A (50 mg·kg-1) and metformin hydrochloride (Met, 200 mg·kg-1) in Sprague-Dawley (SD) rats were examined. Then, the effect of food (standard feed) on the pharmacokinetics of SZ-A was investigated using fasting administration of SZ-A (50 mg·kg-1) in rats as a control. Finally, we investigated the pharmacokinetic characteristics of SZ-A (50 mg·kg-1) in different concentrations alcohol solutions using aqueous solution of SZ-A administered to rats as a control to evaluate the effect of alcohol on the bioabsorption of SZ-A. The results showed no significant pharmacokinetic interactions between SZ-A and Met after combination treatment. The standard feed had little effect on the pharmacokinetic profile of SZ-A. Alcohol retarded the absorption of SZ-A, resulting in a significant decrease in the Cmax of SZ-A. The decrease was greater at higher alcohol concentrations; however, no significant difference was observed in the AUC0-t. These results support the clinical rational applications of SZ-A. All animal protocols were approved by the Ethics Committee of Kangtai Medical Laboratory Service Hebei Co., Ltd. (Hebei, China) (No. MDL2022-01-17-1).

Correlation of maternal drug use and cytochrome P450 geneticpolymorphisms with congenital heart disease in offspring / 西安交通大学学报(医学版)

【Objective】 To investigate the association of maternal medication during early pregnancy and cytochrome P450 (CYP450) genetic polymorphisms with the risk of congenital heart disease (CHD) in offspring. 【Methods】 We selected 127 pregnant women with CHD fetuses as the observation group and 132 pregnant women with non-CHD fetuses as the control group. Their characteristics and medication history were investigated, and CYP450 polymorphisms were detected. Logistic regression analysis was used to assess the association between maternal medication, CYP450 gene variations, and offspring CHD risk. 【Results】 The risk of CHD in offspring was higher in the observation group with maternal use of ovulation induction drugs, antihypertensive drugs, antibiotics, antidepressants, miscarriage prevention drugs, and traditional Chinese medicine (P<0.05). The A/T and T/T genotypes in rs1065852 and the C/G and G/G genotypes in rs16947 increased the risk of CHD in offspring compared to their respective genotypes. The risk of CHDs in offspring increased with the presence of risk genotypes (A/T or T/T) at the rs1065852 locus of the maternal CYP450 gene and early pregnancy medication use (P<0.05); the same was observed for risk genotypes (C/G or G/G) at the rs16947 locus (P<0.05). 【Conclusion】 Maternal medication during early pregnancy may be associated with offspring CHD, and the rs1065852 and rs16947 loci of CYP450 are significantly related to the risk of CHD in offspring.

Identification of chemical components and network pharmacology of Huanglian Decoction based on UPLC-Q-TOF-MS/MS technology / 中国中药杂志

The chemical components of Huanglian Decoction were identified by ultra-performance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry(UPLC-Q-TOF-MS/MS) technology. The gradient elution was conducted in Agilent ZORBAX Extend-C_(18) column(2.1 mm×100 mm, 1.8 μm) with the mobile phase of 0.1% formic acid aqueous solution(A)-acetonitrile(B) at a flow rate of 0.3 mL·min~(-1) and the column temperature of 35 ℃. The MS adopted the positive and negative ion mode of electrospray ionization(ESI), and the MS data were collected under the scanning range of m/z 100-1 500. Through high-resolution MS data analysis, combined with literature comparison and confirmation of reference substances, this paper identified 134 chemical components in Huanglian Decoction, including 12 alkaloids, 23 flavonoids, 22 terpenes and saponins, 12 phenols, 7 coumarins, 12 amino acids, 23 organic acids, and 23 other compounds, and the medicinal sources of the compounds were ascribed. Based on the previous studies, 7 components were selected as the index components. Combined with the network pharmacology research and analysis me-thods, the protein and protein interaction(PPI) network information of the intersection targets was obtained through the STRING 11.0 database, and 20 core targets of efficacy were screened out. In this study, UPLC-Q-TOF-MS/MS technology was successfully used to comprehensively analyze and identify the chemical components of Huanglian Decoction, and the core targets of its efficacy were discussed in combination with network pharmacology, which laid the foundation for clarifying the material basis and quality control of Huanglian Decoction.

Professor HAN Wei's clinical experience of acupuncture and moxibustion with Tongyang Xingshen for adolescent depressive disorder / 中国针灸

Professor HAN Wei 's clinical experience of acupuncture and moxibustion with Tongyang Xingshen (promoting yang and regaining consciousness) for adolescent depressive disorder is introduced. It is believed that the internal causes of adolescent depressive disorder are mostly emotional and physical factors, while the external causes are mainly social factors, and yang-qi stagnation and emotional disorder are the key pathogenesis. The key of acupuncture and moxibustion with Tongyang Xingshen is warming and regulating the governor vessel. The governor vessel acupoints at head, neck and back are selected. At head, Baihui (GV 20) and Yintang (GV 24+) are selected; at neck, Fengfu (GV 16) and Dazhui (GV 14) are selected; at back, Taodao (GV 13), Shenzhu (GV 12), Shendao (GV 11), Zhiyang (GV 9) and Jinsuo (GV 8) are selected. The combination of disease differentiation and syndrome differentiation should be highly valued, and the moxibustion with Tongyang and acupuncture with Xingshen should be used simultaneously, and the strong stimulation is suggested.

Effect of Tongdu Tiaoshen electroacupuncture pretreatment on PPARγ-mediated pyroptosis of cerebral cortex in rats with cerebral ischemia reperfusion injury / 中国针灸

OBJECTIVE@#To observe the effect of Tongdu Tiaoshen (promoting the circulation of the governor vessel and regulating the spirit) electroacupuncture (EA) pretreatment on pyroptosis mediated by peroxisome proliferators-activated receptor γ (PPARγ) of the cerebral cortex in rats with cerebral ischemia reperfusion injury (CIRI) and explore the potential mechanism of EA for the prevention and treatment of CIRI.@*METHODS@#A total of 110 clean-grade male SD rats were randomly divided into a sham-operation group, a model group, an EA group, an EA + inhibitor group and an agonist group, 22 rats in each group. In the EA group, before modeling, EA was applied to "Baihui" (GV 20), "Fengfu" (GV 16) and "Dazhui" (GV 14), with disperse-dense wave, 2 Hz/5 Hz in frequency, 1 to 2 mA in intensity, lasting 20 min; once a day, consecutively for 7 days. On the base of the intervention as the EA group, on the day 7, the intraperitoneal injection with the PPARγ inhibitor, GW9662 (10 mg/kg) was delivered in the EA + inhibitor group. In the agonist group, on the day 7, the PPARγ agonist, pioglitazone hydrochloride (10 mg/kg) was injected intraperitoneally. At the end of intervention, except the sham-operation group, the modified thread embolization method was adopted to establish the right CIRI model in the rats of the other groups. Using the score of the modified neurological severity score (mNSS), the neurological defect condition of rats was evaluated. TTC staining was adopted to detect the relative cerebral infarction volume of rat, TUNEL staining was used to detect apoptosis of cerebral cortical nerve cells and the transmission electron microscope was used to observe pyroptosis of cerebral cortical neural cells. The positive expression of PPARγ and nucleotide-binding to oligomerization domain-like receptor protein 3 (NLRP3) in the cerebral cortex was detected with the immunofluorescence staining. The protein expression of PPARγ, NLRP3, cysteinyl aspartate specific protease-1 (caspase-1), gasdermin D (GSDMD) and GSDMD-N terminal (GSDMD-N) in the cerebral cortex was detected with Western blot. Using the quantitative real-time fluorescence-PCR, the mRNA expression of PPARγ, NLRP3, caspase-1 and GSDMD of the cerebral cortex was detected. The contents of interleukin (IL)-1β and IL-18 in the cerebral cortex of rats were determined by ELISA.@*RESULTS@#Compared with the sham-operation group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were increased (P<0.01), pyroptosis was severe, the protein and mRNA expression levels of PPARγ, NLRP3, caspase-1 and GSDMD were elevated (P<0.01); and the protein expression of GSDMD-N and contents of IL-1β and IL-18 were increased (P<0.01) in the model group. When compared with the model group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were decreased (P<0.01), pyroptosis was alleviated, the protein and mRNA expression levels of PPARγ were increased (P<0.01), the protein and mRNA expression levels of NLRP3, caspase-1 and GSDMD were decreased (P<0.01), the protein expression of GSDMD-N was reduced (P<0.01); and the contents of IL-1β and IL-18 were lower (P<0.01) in the EA group and the agonist group; while, in the EA + inhibitor group, the protein expression of PPARγ was increased (P<0.01), the protein and mRNA expression levels of NLRP3 and GSDMD were decreased (P<0.01, P<0.05), the mRNA expression of caspase-1 was reduced (P<0.01); and the contents of IL-1β and IL-18 were lower (P<0.01). When compared with the EA + inhibitor group, the mNSS, the relative cerebral infarction volume and the TUNEL positive cells rate were decreased (P<0.05, P<0.01), pyroptosis was alleviated, the protein and mRNA expression levels of PPARγ were increased (P<0.01), the protein and mRNA expression levels of NLRP3, caspase-1 and GSDMD were decreased (P<0.01), the protein expression of GSDMD-N was reduced (P<0.01); and the contents of IL-1β and IL-18 were declined (P<0.01) in the EA group. Compared with the agonist group, in the EA group, the relative cerebral infarction volume and the TUNEL positive cells rate were increased (P<0.05, P<0.01), the mRNA expression of PPARγ was decreased (P<0.01) and the protein expression of GSDMD-N was elevated (P<0.05); and the contents of IL-1β and IL-18 were higher (P<0.01).@*CONCLUSION@#Tongdu Tiaoshen EA pretreatment can attenuate the neurological impairment in the rats with CIRI, and the underlying mechanism is related to the up-regulation of PPARγ inducing the inhibition of NLRP3 in the cerebral cortex of rats so that pyroptosis is affected.

Research on Mechanisms of Chinese Medicines in Prevention and Treatment of Postoperative Adhesion / 中国结合医学杂志

Postoperative adhesion (PA) is currently one of the most unpleasant complications following surgical procedures. Researchers have developed several new strategies to alleviate the formation of PA to a great extent, but so far, no single measure or treatment can meet the expectations and requirements of clinical patients needing complete PA prevention. Chinese medicine (CM) has been widely used for thousands of years based on its remarkable efficacy and indispensable advantages CM treatments are gradually being accepted by modern medicine. Therefore, this review summarizes the formating process of PA and the efficacy and action mechanism of CM treatments, including their pharmacological effects, therapeutic mechanisms and advantages in PA prevention. We aim to improve the understanding of clinicians and researchers on CM prevention in the development of PA and promote the in-depth development and industrialization process of related drugs.