[Contamination Characteristics and Ecological Risk of Antibiotics in Contaminated Sites of Typical Pharmaceutical Factories in China].

To understand the contamination characteristics and ecological risk of antibiotics in contaminated fields of pharmaceutical plants， samples of the surface soil， soil column， wastewater treatment process water， ground water， and residue dregs were collected from two typical antibiotic pharmaceutical plants in South and North China. A total of 87 commonly used antibiotics were quantified using ultrasound extraction-solid phase extraction and ultra-high performance liquid chromatography-mass spectrometry. The results showed that a total of 31 antibiotics of five classes were detected in all types of samples， and the maximum concentrations at each sampling point in the surface soil， soil column， residue dregs， wastewater treatment process water， and groundwater were 420 ng·g-1， 595 ng·g-1， 139 ng·g-1， 1 151 ng·L-1， and 6.65 ng·L-1， respectively. Most of the antibiotics were found in the surface soil， showing a decreasing trend with the depth of the soil column. The ecological risk assessment indicated that sulfamethazine， sulfaquinoxaline， tetracycline， chlorotetracycline， and D-sorbitol were at higher risk. Improving the efficiency of antibiotic removal from pharmaceutical wastewater and preventing production shop leaks are effective measures of controlling antibiotic contamination into and around fields in pharmaceutical plants.

Efficacy of Combining Traditional Chinese Manual Therapy (Tuina) and Specific Therapeutic Neck Exercise in Young Adults with Non-Specific Chronic Neck Pain: Study Protocol for a Randomized Controlled Trial.

Purpose: Non-specific chronic neck pain (NSCNP) is an increasingly common musculoskeletal disease and an important issue in the global healthcare system. Some studies have shown that the combination of manual therapy and exercise is effective in treating NSCNP but still with several limitations. Traditional Chinese manual therapy (tuina) is a Chinese manual therapy that consists of soft tissue manipulation and spinal manipulation. This study aims to design a randomized controlled trial to assess the effect of a tuina combined with specific therapeutic neck exercise modified protocol for NSCNP patients. Patients and Methods: This is a study protocol for a randomized, participant-, assessor- and analyst-blinded controlled trial. Eighty-eight eligible NSCNP patients will be randomly allocated into tuina combined with specific therapeutic neck exercise group (TSTE group) and tuina combined with sham therapeutic neck exercise group (TS group) in a ratio of 1:1. All participants will receive 8 treatment sessions applied in 4 weeks and then be followed up for another 12 weeks. Clinical data will be collected at baseline, during treatment phase (at the 2- and 4-week) and at the 8-, 12-, 16-week follow-ups. The primary outcome is the changes in neck pain intensity (visual analogue scale). The secondary outcomes include neck disability (Neck Disability Index), cervical range of motion (ROM), neck muscle endurance, cervical muscle cross-sectional area, cervical curvature and analgesic consumption. Adverse events will be collected and recorded throughout the study. Conclusion: We will discuss whether our tuina combined with specific therapeutic neck exercise modified protocol is more effective at improving pericervical muscle endurance, ROM, cervical muscle cross-sectional area and cervical curvature than tuina alone, thereby decreases neck pain and disability in individuals with NSCNP more effectively. Trial Registration: Chinese Clinical Trials Registry, ChiCTR2300067903. Registered on 31 January 2023.

[Effect of acupuncture on HIF-1α/NLRP3 inflammatory signaling pathway in the rats with cerebral ischemia-reperfusion injury].

OBJECTIVE: To observe the effects of Xingnao Kaiqiao (regaining consciousness and opening orifices) acupuncture therapy on the expression of hypoxia-inducible factor 1α (HIF-1α) and Nod-like receptor protein 3 (NLRP3) in cerebral ischemia-reperfusion rats, and to explore the mechanism of acupuncture against cerebral ischemia-reperfusion injury. METHODS: Seventy-two male SD rats were randomly divided into a sham-operation group, a model group, an acupuncture group and a non-point acupuncture group, with 18 rats in each one. Using modified Longa thread embolization method, the rat model of acute focal cerebral ischemia was prepared; and after 2 h ischemia, the reperfusion was performed to prepared the model of cerebral ischemia-reperfusion. Immediately after reperfusion, Xingnao Kaiqiao acupuncture method was applied to bilateral "Neiguan" (PC 6) and "Shuigou" (GV 26) in the acupuncture group, while in the non-point acupuncture group, acupuncture was delivered at non-points and all of the needles were retained for 30 min in these two groups. The samples were collected 24 h after reperfusion in the rats of each group. Zea-Longa neurological deficit score was used to evaluate the degree of cerebral neurological impairment, TTC staining was adopted to observe the volume percentage of cerebral infarction, HE staining was provided to observe the morphological changes of brain, and Western blot was applied for detecting the expression of HIF-1α and NLRP3 proteins in the cerebral cortex on the right side. RESULTS: Compared with the sham-operation group, neurological deficit score and volume percentage of cerebral infarction were increased in the model group (P<0.01), and HIF-1α and NLRP3 protein expression was elevated (P<0.01). Compared with the model group, neurological deficit score and volume percentage of cerebral infarction were decreased (P<0.01), and HIF-1α and NLRP3 protein expression was lower (P<0.01) in the acupuncture group. There was no significant difference in above indexes in the non-point acupuncture group compared with the model group (P>0.05). Compared with the sham-operation group, the brain tissue of the rats in the model group and the non-point acupuncture group was loose and edema, and the nuclei were shriveled. The brain tissue morphology in the acupuncture group was similar to that of the sham-operation group. CONCLUSION: Acupuncture can alleviate cerebral ischemia-reperfusion injury, and its mechanism may be related to the regulation of HIF-1α/NLRP3 signaling pathway to attenuate inflammatory response.

Integrating metabonomics and metagenomics sequencing to study the anti-liver fibrosis effects of palmatine in Corydalis saxicola Bunting.

ETHNOPHARMACOLOGICAL RELEVANCE: Corydalis saxicola Bunting (CS), a traditional Chinese folk medicine, has been effectively used for treating liver disease in Zhuang nationality in South China. However, the main anti-liver fibrosis ingredients in CS are incompletely understood. AIM OF THE STUDY: To elucidate the main anti-liver fibrosis ingredients in CS and its underlying mechanism. MATERIAL AND METHODS: Firstly, spectrum-effect relationship (SER) strategy was applied to identify the major ingredients against liver fibrosis in CS. Subsequently, 1H NMR metabonomics and metagenomics sequencing techniques were used to clarify the intervention of palmatine (PAL) on liver fibrosis. Furthermore, the expression of tight junction proteins and the levels of liver inflammation factors were examined, the effect of PAL on microbiota was verified by FMT. RESULTS: The SER model revealed that PAL was the most important active ingredient in CS. 1H NMR fecal metabonomics showed that PAL could reserve the abnormal levels of gut microbial-mediated metabolites of liver fibrosis, such as isoleucine, taurine, butyrate, propionate, lactate, glucose, which mainly involved in amino acid metabolism, intestinal flora metabolism and energy metabolism. Metagenomics sequencing found that PAL could callback the abundance of s__Lactobacillus_murinus, s__Lactobacillus_reuteri, s__Lactobacillus_johnsonii, s__Lactobacillus_acidophilus and s__Faecalibaculum_rodentium to varying degree. Furthermore, the intestinal barrier function and the levels of hepatic inflammation factors were significantly ameliorated by PAL. FMT demonstrated that the therapeutic efficiency of PAL was closely associated with gut microbiota. CONCLUSION: The effects of CS on liver fibrosis were attributed in part to PAL by alleviating metabolic disorders and rebalancing gut microbiota. The SER strategy may be a useful method for the discovery of active constituents in natural plants.

The efficacy and safety of acupuncture therapy for sciatica: A systematic review and meta-analysis of randomized controlled trails.

Background and objective: Sciatica is a common type of neuropathic pain disease which poses a huge financial burden to the patient. For patients with sciatica, acupuncture has been recommended as an effective method for pain relief, while there is currently a lack of sufficient evidence to support its efficacy and safety. In this review, we aimed to critically assess the published clinical evidence on the efficacy and safety of acupuncture therapy for treating sciatica. Methods: An extensive literature search strategy was established in seven databases from their inception to 31 March 2022. Two independent reviewers performed the literature search, identification, and screening. Data extraction was performed on studies that meet the inclusion criteria, and a further quality assessment was performed according to the Cochrane Handbook and Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) recommendations. Summary Risk ratio (RR) and standardized mean differences (SMDs) with 95% confidence interval (CI) were calculated using the fixed-effects or the random-effects model. Heterogeneity in effect size across studies was explored using the subgroup analysis and the sensitivity analysis. The quality of evidence was estimated following the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Results: A total of 30 randomized controlled trials (RCTs) involving 2,662 participants were included in the meta-analysis. The results of the integration of clinical outcomes showed that the clinical efficacy of acupuncture was superior to that of medicine treatment (MT) in improving the total effective rate (relative risk (RR) = 1.25, 95% confidence interval (CI) [1.21, 1.30]; moderate certainty of evidence), reducing the Visual Analog Scale (VAS) pain score (standardized mean difference (SMD) = -1.72, 95% CI [-2.61, -0.84]; very low certainty of evidence), increasing pain threshold (SMD = 2.07, 95% CI [1.38, 2.75]; very low certainty of evidence), and decreasing recurrence rate (RR = 0.27, 95% CI [0.13, 0.56]; low certainty of evidence). In addition, a few adverse events (RR = 0.38, 95% CI [0.19, 0.72]; moderate certainty of evidence) were reported during the intervention, which indicated that acupuncture was a safe treatment option. Conclusions: Acupuncture therapy is an effective and safe treatment for patients with sciatica, and it can be considered a suitable replacement for medicine treatment (MT). However, given the high heterogeneity and a low methodological quality of previous studies, future RCTs should be well-designed according to the rigorous methodology. Systematic review registration: International Platform of Registered Systematic Review and Meta-analysis Protocols (INPLASY) (https://inplasy.com/register/), identifier [INPLASY202240060].

Metabonomics and 16S rRNA gene sequencing to study the therapeutic mechanism of Danggui Sini decoction on collagen-induced rheumatoid arthritis rats with Cold Bi syndrome.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by persistent joint inflammation. The development of rheumatoid arthritis is directly correlated with the disturbance of gut microbiome and its metabolites. RA can be effectively treated with the Danggui Sini decoction (DSD), a Traditional Chinese medicine (TCM) prescription from the Treatise on Febrile Diseases. Further research is needed to clarify the precise mechanism of DSD in the treatment of RA. In this study, 1H NMR metabonomics and 16 S rRNA gene sequencing techniques were used to clarify the intervention of DSD on CIA-induced RA. The results of 1H NMR metabolomics of feces revealed that five metabolites (alanine, glucose, taurine, betaine, and xylose) were disturbed, which could be regarded as potential biomarkers of RA. The intestinal microbiome of RA rats had changed, according to the results of 16 S rRNA gene sequencing; eight microbes (g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_group, g_Dubosiell, g_Lactobacillus, g_norank_f_Desulfovibrionaceae, g_Bacteroides, g_Oscillibacter, and g_Romboutsia) occurred significantly at the genus level, and DSD significantly impacted six of them (g_Dubosiell, g_Lactobacillus, g_norank_f_Eubacterium_coprostanoligenes_group, g_Ruminococcus_torques_grou, g_Bacteroides, and g_Romboutsia). Three of them (g_norank_f_Eubacterium_ coprostanoligenes_group, g_Romboutsia, and g_Lactobacillus) were regarded as key microbiomes for DSD to treat RA, and three common metabolic pathways (taurine and hypotaurine metabolism; alanine, aspartate, and glutamate metabolism; primary bile acid biosynthesis) were discovered based on the 1H NMR metabonomics and PICRUST2 prediction of 16 S rRNA gene sequencing. Six SCFAs in feces (acetic acid, butyric acid, propionic acid, caproic acid, isobutyric acid, and valeric acid) increased significantly in RA, according to the outcomes of targeting SCFAs, while five SCFAs (acetic acid, butyric acid, propionic acid, caproic acid, and valeric acid) had decreased significantly due to DSD treatment. In conclusion, our study indicated that DSD could regulate RA's metabolic disorder by affecting intestinal microbiome and its metabolites. It also establishes a framework for future research into exploiting gut microbes therapeutic to treat RA.

Exposure to 10 Hz Pulsed Magnetic Field Induced Slight Apoptosis and Reactive Oxygen Species in Primary Human Gingival Fibroblasts.

Extremely low frequency pulsed magnetic fields (MFs) have been increasingly used as an effective method in oral therapy, but its potential impact on health has not been clarified. In this study, we investigated the impact of 10 Hz pulsed MF exposure on primary human gingival fibroblasts (HGFs) derived from eight healthy persons (four males and four females). Cells were exposed to 10 Hz pulsed MFs at 1.0 mT for 24 h. Cell apoptosis, cell cycle progression, intracellular reactive oxygen species levels, DNA damage, and cell proliferation were determined after exposure. The results showed that 10 Hz pulsed MFs exposure have slight effects on cellular apoptosis, cell cycle progression, and DNA damage in primary HGFs from some but not all samples. In addition, no significant effect was found on cell proliferation. © 2022 Bioelectromagnetics Society.

Procedural Efficiency, Efficacy, and Safety of High-Power, Short-Duration Radiofrequency Ablation Delivered by STSF Catheter for Paroxysmal Atrial Fibrillation.

Objectives: To investigate the procedural efficiency, efficacy, and safety of high-power, short-term radiofrequency ablation delivered by the SmartTouch Surround Flow (STSF) catheter for paroxysmal atrial fibrillation (AF). Methods: We retrospectively analyzed a total of 72 patients who were admitted with paroxysmal AF, and who underwent radiofrequency catheter ablation (RFCA) for the first time. Of these patients, 36 cases underwent low-power, long-duration (LPLD, (30-35 W/20-40 s) pulmonary vein isolation (PVI) delivered by an SmartTouch (ST) catheter (control group), and the other 36 cases underwent high-power, short-duration (HPSD, (45-50 W/10-20 s) PVI delivered by a STSF catheter (study group). The baseline data, duration of PVI, procedural time, fluoroscopy time, the rate of first-pass isolation, irrigation perfusion, eschar and steam pop occurrences, intraoperative complications, and the rate of stable sinus rhythm maintenance following a blanking period of three months were analyzed between the two groups. Results: The isolation time of bilateral PVI and procedural time in the study group were markedly less than in controls (p < 0.01). The rate of first-pass isolation in the study group was significantly higher than in the control group (95.8% vs. 84.7%, p = 0.023), while the fluid perfusion in the study group was approximately 20% less than that in the control group (767 ± 171 vs. 966 ± 227 ml, p < 0.001). We observed no severe complications in any patients. The rate of freedom from AF recurrences following a blanking period of three months showed a tendency to be higher than in controls (93.9% vs. 87.1%, p = 0.348). Conclusions: The HPSD strategy delivered by the STSF catheter was superior to conventional LPLD ablation through the ST catheter with respect to efficiency, acute procedural effectiveness, short-term safety, and the risk of heart failure in patients with paroxysmal AF.

[Series of group standards of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions].

Drug instructions,the statutory and technical documents recording effectiveness and safety information,are an important basis for guiding doctors,pharmacists,and patients to use drugs rationally,and their scientificity,standardization,and accuracy directly affect the medication safety of the public. The sections of adverse drug events,contraindications,precautions,warnings,and application for specific populations in drug instructions directly express safety information and measures for rational use of drugs. In the drug life cycle,marketing authorization holders( MAHs) need to update safety information in the instructions promptly to ensure the safety and effectiveness of clinical drug medication. At present,revising instructions is an important measure to control drug risks. In the drug life cycle,in order to standardize the revision of safety information in the instructions by MAHs and eliminate inexact terms such as " unclear",the Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,have been established under the guidance of Standardization Department,China Association of Chinese Medicine. Therefore,on the basis of the existing rules and regulations,the standardized technical procedures for revising instructions came into being to help clinical safe and rational medication of drugs,and implement the strategy of " Healthy China".

[Interpretation of Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions].

Technical Specifications for Revision of Safety Information in Marketed Chinese Patent Medicine Instructions,a series of group standards,were proposed by Professor ZHANG Bing from Research Center for Pharmacovigilance and Rational Use of Traditional Chinese Medicine,and underwent centralized management by Chinese Association of Chinese Medicine. They were officially released on July 23 and implemented on July 31,2021. The series of group standards consist of six sections,including general principles,adverse drug events,contraindications,precautions,application for special populations,and warnings. The section of general principles is comprised of holistic and programmatic expressions,which explain the general technical requirements for revising the marketed Chinese patent medicine instructions. The other five sections focus on information collection,screening,transformation,and illustration of specific items,forming a standardized revision technical process. This series of standards is the result of multiple rounds of research and the suggestions of more than 200 experts in different professional fields of " medicine-pharmacy-management-law-enterprise" have been gathered therein to reach a consensus. With the purposes of establishing standardized technical specifications for the revision of safety information in the marketed Chinese patent medicine instructions,guiding marketing authorization holders in revising the instructions,filling the gaps in the research of Chinese patent medicine instructions,promoting the deve-lopment of pharmaceutical care and academic research,and encouraging the rational and safe medication of Chinese patent medicine,the series of group standards is of great significance.

Systematic analysis of chemical profiles of Sophorae tonkinensis Radix et Rhizoma in vitro and in vivo using UPLC-Q-TOF-MSE.

Sophorae tonkinensis Radix et Rhizoma (S. tonkinensis) has been recorded as a 'poisonous' Chinese herbal medicine in Chinese Pharmacopoeia 2020. The clinical reaction reports of S. tonkinensis indicated its neurotoxicity; however, there still exists dispute about its toxic substances. At present, no report is available on the blood and brain prototype research of S. tonkinensis. Most studies focused on alkaloids and less on other compounds. Moreover, the constituents absorbed into the blood and brain have been rarely investigated so far. This study established a rapid and efficient qualitative analysis method using UPLC-Q-TOF-MSE to characterize the ingredients of S. tonkinensis and those entering into the rat's body after oral administration. A total of 91 compounds were identified in S. tonkinensis, of which 28 were confirmed by the standards. In addition, 30 and 19 prototypes were also first identified in the rat's blood and brain, respectively. It was found that most flavonoids, except alkaloids, were detected in the rat's body and distributed in the cerebrospinal fluid, suggesting that flavonoids may be one of the important toxic or effective substances of S. tonkinensis. This finding provides new clues and data for clarifying the toxicity or efficacy of this medicinal plant.

Investigation of the Therapeutic Effect of Total Alkaloids of Corydalis saxicola Bunting on CCl4-Induced Liver Fibrosis in Rats by LC/MS-Based Metabolomics Analysis and Network Pharmacology.

Liver fibrosis is a pathological result of liver injury that usually leads to a pathophysiological wound healing response. The total alkaloids of Corydalis saxicola Bunting (TACS) have been used for hepatoprotective effects on the liver. However, its exact therapeutic mechanisms of liver fibrosis are not yet well understood. To explore the potential anti-fibrosis mechanism of TACS, metabolomics coupled with network pharmacology were applied to reveal the underlying mechanisms. Ultra-performance liquid chromatography quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) combined with multivariate statistical analyses were performed to estimate changes in metabolic profiles. As a result, a total of 23 metabolites in rats with liver fibrosis were altered; of these, 11 had been downregulated and 12 had been upregulated compared with the control group. After TACS treatment, the levels of 13 metabolites were significantly restored compared with the CCl4-treated group, of which 4 metabolites were up-regulated and 9 metabolites were down-regulated. Many of these metabolites are involved in the bile acid metabolism, glutathione metabolism, tryptophan metabolism and purine metabolism. Then, three key targets, including cytochrome P450 family1 subfamily A member 1 (CYP1A1), ornithine decarboxylase 1 (OCD1) and monoamine oxidase Type B (MAOB) were predicted as potential therapeutic targets of TACS against liver fibrosis through network pharmacology analysis. Finally, palmatine, tetrahydropalmatine and dehydrocavidine were screened as potential active compounds responsible for the anti-fibrosis effect of TACS by molecular docking analysis. This study reveals that TACS exerted anti-fibrosis effects by regulating the liver metabolic pathway with multiple components and multiple targets, which is helpful to further clarify the hepatoprotective mechanisms of natural plant extracts.

[Metabolites and metabolic pathways of maackiain in rats based on UPLC-Q-TOF-MS].

Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry(UPLC-Q-TOF-MS) was used to investigate the metabolites of maackiain in rats based on the prediction function of UNIFI data processing system and liver microsomal incubation in vitro. Ten metabolites of maackiain after oral absorption were reasonably deduced and characterized. It was found that the biotransformation of maackiain mainly included phase Ⅰ oxidation, dehydrogenation, phase Ⅱ sulfate conjugation, glucosylation conjugation, and glucuronic acid conjugation. Among them, the product of glucosylation conjugation, trifolirhizin, was identified by comparison with the reference for the first time. Liver microsomal incubation in vitro further confirmed the metabolites and metabolic pathways of maackiain in rats. The metabolites in the blood, urine, and feces complemented each other, which revealed the migration, metabolism, and excretion modes of maackiain in rats. This study lays a foundation for the further investigation of the metabolic mechanism of maackiain in vivo and the in-depth research on the mechanism of pharmacodynamics and toxicity.

Smart Design of Mitochondria-Targeted and ROS-Responsive CPI-613 Delivery Nanoplatform for Bioenergetic Pancreatic Cancer Therapy.

Mitochondria, as the powerhouse of most cells, are not only responsible for the generation of adenosine triphosphate (ATP) but also play a decisive role in the regulation of apoptotic cell death, especially of cancer cells. Safe potential delivery systems which can achieve organelle-targeted therapy are urgently required. In this study, for effective pancreatic cancer therapy, a novel mitochondria-targeted and ROS-triggered drug delivery nanoplatform was developed from the TPP-TK-CPI-613 (TTCI) prodrug, in which the ROS-cleave thioketal functions as a linker connecting mitochondrial targeting ligand TPP and anti-mitochondrial metabolism agent CPI-613. DSPE-PEG2000 was added as an assistant component to increase accumulation in the tumor via the EPR effect. This new nanoplatform showed effective mitochondrial targeting, ROS-cleaving capability, and robust therapeutic performances. With active mitochondrial targeting, the formulated nanoparticles (TTCI NPs) demonstrate much higher accumulation in mitochondria, facilitating the targeted delivery of CPI-613 to its acting site. The results of in vitro antitumor activity and cell apoptosis revealed that the IC50 values of TTCI NPs in three types of pancreatic cancer cells were around 20~30 µM, which was far lower than those of CPI-613 (200 µM); 50 µM TTCI NPs showed an increase in apoptosis of up to 97.3% in BxPC3 cells. Therefore, this mitochondria-targeted prodrug nanoparticle platform provides a potential strategy for developing safe, targeting and efficient drug delivery systems for pancreatic cancer therapy.

Loganin Inhibits Angiotensin II-Induced Cardiac Hypertrophy Through the JAK2/STAT3 and NF-κB Signaling Pathways.

Loganin is an iridoid glycoside extracted from Cornus officinalis, which is a traditional oriental medicine, and many biological properties of loganin have been reported. Nevertheless, it is not clear whether loganin has therapeutic effect on cardiovascular diseases. Hence, the aim of the present study was to investigate the effect of loganin on Ang II-induced cardiac hypertrophy. In the present study, we reported for the first time that loganin inhibits Ang II-provoked cardiac hypertrophy and cardiac damages in H9C2 cells and in mice. Furthermore, loganin can achieve cardioprotective effects through attenuating cardiac fibrosis, decreasing pro-inflammatory cytokine secretion, and suppressing the phosphorylation of critical proteins such as JAK2, STAT3, p65, and IκBα. Besides, the outstanding findings of the present study were to prove that loganin has no significant toxicity or side effects on normal cells and organs. Based on these results, we conclude that loganin mitigates Ang II-induced cardiac hypertrophy at least partially through inhibiting the JAK2/STAT3 and NF-κB signaling pathways. Accordingly, the natural product, loganin, might be a novel effective agent for the treatment of cardiac hypertrophy and heart failure.

Integrative analysis of epigenomics, transcriptomics, and proteomics to identify key targets and pathways of Weining granule for gastric cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Weining granule (WNG) is a "Qi-Enriching and Kidney-Tonifying, Spleen-Reinforcing and Stasis-Removing" formula for gastric cancer (GC). Past research we noted WNG inhibited cell growth and raised apoptosis in GC. However, the underlying mechanism of WNG for GC have yet to be systematically clarified. AIM OF THE STUDY: We sought to characterize the molecular landscape of GC cells in vitro after WNG treated, to identify the molecular targets and pathways that were associated with WNG for inducing the apoptosis of GC cells, and further to clarify underlying molecular mechanism of WNG for GC. MATERIALS AND METHODS: We performed the techniques of RNA sequencing, tandem mass tags (TMT) based quantitative proteomics, and reduced representation bisulfite sequencing (RRBS) in WNG-treated/or untreated SGC-7901 GC cells to gain a comprehensive molecular portrait of WNG treatment. Then we integrated methylomics, transcriptomics, and proteomics data to carry out the bioinformatics analysis, and constructed the protein-protein interaction (PPI) network to identify molecular targets, and to discover the underlying signaling pathways associated with WNG for GC by network analysis. Besides, we verified the candidate target genes by Kaplan-Meier plotter database. RESULTS: We identified 1249 significant differentially expressed genes (DEGs) from RNA expression datasets, 191 significant differentially abunabundant proteins (DAPs) from proteomics datasets, and 8293 significant differentially methylated regions (DMRs) from DNA methylation datasets. GO and KEGG analysis showed DEGs, DAPs, and DMRs enriched in the cancer-related biological processes of calcium signaling pathway, pathways in cancer, metabolic pathways, MAPK signaling pathway, PI3K-Akt signaling pathway, and transcriptional misregulation in cancer. We integrated three profile datasets and performed network analysis to distinguish the hub genes, and finally the genes of SOD2, HMOX1, MMP1, SRXN1, NOTCH1, MAPK14, TXNIP, VEGFA, POLR2F, and HSPA9 were identified. The Kaplan-Meier plotter confirmed that SOD2, MMP1, SRXN1, NOTCH1, MAPK14, TXNIP, VEGFA, and HSPA9 were significantly correlated with OS in GC patients (P < 0.01), while HMOX1 and POLR2F expression were not significantly relevant to survival of GC patients (P > 0.01). CONCLUSIONS: SOD2, MMP1, SRXN1, NOTCH1, MAPK14, TXNIP, VEGFA, and HSPA9 were the predictive pharmaceutical targets of WNG for GC. The anticancer function of WNG was significantly associated with the pathways of focal adhesion pathway, PI3K-Akt signaling pathway, MAPK signaling pathway, and Wnt signaling pathway.

[Involvement of NF-κB signal pathway in acupuncture treatment of patients with rheumatoid arthritis].

OBJECTIVE: To observe the effect of acupuncture on nuclear factor kappa-B(NF-κB)signaling pathway in patients with rheumatoid arthritis (RA), so as to explore the mechanism of acupuncture in the treatment of RA. METHODS: A total of 120 RA patients admitted to the Xinyu Hospital of Traditional Chinese Medicine in Jiangxi Province from June 2018 to June 2019 were selected and randomly divided into a control group and a treatment group, with 60 cases in each group. The patients in the control group received oral administration of Methotrexate, (10-15) mg/time, once a week, for a total of 10 weeks. On the basis of oral administration of Methotrexate, patients in the treatment group were treated with acupuncture at Quchi(LI11), Zusanli(ST36), Taichong(LR3), Hegu(LI4), Shenshu(BL23), Geshu(BL17) and Dazhui(GV14) once daily. The treatment was conducted 6 consecutive times as a course for 10 courses. The serum C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR), pain visual analog scale (VAS) score, number of swollen joints, and morning stiffness time before and after treatment were compared between the two groups. The expression levels of inflammatory related factors and NF-κB p65 protein in the synovial fluid were detected by enzyme-linked immunosorbent assay and Western blot separately. RESULTS: After treatment, both groups had significant decrease in CRP, ESR, VAS score, number of swollen joints and morning stiffness time, levels of NF-κB p65 protein, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 (P<0.05) in the joint fluid, and increase in transforming growth factor-ß (TGF-ß) and IL-10 (P<0.05). After treatment, compared with the control group, CRP, ESR, VAS score and morning stiffness time, and the levels of NF-κB p65, TNF-α, IL-1ß and IL-6 in the treatment group were down-regulated (P<0.05), while the level of TGF-ß was up-regulated (P<0.05). The treatment group had a higher total effective rate than the control groupï¼»85.0%(51/60) vs 75.0%(45/60), P<0.05ï¼½. CONCLUSION: Acupuncture can inhibit the expression of NF-κB signaling pathway in RA patients, regulate the levels of related inflammatory factors, and thus improve the symptoms of RA patients.

One-week phonemic training rebuilds the memory traces of merged phonemes in merged speakers.

The phonemic merger is a unique phenomenon which is referred to as acoustically very different phonemes are recognized as the same phoneme. In our previous study, we demonstrated that the merged speakers had lost the ability to discriminate the merged phonemes pre-attentively, as revealed by their failure in mismatch negativity (MMN) elicitation in the oddball stream of the merged phonemes /n/-/l/. In this study, we investigated the recovery of the discrimination ability via phonemic training and found that the merged speakers regained the ability of discriminating merged phonemes pre-attentively, after a 7-day /n/-/l/ phonemic training, as revealed by the reactivation of MMN brain response to the /n/-/l/ phoneme categories. Our finding indicates that separate memory traces of merged phonemes could be rebuilt during the training process.

Triterpenoid saponins from the roots of Psammosilene tunicoides.

Seven oleanane-type triterpenoid saponins, tunicosaponins B-D (1-3), F-I (4-7), along with eight known triterpenoid saponins (8-15), were isolated from the roots of Psammosilene tunicoides. The structures of compounds 1-7 were determined by comprehensive spectroscopic analysis, including 1D and 2D NMR techniques, mass spectrometry and chemical methods. Triterpene glycosides have been considered as major active constituents of P. tunicoides. This work provides a more complete insight into the saponin constituents of P. tunicoides.

[Analysis of property and efficacy of traditional Chinese medicine in staging revention and treatment of coronavirus disease 2019].

Coronavirus disease 2019(COVID-19) triggered a severe and complicated epidemic situation, and it is of great significance to discuss the rules and characteristics of the prescription of COVID-19 in traditional Chinese medicine. This study collected prevention and treatment approaches of traditional Chinese medicine for COVID-19 released from the National Health Committee of China, 7 provinces and municipal health committees, the Chinese Medicine Administration and Handbook of Traditional Chinese Medicine Diagnosis and Treatment of COVID-19 between January 1 and February 18, 2020, and prescriptions prepared by 3 masters of Chinese medicine and 4 well-known Chinese medicine experts. These information were selected according to the inclusion and exclusion criteria, and EpiData 3.0 software was used to establish the "Traditional Chinese Medicine Prescription Library for the Prevention and Treatment of COVID-19" and the "Common Database of Traditional Chinese Medicine for the Prevention and Treatment of COVID-19". A total of 93 effective Chinese medicine prescriptions and a total of 157 kinds of constituent medicines were collected. Data analysis was performed by SPSS 18.0 software. The results showed that: ①most of the medicines are with cold and warm properties, 69 with cold medicines, accounting for 43.95%, 57 with warm medicines, accounting for 36.31%, and less with hot medicines, taking up 1.27%; ②there are many pungent, bitter and sweet medicines, and the distribution of medicinal flavors is different at different disease stage. The pungent medicines are mostly found in the early stage, the bitter drugs are the main flavor in the middle and severe stage, and the sweet medicines are mostly used in the recovery stage; ③the meridian of the drug is more concentrated at the lung, stomach, and heart, and most of drugs are into the lung meridian, accounting for 24.55%; these medicines are mostly into the lungs and stomach in the initial and middle stages, and into the heart and kidney in severe stages; ④oral drugs are mostly non-toxic, among which only 6 kinds are toxic, namely Armeniacae Semen Amarum, Dryopteridis Crassirhizomatis Rhizoma, Paridis Rhizoma, Pinelliae Rhizoma, Aconiti Lateralis Radix Praeparaia; ⑤most of the drugs have five types of functions: treating exterior syndromes, resolving dampness, clearing heat, replenishing deficiency, resolving phlegm, cough, and asthma. In the early stage, both drugs for treating exterior syndromes and heat clearing drugs were equally used, accounting for 18.81% each. In the middle stage, drugs resolving phlegm, cough, and asthma drugs are more often used, accounting for 29.61%. In the severe stage, heat clearing drugs are mostly used, accounting for 33.33%. During the recovery period, tonic deficiency drugs are used the most, accounting for 36.47%. The medical characteristics and efficacy of Chinese medicine in preventing and treating COVID-19 are closely related to the understanding of the etiology of Chinese medicine and the location and pathogenesis of the disease. Staged medication and local conditions need attention during the identification and treatment of COVID-19 clinical syndromes.