OBJECTIVES: To investigate the therapeutic effect of Ziwuliuzhu acupuncture in a rat model of insomnia and its regulatory effect on the glutamic acid (Glu)/γ-aminobutyric acid (GABA)-glutamine (Gln) metabolic loop. METHODS: Forty male SD rats were randomly assigned to control group, model group, Najia group and Nazi group (n=10). In the latter 3 groups, rat models of insomnia were established by intraperitoneal injections of p-chlorophenylalanine and verified using a sodium pentobarbital-induced sleep test. After modeling, the rats in Najia and Nazi groups received acupuncture for 7 days at specifically chosen sets of acupoints based on the Ziwuliuzhu rationale in traditional Chinese medicine. Pathological changes in the hypothalamic tissue of the rats were examined with HE staining, and the levels of Glu and GABA in the hypothalamus were determined with high-performance liquid chromatography (HPLC)-mass spectrometry (MS)/MS. Immunohistochemistry was used to detect the expressions of GABAA receptors (GABAARs) in the hypothalamus, and the expression levels of glutamate decarboxylase (GAD65/67) and glutamine synthetase (GS) were determined with Western blotting. RESULTS: Compared with the model group, the rats in Najia and Nazi groups exhibited decreased Glu levels and GABAA receptor expression and increased GABA levels with a decreased Glu/GABA ratio in the hypothalamus. Ziwuliuzhu acupuncture significantly increased the protein expressions of GAD65 and GAD67 and lowered the expression of GS in the hypothalamus in the rat models of insomnia. CONCLUSIONS Ziwuliuzhu acupuncture produces sedative and hypnotic effects in rat models of insomnia possibly by regulating Glu and GABA-Gln metabolism to restore the excitatory/inhibitory balance between Glu and GABA.
Animals ; Rats, Sprague-Dawley ; Male ; Rats ; gamma-Aminobutyric Acid/metabolism* ; Sleep Initiation and Maintenance Disorders/therapy* ; Glutamine/metabolism* ; Glutamic Acid/metabolism* ; Acupuncture Therapy ; Hypothalamus/metabolism* ; Receptors, GABA-A/metabolism* ; Acupuncture Points

Objective To investigate the therapeutic effect of Ziwuliuzhu acupuncture in a rat model of insomnia and its regulatory effect on the glutamic acid(Glu)/γ-aminobutyric acid(GABA)-glutamine(Gln)metabolic loop.Methods Forty male SD rats were randomly assigned to control group,model group,Najia group and Nazi group(n=10).In the latter 3 groups,rat models of insomnia were established by intraperitoneal injections of p-chlorophenylalanine and verified using a sodium pentobarbital-induced sleep test.After modeling,the rats in Najia and Nazi groups received acupuncture for 7 days at specifically chosen sets of acupoints based on the Ziwuliuzhu rationale in traditional Chinese medicine.Pathological changes in the hypothalamic tissue of the rats were examined with HE staining,and the levels of Glu and GABA in the hypothalamus were determined with high-performance liquid chromatography(HPLC)-mass spectrometry(MS)/MS.Immunohistochemistry was used to detect the expressions of GABAA receptors(GABAARs)in the hypothalamus,and the expression levels of glutamate decarboxylase(GAD65/67)and glutamine synthetase(GS)were determined with Western blotting.Results Compared with the model group,the rats in Najia and Nazi groups exhibited decreased Glu levels and GABAA receptor expression and increased GABA levels with a decreased Glu/GABA ratio in the hypothalamus.Ziwuliuzhu acupuncture significantly increased the protein expressions of GAD65 and GAD67 and lowered the expression of GS in the hypothalamus in the rat models of insomnia.Conclusion Ziwuliuzhu acupuncture produces sedative and hypnotic effects in rat models of insomnia possibly by regulating Glu and GABA-Gln metabolism to restore the excitatory/inhibitory balance between Glu and GABA.

Metabolic associated fatty liver disease(MAFLD)is a metabolic disorder liver disease closely related to insulin resistance(IR)and genetic susceptibility.Hepatocyte steatosis is the main pathological change.In recent years,the prevalence of MAFLD has increased significantly,so it is necessary to provide interventions as soon as possible.Glucagon-like peptide-1 receptor agonist plays a hypoglycemic effect by promoting insulin release and reducing IR.Studies shows that it has significant benefits on body weight,lipid metabolism,inflammation and fibrosis in patients with MAFLD,and is expected to be an effective drug for the treatment of MAFLD.

Sarcopenia refers to the gradual decrease in skeletal muscle mass and function with age,and is an important factor in disability and mortality in elderly population.The pathogenesis of sarcopenia may be related to insulin resistance,oxidative stress,inflammation,mitochondrial dysfunction,and impaired autophagy caused by abnormal glucose and lipid metabolism.Sarcopenia can reduce daily activity ability and prolong recovery time from diseases.This article reviews the research progress on the relationship between abnormal glucose and lipid metabolism and the pathogenesis of sarcopenia.

Objective:The impact and mechanism system of the National Centralized Volume-Based Procurement(NCVBP)on innovation investment in pharmaceutical companies.Methods:Based on listed company data from 2015 to 2023,it uses the first eight rounds of NCVBP as a quasi-natural experiment and applies a staggered difference-in-differences model to control the industries and year fixed effects,test the impact of NCVBP on innovation investment in pharmaceutical companies,conduct the parallel trend and placebo test,and verify the robustness of the results.Results:The innovation investment of the winning enterprises was significantly increased by NCVBP.The ratio of Research&Development expenses to operating revenues of winning firms in the next quarter increases by 1.4%.The centralized procurement promotes innovation investment by enhancing the cost efficiency of enterprises and strengthening market competition in the industry.Conclusion:Collective purchasing significantly increases the innovation investment of winning enterprises,the improvement of cost efficiency is an important influence path to improve the innovation investment of enterprises.The industry market competition has a significant moderating effect on the collective purchasing and the innovation investment of enterprises;the national drug collective purchasing system can be improved from the aspects of innovation incentives,communication system,market competition,and so on.

Objective:The impact and mechanism system of the National Centralized Volume-Based Procurement(NCVBP)on innovation investment in pharmaceutical companies.Methods:Based on listed company data from 2015 to 2023,it uses the first eight rounds of NCVBP as a quasi-natural experiment and applies a staggered difference-in-differences model to control the industries and year fixed effects,test the impact of NCVBP on innovation investment in pharmaceutical companies,conduct the parallel trend and placebo test,and verify the robustness of the results.Results:The innovation investment of the winning enterprises was significantly increased by NCVBP.The ratio of Research&Development expenses to operating revenues of winning firms in the next quarter increases by 1.4%.The centralized procurement promotes innovation investment by enhancing the cost efficiency of enterprises and strengthening market competition in the industry.Conclusion:Collective purchasing significantly increases the innovation investment of winning enterprises,the improvement of cost efficiency is an important influence path to improve the innovation investment of enterprises.The industry market competition has a significant moderating effect on the collective purchasing and the innovation investment of enterprises;the national drug collective purchasing system can be improved from the aspects of innovation incentives,communication system,market competition,and so on.

Sarcopenia refers to the gradual decrease in skeletal muscle mass and function with age,and is an important factor in disability and mortality in elderly population.The pathogenesis of sarcopenia may be related to insulin resistance,oxidative stress,inflammation,mitochondrial dysfunction,and impaired autophagy caused by abnormal glucose and lipid metabolism.Sarcopenia can reduce daily activity ability and prolong recovery time from diseases.This article reviews the research progress on the relationship between abnormal glucose and lipid metabolism and the pathogenesis of sarcopenia.

Metabolic associated fatty liver disease(MAFLD)is a metabolic disorder liver disease closely related to insulin resistance(IR)and genetic susceptibility.Hepatocyte steatosis is the main pathological change.In recent years,the prevalence of MAFLD has increased significantly,so it is necessary to provide interventions as soon as possible.Glucagon-like peptide-1 receptor agonist plays a hypoglycemic effect by promoting insulin release and reducing IR.Studies shows that it has significant benefits on body weight,lipid metabolism,inflammation and fibrosis in patients with MAFLD,and is expected to be an effective drug for the treatment of MAFLD.

Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective:To evaluate the feasibility and safety of PT Scope (short for intelligent pressure and temperature controlled flexible ureteroscopy)combined with Thulium laser in the intracavitary treatment of upper urinary tract stones.Methods:A retrospective analysis was conducted on the clinical data of 13 patients with upper urinary tract stones who were treated with PT Scope combined with Thulium laser lithotripsy in Sun Yat-Sen Memorial Hospital from February to April 2024. There were 7 males and 6 females. The patients had a mean age of (46±10) years old, with an accumulated stone diameter of (25.8±13.3) mm. There were 7 cases of lower calyx stones (53.8%), and 3 cases of concomitant ureteral stones (23.1%).Four patients (30.8%) had positive preoperative urine cultures, and six patients (46.2%) had leukocyte counts greater than 100 cells/μl in their urine tests. The Thulium laser power was set at 45 W (1.5 J at 30 Hz, 0.3 J at 150 Hz). The renal pelvic pressure threshold was set at 30 mmHg (1 mmHg=0.133 kPa), and the temperature threshold at 43 ℃. Postoperatively, double J stents were placed for 2 to 4 weeks.Results:All 13 patients successfully completed the surgery. The median operative time was 30 (25, 90) minutes. The intraoperative average renal pelvic pressure in these 13 patients ranged from 8 mmHg to 24 mmHg, and the average renal pelvic temperature ranged from 25 ℃ to 34 ℃. Postoperatively, 1 patient experienced a fever (38.0 ℃) and 2 patients required analgesic treatment due to postoperative pain. There were no other intraoperative or postoperative complications. The median postoperative hospital stay was (1.5±0.8) days. The stone-free rate of 1 month was 84.6%(11/13).Conclusions:PT Scope combined with Thulium laser could effectively control renal pelvic pressure and temperature, achieve a high stone-free rate, and have a low complication rate. It is a safe and effective treatment for upper urinary tract stones.