OBJECTIVE To analyze the chemical constituents of the active parts of Piper wallichii. METHODS The petroleum ether-extract fraction was prepared from the methanol extract of P. wallichii. Separation and purification were performed using semi-preparative high-performance liquid chromatography. The structures of the compounds were identified by nuclear magnetic resonance spectroscopy. RESULTS Nineteen compounds were isolated from the petroleum ether-extract fraction from the methanol extract of P. wallichii， identified as 3-acetoxybenzyl benzoate （1）， 2-acetoxybenzyl benzoate （2）， 2-methoxybenzyl benzoate （3）， 3-methoxybenzyl benzoate （4）， 4-hydroxy-3-methoxybenzyl benzoate （5）， 3-hydroxybenzyl benzoate（6）， benzyl benzoate （7）， ganschisandrine （8）， lancifolin A （9）， （7R，8R，3′R）-7-acetoxy-3′，4′-dimethoxy-3，4-methylenedioxy-6′-oxo- Δ1′，4′，8′-8.3′-lignan （10）， （7S，8R，3′S）-Δ8′-3′，6′-dihydro-3′-methoxy-3，4-methylenedioxy-6′-oxo-8.3′，7.O.4′-lignan （11）， （7R， 8R，3′S）-Δ8′-3′，6′-dihydro-3′-methoxy-3，4-methylenedioxy-6′-oxo-8.3′，7.O.4′-lignan （12）， isodihydrofutoquinol A （13）， licarin A （14）， licarin B （15）， 2-（2′，5′-dimethoxyphenyl）-3，4- dimethyl-5-（3″，4″-dimethoxyphenyl）- tetrahydrofuran （16）， galgravin （17）， velutin （18）， and piyunin A （19）. CONCLUSIONS Compound 1 is a new benzyl benzoate compound. Compounds 3-5， 8 and 9 are isolated from the Piper genus for the first time， while compounds 2， 6， 10-13 and 15-19 are isolated from P. wallichii for the first time.

OBJECTIVE: To observe the effects of moxibustion at "Xinshu" (BL15) and "Feishu" (BL13) on myocardial transferrin receptor 1 (TfR1), ferroptosis suppressor protein 1 (FSP1), atrial natriuretic peptide (ANP), and typeⅠcollagen myocardial collagen fibers (CollagenⅠ) in rats with chronic heart failure (CHF), and to explore the mechanism of moxibustion for ameliorating myocardial fibrosis and improving cardiac function in CHF. METHODS: Fifty SD rats were randomly divided into a normal group (n=10) and a modeling group (n=40). The CHF model was established in the modeling group by ligating the left anterior descending coronary artery. After successful modeling, the rats were randomly divided into a model group (n=9), a moxibustion group (n=8), a rapamycin (RAPA) group (n=9), and a moxibustion+RAPA group (n=9). In the moxibustion group, moxibustion was delivered at bilateral "Feishu"(BL13) and "Xinshu" (BL15), 15 min at each point in each intervention, once daily, for 4 consecutive weeks. In the RAPA group, RAPA solution was administered intraperitoneally at a dose of 1 mg/kg, once daily for 4 consecutive weeks. In the moxibustion+RAPA group, RAPA solution was administered intraperitoneally after moxibustion. Ejection fraction (EF) and left ventricular fractional shortening (FS) were measured after modeling and intervention. After intervention, morphology of cardiac muscle was observed using HE staining and Masson's trichrome staining. Total iron content in myocardial tissue was detected using a colorimetric method. Western blot and qPCR were adopted to detect the protein and mRNA expression of TfR1, FSP1, ANP, and CollagenⅠ in myocardial tissue. RESULTS: Compared with the normal group, the EF and FS values decreased (P<0.01); necrosis, edema, degeneration, and arrangement disorder were presented in cardiomyocytes; inflammatory cells were obviously infiltrated, the structure of myocardial fibers was disarranged, the collagen fibers were obviously deposited and fibrosis increased (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue were elevated (P<0.01), while the protein and mRNA expression of FSP1 were reduced (P<0.01) in the model group. Compared with the model group, the moxibustion group showed that EF and FS increased (P<0.01); myocardial cell morphology was improved, and myocardial fibrosis was alleviated (P<0.01); the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while the protein and mRNA expression of FSP1 increased (P<0.01, P<0.05). Compared with the model group, the myocardial fibrosis was increased (P<0.05); the total iron content and the protein and mRNA expression of TfR1, ANP, CollagenⅠ in myocardial tissue were increased (P<0.01), while protein and mRNA expression of FSP1 decreased (P<0.01) in the RAPA group. When compared with the RAPA group and the moxibustion + RAPA group, EF and FS were elevated (P<0.01, P<0.05); myocardial cells were improved in morphology, the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue decreased (P<0.01), while protein and mRNA expression of FSP1 increased (P<0.01) in the moxibustion group. In comparison with the moxibustion + RAPA group, the RAPA group showed the decrease in EF and FS (P<0.01), the worsened myocardial fibrosis (P<0.01), the increase in the total iron content and the protein and mRNA expression of TfR1, ANP, and CollagenⅠ in myocardial tissue (P<0.01), and the decrease in the protein and mRNA expression of FSP1 (P<0.01). CONCLUSION Moxibustion at "Feishu" (BL13) and "Xinshu" (BL15) can slow down the process of myocardial fibrosis and improve cardiac function in CHF rats. The mechanism of moxibustion may be related to inhibiting ferroptosis through regulating autophagy.
Animals ; Rats ; Heart Failure/physiopathology* ; Moxibustion ; Rats, Sprague-Dawley ; Male ; Receptors, Transferrin/genetics* ; Myocardium/metabolism* ; Acupuncture Points ; Humans ; Chronic Disease/therapy* ; Antigens, CD/metabolism*

BACKGROUND: The use of potentially inappropriate medications (PIMs) is a major concern for medication safety as it may entail more harm than potential benefits for older adults. This study aimed to explore the prescribing rate, healthcare utilization, and expenditure of older adults using PIMs in China. METHODS: A cross-sectional analysis was conducted using a national representative database of all medical insurance beneficiaries across China, extracting ambulatory visit records of adults aged 65 years and above between 2015 and 2017. Descriptive analysis was conducted to measure the rate of patients exposed to PIM, prescribing rate of each PIM, average annual outpatient visits per patient, average total medication costs for each visit, average annual cost of PIMs for each patient, and average annual medication costs for each patient. Generalized linear model with logit link function and binomial distribution was used to examine the adjusted associations between PIMs and independent variables. RESULTS: In total, 845,278 (33.2%) participants were identified to be exposed to at least one PIM. Patients aged 75-84 years (38.1%, 969,809/2,545,430) and ≥85 years (37.9%, 964,718/2,545,430) were more likely to be prescribed with PIMs. Beneficiaries of the Urban Employee Basic Medical Insurance (UEBMI) and living in eastern and southern regions were more frequently prescribed with PIMs. Compared with patients without PIM exposure (7.5 visits, drug cost of RMB 1545.0 Yuan), patients with PIM exposure showed higher adjusted average annual number of outpatient visits (10.7 visits, β = 3.228, 95% confidence interval [CI] = 3.196-3.261) and higher annual drug costs (RMB 2461.8 Yuan, Coef. = 916.864, 95% CI = RMB 906.292-927.436 Yuan). CONCLUSIONS The results showed that the use of PIM among older adults was common in China. This study suggests that the use of PIM could be considered as a clear target, pending multidimensional efforts, to promote rational prescribing for older adults.
Humans ; Aged ; Cross-Sectional Studies ; Aged, 80 and over ; Male ; Female ; China ; Inappropriate Prescribing/economics* ; Patient Acceptance of Health Care/statistics & numerical data* ; Potentially Inappropriate Medication List/statistics & numerical data* ; Health Expenditures/statistics & numerical data*

This study predicts the quality markers(Q-markers) for the cough-relieving and phlegm-expelling effects of Kening Granules based on pharmacodynamics, plasma drug chemistry, network pharmacology, and pharmacokinetics. Strong ammonia solution spray and phenol red secretion assays were employed to evaluate the cough-relieving and phlegm-expelling effects of Kening Granules. Twentysix absorbed prototype components of Kening Granules were identified by ultra high performance liquid chromatography coupled with QExactive Plus quadrupole/Orbitrap high resolution mass spectrometry(UHPLC-Q-Exactive Plus Orbitrap HRMS). Through network pharmacology, 11 potential active components were screened out for the cough-relieving and phlegm-expelling effects of Kening Granules. The 11 components acted on 40 common targets such as IL6, TLR4, and STAT3, which mainly participated in PI3K/Akt, HIF-1, and EGFR signaling pathways. Pharmacokinetic quantitative analysis was performed for 7 prototype components. Three compounds including azelaic acid, caffeic acid, and vanillin were identified as Q-markers for the cough-relieving and phlegm-expelling effects of Kening Granules based on their effectiveness, transmissibility, and measurability. The results of this study are of great significance for clarifying the pharmacological substance basis, optimizing the quality standards, and promoting the clinical application of Kening Granules.
Drugs, Chinese Herbal/administration & dosage* ; Network Pharmacology ; Cough/blood* ; Male ; Humans ; Animals ; Rats ; Rats, Sprague-Dawley ; Biomarkers/blood* ; Quality Control ; Chromatography, High Pressure Liquid ; Antitussive Agents/chemistry*

OBJECTIVE: To investigate the clinical effect and adverse reactions of dapoxetine hydrochloride versus paroxetine in the treatment of primary premature ejaculation by cross-comparison. METHODS: Based on the clinic-visit time, we equally randomized 148 patients with primary premature ejaculation into groups A and B for a cross-comparison test, the former treated with paroxetine at 20 mg once nightly and the latter with dapoxetine hydrochloride at 30 mg on demand, both for 6 successive weeks, during which we observed the therapeutic effects and adverse reactions. Following 4 weeks of drug discontinuance, we administered dapoxetine hydrochloride at 30 mg on demand for group A and paroxetine at 20 mg once nightly for group B, both for another 6 successive weeks, followed by observation and comparison of the therapeutic effects and adverse reactions. RESULTS: There were no statistically significant differences in the initial characteristics of the two groups of patients (P > 0.05). Compared with the baseline, the mean intra-vaginal ejaculation latency time (IELT) was dramatically improved after treatment in both groups A (4.43 min) and B (7.12 min), increased by 3.99% and 6.72%, respectively (P<0.001). The patients treated with paroxetine showed significantly longer IELT than those taking dapoxetine hydrochloride in both groups (P<0.001). Findings of the Premature Ejaculation Profile (PEP) and spouses' conditions indicated significant improvement after treatment in the average scores of the four indicators of PEP, that is, perceived control over ejaculation, ejaculation-related personal distress, satisfaction with sexual intercourse and ejaculation-related interpersonal difficulty, as well as in the overall experience and partner's satisfaction and orgasm frequency. Adverse reactions to medication were found in 20.8% of the cases in group A and 9.7% in group B, but none was serious. Preference survey following drug withdrawal revealed a preference for paroxetine (61.9%) over dapoxetine (26.8%), and that only a few of the patients thought of the two drugs as comparable or both ineffective. CONCLUSION In term of overall effectiveness, paroxetine was superior to dapoxetine in the treatment of primary premature ejaculation. And the patients obviously preferred the former to the latter, which might be partly attributed to the higher price of dapoxetine.
Humans ; Benzylamines/therapeutic use* ; Male ; Premature Ejaculation/drug therapy* ; Naphthalenes/therapeutic use* ; Paroxetine/therapeutic use* ; Adult ; Treatment Outcome ; Middle Aged ; Young Adult ; Selective Serotonin Reuptake Inhibitors/therapeutic use*

OBJECTIVE: To evaluate the efficacy and safety of Shexiang Tongxin Dropping Pill (STDP) in treating stable angina patients with phlegm-heat and blood-stasis syndrome by exercise duration and metabolic equivalents. METHODS: This multicenter, randomized, double-blind, placebo-controlled clinical trial enrolled stable angina patients with phlegm-heat and blood-stasis syndrome from 22 hospitals. They were randomized 1:1 to STDP (35 mg/pill, 6 pills per day) or placebo for 56 days. The primary outcome was the exercise duration and metabolic equivalents (METs) assessed by the standard Bruce exercise treadmill test after 56 days of treatment. The secondary outcomes included the total angina symptom score, Chinese medicine (CM) symptom scores, Seattle Angina Questionnaire (SAQ) scores, changes in ST-T on electrocardiogram and adverse events (AEs). RESULTS: This trial enrolled 309 patients, including 155 and 154 in the STDP and placebo groups, respectively. STDP significantly prolonged exercise duration with an increase of 51.0 s, compared to a decrease of 12.0 s with placebo (change rate: -11.1% vs. 3.2%, P<0.01). The increase in METs was significantly greater in the STDP group than in the placebo group (change: -0.4 vs. 0.0, change rate: -5.0% vs. 0.0%, P<0.01). The improvement of total angina symptom scores (25.0% vs. 0.0%), CM symptom scores (38.7% vs. 11.8%), reduction of nitroglycerin consumption (100.0% vs. 11.3%), and all domains of SAQ, were significantly greater with STDP than placebo (all P<0.01). The changes in Q-T intervals at 28 and 56 days from baseline were similar between the two groups (both P>0.05). Twenty-five participants (16.3%) with STDP and 16 (10.5%) with placebo experienced AEs (P=0.131), with no serious AEs observed. CONCLUSION STDP could improve exercise tolerance in patients with stable angina and phlegm-heat and blood stasis syndrome, with a favorable safety profile. (Registration No. ChiCTR-IPR-15006020).
Humans ; Double-Blind Method ; Drugs, Chinese Herbal/adverse effects* ; Male ; Female ; Middle Aged ; Angina, Stable/physiopathology* ; Aged ; Syndrome ; Treatment Outcome ; Placebos ; Tablets

Ferroptosis is a form of programmed cell death characterized by overwhelmed lipid oxidation, and it has emerged as a promising strategy for cancer therapy. Enhanced ferroptosis could overcome the limitations of conventional therapeutic modalities, particularly in difficult-to-treat tumors. In this study, we developed a dual-modality therapy in nanomedicine by combining paclitaxel (PTX) chemotherapy and pyropheophorbide-a (Ppa) phototherapy. Heparin (HP) was grafted with poly(N-(2'-hydroxy) propyl methacrylamide) (pHPMA) using reversible addition-fragmentation chain transfer polymerization to form HP-pHPMA (HH), which was utilized to deliver Ppa and PTX, yielding HP-pHPMA-Ppa (HH-Ppa) and HP-pHPMA-PTX (HH-PTX), respectively. The prodrug-based combinational nanomedicine (HH-PP) was formed by co-assembly of HH-PTX and HH-Ppa. It was found that HH-PP treatment significantly disrupted lipid metabolism in triple-negative breast cancer (TNBC) cells, induced extensive lipid oxidation, and promoted ferroptosis. In vivo, HH-PP intervention achieved a tumor growth inhibition rate of 86.63% and activated adaptive immunity with an elevated CD8⁺ cytotoxic T cell infiltration level. This combinational nanomedicine offers a promising platform for co-delivery of multiple therapeutic agents. It exerts a promising anti-tumor effect via enhanced ferroptosis and ferroptosis-induced immune activation by disrupting lipid metabolism in TNBC cancer cells.

Infectious keratitis (IK) is a leading cause of blindness worldwide, primarily resulting from improper contact lens use, trauma, and a compromised immune response. The pathogenic microorganisms responsible for IK include bacteria, fungi, viruses, and Acanthamoeba. This review examines standard therapeutic agents for treating IK, including broad-spectrum empiric antibiotics for bacterial keratitis (BK), antifungals such as voriconazole and natamycin for fungal infections, and antiviral nucleoside analogues for viral keratitis (VK). Additionally, this review discusses therapeutic agents, such as polyhexamethylene biguanide (PHMB), for the treatment of Acanthamoeba keratitis (AK). The review also addresses emerging drugs and the challenges associated with their clinical application, including anti-biofilm agents that combat drug resistance and nuclear factor kappa-B (NF-κB) pathway-targeted therapies to mitigate inflammation. Furthermore, methods of Photodynamic Antimicrobial Therapy (PDAT) are explored. This review underscores the importance of integrating novel and traditional therapies to tackle drug resistance and enhance drug delivery, with the goal of advancing treatment strategies for IK.

Nuclear factor E2-related factor 2 (Nrf2) is a major regulator of redox homeostasis in cells, and Nrf2 signaling pathway has anti-inflammatory, anti-oxidative stress, and anti-fibrosis effects while plays an important role in wound healing and pathological scar formation and progression. This article reviewed the related research regarding the effect of oxidative stress and Nrf2 signaling pathway on pathological scars, furthermore, it investigated the relationship between Nrf2 signaling pathway, oxidative stress and pathological scars, providing a new perspective for the study of mechanism and clinical prevention and treatments of pathological scars.

Nuclear factor E2-related factor 2 (Nrf2) is a major regulator of redox homeostasis in cells, and Nrf2 signaling pathway has anti-inflammatory, anti-oxidative stress, and anti-fibrosis effects while plays an important role in wound healing and pathological scar formation and progression. This article reviewed the related research regarding the effect of oxidative stress and Nrf2 signaling pathway on pathological scars, furthermore, it investigated the relationship between Nrf2 signaling pathway, oxidative stress and pathological scars, providing a new perspective for the study of mechanism and clinical prevention and treatments of pathological scars.