[Effect of Spatholobi Caulis extract from ethyl acetate on immune killing function of NK cells].

This study aims to investigate the regulatory effect of the Spatholobi Caulis extract from ethyl acetate(SEA) on natural killer(NK) cells under physiological conditions and elucidate the underlying mechanism. The C57BL/6 mice were randomized into NC and SEA groups, and NK-92 cells were respectively treated with 0, 25, 50, and 100 µg·mL~(-1) SEA. The body weight and immune organ index of the mice were compared between groups. The lactate dehydrogenase(LDH) assay was employed to examine the cytotoxicity of NK-92 cells treated with SEA and the killing activity of mouse NK cells against YAC-1 cells. The cell-counting kit-8(CCK-8) was used to examine the impact of SEA on the proliferation of NK-92 cells. Flow cytometry was employed to measure the number of NK cells in the peripheral blood as well as the expression levels of natural killer group 2 member A(NKG2A) and natural killer group 2 member D(NKG2D). The enzyme-linked immunosorbent assay(ELISA) was performed to determine the interferon(IFN)-γ secretion in the serum. Semi-quantitative PCR was conducted to determine the mRNA levels of NKG2A, NKG2D, and IFN-γ in spleen cells. Western blot was employed to investigate the involvement of phosphoinositide 3-kinase(PI3K)/extracellular regulated protein kinase 1(ERK1) signaling pathway. The results showed that SEA exhibited no adverse effects on the body, while significantly enhance the number of NK cells and augment the cytotoxicity of NK-92 cells against YAC-1 cells. Moreover, it suppressed the expression of NKG2A, enhanced the expression of NKG2D, promoted IFN-γ secretion, and upregulated the protein levels of PI3K and ERK. The findings suggest that SEA has the potential to enhance the immune recognition and effector function of NK cells by increasing the cell number, modulating the expression of functional receptors, and promoting IFN-γ secretion via the PI3K/ERK signaling pathway.

Phenolic composition, antioxidant, cytotoxic activities and cardioprotective effect of hydroalcoholic extract from aerial-parts of Hypericum attenuatum Fisch. ex Choisy.

This study investigated phenolic metabolites, antioxidant, cytotoxic and cardioprotective effects of the hydroalcoholic extract from the aerial parts of Hypericum attenuatum Fisch. ex Choisy. The total phenolic and flavonoid contents of the extract were 132.40 ± 2.06 mg GAE/g and 101.46 ± 1.47 mg QE/g respectively. The extract exhibited antioxidant activities with an EC50 value against DPPH radical of 0.099 ± 0.03 mg/mL and a FRAP value of 1.22 ± 0.086 mmol/L Fe2+. The extract could protect H9c2 cardiomyoblasts from the injury of H2O2, while it restored the H9c2 cell viability to 82.69 ± 2.33% at 100 µg/mL. The extract possessed cytotoxicity on MGC803, C666-1 and SW620 cells with IC50 values of 69.77 ± 2.43 µg/mL, 74.97 ± 1.08 µg/mL and 58.91 ± 1.81 µg/mL, respectively. Moreover, it could promote apoptosis of the tested cancer cells. This research provided useful information for the utilization of H. attenuatum as herbal medicine.

Sorafenib plus triplet therapy with venetoclax, azacitidine and homoharringtonine for refractory/relapsed acute myeloid leukemia with FLT3-ITD: A multicenter phase 2 study.

BACKGROUND: Patients with relapsed or refractory acute myeloid leukemia (R/R AML) and FLT3-internal tandem duplication (FLT3-ITD) respond infrequently to salvage chemotherapy. OBJECTIVE: To investigate the efficacy of sorafenib plus triplet therapy with venetoclax, azacitidine, and homoharringtonine (VAH) as a salvage therapy in this population. METHODS: This multicenter, single-arm, phase 2 study was conducted at 12 hospitals across China. Eligible patients had R/R AML with FLT3-ITD (aged 18-65 years) who were treated with VAH. The primary endpoint was composite complete remission (CRc) after two cycles. Secondary outcomes included the overall response rate (ORR), safety, and survival. RESULTS: Between July 9, 2020, and March 19, 2022, 58 patients were assessed for eligibility, 51 of whom were enrolled. The median patient age was 47 years (interquartile range [IQR] 31-57). CRc was 76.5% with ORR of 82.4%. At a median follow-up of 17.7 months (IQR, 8.7-24.7), the median duration of CRc was not reached (NR), overall survival was 18.1 months (95% confidence interval [CI], 11.8-NR) and event-free survival was 11.4 months (95% CI, 5.6-NR). Grade 3 or 4 adverse events occurring in ≥10% of patients included neutropenia in 47 (92.2%), thrombocytopenia in 41 (80.4%), anemia in 35 (68.6%), febrile neutropenia in 29 (56.9%), pneumonia in 13 (25.5%), and sepsis in 6 (11.8%) patients. Treatment-related death occurred in two (3.9%) patients. CONCLUSIONS: The sorafenib plus VAH regimen was well tolerated and highly active against R/R AML with FLT3-ITD. This regimen may be a suitable therapeutic option for this population, but larger population trials are needed to be explored. TRIAL REGISTRATION: Clinical Trials Registry: NCT04424147.

[Application of single-arm objective performance criteria/performance goal in acupuncture-moxibustion clinical trials].

Due to various constraints, such as clinical implementation conditions and unique characteristics of acupuncture-moxibustion, some randomized controlled trials (RCTs) of acupuncture-moxibustion still suffer from relatively low quality and limited applicability. The single-arm objective performance criteria/performance goal can be considered as an ideal supplementary and alternative research approach to RCTs. In this paper, the feasibility of applying the single-arm objective performance criteria/performance goal in acupuncture-moxibustion clinical research is explored from the limitations of conducting acupuncture-moxibustion RCTs, the principles, the essential design considerations and key statistical steps. In addition, illustrative examples are provided. The objective is to offer insights into resolving practical difficulties in acupuncture-moxibustion clinical research.

Phenome-wide association study and precision medicine of cardiovascular diseases in the post-COVID-19 era.

SARS-CoV-2 infection causes injuries of not only the lungs but also the heart and endothelial cells in vasculature of multiple organs, and induces systemic inflammation and immune over-reactions, which makes COVID-19 a disease phenome that simultaneously affects multiple systems. Cardiovascular diseases (CVD) are intrinsic risk and causative factors for severe COVID-19 comorbidities and death. The wide-spread infection and reinfection of SARS-CoV-2 variants and the long-COVID may become a new common threat to human health and propose unprecedented impact on the risk factors, pathophysiology, and pharmacology of many diseases including CVD for a long time. COVID-19 has highlighted the urgent demand for precision medicine which needs new knowledge network to innovate disease taxonomy for more precise diagnosis, therapy, and prevention of disease. A deeper understanding of CVD in the setting of COVID-19 phenome requires a paradigm shift from the current phenotypic study that focuses on the virus or individual symptoms to phenomics of COVID-19 that addresses the inter-connectedness of clinical phenotypes, i.e., clinical phenome. Here, we summarize the CVD manifestations in the full clinical spectrum of COVID-19, and the phenome-wide association study of CVD interrelated to COVID-19. We discuss the underlying biology for CVD in the COVID-19 phenome and the concept of precision medicine with new phenomic taxonomy that addresses the overall pathophysiological responses of the body to the SARS-CoV-2 infection. We also briefly discuss the unique taxonomy of disease as Zheng-hou patterns in traditional Chinese medicine, and their potential implications in precision medicine of CVD in the post-COVID-19 era.

Exploration of the Clinical Value and Significance of Body Mass Index, Mean Platelet Volume, and Left Atrial Structural Changes in Recurrence after Radiofrequency Ablation of Atrial Fibrillation.

Objective: This study aimed to analyze the clinical significance of body mass index (BMI), mean platelet volume (MPV), and left atrial structure in the recurrence of atrial fibrillation (AF) after treatment with catheter radiofrequency ablation. Methods: A total of 69 patients with AF who underwent catheter radiofrequency ablation at Beijing Anzhen Hospital from January 2020 to July 2021 (research group) were compared to 75 patients who underwent physical examination during the same period (control group). MPV levels were measured before and after treatment in both groups. Additionally, height and weight measurements were used to calculate BMI, while left atrial anteroposterior diameter, left atrial volume, and left atrial volume index were recorded using cardiac ultrasonography. Results: The research group exhibited higher BMI, MPV, left atrial anteroposterior diameter, left atrial volume, and left atrial volume index compared to the control group, and these parameters decreased after treatment (P < .05). Prognostic follow-up revealed that patients with AF recurrence had higher values for these parameters than those without recurrence (P < .05). Receiver Operating Characteristic analysis indicated that all these parameters had good predictive value for prognostic recurrence of AF (P < .05). Logistic regression analysis demonstrated that all the parameters were independent risk factors for prognostic atrial fibrillation recurrence (P < .05). Conclusions: BMI, MPV, and left atrial structure are associated with the occurrence and development of atrial fibrillation. These parameters provide an excellent assessment of the prognosis for AF recurrence after catheter radiofrequency ablation treatment. Monitoring changes in BMI, MPV, and left atrial structure in atrial fibrillation patients can contribute to more reliable prognostic information in clinical settings.

Shenlian extract protected ox-LDL-loaded macrophages against ER stress by promoting LAL-LXRα mediated cholesterol flux.

ETHNOPHARMACOLOGICAL RELEVANCE: Shenlian (SL) extract is consisted of extracts from Salvia miltiorrhiza Bunge and Andrographis paniculata (Burm.f.) Nees, two herbs commonly used in Chinese clinical formula to treat atherosclerosis by removing blood stasis and clearing away heat. Pharmacologically, the anti-atherosclerotic effects of these two herbs are related to unresolved inflammation and the macrophage anergy or apoptosis in lesions led by the lipid flux blockage and ER stress. However, the deeper understanding of SL extract in protecting macrophage in plaques remains unknown. AIM OF THE STUDY: This study aimed to investigate the underlying mechanism of SL extract in protecting ER-stressed macrophages from apoptosis in atherosclerosis. METHODS: The ApoE-/- atherosclerotic mice model and ox-LDL loaded macrophages model were established to assess the effect of SL extract on ER stress in vivo and in vitro. Key markers related to ER stress in plaque were determined by immunohistochemical staining. Proteins involved in apoptosis and ER stress in macrophages loaded by ox-LDL were assessed by Western blot. ER morphology was observed by electron microscope. Lipid flux was temporally and quantitatively depicted by Oil red staining. The LAL and LXRα were blocked by lalistat and Gsk 2033 respectively to investigate whether SL extract protected the function of macrophages by the activation of LAL-LXRα axis. RESULTS: Our study reported that, in ApoE-/- atherosclerotic mice, SL extract effectively relieved ER stress of carotid artery plaque. In lipid-overloaded macrophage models, SL extract significantly alleviated ER stress by promoting cholesterol degradation and efflux, which finally prevented apoptosis of foam cells induced by ox-LDL. Blockage of ER stress by 4-Phenylbutyric acid (4-PBA), an inhibitor of Endoplasmic Reticulum (ER) stress, largely attenuated the protective effects of SL extract on macrophage. By utilizing the selective antagonists against both LAL and LXRα, this study further revealed that the beneficial effects of SL extract in macrophages was dependent on the proper functionalization of LAL-LXRα axis. CONCLUSIONS: By highlighting the therapeutic significance of macrophage protection in resolving atherosclerosis inflammation, our study pharmacologically provided convincing mechanistic evidence of SL extract in the activation LAL-LXRα axis and revealed its promising potential in the promotion of cholesterol turnover and prevention of ER stress induced apoptosis in lipid-loaded macrophages.

Effects of calcium supplements on oral bioavailability of fluoride in soil based on In Vivo and In Vitro methods.

Dietary calcium (Ca) intake can alleviate fluoride (F) induced fluorosis to maintain bone health. However, it is unclear whether calcium supplements can reduce the oral bioavailability of F present in contaminated soils. Here we evaluated the effects of Ca supplements on F bioavailability in three soils using an in vitro method (Physiologically Based Extraction Test) and an in vivo mouse model. Seven Ca salts, commonly used in calcium supplements, significantly reduced the F bioaccessibility in the gastric and small intestinal phases. Particularly for Ca phosphate at 150 mg Ca supplementation, F bioaccessibility in the small intestinal phase was reduced from 35.1-38.8% to 0.7-1.9% where soluble F concentrations were less than 1 mg/L. Overall, the eight Ca tablets tested in this study showed greater efficiency at decreasing F solubility. The in vitro bioaccessibility after Ca supplementation was consistent with the relative bioavailability of F. As supported by X-ray photoelectron spectroscopy, a possible mechanism is that freed F can be bound by Ca to form insoluble CaF2 and exchanged with OH groups from Al/Fe hydroxide to strongly adsorb F. These findings provide evidence of Ca supplementation in reducing health risks associated soil F exposure.

[Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography].

The kidney-shaped, red-colord fruit from the plant, Schisandra chinensis (Turcz.) Baill, which belongs to the Schisandraceae family, is among the most popular remedies used in traditional Chinese medicine. The English name of the plant is "Chinese magnolia vine". It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. In some cases, these constituents affects the pharmacological efficacy of the plant. Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. However, because of the complex composition of Schisandra chinensis, the extraction yields of lignans are low. Thus, it is particularly important to study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine. Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. First, the effects of 12 adsorbents, including silica gel, acidic alumina, neutral alumina, alkaline alumina, Florisil, Diol, XAmide, Xion, and the inverse adsorbents, C18, C18-ME, C18-G1, and C18-HC, on the extraction yields of lignans were investigated. Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. Xion was chosen as an adsorbent for MSPD-HPLC analysis of lignans from Schisandra chinensis. Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. The limits of detection and quantification ranged from 0.0089 to 0.0294 µg/mL and 0.0267 to 0.0882 µg/mL, respectively. Lignans were tested at low, medium, and high levels. The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. Both intra-day and inter-day precisions were less than 3.6%. Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. Finally, the optimized method was successfully applied to analyze five lignans from Schisandra chinensis samples from 17 cultivation areas.

[Research status and prospect of remyelination in multiple sclerosis based on "inflammation-tissue" homeostatic coupling].

Multiple sclerosis(MS) shows the pathological characteristics of "inflammatory injury of white matter" and "myelin repair disability" in the central nervous system(CNS). It is very essential for MS treatment and reduction of disease burden to strengthen repair, improve function, and reduce disability. Accordingly, different from the simple immunosuppression, we believe that key to strengthening remyelination and maintaining the "damage-repair" homeostasis of tissue is to change the current one-way immunosuppression strategy and achieve the "moderate pro-inflammation-effective inflammation removal" homeostasis. Traditional Chinese medicine shows huge potential in this strategy. Through literature research, this study summarized the research on remyelination, discussed the "mode-rate pro-inflammation-effective inflammation removal" homeostasis and the "damage-repair" homeostasis based on microglia, and summed up the key links in remyelination in MS. This review is expected to lay a theoretical basis for improving the function of MS patients and guide the application of traditional Chinese medicine.

[Observation on clinical effect of fire needling for mild to moderate benign prostatic hyperplasia with kidney yang deficiency].

OBJECTIVE: To observe the effect of fire needling on prostate symptoms, quality of life, average daily number of nightly urination, urine flow rate and prostat volume in patients with mild to moderate benign prostatic hyperplasia (BPH) of kidney yang deficiency. METHODS: A total of 60 patients with mild to moderate BPH of kidney yang deficiency were randomly divided into an observation group (30 cases, 3 cases dropped off) and a control group (30 cases, 4 cases dropped off). The observation group was treated with fire needling at Guanyuan (CV 4), Shuidao (ST 28) and Qugu (CV 2) twice a week (2-3 d interval between each treatment), continuous treatment for 4 weeks. The control group received lifestyle advice and education, once a week for 4 weeks. In the two groups, the international prostate symptom score (IPSS), the quality of life (QoL) score and the average daily number of nightly urination were observed before treatment, after treatment and during the follow-up of the 4th week; the urinary maximum flow rate (Qmax), the average flow rate (Qave), and the prostate volume were assessed before and after treatment in the two groups. The safety was observed in the observation group. RESULTS: After treatment and during follow-up, the IPSS scores, QoL scores, and the average daily number of nightly urination in the observation group were decreased compared with those before treatment (P<0.05), and those in the observation group were lower than the control group (P<0.05). After treatment, there was no significant difference in Qmax, Qave and prostate volume between the two groups and within the each group (P>0.05). There were no fire needling-related adverse reactions, and no obvious abnormality was found in urine routine and coagulation function tests before and after treatment in the observation group. CONCLUSION: Fire needling can improve lower urinary tract symptoms and quality of life, reduce frequency of nightly urination in patients with mild to moderate BPH of kidney yang deficiency, and has good safety.

Astragalus polysaccharide (APS) supplement in beagle dogs after castration: Effects on the haematology and serum chemistry profiles, immune response, and oxidative stress status.

BACKGROUND: Castration is one of the most common surgical procedures performed in dogs. However, based on increasing evidence, male animals experience significant pain after castration. Astragalus polysaccharide (APS), one of the main bioactive components in A. membranaceus bunge, has been widely used as part of Fu-Zheng therapy to enhance natural defense mechanisms. INTRODUCTION: This study was carried out to determine the effects of supplementing different doses of Astragalus polysaccharide (APS; control, 0 mg/kg; APSL, 400 mg/kg; and APSH, 800 mg/kg) for 8 weeks on the haematology and serum chemistry profiles, immune response, and oxidative stress status in weanling beagle dogs. METHODS: After adapting to the experimental environment for 1 week, 18 male beagle dogs (Sichuan Institute of Musk Deer Breeding, China; average initial weight, 3.80 ± 0.43 g; age, 3-month-old) were randomly allotted to diets supplemented with three doses of APS (Control, 0 mg/kg; low, 400 mg/kg; and high, 800 mg/kg), referred to as control, APSL, and APSH, respectively; six dogs were assigned to each treatment. The dogs were fed the respective diets twice daily at 08:30 and 16:30 h in sufficient quantity to supply the metabolizable energy requirements for 8 weeks. On day 43 (19 weeks old), the dogs were castrated. On days 42 (prior to castration, 19 weeks old), 50 (day 7 after castration, 20 weeks old), and 57 (day 14 after castration, 21 weeks old) to measure the haematology, blood chemistry, immune response, and oxidative stress status parameters. RESULTS: Based on our findings, the APSH diet decreased weight gain and increased the feed to gain ratio in dogs (P < 0.05). At 14 days after castration, the wound was almost closed, slightly swollen, dry, and clean in the groups supplemented with APS. In addition, optimal APS supplementation was found to decrease erythrocyte count (RBC), haematocrit (HCT), alkaline phosphatase (ALP), alanine aminotransferase (ALT), C-reactive protein (CRP), interleukin 1ß (IL-1ß), and tumor necrosis factor-α (TNF-α) levels, and cortisol and protein carbonyl (PC) concentrations (P < 0.05). Moreover, the mean corpuscular haemoglobin (MCH) and platelet (PLT) levels, interleukin 10 (IL-10) and glutathione (GSH) content, and Cu/Zn superoxide dismutase (SOD1), catalase (CAT), and glutathione peroxidase (Se-GPx) activities were increased in the APS supplemented groups (P < 0.05) CONCLUSION: This study demonstrated that supplementing weanling beagle dogs with optimum APS could positively affect wound healing by improving their haematological profile (decreased RBC and HCT content, increased MCH and PLT levels), serum biochemical parameters (decreased ALP and ALT content), immune status (decreased CRP, IL-1ß, and TNF-α levels; increased IL-10 content), and antioxidant defense (decreased cortisol and PC content; increased GSH content, and SOD1, CAT, and Se-GPx activities). However, the detailed mechanism whereby APS regulates these changes requires further investigation. In addition, the results of this study suggest that 400 mg/kg diet is the optimum APS dose for beagle dogs.

Mechanism of traditional Chinese medicine in treating overactive bladder.

Overactive bladder syndrome (OAB) has made increasing progress in mechanism and treatment research. Traditional Chinese medicine (TCM) is a common complementary therapy for OAB, and it has been found to be effective. However, the intervention mechanism of TCM in the treatment of OAB is still unclear. The aim of this review is to consolidate the current knowledge about the mechanism of TCM: acupuncture, moxibustion, herbs in treating OAB, and the animal models of OAB commonly used in TCM. Finally, we put forward the dilemma of TCM treatment of OAB and discussed the insufficiency and future direction of TCM treatment of OAB.

Plastome characteristics and species identification of Chinese medicinal wintergreens (Gaultheria, Ericaceae).

Wintergreen oil is a folk medicine widely used in foods, pesticides, cosmetics and drugs. In China, nine out of 47 species within Gaultheria (Ericaceae) are traditionally used as Chinese medicinal wintergreens; however, phylogenetic approaches currently used to discriminating these species remain unsatisfactory. In this study, we sequenced and characterized plastomes from nine Chinese wintergreen species and identified candidate DNA barcoding regions for Gaultheria. Each Gaultheria plastome contained 110 unique genes (76 protein-coding, 30 tRNA, and four rRNA genes). Duplication of trnfM, rps14, and rpl23 genes were detected, while all plastomes lacked ycf1 and ycf2 genes. Gaultheria plastomes shared substantially contracted SSC regions that contained only the ndhF gene. Moreover, plastomes of Gaultheria leucocarpa var. yunnanensis contained an inversion in the LSC region and an IR expansion to cover the ndhF gene. Multiple rearrangement events apparently occurred between the Gaultheria plastomes and those from several previously reported families in Ericales. Our phylogenetic reconstruction using 42 plastomes revealed well-supported relationships within all nine Gaultheria species. Additionally, seven mutational hotspot regions were identified as potential DNA barcodes for Chinese medicinal wintergreens. Our study is the first to generate complete plastomes and describe the structural variations of the complicated genus Gaultheria. In addition, our findings provide important resources for identification of Chinese medicinal wintergreens.

Multimorbidity, polypharmacy and inappropriate prescribing in elderly patients with atrial fibrillation: A report from the China Atrial Fibrillation Registry Study.

Background: Multimorbidity, polypharmacy and inappropriate prescribing is common in elderly patients worldwide. We aimed to explore the current status of multimorbidity, polypharmacy and the appropriateness of pharmacological therapy among elderly patients with atrial fibrillation (AF) in China. Materials and methods: We randomly selected 500 patients aged 65 years or older from the China AF Registry study. Multimorbidity was defined as ≥2 comorbidities and polypharmacy was defined as ≥5 long-term prescribed drugs. Appropriateness of prescribing was evaluated using the Screening Tool of Older People's Prescriptions/Screening Tool to Alert to Right Treatment (STOPP/START) criteria version 2. Patients' attitudes toward polypharmacy were evaluated by the Patients' Attitudes Towards Deprescribing (PATD) questionnaire. Results: Among the 500 patients included (mean age 75.2 ± 6.7 years, 49.0% male), 98.0% had multimorbidity and 49.4% had polypharmacy. The prevalence of potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) was 43.6% (n = 218) and 71.6% (n = 358), respectively. Traditional Chinese medicine attributed largely to PIMs. Anticoagulants were the most common PPOs. Many clinical factors increased the risk of PIMs and PPOs. However, polypharmacy increased the risk of PIMs (OR 2.70, 95%CI 1.78-4.11; p < 0.0001), but not PPOs. In addition, 73.7% patients with polypharmacy were willing to have one or more of their medications prescribed if advised by their doctor. Conclusion: Multimorbidity and polypharmacy were highly prevalent in elderly patients with AF in China. A high prevalence of inappropriate prescribing was also observed. Therefore, much more attention should be paid to the serious health problem in the elderly population.

Preclinical evidence and possible mechanisms of ß-asarone for rats and mice with Alzheimer's disease: A systematic review and meta-analysis.

Background: Currently, there are many different drugs to improve Alzheimer's disease (AD) from different pathways. As a supplement and alternative medicine, traditional Chinese medicine (TCM) targets multiple pathways which may be different from classical Western medicine, which may be orchestrated with Western medicine to materialize multiplying efficacy in AD patients. Objective: To investigate the therapeutic effect and assess the available preclinical evidence and possible mechanisms of ß-asarone which was extracted from Acorus gramineus Soland (Araceae, AGS) for AD based on rat and mouse animal models. Methods: PubMed, Embase, Scopus, Cochrane Library, BIOSIS Previews, Web of Science, EBSCO, and Google Scholar were searched from inception to 5 May 2022. Rat and mouse experiments assessing the therapeutic effects of ß-asarone for AD were included. Primary outcomes were neuroethology, including escape latency and times of crossing platform. Second outcomes were cell apoptosis, including Bax and Bcl-2. The weighted mean difference (WMD) was generated for continuous variables. The relative outcomes were analyzed with the aid of Get Data Graph Digitizer 2.26 and software STATA version 16.0 MP. Results: For the primary endpoint, compared with the modeling group, ß-asarone significantly decreased the escape latency (WMD = -12.61, 95% CI: -18.66 to -6.57) and increased the times of crossing platform (WMD = 1.50, 95% CI: 0.31-2.70). For the secondary endpoint, ß-asarone remarkably reduced the relative expression of the amyloid precursor protein (APP) (WMD = -2.25, 95% CI: -2.49 to -2.01), decreased the expression of the apoptosis-related protein, associated X protein (Bax) (WMD = -2.40, 95% CI: -3.51 to -1.29), lowered the expression of apoptosis-related protein, B-cell lymphoma-2 (Bcl-2) (WMD = 0.42, 95% CI: 0.38-0.46), and decreased the signal pathway-related proteins, phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) (WMD = -0.70, 95% CI: -0.93 to -0.47) over the control group. Conclusion: ß-asarone spectacularly improved the learning ability and memory in rats and mice, which might be correlated with its potential neuroprotective effect through multiple signaling pathways.

Alternative splicing analysis showed the splicing factor polypyrimidine tract-binding protein 1 as a potential target in acute myeloid leukemia therapy.

Alternative splicing (AS) is a universal post-transcriptional regulation process in cells, and increasing evidences have validated its crucial role in tumors. We collected AS event, gene expression, and clinical data of 178 AML patients from The Cancer Genome Atlas (TCGA) project. More than 1,000 AS events were found associated with overall survival (OS), and alternate promoter (AP) events were the most significant. The expression of the KIAA0930 transcript was the most significantly different AS event selected from AP events and significantly correlated with the expression of the splicing factor (SF) polypyrimidine tract-binding protein 1 (PTBP1). Then, the roles of PTBP1 on AS of the KIAA0930 and the proliferation of AML cells were confirmed. KIAA0930 variant 1 (KIAA0930-1) was upregulated and variant 2 (KIAA0930-2) downregulated with knockdown PTBP1 expression of AML cells by specific shRNA. A low level of PTBP1 can decrease the proliferation ability of AML cells. In conclusion, the results showed that PTBP1 might be a potential target for AML therapy.

Effect of acupuncture on long-term outcomes in patients with post-stroke dysphagia.

BACKGROUND: Acupuncture has been used to treat patients with post-stroke neurological dysfunction. OBJECTIVE: The purpose of our observational study was to observe the long-term efficacy of acupuncture and investigate whether the acupuncture treatment could short the recovery time of patients with post-stroke dysphagia. METHODS: Medical records were reviewed to select patients who met the inclusion criteria for post-stroke dysphagia. Exposure factor was defined as received acupuncture during inpatient. Clinical data were obtained at the 6-month follow-up. The primary outcome was the time to improve the score of Food Intake Level Scale (FILS, 0-10) by 3 grades. Cox regression models were used to assess the relationship between acupuncture and recovery of dysphagia. RESULTS: In acupuncture group, the median time to achieve clinical improvement of dysphagia was 97 days (95% CI, 93-124) compared with 119 days (95% CI, 108-145) in control group, with a statistically significant difference between the two groups (HR = 1.48; 95% CI 1.14-1.92; P = 0.003). At 6 months, 78 patients (60.5%) in acupuncture group reached excellent function and 61 patients (47.3%) in control group (RR = 1.28; 95% CI, 1.02-1.62; P = 0.045). 106 patients (82.2%) in acupuncture group achieved favorable function and 91 patients (70.5%) in control group (RR = 1.17; 95% CI, 1.02-1.35; P = 0.039). The outcome of adjusted multivariable Cox regression models showed that there was a difference in the recovery time of dysphagia between groups, HR = 1.79, 95% CI 1.34-2.39. The rates of adverse events were similar in both groups. CONCLUSIONS: Acupuncture can promote the recovery of post-stroke dysphagia, and has a better long-term efficacy. Besides, it can reduce the degree of disability and improve the quality of life.

[GAO Shu-zhong's clinical experience in "seeking yin from yang needling method" based on "qi street" and "four seas" theories].

The paper introduces professor GAO Shu-zhong's understanding on "seeking yin from yang needling method" and its clinical application on the basis of "qi street" and "four seas" theories. Through professor GAO's clinical practice for years, he integrates and extendes the theories of "seeking yin from yang", "qi street" and "four seas" in Huangdi Neijing (The Yellow Emperor's Inner Classic). In this specific acupuncture method, in reference with the theories of "qi street" and "four seas", acupuncture is exerted on yang part of body, e.g. the back and lumber region to treat the diseases of yin parts, e.g. the chest and abdomen, which is differentiated as yin-yang imbalance in pathogenesis. In order to fully explain the clinical curative effect of "seeking yin from yang needling method", the common diseases in clinic, e.g. the disorders of heart, spleen and stomach systems, as well as the gynecology are taken as examples in the paper.

Xueshuantong injection combined with Salvianolate lyophilized injection improves the synaptic plasticity against focal cerebral ischemia/reperfusion injury in rats through PI3K/AKT/mTOR and RhoA/ROCK pathways.

The combined use of two or more different drugs can better promote nerve recovery and its prognosis for treatment of stroke. Salvianolate lyophilized injection (SLI) made from the aqueous extraction of salvia miltiorrhiza and Xueshuantong injection (lyophilized) (XST) made from the Panax Notoginseng extraction are two herbal standardized preparations that have been widely used in China for the treatment of ischemic stroke. In this study, we investigated the neuroprotective effects of XST combined with SLI in the recovery stage of middle cerebral artery occlusion / reperfusion (MCAO/R) injury rat. Wistar rats were subjects to MCAO/R, then were treated with SLI or XST alone, or with their combination (1X1S) via tail injection daily for 14 days. The pathological status of the brain was detected by neurological deficit scores, TTC, regional cerebral blood flow and Nissl staining. Golgi-Cox staining was used to assess dendritic, axonal and synaptic remodeling. The expression of MAP-2, ß-Tubulin, PSD95, SYN, BDNF and VEGF were analyzed by western blotting and immunofluorescence. The results showed that administration of 1X1S not only significantly decreased neurological scores and infarct volumes, but also increased regional cerebral blood flow, strengthened dendritic and synaptic remodeling compared with XST, SLI used alone. And the mechanism of combined of 1X1S to exert neuroprotection may be associated with PI3K/ AKT/ mTOR and RhoA/ROCK2 pathways. Overall, these findings suggest that combination of XST and SLI promotes dendritic spine density and synaptic plasticity via upregulation of the PI3K/ AKT/ mTOR pathways and inhabitation the RhoA/ROCK2 signaling pathway in rat with MCAO/R, showing its multiple-action-multiple-target efficacy and suggest a potential new strategy for ischemia.