Based on commonly used acupoints in the clinical acupuncture treatment of functional dyspepsia （FD）， this study systematically analyzes the therapeutic differences and synergistic effects between local and distal point selection. It also examines the suitability of primary acupoint selection for different FD subtypes， postprandial distress syndrome （PDS） and epigastric pain syndrome （EPS）. The findings suggest that a combination of local and distal acupoints may be more appropriate as primary points for PDS， whereas local acupoints alone may be more suitable for EPS. Additionally， the study explores the impact of various factors， such as stimulation techniques， needling order， intensity or stimulation parameters， and depth， on the efficacy of acupuncture. It concludes that the intrinsic properties of acupoints are the primary determinants of therapeutic direction. Other factors mainly influence the magnitude rather than the direction of the effect. Future research may further investigate how different acupoint combinations， local versus distal， affect the treatment outcomes of FD subtypes， providing new insights for clinical acupuncture prescriptions.

ObjectiveTo explore the sequential effects of hypoxic exercising on miR-27/PPARγ and lipid metabolism target gene and protein expression levels in the obesity rats’ liver. Methods13-week-old male diet-induced obesity rats were randomly divided into three groups (n＝10): normal oxygen concentration quiet group (N), hypoxia quiet group (H), hypoxic exercise group (HE). Exercise training on the horizontal animal treadmill for 1 h/d, 5 d/week for a total of 4 week, and the intensity of horizontal treadmill training was 20 m/min (hypoxic concentration was 13.6%). Comparison of the weights of perirenal fat and epididymal fat in rats across different groups and calculation of Lee’s index based on body weight and body length of rats in each group were done. And the serum concentrations of total cholesterol (TC), triglyceride (TG), low density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) levels were detected. RT-PCR and Western Blot were used to detect the levels of miR-27, PPARγ, CYP7A1 and CD36. ResultsHypoxic exercise decreased the expression levels of miR-27 in the obese rats’ liver, however, the expression level of PPARγ was gradually increased. The expression levels of miR-27 in HE group were significantly lower than N group (P<0.05). The expression levels of PPARγ mRNA in N group were significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The protein expression of PPARγ protein in N group was significantly lower than that other groups (P<0.01). The expression of lipid metabolism-related genes and proteins increased in the obese rats’ liver. The expression of CYP7A1 mRNA in N group was significantly lower than H group (P<0.05), especially lower than HE group (P<0.01). The expression of CYP7A1 protein in the obese rats’ liver in N group was extremely lower than H group and HE group (P<0.01). The protein expression of CD36 in N group was significantly lower than that in HE group (P<0.05). Hypoxia exercise improved the related physiological and biochemical indexes of lipid metabolism disorder. The perirenal fat weight of obese rats in HE group was extremely lower than N group and H group (P<0.01), and the perirenal fat weight in N group was significantly higher than H group (P<0.05). The epididymal fat weight in N group was significantly higher than H group (P<0.05), and extremely higher than HE group (P<0.01). The Lee’s index in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TC in obese rats in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of TG in HE group was extremely lower than N group and H group (P<0.01). The serum concentration of LDL-C in N group was extremely higher than HE group (P<0.01). The serum concentration of HDL-C in N group was extremely lower than H group (P<0.01). ConclusionHypoxia and hypoxia exercise may negatively regulate the levels of PPARγ by inhibiting miR-27 in the obese rats’ liver, thereby affecting the expression of downstream target genes CYP7A1 and CD36, and promoting cholesterol, fatty acid oxidation and HDL-C transport in the liver, and ultimately the lipid levels in obese rats were improved. The effect of hypoxia exercise on improving blood lipid is better than simple hypoxia intervention.

OBJECTIVE To explore the effects of prescription pre-review system on rational drug use and off-label drug use management in outpatient and emergency department. METHODS A retrospective analysis was conducted on outpatient and emergency department prescription data from three phases in our hospital： January to May 2023 （silent review phase， control group）， June to October 2023 （systematic automatic review phase， intervention group 1）， and November 2023 to March 2024 （phase combining systematic automatic review with centralized feedback from pharmacists to physicians regarding irrational prescriptions， intervention group 2）. These phases followed the implementation of our hospital’s pre-prescription review software. Statistical analysis of the prompt rate of alert， rate of irrational prescriptions， registered the off-label drug use rate and false positive irrationality prescription rate were conducted. Meanwhile， the composition of irrational prescriptions was analyzed， and evidence- based evaluation of the off-label drug use proposed by clinicians was also conducted. RESULTS Compared with control group， the prompt rate of alert and the rate of irrational prescriptions in intervention group 1 were all decreased significantly after receiving pop-up notification， with statistically significant differences （P＜0.05）. With the help of system warning and the pharmacists feedback， the prompt rate of alert and the rate of irrational prescriptions declined further in the intervention group 2， but there was no statistically significant difference when compared with intervention group 1 （P＞0.05）. The main type of irrational drug use was improper administration routes. When comparing intervention group 1 with the control group， as well as intervention group 2 with intervention group 1， a significant decrease in the rate of improper administration routes was observed， with statistically significant differences （P＜0.05）. Compared with control group， there was no significant difference in the registered off-label drug use rate of intervention group 1 and intervention group 2 （P＞0.05）. The doctor’s awareness of off-label drug use registration increased due to the real-time alerts from the pre-prescription review software， along with the pharmacists’ regular summarization and feedback. Total 13 items registrations of off-label drug use were proposed by clinicians from June 2023 to March 2024， all of which were supported by evidence of varying levels； among them， 3 items received FDA approval， 4 items were included in the Micromedex database， and the remaining 6 items were supported by evidence from system reviews or randomized controlled trials. CONCLUSIONS Prescription pre-review system can improve the level of rational drug use and assist in the standardized management of off-label drug use.

Diabetic cardiomyopathy is a distinct form of cardiomyopathy that can lead to heart failure, arrhythmias, cardiogenic shock, and sudden death. It has become a major cause of mortality in diabetic patients. The pathogenesis of diabetic cardiomyopathy is complex, involving increased oxidative stress, activation of inflammatory responses, disturbances in glucose and lipid metabolism, accumulation of advanced glycation end products (AGEs), abnormal autophagy and apoptosis, insulin resistance, and impaired intracellular Ca²⁺ homeostasis. Recent studies have shown that adenosine monophosphate-activated protein kinase (AMPK) plays a crucial protective role by lowering blood glucose levels, promoting lipolysis, inhibiting lipid synthesis, and exerting antioxidant, anti-inflammatory, anti-apoptotic, and anti-ferroptotic effects. It also enhances autophagy, thereby alleviating myocardial injury under hyperglycemic conditions. Consequently, AMPK is considered a key protective factor in diabetic cardiomyopathy. As part of diabetes prevention and treatment strategies, both pharmacological and exercise interventions have been shown to mitigate diabetic cardiomyopathy by modulating the AMPK signaling pathway. However, the precise regulatory mechanisms, optimal intervention strategies, and clinical translation require further investigation. This review summarizes the role of AMPK in the prevention and treatment of diabetic cardiomyopathy through drug and/or exercise interventions, aiming to provide a reference for the development and application of AMPK-targeted therapies. First, several classical AMPK activators (e.g., AICAR, A-769662, O-304, and metformin) have been shown to enhance autophagy and glucose uptake while inhibiting oxidative stress and inflammatory responses by increasing the phosphorylation of AMPK and its downstream target, mammalian target of rapamycin (mTOR), and/or by upregulating the gene expression of glucose transporters GLUT1 and GLUT4. Second, many antidiabetic agents (e.g., teneligliptin, liraglutide, exenatide, semaglutide, canagliflozin, dapagliflozin, and empagliflozin) can promote autophagy, reverse excessive apoptosis and autophagy, and alleviate oxidative stress and inflammation by enhancing AMPK phosphorylation and its downstream targets, such as mTOR, or by increasing the expression of silent information regulator 1 (SIRT1) and peroxisome proliferator-activated receptor‑α (PPAR‑α). Third, certain anti-anginal (e.g., trimetazidine, nicorandil), anti-asthmatic (e.g., farrerol), antibacterial (e.g., sodium houttuyfonate), and antibiotic (e.g., minocycline) agents have been shown to promote autophagy/mitophagy, mitochondrial biogenesis, and inhibit oxidative stress and lipid accumulation via AMPK phosphorylation and its downstream targets such as protein kinase B (PKB/AKT) and/or PPAR‑α. Fourth, natural compounds (e.g., dihydromyricetin, quercetin, resveratrol, berberine, platycodin D, asiaticoside, cinnamaldehyde, and icariin) can upregulate AMPK phosphorylation and downstream targets such as AKT, mTOR, and/or the expression of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby exerting anti-inflammatory, anti-apoptotic, anti-pyroptotic, antioxidant, and pro-autophagic effects. Fifth, moderate exercise (e.g., continuous or intermittent aerobic exercise, aerobic combined with resistance training, or high-intensity interval training) can activate AMPK and its downstream targets (e.g., acetyl-CoA carboxylase (ACC), GLUT4, PPARγ coactivator-1α (PGC-1α), PPAR-α, and forkhead box protein O3 (FOXO3)) to promote fatty acid oxidation and glucose uptake, and to inhibit oxidative stress and excessive mitochondrial fission. Finally, the combination of liraglutide and aerobic interval training has been shown to activate the AMPK/FOXO1 pathway, thereby reducing excessive myocardial fatty acid uptake and oxidation. This combination therapy offers superior improvement in cardiac dysfunction, myocardial hypertrophy, and fibrosis in diabetic conditions compared to liraglutide or exercise alone.

The aim of this study is to investigate the regulation of Kaixin San-medicated serum(KXS-MS) on autophagy induced by Aβ_(25-35) in SH-SY5Y cells. The SH-SY5Y cell model of Aβ_(25-35)(25 μmol·L~(-1))-induced injury was established, and different concentrations of KXS-MS were added into the culture media of cells, which were then incubated for 24 h. Cell viability was measured by the methyl thiazolyl tetrazolium(MTT) assay. The protein levels of microtubule-associated protein 1 light chain 3(LC3)Ⅰ, LC3Ⅱ, protein kinase B(Akt), p-Akt, mammalian target of rapamycin(mTOR), and p-mTOR were assessed by Western blot. Furthermore, the combination of rapamycin(Rapa)/3-methyladenine(3-MA) and low concentration of KXS-MS was added to the culture medium of SH-SY5Y cells injured by Aβ_(25-35), and the cell viability and the expression levels of the above proteins were determined. The results showed that Aβ_(25-35) decreased the cell viability, up-regulated the expression levels of LC3Ⅱ and LC3Ⅱ/LC3Ⅰ, and down-regulated the expression levels of p-Akt, p-mTOR, p-Akt/Akt, and p-mTOR/mTOR. Compared with the Aβ_(25-35) model group, KXS-MS treatment attenuated Aβ_(25-35)-induced injury and enhanced the survival of SH-SY5Y cells. Meanwhile, KXS-MS down-regulated the LC3Ⅱ/LC3Ⅰ level and up-regulated the p-Akt/Akt and p-mTOR/mTOR levels. Compared with the low-concentration KXS-MS group, Rapa did not affect the cell survival and the levels of p-Akt and p-Akt/Akt, while it up-regulated the levels of LC3Ⅱ and LC3Ⅱ/LC3Ⅰ and down-regulated the levels of p-mTOR and p-mTOR/mTOR. 3-MA significantly reduced the cell survival rate and p-Akt, p-Akt/Akt level in the KXS-MS group, while it had no significant effect on the levels of LC3Ⅱ, LC3Ⅱ/LC3Ⅰ, p-mTOR, and p-mTOR/mTOR. The above results indicate that KXS-MS exhibits protective effects against Aβ_(25-35)-induced damage in SH-SY5Y cells by up-regulating Akt/mTOR activity to inhibit autophagy.
Humans ; Autophagy/drug effects* ; TOR Serine-Threonine Kinases/genetics* ; Amyloid beta-Peptides/toxicity* ; Proto-Oncogene Proteins c-akt/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Cell Line, Tumor ; Cell Survival/drug effects* ; Peptide Fragments/toxicity* ; Microtubule-Associated Proteins/genetics*

Extensive studies have identified potential adverse effects on semen quality of obesity, based on body mass index, but the association between body fat distribution, a more relevant indicator for obesity, and semen quality remains less clear. We conducted a longitudinal study of 4304 sperm donors from the Guangdong Provincial Human Sperm Bank (Guangzhou, China) during 2017-2021. A body composition analyzer was used to measure total and local body fat percentage for each participant. Generalized estimating equations were employed to assess the association between body fat percentage and sperm count, motility, and morphology. We estimated that each 10% increase in total body fat percentage (estimated change [95% confidence interval, 95% CI]) was significantly associated with a 0.18 × 10 6 (0.09 × 10 6 -0.27 × 10 6 ) ml and 12.21 × 10 6 (4.52 × 10 6 -19.91 × 10 6 ) reduction in semen volume and total sperm count, respectively. Categorical analyses and exposure-response curves showed that the association of body fat distribution with semen volume and total sperm count was stronger at higher body fat percentages. In addition, the association still held among normal weight and overweight participants. We observed similar associations for upper limb, trunk, and lower limb body fact distributions. In conclusion, we found that a higher body fat distribution was significantly associated with lower semen quality (especially semen volume) even in men with a normal weight. These findings provide useful clues in exploring body fat as a risk factor for semen quality decline and add to evidence for improving semen quality for those who are expected to conceive.
Humans ; Male ; Adult ; Semen Analysis ; China ; Body Fat Distribution ; Longitudinal Studies ; Sperm Count ; Sperm Motility ; Body Mass Index ; Tissue Donors ; Obesity/complications* ; Spermatozoa ; Young Adult ; Middle Aged ; East Asian People

Magnetic resonance imaging (MRI), as a non-invasive neuroimaging technique, has been widely employed to investigate changes in functional brain regions. In recent years, the application of MRI in the study of lifelong premature ejaculation (LPE) has progressively uncovered the pathological mechanisms underlying abnormalities in LPE-associated brain regions. These mechanisms involve brain areas associated with higher-order cognitive and decision-making regulation, sensory and perceptual processing, as well as emotional regulation and reward systems. The application and findings of MRI in the study of LPE mechanisms will be introduced in this review, with the goal of deepening our understanding of the neuroimaging-based mechanisms of LPE.
Humans ; Premature Ejaculation/physiopathology* ; Male ; Magnetic Resonance Imaging ; Neuroimaging ; Brain

BACKGROUND: Postherpetic neuralgia (PHN) is the most common complication of herpes zoster infection and affects patients' quality of life. Acupuncture therapy is regarded as a competitive method of treatment for analgesia. OBJECTIVE: To summarize evidence from systematic reviews (SRs) and evaluate the effectiveness and safety of different acupuncture therapies for treating PHN. METHODS: Eight electronic databases were searched from their inception to August 5, 2022, including 4 international electronic databases (PubMed, EMBASE, the Cochrane Library, and Web of Science) and 4 Chinese databases (Chinese Biomedical Database, China National Knowledge Infrastructure, VIP Database and Wanfang Database). Methodological quality was assessed by A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). The Risk of Bias in Systematic Review (ROBIS) tool was used to assess the risk of bias in SRs. Evidence level was assessed by the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Totally, 7 SRs were included, including 128 studies and 9,792 patients. In AMSTAR 2, most of the SRs were of low or critically low levels since they had more than 1 critical deficiency. In ROBIS, 1 SR (14.29%) was rated as high risk, and the other 6 (85.71%) were rated as low risk. In the GRADE system, 9 outcomes (28.13%) were valued as high level, 5 (15.63%) as moderate level, 1 (3.13%) as low, and 17 (53.13%) as very low. In the effectiveness of acupuncture therapy, the group "moxibustion vs. original medical treatment" [mean difference (MD)=-1.44, 95% confidence interval (CI): -1.80 to -1.08, I²=99%, P<0.00001] was of the highest heterogeneity and the group "bloodletting vs. original medical treatment" (MD=-2.80, 95% CI: -3.14 to -2.46, I²=0, P<0.00001) was of the lowest heterogeneity. Six SRs have reported the safety of their studies and no serious events were shown in the treatment and control groups. CONCLUSIONS Acupuncture therapy seems to be effective in treating PHN. Despite the evidence that suggested the advantages of acupuncture therapy in relieving pain and promoting efficacy and safety, the methodological quality was quite low. Further studies should pay more attention to the quality of original studies and evidence for SRs to confirm these findings. (PROSPERO registration No. CRD42022344790).
Humans ; Neuralgia, Postherpetic/therapy* ; Acupuncture Therapy/methods* ; Systematic Reviews as Topic

Long-term hypertension causes excessive vascular remodeling and leads to adverse cardiovascular events. Balance of ubiquitination and deubiquitination has been linked to several chronic conditions, including pathological vascular remodeling. In this study, we discovered that the expression of ubiquitin-specific protease 25 (USP25) is significantly up-regulated in angiotensin II (Ang II)-challenged mouse aorta. Knockout of Usp25 augments Ang II-induced vascular injury such as fibrosis and endothelial to mesenchymal transition (EndMT). Mechanistically, we found that USP25 interacts directly with Forkhead box O3 (FOXO3) and removes the K63-linked ubiquitin chain on the K258 site of FOXO3. We also showed that this USP25-mediated deubiquitination of FOXO3 increases its binding to light chain 3 beta isoform and autophagosomic-lysosomal degradation of FOXO3. In addition, we further validated the biological function of USP25 by overexpressing USP25 in the mouse aorta with AAV9 vectors. Our studies identified FOXO3 as a new substrate of USP25 and showed that USP25 may be a potential therapeutic target for excessive vascular remodeling-associated diseases.