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

Neuraxial opioids, widely used in obstetric and perioperative pain management, often lead to unwanted itch, reducing patient satisfaction. While the μ-opioid receptor has been implicated in opioid-induced itch, the genetic basis for variable itch incidence remains unknown. This study examined 3616 patients receiving epidural opioids, revealing an itch occurrence of 26.55%, with variations among opioid types and gender. Analysis of the OPRM1 gene identified six single-nucleotide polymorphisms, notably rs1799971 (A118G), that correlated with opioid-induced itch. Mouse models with an equivalent A112G mutation showed reduced neuraxial opioid-induced itch and light touch-evoked itch, mirroring human findings. The 118G allele demonstrated an anti-itch effect without impacting analgesia, addiction, or tolerance, offering insights for risk stratification and potential anti-itch pretreatment strategies.
Receptors, Opioid, mu/genetics* ; Pruritus/chemically induced* ; Humans ; Analgesics, Opioid/administration & dosage* ; Female ; Male ; Animals ; Polymorphism, Single Nucleotide/genetics* ; Adult ; Mice ; Middle Aged

Objective:To investigate the clinical efficacy and major complications (postoperative hemorrhage and cerebral edema) of 3 surgical methods in spontaneous supratentorial intracerebral hemorrhage (SSICH).Methods:A retrospective analysis was performed; 294 patients with SSICH admitted to Department of Neurosurgery, Renmin Hospital of Wuhan University from December 2018 to October 2021 were selected. According to different surgical methods, these patients were divided into neuroendoscopic hematoma removal group ( n=126), stereotactic drilling and drainage group ( n=98), and craniotomy hematoma removal group ( n=70). The surgical efficacy and complications in the 3 groups were analyzed, and the postoperative residual hematoma and edema volumes were quantitatively calculated based on 3D Slicer software. Results:The hematoma evacuation rate in the neuroendoscopic hematoma removal group, stereotactic drilling and drainage group, and craniotomy hematoma removal group was 86.25%±2.27%, 44.45%±3.61%, and 75.45%±2.89%, respectively; Glasgow coma Scale scores at discharge were 13.51±1.28, 11.24±2.17 and 10.25±2.56, respectively; postoperative hemorrhage incidence was 16.1%, 26.0% and 22.9%, respectively; postoperative residual hematoma volume was (18.90±12.33) mL, (25.75±11.43) mL and (22.91±7.93) mL, and postoperative peak edema volume was (37.43±11.07) mL, (39.54±9.43) mL, and (42.26±10.94) mL, respectively; percentage of patients with peak edema on 3-5 days after surgery was 31.0%, 65.3% and 68.6%; the diameter of edema zone was (20.04±2.98) mm, (24.12±5.85) mm and (23.59±3.81) mm, respectively, on 7 days after surgery; percentage of patients with edema resolution was 45.2%, 24.5%, 42.9% and 76.2%, 57.1%, 62.9%, respectively, on 9-11 days and 12-14 days after surgery; these indexes in the neuroendoscopic hematoma removal group were significantly different compared with those in the other two groups ( P<0.05). Conclusion:Compared with stereotactic drilling and drainage or craniotomy hematoma removal, neuroendoscopic surgery can effectively remove the hematoma and reduce the occurrences of postoperative hemorrhage and brain edema.

Objective To investigate the biological function and molecular mechanism of solute carrier family 4,member 3(SLC43)in glioblastoma(GBM).Methods The expression difference of SLC4A3 in 30 GBM and 10 normal brain tissues were analyzed by immu-nohistochemistry.Kaplan-Meier survival analysis was used to evaluate the effect of SLC4A3 on the prognosis of GBM patients.The ex-pression of SLC4A3 in U87 and U251 cells was reduced by shRNA,and the changes in the proliferation,migration and invasion ability of GBM cells were detected after the knockdown,and Western blot was used to investigate the expression of epithelial-mesenchymal transi-tion(EMT)and NF-κB signaling pathway related proteins after SLC4A3 knockdown.Results SLC4A3 was overexpressed in GBM,and high expression of SLC4A3 was associated with poor prognosis.Knocking down SLC4A3 inhibited the proliferation,migration and in-vasion of U87 and U251 cells,and the expression levels of N-cadherin and Vimentin were down-regulated,while the expression levels of E-cadherin were increased.In addition,knocking down SLC4A3 inhibited the NF-κB signaling pathway and further found that nu-clear translocation of NF-κB p65 was inhibited.Conclusion SLC4A3mediates the NF-κB signaling pathway by regulating the nuclear translocation of NF-κB p65 to influence the growth and EMT of GBM cells,which is a novel prognostic biomarker for GBM.

Objective To investigate the biological function and molecular mechanism of solute carrier family 4,member 3(SLC43)in glioblastoma(GBM).Methods The expression difference of SLC4A3 in 30 GBM and 10 normal brain tissues were analyzed by immu-nohistochemistry.Kaplan-Meier survival analysis was used to evaluate the effect of SLC4A3 on the prognosis of GBM patients.The ex-pression of SLC4A3 in U87 and U251 cells was reduced by shRNA,and the changes in the proliferation,migration and invasion ability of GBM cells were detected after the knockdown,and Western blot was used to investigate the expression of epithelial-mesenchymal transi-tion(EMT)and NF-κB signaling pathway related proteins after SLC4A3 knockdown.Results SLC4A3 was overexpressed in GBM,and high expression of SLC4A3 was associated with poor prognosis.Knocking down SLC4A3 inhibited the proliferation,migration and in-vasion of U87 and U251 cells,and the expression levels of N-cadherin and Vimentin were down-regulated,while the expression levels of E-cadherin were increased.In addition,knocking down SLC4A3 inhibited the NF-κB signaling pathway and further found that nu-clear translocation of NF-κB p65 was inhibited.Conclusion SLC4A3mediates the NF-κB signaling pathway by regulating the nuclear translocation of NF-κB p65 to influence the growth and EMT of GBM cells,which is a novel prognostic biomarker for GBM.

Objective:To investigate the clinical efficacy and major complications (postoperative hemorrhage and cerebral edema) of 3 surgical methods in spontaneous supratentorial intracerebral hemorrhage (SSICH).Methods:A retrospective analysis was performed; 294 patients with SSICH admitted to Department of Neurosurgery, Renmin Hospital of Wuhan University from December 2018 to October 2021 were selected. According to different surgical methods, these patients were divided into neuroendoscopic hematoma removal group ( n=126), stereotactic drilling and drainage group ( n=98), and craniotomy hematoma removal group ( n=70). The surgical efficacy and complications in the 3 groups were analyzed, and the postoperative residual hematoma and edema volumes were quantitatively calculated based on 3D Slicer software. Results:The hematoma evacuation rate in the neuroendoscopic hematoma removal group, stereotactic drilling and drainage group, and craniotomy hematoma removal group was 86.25%±2.27%, 44.45%±3.61%, and 75.45%±2.89%, respectively; Glasgow coma Scale scores at discharge were 13.51±1.28, 11.24±2.17 and 10.25±2.56, respectively; postoperative hemorrhage incidence was 16.1%, 26.0% and 22.9%, respectively; postoperative residual hematoma volume was (18.90±12.33) mL, (25.75±11.43) mL and (22.91±7.93) mL, and postoperative peak edema volume was (37.43±11.07) mL, (39.54±9.43) mL, and (42.26±10.94) mL, respectively; percentage of patients with peak edema on 3-5 days after surgery was 31.0%, 65.3% and 68.6%; the diameter of edema zone was (20.04±2.98) mm, (24.12±5.85) mm and (23.59±3.81) mm, respectively, on 7 days after surgery; percentage of patients with edema resolution was 45.2%, 24.5%, 42.9% and 76.2%, 57.1%, 62.9%, respectively, on 9-11 days and 12-14 days after surgery; these indexes in the neuroendoscopic hematoma removal group were significantly different compared with those in the other two groups ( P<0.05). Conclusion:Compared with stereotactic drilling and drainage or craniotomy hematoma removal, neuroendoscopic surgery can effectively remove the hematoma and reduce the occurrences of postoperative hemorrhage and brain edema.

Objective To observe the effects of melatonin on autophagy in cortical neurons of neonatal rats with hypoxic-ischemic brain damage(HIBD)and to explore its mechanisms via the PI3K/AKT signaling pathway,aiming to provide a basis for the clinical application of melatonin.Methods Seven-day-old Sprague-Dawley neonatal rats were randomly divided into a sham operation group,an HIBD group,and a melatonin group(n=9 each).The neonatal rat HIBD model was established using the classic Rice-Vannucci method.Neuronal morphology in the neonatal rat cerebral cortex was observed with hematoxylin-eosin staining and Nissl staining.Autophagy-related protein levels of microtubule-associated protein 1 light chain 3(LC3)and Beclin-1 were detected by immunofluorescence staining and Western blot analysis.Phosphorylated phosphoinositide 3-kinase(p-PI3K)and phosphorylated protein kinase B(p-AKT)protein expression levels were measured by immunohistochemistry and Western blot.The correlation between autophagy and the PI3K pathway in the melatonin group and the HIBD group was analyzed using Pearson correlation analysis.Results Twenty-four hours post-modeling,neurons in the sham operation group displayed normal size and orderly arrangement.In contrast,neurons in the HIBD group showed swelling and disorderly arrangement,while those in the melatonin group had relatively normal morphology and more orderly arrangement.Nissl bodies were normal in the sham operation group but distorted in the HIBD group;however,they remained relatively intact in the melatonin group.The average fluorescence intensity of LC3 and Beclin-1 was higher in the HIBD group compared to the sham operation group,but was reduced in the melatonin group compared to the HIBD group(P<0.05).The number of p-PI3K+and p-AKT+cells decreased in the HIBD group compared to the sham operation group but increased in the melatonin group compared to the HIBD group(P<0.05).LC3 and Beclin-1 protein expression levels were higher,and p-PI3K and p-AKT levels were lower in the HIBD group compared to the sham operation group(P<0.05);however,in the melatonin group,LC3 and Beclin-1 levels decreased,and p-PI3K and p-AKT increased compared to the HIBD group(P<0.05).The correlation analysis results showed that the difference of the mean fluorescence intensity of LC3 and Beclin-1 protein in the injured cerebral cortex between the melatonin and HIBD groups was negatively correlated with the difference of the number of p-PI3K+and p-AKT+cells between the two groups(P<0.05).Conclusions Melatonin can inhibit excessive autophagy in cortical neurons of neonatal rats with HIBD,thereby alleviating HIBD.This mechanism is associated with the PI3K/AKT pathway.

Objective Explore effective strategies for hospitals to manage the National Natural Science Foundation of China.Methods A retrospective analysis was conducted on the population characteristics of a certain tertiary comprehensive hospital's National Natural Science Foundation project application and approval from 2016 to 2022.Single factor analysis and bi-nary multivariate logistic regression analysis were used to analyze the factors that affect the approval of the National Natural Sci-ence Foundation project,and a function prediction model was established.Results A total of 1 098 applicants were collected in this study,including 653 young project applicants and 178 approved,445 general project applicants and 114 approved;Multi fac-tor logistic results show that in youth programs,the younger the age,the doctor's degree,scientific research posts,the experi-ence of studying abroad,the average impact factor of publishing SCI papers as the first/corresponding author is 3-5 points Appli-cants who have published SCI papers as the first/corresponding author with an average impact factor of more than 5 points,pub-lished SCI papers in four districts as the first/corresponding author,presided over national level and academic level topics are more likely to be approved by the Youth Program of the National Natural Science Foundation of China;Among general programs,applicants who have doctoral degree,overseas study experience,published Zone 1and Zone 2 SCI essays,and presided over na-tional projects as the first/corresponding author are more likely to be approved as general programs of the National Natural Science Foundation of China.The area under the AUC curve of the youth project regression prediction model is 0.860,and the area under the AUC curve of the surface project regression prediction model is 0.838.The model has high predictive value.Conclusion Hospitals should strengthen policy guidance,increase economic investment,encourage applicants to carry out preliminary work layout,focus on talent cultivation,and comprehensively promote the effective management of the National Natural Science Foun-dation of the hospital.

ObjectiveA rapid method for identification of chemical constituents in Baoyuantang reference sample was established in order to clarify the material basis of this formula. MethodBased on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） and self-established database information， the chemical components in Baoyuantang were systematically characterized and identified. The chromatography was performed on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with mobile phase of 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） for gradient elution（0-3 min， 2%-19%B； 3-8 min， 19%B； 8-8.1 min， 19%-22%B； 8.1-14 min， 22%-29%B； 14-16 min， 29%B； 16-32 min， 29%-45%B； 32-32.1 min， 45%-90%B； 32.1-35 min， 90%-95%B； 35-36 min， 95%-98%B； 36-37 min， 98%-2%B； 37-40 min， 2%B）. Based on electrospray ionization（ESI）， continuum data format was collected in both positive and negative ion modes with a scanning range of m/z 50-1 500. Chemical constituents in the decoction of Baoyuantang were systematically analyzed by UNIFI 1.9.4 software matching， control comparison， The Encyclopedia of Traditional Chinese Medicine（ETCM） database search and literature reports. ResultA total of 229 components were identified under negative ion mode and 181 under positive ion mode， with a total of 322 components after removing duplicates， including 116 triterpene saponins， 66 flavonoids， 19 organic acids， 6 gingerphenols， 6 gingerols， 5 gingerones， 10 amino acids， 7 saccharides， 5 coumarins and 82 other components. Among them， 83， 141， 39， 35 and 38 components were attributed to Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Astragali Radix， Cinnamomi Cortex and Zingiberis Rhizoma Recens， respectively. ConclusionIn this study， the rapid characterization and identification of multi-class components in Baoyuantang was realized， and it was confirmed that the material basis of this formula was mainly triterpenoid saponins， flavonoids， gingerols and organic acids， and the chemical composition was attributed and analyzed， which provided a reference for the subsequent quality control research.

Objective To evaluate the effectiveness and safety of moxibustion for knee osteoarthritis and the methodological quality of systematic reviews(SRs).Methods SRs of moxibustion for knee osteoarthritis were retrieved from CNKI,VIP,Wanfang Data,SinoMed,PubMed,Cochrane Library,Embase and Web of Science was conducted from the establishment of the databases to February 10,2022.AMSTAR 2 was used to assess the methodological quality of SRs.The randomized controlled trials(RCTs)included in these SRs were screened and summarized according to inclusion standard.RevMan 5.4 software was used for Meta-analysis,and GRADE approach was used to assess the certainty of evidence.Results A total of 15 SRs were included.The evaluation results of the AMSTAR 2 showed that the methodological quality was very low for 14 SRs,and low for other 1 SR.A total of 36 RCTs were included.Meta-analysis results showed that compared with the non-steroidal anti-inflammatory drugs(NSAIDs),the moxibustion group had better effects on improvement of WOMAC scores[mean difference(MD)=-5.95;95%confidence interval(CI):-9.25 to-2.65;low quality],relieving pain[MD=-1.26;95%CI:-2.19 to-0.32;very low quality],and improving effective rate[risk ratio(RR)=1.16;95%CI:1.11 to 1.22;low quality].In the moxibustion group,some patients experienced blisters,and most healed in 3 days.Conclusion Moxibustion has advantages in pain reduction and improving effective rate compared with routine Western therapy for knee osteoarthritis.However,well-designed high-quality RCTs are needed for further verification.