Exploring the Mechanism of Zilongjin in Treating Lung Adenocarcinoma Based on Network Pharmacology Combined with Experimental Verification.

Zilongjin (ZLJ) is a common traditional Chinese medicine for lung adenocarcinoma (LUAD) treatment. However, its mechanisms of action remain to be elucidated. Network pharmacology was used to explore the underlying mechanisms of ZLJ on LUAD treatment. The disease-related targets were determined from the Gene-Cards and DisGeNET databases. Active compounds and targets of ZLJ were obtained from the HIT, TCMSP, and TCMID databases. Then the protein-protein interaction (PPI) network was built by the STRING database to identify core-hub targets of ZLJ in LUAD. Next, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to analyze the enriched regulatory pathways of targets. Molecular docking analysis was used to evaluate interactions between potential targets and active compounds. Finally, qRT-PCR was used to further verify the results of network pharmacology. A total of 124 LUAD-related targets of ZLJ and 5 active compounds of ZLJ from the relevant databases were screened out. Among these target proteins, JUN, CDH1, PPARG, and FOS were core hub-genes in the PPI network. GO and KEGG pathway enrichment analysis indicated that these targets might regulate the PPAR signaling pathway in LUAD. JUN, PPARG, and FOS levels were upregulated, while CDH1 level was downregulated in LUAD cells. This study discerned that ZLJ may target genes such as JUN, FOS, PPARG, and CDH1 via the PPAR signaling pathway in LUAD, offering foundational insights for further exploration of ZLJ in clinical applications.

Differentiation of intestinal stem cells toward goblet cells under systemic iron overload stress are associated with inhibition of Notch signaling pathway and ferroptosis.

Iron overload can lead to oxidative stress and intestinal damage and happens frequently during blood transfusions and iron supplementation. However, how iron overload influences intestinal mucosa remains unknown. Here, the aim of current study was to investigate the effects of iron overload on the proliferation and differentiation of intestinal stem cells (ISCs). An iron overload mouse model was established by intraperitoneal injection of 120 mg/kg body weight iron dextran once a fortnight for a duration of 12 weeks, and an iron overload enteroid model was produced by treatment with 3 mM or 10 mM of ferric ammonium citrate for 24 h. We found that iron overload caused damage to intestinal morphology with a 64 % reduction in villus height/crypt depth ratio, and microvilli injury in the duodenum. Iron overload mediated epithelial function by inhibiting the expression of nutrient transporters and enhancing the expression of secretory factors in the duodenum. Meanwhile, iron overload inhibited the proliferation of ISCs and regulated their differentiation into secretory mature cells, such as goblet cells, through inhibiting Notch signaling pathway both in mice and enteroid. Furthermore, iron overload caused oxidative stress and ferroptosis in intestinal epithelial cells. In addition, ferroptosis could also inhibit Notch signaling pathway, and affected the proliferation and differentiation of ISCs. These findings reveal the regulatory role of iron overload on the proliferation and differentiation of ISCs, providing a new insight into the internal mechanism of iron overload affecting intestinal health, and offering important theoretical basis for the scientific application of iron nutrition regulation.

Broad environmental adaptation of abundant microbial taxa in Robinia pseudoacacia forests during long-term vegetation restoration.

Vegetation restoration has significant impacts on ecosystems, and a comprehensive understanding of microbial environmental adaptability could facilitate coping with ecological challenges such as environmental change and biodiversity loss. Here, abundant and rare soil bacterial and fungal communities were characterized along a 15-45-year chronosequence of forest vegetation restoration in the Loess Plateau region. Phylogenetic-bin-based null model analysis (iCAMP), niche breadth index, and co-occurrence network analysis were used to assess microbial community assembly and environmental adaptation of a Robinia pseudoacacia plantation under long-term vegetation restoration. The drift process governed community assembly of abundant and rare soil fungi and bacteria. With increasing soil total phosphorus content, the relative importance of drift increased, while dispersal limitation and heterogeneous selection exhibited opposite trends for abundant and rare fungi. Rare soil fungal composition dissimilarities were dominated by species replacement processes. Abundant microbial taxa had higher ecological niche width and contribution to ecosystem multifunctionality than rare taxa. Node property values (e.g., degree and betweenness) of abundant microbial taxa were substantially higher than those of rare microbial taxa, indicating abundant species occupied a central position in the network. This study provides insights into the diversity and stability of microbial communities during vegetation restoration in Loess Plateau. The findings highlight that abundant soil fungi and bacteria have broad environmental adaptation and major implications for soil multifunctionality under long-term vegetation restoration.

Development of a recombinant reporter Getah virus for antiviral drug screening assays.

Getah virus (GETV), is an often neglected and re-emerging mosquito-borne RNA virus. GETV can cause illness accompanied with high fever, rash, incapacitating arthralgia and chronic arthritis or encephalitic disease in affected animals. Currently, there is no specific treatment or vaccine against GETV infection. In this study, we developed three recombinant viruses by inserting different reporter protein genes between the Cap and pE2 genes. The reporter viruses exhibited high replication capacity similar to the parental virus. The rGECiLOV and rGECGFP viruses were genetically stable within at least ten rounds of passages in BHK-21 cells. We confirmed that the reporter virus, rGECGFP, facilitated the antiviral assays against GETV by testing it with the known inhibitor, ribavirin. It was also found that the compound, doxycycline, showed an inhibitory effect on GETV replication. In addition, rGECGFP was found to be an authentic mimic of the parental virus infection in 3-day-old mice, but with milder pathogenicity. The reporter viruses will contribute to the assessment of viral replication and proliferation, tracking and elucidating of alphavirus-host interactions. In addition, they will help in the screening of potential antiviral compounds.

Initial Studies on the Effect of the Rice-Duck-Crayfish Ecological Co-Culture System on Physical, Chemical, and Microbiological Properties of Soils: A Field Case Study in Chaohu Lake Basin, Southeast China.

Rice-duck and rice-crayfish co-culture patterns can increase soil productivity and sustainability and reduce the use of chemical pesticides and fertilizers, thereby reducing the resulting negative environmental impacts. However, most studies have focused on the rice-duck and rice-crayfish binary patterns and have ignored integrated systems (three or more), which may have unexpected synergistic effects. To test these effects, a paddy field experiment was carried out in the Chaohu Lake Basin, Hefei city, Southeast China. Four groups, including a rice-duck-crayfish ecological co-culture system (RDC), idle field (CK), single-season rice planting system (SSR), and double-season rice planting system (DSR), were established in this study. The results showed that the RDC improved the soil physical properties, fertility, humus content, and enzyme activity. In the RDC system, the soil total nitrogen content ranged from 8.54% to 28.37% higher than other systems in the 0-10 cm soil layer. Similar increases were found for soil total phosphorus (8.22-30.53%), available nitrogen (6.93-22.72%), organic matter (18.24-41.54%), urease activity (16.67-71.51%), and acid phosphatase activity (23.41-66.20%). Relative to the SSR treatment, the RDC treatment reduced the total losses of nitrogen and phosphorus runoff by 24.30% and 10.29%, respectively. The RDC also did not cause any harm to the soil in terms of heavy metal pollution. Furthermore, the RDC improved the yield and quality of rice, farmer incomes, and eco-environmental profits. In general, the RDC can serve as a valuable method for the management of agricultural nonpoint-source pollution in the Chaohu Lake area and the revitalization of the countryside.

[Network Meta-analysis of different Chinese medicine injections combined with conventional therapy in treatment of stroke-associated pneumonia].

Network Meta-analysis was conducted to compare the efficacy and safety of different Chinese medicine injections combined with conventional therapy in the treatment of stroke-associated pneumonia. CNKI, Wanfang, VIP, PubMed, Web of Science, and Cochrane Library were searched for the relevant literature pubslished from inception to April 1, 2022. Stata 17 was used for data analysis. After screening of 1 189 papers, 72 studies were finally selected, which involved 5 819 patients and 6 Chinese medicine injections(Tanreqing Injection, Xingnaojing Injection, Xuebijing Injection, Xiyanping Injection, Shenfu Injection, and Shenmai Injection). The network Meta-analysis ranked the injections as follows.(1) In terms of improving the total clinical effective rate, the surface under the cumulative ranking curve(SUCRA) followed the order of Xiyanping Injection + conventional therapy > Xuebijing Injection + conventional therapy > Tanreqing Injection + conventional therapy > Shenmai Injection + conventional therapy > Xingnaojing Injection + conventional therapy > Shenfu Injection + conventional therapy > conventional therapy.(2) In terms of recovering the National Institute of Health stroke scale(NIHSS) scores, the SUCRA followed the order of Xuebijing Injection + conventional therapy > Xingnaojing Injection + conventional therapy > Tanreqing Injection + conventional therapy > Shenfu Injection + conventional therapy > conventional therapy.(3) In reducing the average time to abatement of fever, the SUCRA followed the order of Xiyanping Injection + conventional therapy > Tanreqing Injection + conventional therapy > Xuebijing Injection + conventional therapy > conventional therapy.(4) In terms of reducing the mean hospital stay, the SUCRA followed the order of Xiyanping Injection + conventional therapy > Xubijing Injection + conventional therapy > Tanreqing Injection + conventional therapy > Shenmai Injection + conventional therapy > conventional therapy. The clinical efficacy of Tanreqing Injection, Xuebijing Injection, Xiyanping Injection, Xingnaojing Injection, Shenmai Injection, or Shenfu Injection combined with conventional therapy was superior to that of conventional therapy alone. However, due to the limitations of the quality and methodology of different intervention measures, this conclusion needs to be verified by more high-quality and rigorously designed randomized controlled trial.

Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism.

The SLC25A32 dysfunction is associated with neural tube defects (NTDs) and exercise intolerance, but very little is known about disease-specific mechanisms due to a paucity of animal models. Here, we generated homozygous (Slc25a32Y174C/Y174C and Slc25a32K235R/K235R) and compound heterozygous (Slc25a32Y174C/K235R) knock-in mice by mimicking the missense mutations identified from our patient. A homozygous knock-out (Slc25a32-/-) mouse was also generated. The Slc25a32K235R/K235R and Slc25a32Y174C/K235R mice presented with mild motor impairment and recapitulated the biochemical disturbances of the patient. While Slc25a32-/- mice die in utero with NTDs. None of the Slc25a32 mutations hindered the mitochondrial uptake of folate. Instead, the mitochondrial uptake of flavin adenine dinucleotide (FAD) was specifically blocked by Slc25a32Y174C/K235R, Slc25a32K235R/K235R, and Slc25a32-/- mutations. A positive correlation between SLC25A32 dysfunction and flavoenzyme deficiency was observed. Besides the flavoenzymes involved in fatty acid ß-oxidation and amino acid metabolism being impaired, Slc25a32-/- embryos also had a subunit of glycine cleavage system-dihydrolipoamide dehydrogenase damaged, resulting in glycine accumulation and glycine derived-formate reduction, which further disturbed folate-mediated one-carbon metabolism, leading to 5-methyltetrahydrofolate shortage and other folate intermediates accumulation. Maternal formate supplementation increased the 5-methyltetrahydrofolate levels and ameliorated the NTDs in Slc25a32-/- embryos. The Slc25a32K235R/K235R and Slc25a32Y174C/K235R mice had no glycine accumulation, but had another formate donor-dimethylglycine accumulated and formate deficiency. Meanwhile, they suffered from the absence of all folate intermediates in mitochondria. Formate supplementation increased the folate amounts, but this effect was not restricted to the Slc25a32 mutant mice only. In summary, we established novel animal models, which enabled us to understand the function of SLC25A32 better and to elucidate the role of SLC25A32 dysfunction in human disease development and progression.

[Butyl alcohol extract of Baitouweng Decoction alleviates vulvovaginal candidiasis in mice by downregulating NLRP3 inflammasome and related signal pathways].

This study aims to explore the effect of butyl alcohol extract of Baitouweng Decoction(BAEB) on vulvovaginal candidiasis(VVC) in mice and to clarify the mechanism from Toll-like receptors(TLRs)/MyD88 and Dectin-1/Syk signal pathways and NLRP3 inflammasome. To be specific, female KM mice were randomized into control group(i.g., normal saline), model group, fluco-nazole group(i.g., 20 mg·kg~(-1)), and low-dose, medium-dose, and high-dose BAEB groups(i.g., 20, 40, and 80 mg·kg~(-1), respectively). VVC was induced in mice except the control group. After the modeling, administration began and lasted 7 days. The ge-neral conditions and body weight of mice were recorded every day. On the 1 st, 3 rd, 7 th, and 14 th after vaginal infection by Candida albicans, the fungal load in the vaginal lavage fluid of the mice was measured with the plate method, and the morphology of C. albicans in vaginal lavage fluid was observed based on Gram staining. After the mice were killed, vaginal tissues were subjected to hematoxylin-eosin(HE) staining and periodic acid-Schiff(PAS) staining for vaginal histopathological analysis. The content of cytokines in vaginal lavage fluid, such as interleukin(IL)-1ß, IL-18, tumor necrosis factor-α(TNF-α), IL-6, and S100 a8, was determined by enzyme-linked immunosorbent assay(ELISA), and content of reactive oxygen species(ROS) in vaginal tissues by tissue ROS detection kit. The protein expression of NLRP3, ASC, caspase-1, Dectin-1, Syk, MyD88, TLR2, TLR4, and nuclear factor-κB(NF-κB) in vaginal tissues was detected by Western blot, and the levels and distribution of NLRP3, Dectin-1, Syk, MyD88, TLR2, and TLR4 in vaginal tissues were determined with the immunohistochemical method. The results show that BAEB can improve the general conditions of VVC mice, reduce the fungal load and C. albicans hyphae in vaginal secretion, decrease ROS content in vaginal tissues and content of cytokines in vaginal lavage fluid, and down-regulate the expression of NLRP3, ASC, caspase-1, Dectin-1, Syk, MyD88, TLR2, TLR4, and NF-κB in vaginal tissues. The above results indicate that BAEB exerts therapeutic effect on VVC mice by down-regulating the key proteins in the TLRs/MyD88 and Dectin-1/Syk signal pathways and NLRP3 inflammasome.

Phillygenin activates PKR/eIF2α pathway and induces stress granule to exert anti-avian infectious bronchitis virus.

The prevalence of avian infectious bronchitis virus (IBV) is still one of causes inducing severe losses of production in the poultry industry worldwide. Vaccination does not completely prevent IBV infection and spread due to immune failure and viral mutations. ForsythiaeFructus and its compounds have been widely used in a lot of prescriptions of the traditional Chinese medicine for a long history, and it is well-known as safety and efficiency in heat-clearing and detoxifying. This study aims to investigate the anti-IBV activity and mechanism of phillygenin. The results showed that phillygenin inhibited IBV replication by disturbing multiple stages of the virus life cycle, including viral adsorption, invasion, internalization, and release in Vero cells. After being treated with 100, 125 and 150 µg/mL phillygenin, the expression of G3BP1 was significantly increased and the phosphorylation of PKR/eIF2α was activated, which increased stress granule, thereby triggering the antiviral response in Vero cells. The anti-virus activity of PHI was decreased when G3BP1 was interfered by si-RNA, and G3BP1 was down-regulated when PKR/eIF2α was interfered by si-RNA. In conclusion, our findings indicate that phillygenin activates PKR/eIF2α pathway and induces stress granule formation to exert anti-IBV, which holds promise to develop into a novel anti-IBV drug. Further study in vivo is needed to explore phillygenin as a potential and effective drug to prevent IB in poultry.

Huang Bai Jian Pi decoction alleviates diarrhea and represses inflammatory injury via PI3K/Akt/NF-κB pathway: In vivo and in vitro studies.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang Bai Jian Pi (HBJP) decoction, a Chinese herbal formula based on the Pulsatilla decoction (PD) and Si Junzi decoction, is efficacy to treat clinical diarrhea in calves. AIM OF THE STUDY: The mechanism of HBJP decoction to treat calf diarrhea remains unclear. This study was to investigate the therapeutic effect and anti-inflammatory mechanism of HBJP decoction on diarrhea in rats. MATERIALS AND METHODS: Thirty-six Sprague Dawley rats were randomly divided into control group, model group, PD group and three treated groups with HBJP decoction. The diarrheal model in rats was established by multiple factors including high-sugar and fat diet, high temperature and dampness environment, biological pathogenic factors. The diarrheal animals were treated with HBJP decoction or PD for 5 days. The inflammatory model of the intestinal epithelioid cell line 6 (IEC-6) was induced by TNF-α. The clinical symptoms, blood routine and biochemistry parameters, histopathology of main organs were detected. The proteins associated with PI3K/Akt/NF-κB pathway and the expression levels of cytokines associated with inflammation were detected in vivo and in vitro by Western blot and ELISA. RESULTS: The model rats showed obvious diarrheal symptoms, and the obvious systemic inflammatory response accompanied with abnormal change in blood routine, biochemistry parameters and histopathology. HBJP decoction alleviated obviously the clinical symptoms, and pathological changes of the liver, colon and lung, and abnormal blood routine and biochemistry indexes in rats. The expression of P-PI3K, P-Akt, P-NF-κB, IL-1ß, IL-6 was significantly increased, and the expression of IL-10 was markedly decreased in diarrheal rats and IEC-6 with inflammation. HBJP decoction significantly inhibited the PI3K/AKT/NF-κB signal pathway and adjusted the expression of these inflammatory cytokines. CONCLUSIONS: The finding suggested that HBJP decoction alleviate the inflammation in diarrhea through inhibiting the PI3K/Akt/NF-κB signal pathway, which provides scientific evidences for the clinical application of HBJP decoction in diarrhea.

Schisandrin Protects against Norepinephrine-Induced Myocardial Hypertrophic Injury by Inhibiting the JAK2/STAT3 Signaling Pathway.

Aims. Heart failure is closely associated with norepinephrine-(NE-) induced cardiomyocyte hypertrophy. Schisandrin is derived from the traditional Chinese medicine Schisandra; it has a variety of pharmacological activities, and the mechanism of schisandrin-mediated protection of the cardiovascular system is not clear. Main Methods. NE was used to establish a cardiomyocyte hypertrophy model to explore the mechanism of action of schisandrin. An MTT assay was used for cell viability; Hoechst fluorescence staining was used to observe the cell morphology and calculate the apoptosis rate. The cell surface area was measured and the protein to DNA ratio was calculated, changes in mitochondrial membrane potential were detected, and the degree of hypertrophic cell damage was evaluated. WB, QRT-PCR, and immunofluorescence were used to qualitatively, quantitatively, and quantitatively detect apoptotic proteins in the JAK2/STAT3 signaling pathway. Key Findings. In the NE-induced model, schisandrin treatment reduced the apoptosis rate of cardiomyocytes, increased the ratio of the cell surface area to cardiomyocyte protein/DNA, and also, increased the membrane potential of the mitochondria. The expression of both JAK2 and STAT3 was downregulated, and the BAX/Bcl-2 ratio was significantly reduced. In conclusion, schisandrin may protect against NE-induced cardiomyocyte hypertrophy by inhibiting the JAK2/STAT3 signaling pathway and reducing cardiomyocyte apoptosis.

The genome evolution and low-phosphorus adaptation in white lupin.

White lupin (Lupinus albus) is a legume crop that develops cluster roots and has high phosphorus (P)-use efficiency (PUE) in low-P soils. Here, we assemble the genome of white lupin and find that it has evolved from a whole-genome triplication (WGT) event. We then decipher its diploid ancestral genome and reconstruct the three sub-genomes. Based on the results, we further reveal the sub-genome dominance and the genic expression of the different sub-genomes varying in relation to their transposable element (TE) density. The PUE genes in white lupin have been expanded through WGT as well as tandem and dispersed duplications. Furthermore, we characterize four main pathways for high PUE, which include carbon fixation, cluster root formation, soil-P remobilization, and cellular-P reuse. Among these, auxin modulation may be important for cluster root formation through involvement of potential genes LaABCG36s and LaABCG37s. These findings provide insights into the genome evolution and low-P adaptation of white lupin.

The effects of Chinese herbal medicines for treating diabetic foot ulcers: A systematic review of 49 randomized controlled trials.

OBJECTIVE: To assess the effects and associated risks of Chinese herbal medicine (CHM) for diabetic foot ulcer (DFU). METHODS: We systematically searched seven electronic databases for randomized controlled trials (RCTs) about Chinese herbal medicines for treating diabetic foot ulcers. The methodological quality of RCTs was assessed by the Cochrane risk of bias tool. Data was synthesized using review manager (RevMan) 5.3. Meta-analysis was conducted if the data were available. A summary of finding table was generated by The GRADEpro Guideline Development Tool (GDT) online. RESULTS: Forty-nine RCTs, all conducted in China, involving 3646 participants were included. Most of the included trials had unclear or high risk of bias. Twenty-six trials could be pooled in five Meta-analyses, the remaining trials could not be pooled due to the obvious clinical heterogeneity. Only low evidence showed CHM therapy may have 42%-60.4% participants healed completely after treatment, approximately twice (RR 1.42-1.76) as much as the healed rates in conventional therapy (or plus hot water foot bath) group. Majority of the included trials reported benefit of CHM group on shortening healing time (4-23 days) and reducing ulcer wound size (at least 2 cm2). No serious adverse events were reported related to the medication in all trials. CONCLUSION: Weak evidence showed benefit of CHM as add-on treatment of conventional therapy on increasing number of ulcer heals in patients with DFU. That's about twice the healing rate of the conventional treatment (or plus hot water foot bath) group. With insufficient information, we could not draw confirmative conclusion on safety of CHM administration. These findings need to be tested in further large, rigorous trials.

Zusanli (ST36) Acupoint Injection for Diabetic Peripheral Neuropathy: A Systematic Review of Randomized Controlled Trials.

Background: Acupuncture point (acupoint) injection is a common practice in China. Some trials showed that Chinese herbal extracts and/or conventional medication are injected at the Zusanli (ST36) acupoint for the treatment of diabetic peripheral neuropathy (DPN). The study aimed to assess the effectiveness and safety of acupoint injection for DPN at the ST36 by systematically evaluating the evidence published to date. Methods: Six databases were searched for randomized controlled trials (RCTs) of ST36 injection for DPN with primary outcome of pain, global symptom improvement, and quality of life. Methodological quality was assessed by the Cochrane risk of bias (ROB) tool. Data were analyzed using RevMan 5.3. Results: Fourteen RCTs involving 1,071 participants with DPN were included. All RCTs were assessed as unclear or high ROB. Few RCTs adequately reported methodology-related items and needling details according to Consolidated Standards of Reporting Trials (CONSORT) and Standards for Reporting Interventions in Controlled Trials of Acupuncture (STRICTA) statement. Medications injected at ST36 included conventional medications (11 RCTs) and Chinese herbal extracts (3 RCTs). The authors of this study did not perform any meta-analysis due to the heterogeneity of medications used for injections. Two individual RCTs favored ST36 injection in relieving pain compared with intramuscular injection of the same medication. For global symptom measured by Toronto clinical scoring system, one RCT showed that ST36 injection of Fufang Danggui was more effective than intramuscular injection of vitamin B12, two RCTs demonstrated that ST36 injection of mecobalamin or Danhong with cointervention was superior, while one RCT showed no significant differences between ST36 injection and intramuscular injection of mecobalamin. For improving nerve conduction velocity (NCV), three of four individual RCTs showed that ST36 injection was better than intramuscular or intravenous injection of the same medication, two RCTs favored ST36 injection with cointervention, and one RCT favored ST36 injection without cointervention. Four RCTs reported monitoring adverse events, all of which showed no significant difference between groups. Conclusions: Limited evidence suggests that ST36 injection appears to be safe, and potentially effective in reducing pain score and improving NCV compared with intramuscular injection of the same medication. However, poor methodological and reporting quality reduced confidence in the findings. Rigorously designed and well-reported RCTs evaluating the effectiveness of ST36 injection for DPN are warranted.

Functionalized MoS2 Nanosheets as Multi-Gene Delivery Vehicles for In Vivo Pancreatic Cancer Therapy.

Transition metal dichalcogenides (TMDCs) are categorized as novel two-dimensional (2D) nanomaterials with unique physical and chemical properties, bearing varied applications in medical and materials sciences. However, only a few works report the application of TMDCs for gene therapy in cancer treatment. Here, we engineer a multi-gene delivery system based on functionalized monolayer MoS2, which can co-deliver HDAC1 and KRAS small interfering RNAs (siRNAs) to Panc-1 cancer cells for combinational cancer therapy. The synergistic effect of gene silencing therapy and NIR phototherapy is demonstrated by inhibition of both genes, in vitro cell growth rate, and in vivo tumor volume growth rate, exemplifying pre-eminent anticancer efficacy. This anti-tumor effect is a result of the photothermal effect of MoS2 induced by NIR excitation and inactivation of HDAC1 and KRAS genes, which consequently bring about apoptosis, inhibit migration, and induce cell cycle arrest in the treated Panc-1 cells. Moreover, good biocompatibility and reduced cytotoxicity of MoS2-based nanocarriers enable their metabolism within in vitro and in vivo mouse models over a prolonged duration without any evident ill-effects. In summary, we demonstrate the promising potential of low-toxicity, functionalized MoS2 nanocarriers as a biocompatible gene delivery system for in vivo pancreatic adenocarcinoma therapy.

Who are the users of a traditional Chinese sanfu acupoint herbal patching therapy in China?: A cross-sectional survey.

Sanfu acupoint herbal patching (SAHP) is a unique traditional Chinese medicine therapy, which has become popular for preventing acute attack of respiratory diseases such as asthma and chronic obstructive pulmonary disease, in many regions of mainland China. However, the knowledge about its users is lacking, especially the characteristics of the users and their experience and perspectives.To investigate the demographics of users, conditions for its use and the previous experience of SAHP, as well as users' perspectives to provide baseline information for its practice.A cross-sectional consecutive-sample survey was conducted at outpatient departments from 3 traditional Chinese medicine hospitals in northern China. Each participant completed a questionnaire, after informed consent. Data description and analyses were done using SPSS 20.0.Among 949 SAHP users from 3 hospitals, female was predominant (n = 592; 62.4%), aged from 2 to 96 years (median = 52 years). 64.7% (380/587) of regular users have applied consecutively for 3 years or over, and the self-perceived satisfaction rates of respiratory diseases were from 45.9% to 77.7%. Positive attitude toward traditional Chinese medicine was the top reason for choosing SAHP. 42.4% of users held a motivation of being cured by SAHP and with great outcome expectancy on SAHP (70.8%).SAHP users were mainly female adults or elderly population; more than half were regular users, who predominantly used SAHP for various chronic respiratory diseases during their stable stage. The majority of users expressed satisfaction to previous SAHP for their respiratory diseases. 42.4% of users held a motivation of being cured by SAHP and with great outcome expectancy on SAHP (70.8%). The findings from this survey deserve further clinical trials for their clinical effectiveness.

The effect of berberine on insulin resistance in women with polycystic ovary syndrome: detailed statistical analysis plan (SAP) for a multicenter randomized controlled trial.

BACKGROUND: Although Traditional Chinese Medicine (TCM) has been widely used in clinical settings, a major challenge that remains in TCM is to evaluate its efficacy scientifically. This randomized controlled trial aims to evaluate the efficacy and safety of berberine in the treatment of patients with polycystic ovary syndrome. In order to improve the transparency and research quality of this clinical trial, we prepared this statistical analysis plan (SAP). METHODS: The trial design, primary and secondary outcomes, and safety outcomes were declared to reduce selection biases in data analysis and result reporting. We specified detailed methods for data management and statistical analyses. Statistics in corresponding tables, listings, and graphs were outlined. DISCUSSION: The SAP provided more detailed information than trial protocol on data management and statistical analysis methods. Any post hoc analyses could be identified via referring to this SAP, and the possible selection bias and performance bias will be reduced in the trial. TRIAL REGISTRATION: This study is registered at ClinicalTrials.gov, NCT01138930 , registered on 7 June 2010.

Clinical effects of a standardized Chinese herbal remedy, Qili Qiangxin, as an adjuvant treatment in heart failure: systematic review and meta-analysis.

BACKGROUND: Qili Qiangxin capsule is a standardized Chinese herbal treatment that is commonly used in China for heart failure (HF) alongside conventional medical care. In 2014, Chinese guidelines for the treatment of chronic HF highlighted Qili Qiangxin capsules as a potentially effective medicine. However, there is at present no high quality review to evaluate the effects and safety of Qili Qiangxin for patients with HF. METHODS: We conducted a systematic review and meta-analysis and followed methods described in our registered protocol [PROSPERO registration: CRD42013006106]. We searched 6 electronic databases to identify randomized clinical trials (RCTs) irrespective of blinding or placebo control of Qili Qiangxin used as an adjuvant treatment for HF. RESULTS: We included a total of 129 RCTs published between 2005 and 2015, involving 11,547 patients, aged 18 to 98 years. Meta-analysis showed no significant difference between Qili Qiangxin plus conventional treatment and conventional treatment alone for mortality (RR 0.53, 95 % CI 0.27 to 1.07). However, compared with conventional treatment alone, Qili Qiangxin plus conventional treatment demonstrated a significant reduction in major cardiovascular events (RR 0.46, 95 % CI 0.34 to 0.64) and a significant reduction in re-hospitalization rate due to HF (RR 0.49, 95 % CI 0.38 to 0.64). Qili Qiangxin also showed significant improvement in cardiac function measured by the New York Heart Association scale (RR 1.38, 95 % CI 1.29 to 1.48) and quality of life as measured by Minnesota Living with Heart Failure Questionnaire (MD -8.48 scores, 95 % CI -9.56 to -7.39). There were no reports of serious adverse events relating to Qili Qiangxin administration. The majority of included trials were of poor methodological quality. CONCLUSIONS: When compared with conventional treatment alone, Qili Qiangxin combined with conventional treatment demonstrated a significant effect in reducing cardiovascular events and re-hospitalization rate, though not in mortality. It appeared to significantly improve quality of life in patients with HF and data from RCTs suggested that Qili Qiangxin is likely safe. This data was drawn from low quality trials and the results of this review must therefore be interpreted with caution. Further research is warranted, ideally involving large, prospective, rigorous trials, in order to confirm these findings.