Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.
Methicillin-Resistant Staphylococcus aureus/genetics* ; Anti-Bacterial Agents/chemistry* ; Naphthoquinones/administration & dosage* ; Animals ; Microbial Sensitivity Tests ; Mice ; Humans ; Staphylococcal Infections/microbiology* ; Molecular Structure

Objective To investigate the expression of calumenin(CALU)in gastric cancer and its effect on metastasis and invasion of gastric cancer,and analyze its relationship with the prognosis of gastric cancer patients.Methods The Cancer Genome Atlas(TCGA)database was used to analyze the expression level of CALU in gastric cancer and its impact on patient prognosis.A total of 102 pairs of gastric cancer and paracancerous tissue samples were collected from 189 gastric cancer patients who underwent partial gastrectomy in First Affiliated Hospital of Army Medical University from January 2018 to December 2022.The expression of CALU in gastric cancer and paracancerous tissues was detected by immunohistochemical assay,and the relationship of its expression with clinicopathological parameters was statistically analyzed.After gastric cancer cells with CALU knockdown and overexpression were constructed,and the efficiencies of knockdown and overexpression were evaluated by Western blotting as well as RT-qPCR.Transwell assay was applied to determine the effect of CALU on the migration and invasion abilities of gastric cancer cells.Results Bioinformation analysis found that CALU was significantly highly expressed in gastric cancer tissues(P<0.05),and its expression level was negatively correlated with the prognosis of patients(P<0.05).Immunohistochemical results showed that the expression level of CALU was obviously highly in gastric cancer tissues than the paracancerous tissues(P<0.01),and its level was positively correlated with the depth of infiltration(P<0.01),lymph node metastasis(P<0.01),and TNM stage(P<0.05).Statistical analysis revealed that the clinical data of 102 patients showed that CALU expression was positively correlated with the TNM stage(P=0.021)and T stage(P<0.001)and N stage(P=0.028).CALU knockdown significantly inhibited the migration and invasion abilities of gastric cancer cells(P<0.01),while over-expression obtained the opposite results.Conclusion CALU is highly expressed in gastric cancer tissues and promotes metastasis and invasion of gastric cancer and thus leads to poor prognosis in patients.

Objective To investigate the distribution of gender,age,and traditional Chinese medicine(TCM)syndrome elements and syndrome types in patients suffering from novel coronavirus infection complicated with asthma,and to explore the medication rules for the patients,thus to provide reference for the formulation of clinical diagnosis and treatment plans for novel coronavirus infection complicated with asthma.Methods From December 2022 to January 2023,the information of gender,age,syndrome elements,TCM syndrome types and medication frequency of the herbal medicine was collected among the patients suffering from novel coronavirus infection complicated with asthma who were treated in outpatient clinics of the respiratory department and emergency department of Shenzhen Traditional Chinese Medicine Hospital.The information data were statistically analyzed and then the network visualization of results was presented.Results A total of 63 cases were included,including 27 males and 36 females,with an average age of 51.8 years old.Thirteen TCM syndrome types were involved,of which the three with the leading occurrence frequency were wind-phlegm syndrome(17 cases),spleen deficiency with dampness accumulation syndrome(11 cases),and phlegm-heat stagnation in the lung syndrome(8 cases).There were four disease-location syndrome elements,and the top two were lung(36 cases)and spleen(12 cases).Eight disease-nature syndrome elements were involved,and the top three were wind(36 cases),phlegm(28 cases)and qi deficiency(24 cases).A total of 128 Chinese herbal medicines were used,and their properties and flavors were predomiated by being pungent,bitter,sweet and cold.Most of the Chinese herbal medicines had the meridian tropism of lung,spleen,liver and stomach meridians,and most of the Chinese herbal medicines had the therapeutic actions of resolving phlegm,easing cough and relieving asthma.The top four Chinese herbal medicines with higher medication frequency were Glycyrrhizae Radix et Rhizoma(51 times),Ephedrae Herba(47 times),blanching Armeniacae Semen Amarum(44 times),and Schisandrae Chinensis Fructus(40 times).The core two-drug groups were Ephedrae Herba-Glycyrrhizae Radix et Rhizoma,Ephedrae Herba-Schisandrae Chinensis Fructus,and blanching Armeniacae Semen Amarum-Pinelliae Rhizoma.The core three-drug groups were Pinelliae Rhizoma-blanching Armeniacae Semen Amarum-Ephedrae Herba,and Ephedrae Herba-Schisandrae Chinensis Fructus-Glycyrrhizae Radix et Rhizoma.Conclusion Pathogenic phlegm retention in lung is the core pathogenesis of novel coronavirus infection complicated with asthma,which is protracted through the disease.The pathogenic wind is the driving factor of the disease's development and progression,and in the middle and late stages of the disease,the complicated syndrome manifestations of pathogenic heat,qi deficiency,qi and yin deficiency,and blockage of upper orifice are commonly seen.Its therapeutic principles are to relieve exterior syndrome and clear heat,resolve phlegm,ease cough and relieve asthma,thus to restore the qi movement of the zang-fu organs,support the healthy qi,eliminate pathogens and strengthen body resistance.

Objective:To investigate whether repeated tirofiban injections can continuously inhibit platelet aggregation in the arterial duct and affect its closure in neonatal canines.Methods:Four 24-month-old pregnant beagles underwent cesarean sections in two batches (two dogs per batch) 1-2 days before the expected delivery date at the Xuzhou Medical University Animal Experiment Center. The first litter of 21 neonates served as the control group (receiving 10 ml/kg normal saline) and were randomly divided into 1-h ( n=7, injected immediately after birth), 4-h ( n=7, injected at 0 h and 2 h after birth), and 12-h subgroups ( n=7, injected at 0 h, 2 h, 4 h, 6 h, 8 h, and 10 h after birth). The second litter of 18 neonates served as the experimental group (receiving 10 ml/kg tirofiban) with identical subgroup assignments ( n=6 per subgroup). Echocardiography was performed at 1 h, 4 h, and 12 h after birth to measure arterial duct inner diameter, maximum shunt velocity, and left atrial diameter/aortic root diameter (LA/Ao) ratio. Plasma platelet-derived growth factor (PDGF) was detected by enzyme-linked immunosorbent assay, while platelet membrane glycoprotein Ⅱb-Ⅲa in the arterial duct was assessed by Western blot and immunohistochemistry. Data were analyzed using t-tests, one-way ANOVA, Chi square tests, or Fisher's exact test. Results:No significant bleeding tendency occurred in either group. Two control neonates (one each in the 4-h and 12-h subgroups) died. In both control and experimental 1-h subgroups, all arterial ducts remained open, with no significant differences in ductal diameter, shunt velocity, or LA/Ao between groups (all P>0.05). In the 4-h subgroups, all experimental neonates had patent ducts arteriosus, while two controls exhibited closure; the experimental group had larger ductal diameters [(1.05±0.05) vs. (0.55±0.44) mm, t=－2.75, P<0.05)] and higher LA/Ao ratios (1.31±0.09 vs. 1.14±0.03, t=－4.90, P<0.05), but lower maximum shunt velocities [(107.06±17.47) vs. (153.74±12.78) cm/s, t=4.54, P=0.002). In the 12-h subgroups, all the controls had closed arterial ducts, while four of six experimental neonates exhibited closure, though the difference in closure rate was not statistically significant (6/6 vs. 4/6, Fisher's exact test, P=0.455). Plasma PDGF and glycoprotein Ⅱb-Ⅲa levels did not differ between two 1-h subgroups (all P>0.05). However, the 4-h and 12-h experimental subgroups showed lower PDGF levels [(373.5±13.1) vs. (880.3±80.2) pg/ml, t=10.81; (356.7±35.0) vs. (1 111.2±125.3) pg/ml, t=9.74; both P<0.05] and reduced glycoprotein Ⅱb-Ⅲa expression (0.32±0.07 vs. 0.80±0.23, t=3.29; 0.42±0.07 vs. 0.92±0.26, t=3.24; both P<0.05) compared to controls. Conclusion:Repeated tirofiban injections sustainably inhibit platelet aggregation in the arterial duct of neonatal canines and delay ductal closure, suggesting that intraductal platelet aggregation may be one factor influencing this process.

Objective To systematically evaluate the effectiveness of acupuncture in treating chronic cough and analyze its acupoint selection patterns.Methods Randomized controlled trials(RCTs)on acupuncture for chronic cough were retrieved from databases including CNKI,VIP,Wan Fang Data,CBM,PubMed,and Web of Science,Cochrane Library and Embase from their inception to April 2025.Original data from the included studies were extracted.Meta-analysis was performed to compare the acupuncture treatment group with the western medicine control group[using leukotriene receptor antagonists(LTRAs)and/or glucocorticoids]on outcomes including cough symptom scores,serum tumor necrosis factor-α(TNF-α)levels,pulmonary function indicators[forced vital capacity(FVC)and forced expiratory volume in the first second(FEV1)],overall clinical effectiveness,and incidence of adverse reactions.Publication bias was assessed using funnel plots,and descriptive analysis of the acupoint prescriptions from the included studies was conducted using Rstudio software to summarize the patterns of acupoint selection for chronic cough.Results A total of 10 studies involving 806 patients were included.Meta-analysis results showed that acupuncture was superior to the western medicine control group in improving cough symptom scores,reducing serum TNF-α levels,enhancing pulmonary function(FVC and FEV1),increasing overall clinical effectiveness,and reducing adverse reactions,with statistically significant differences.Further analysis of the 10 included studies revealed that the most frequently used acupoints were Feishu(BL13)(n=9 times),Zusanli(ST36)(n=7 times),Lieque(LU7)(n=6 times),and Pishu(BL20)(n=5 times).The most frequently utilized meridians were the Bladder Meridian of Foot-Taiyang(BL)(n=10 times),the Stomach Meridian of Foot-Yangming(ST)(n=7 times),and the Lung Meridian of Hand-Taiyin(LU)(n=7 times).Acupoints were primarily located on the lower back(36.92%),upper limbs(26.15%),and lower limbs(21.53%).Conclusion Acupuncture is effective in treating chronic cough.The acupoint prescriptions for chronic cough should follow the principles of symptomatic point selection and anterior-posterior point pairing,emphasizing the back-shu and front-mu point pairing method,as well as the upper-lower point pairing method.Points are predominantly selected from the Bladder meridian(BL),lung meridian(LU),and stomach meridian(ST).

Objective To systematically evaluate the effectiveness of acupuncture in treating chronic cough and analyze its acupoint selection patterns.Methods Randomized controlled trials(RCTs)on acupuncture for chronic cough were retrieved from databases including CNKI,VIP,Wan Fang Data,CBM,PubMed,and Web of Science,Cochrane Library and Embase from their inception to April 2025.Original data from the included studies were extracted.Meta-analysis was performed to compare the acupuncture treatment group with the western medicine control group[using leukotriene receptor antagonists(LTRAs)and/or glucocorticoids]on outcomes including cough symptom scores,serum tumor necrosis factor-α(TNF-α)levels,pulmonary function indicators[forced vital capacity(FVC)and forced expiratory volume in the first second(FEV1)],overall clinical effectiveness,and incidence of adverse reactions.Publication bias was assessed using funnel plots,and descriptive analysis of the acupoint prescriptions from the included studies was conducted using Rstudio software to summarize the patterns of acupoint selection for chronic cough.Results A total of 10 studies involving 806 patients were included.Meta-analysis results showed that acupuncture was superior to the western medicine control group in improving cough symptom scores,reducing serum TNF-α levels,enhancing pulmonary function(FVC and FEV1),increasing overall clinical effectiveness,and reducing adverse reactions,with statistically significant differences.Further analysis of the 10 included studies revealed that the most frequently used acupoints were Feishu(BL13)(n=9 times),Zusanli(ST36)(n=7 times),Lieque(LU7)(n=6 times),and Pishu(BL20)(n=5 times).The most frequently utilized meridians were the Bladder Meridian of Foot-Taiyang(BL)(n=10 times),the Stomach Meridian of Foot-Yangming(ST)(n=7 times),and the Lung Meridian of Hand-Taiyin(LU)(n=7 times).Acupoints were primarily located on the lower back(36.92%),upper limbs(26.15%),and lower limbs(21.53%).Conclusion Acupuncture is effective in treating chronic cough.The acupoint prescriptions for chronic cough should follow the principles of symptomatic point selection and anterior-posterior point pairing,emphasizing the back-shu and front-mu point pairing method,as well as the upper-lower point pairing method.Points are predominantly selected from the Bladder meridian(BL),lung meridian(LU),and stomach meridian(ST).

Objective:To investigate whether repeated tirofiban injections can continuously inhibit platelet aggregation in the arterial duct and affect its closure in neonatal canines.Methods:Four 24-month-old pregnant beagles underwent cesarean sections in two batches (two dogs per batch) 1-2 days before the expected delivery date at the Xuzhou Medical University Animal Experiment Center. The first litter of 21 neonates served as the control group (receiving 10 ml/kg normal saline) and were randomly divided into 1-h ( n=7, injected immediately after birth), 4-h ( n=7, injected at 0 h and 2 h after birth), and 12-h subgroups ( n=7, injected at 0 h, 2 h, 4 h, 6 h, 8 h, and 10 h after birth). The second litter of 18 neonates served as the experimental group (receiving 10 ml/kg tirofiban) with identical subgroup assignments ( n=6 per subgroup). Echocardiography was performed at 1 h, 4 h, and 12 h after birth to measure arterial duct inner diameter, maximum shunt velocity, and left atrial diameter/aortic root diameter (LA/Ao) ratio. Plasma platelet-derived growth factor (PDGF) was detected by enzyme-linked immunosorbent assay, while platelet membrane glycoprotein Ⅱb-Ⅲa in the arterial duct was assessed by Western blot and immunohistochemistry. Data were analyzed using t-tests, one-way ANOVA, Chi square tests, or Fisher's exact test. Results:No significant bleeding tendency occurred in either group. Two control neonates (one each in the 4-h and 12-h subgroups) died. In both control and experimental 1-h subgroups, all arterial ducts remained open, with no significant differences in ductal diameter, shunt velocity, or LA/Ao between groups (all P>0.05). In the 4-h subgroups, all experimental neonates had patent ducts arteriosus, while two controls exhibited closure; the experimental group had larger ductal diameters [(1.05±0.05) vs. (0.55±0.44) mm, t=－2.75, P<0.05)] and higher LA/Ao ratios (1.31±0.09 vs. 1.14±0.03, t=－4.90, P<0.05), but lower maximum shunt velocities [(107.06±17.47) vs. (153.74±12.78) cm/s, t=4.54, P=0.002). In the 12-h subgroups, all the controls had closed arterial ducts, while four of six experimental neonates exhibited closure, though the difference in closure rate was not statistically significant (6/6 vs. 4/6, Fisher's exact test, P=0.455). Plasma PDGF and glycoprotein Ⅱb-Ⅲa levels did not differ between two 1-h subgroups (all P>0.05). However, the 4-h and 12-h experimental subgroups showed lower PDGF levels [(373.5±13.1) vs. (880.3±80.2) pg/ml, t=10.81; (356.7±35.0) vs. (1 111.2±125.3) pg/ml, t=9.74; both P<0.05] and reduced glycoprotein Ⅱb-Ⅲa expression (0.32±0.07 vs. 0.80±0.23, t=3.29; 0.42±0.07 vs. 0.92±0.26, t=3.24; both P<0.05) compared to controls. Conclusion:Repeated tirofiban injections sustainably inhibit platelet aggregation in the arterial duct of neonatal canines and delay ductal closure, suggesting that intraductal platelet aggregation may be one factor influencing this process.

Objective To determine the chemical constituents in BSLYT by ultra-high performance liquid chromatography-mass spectrometry(UHPLC-MS/MS),and to establish a high-performance liquid chromatographic fingerprint of the material basis of BSLYT and the content determination of its six main constituents,mononoside,loganin,oroxin A,oroxin B,baicalein and astilbin,providing a reference for the quality control.Methods The mass spectrometry data were used to establish the fingerprints.The content of the main components in the BSLYT samples was calculated by using the external method,and the discrepency between different batches of samples were analyzed by combining with chemometric methods.Results A total of 69 compounds were identified by mass spectrometry,and 13 compounds were identified after comparison with high-performance liquid chromatography(HPLC).The similarity of the baseline characterization profiles of the 15 batches of BSLYT substances was above 0.90,and a total of 27 common peaks were identified.Cluster analysis(CA)classified the substance benchmarks into 2 classes,S1,S2,S5,S8,S9,S13,and S15 were clustered into one class,and S3,S4,S6,S7,S10-S12,and S16 were clustered into one class.By combining PCA and OPLS-DA,the chemical components affecting the baseline classification of the substances were screened and attributed to wood butterfly,cornelian cherry and cocos nigra,respectively.The contents of six components were determined by MICS,which ranged from 0.31%-0.51%,0.12%-0.22%,0.09%-0.19%,0.09%-0.24%,0.07%-0.18%,and 0.08%-0.29%for mononoside,loganin,oroxin A,oroxin B,baicalein and astilbin respectively.Conclusion The fingerprint and multi-indicator content determination method established in this paper are accurate and stable,which provide a basis for the quality control of the material benchmark of Kidney and Pharynx Formula and its related preparations.

Objective:To explore the characteristics of natural foci of hemorrhagic fever with renal syndrome (HFRS) in Gansu Province.Methods:The information of HFRS case data and rodent density monitoring data from 2012 to 2022 in Gansu Province were collected and epidemiological methods were used to analyze and investigate the characteristics of the epidemic focus.Results:A total of 869 cases of HFRS were reported, and four patients died from 2012 to 2022. The annual incidence rate is between 0.05 per 100 000 and 1.21 per 100 000. The cases were mainly distributed in the eastern, southeast, southern, and south of the central region of Gansu Province. Most cases were distributed between age 20-60, and the sex ratio was 1.85∶1 (564∶305). Most cases were farmers (61.80%, 537/869), herdsmen (19.79%,172/869) and students (6.33%, 55/869). In a wild rat-type epidemic focus,the incidence peak was from November to January of the following year. The natural rodent hosts of HFRS were Rattus norvegicus, Apodemus agrarius, and Mus musculus. The hantaan virus carriage rates were 2.79% (21/754), 0.42% (5/1 179) and 0.31% (2/643),respectively. Three epidemic foci were defined: two derived from the Pingliang and Gannan prefecture new outbreaks epidemic foci, respectively, while the other was the residue of the Dingxi epidemic focus. Conclusions:The southern, south of the central region and eastern part of Gansu Province are current key HFRS epidemic foci dominated by Rattus norvegicus, Apodemus agrarius, and Mus musculus, respectively. The virus genotype is hantaan virus. Case reporting areas should strengthen epidemic monitoring; the key epidemic areas should strengthen and implement various prevention and control measures to reduce the harm caused by HFRS.

Objective To evaluate the therapeutic efficacies of neoadjuvant immunochemotherapy (NAIC )and neoadjuvant chemotherapy (NAC )for local advanced gastric adenocarcinoma and analyze the clinicopathological characteristics.Methods A retrospective cohort study was conducted on 243 patients with locally advanced gastric cancer admitted in Army Medical Center of PLA (Daping Hospital)and the First Affiliated Hospital of China Medical University from January 2017 to July 2023. After balancing the confounding factors by inclusion and exclusion criteria and propensity score matching (PSM),the tumor pathological regression (TRG)rate and safety of the 2 neoadjuvant treatment regimens were analyzed,and the clinical pathological characteristics were analyzed to find clinical pathological characteristics related to efficacy.Results After using PSM to balance the baseline characteristics of the 2 groups of patients,53 subjects in each group were included in the analysis.In terms of TRG,the pathological complete response (pCR)rate in the NAIC group (13 patients,25％)was significantly higher than that in the NAC group (2 patients,3.8％,P<0.05 ).Similar results were observed in terms of major pathological response (MPR),with 23 patients (43％)in the NAIC group achieving MPR,while 9 patients (17％)in the NAC group achieved MPR (P<0.05 ).In terms of safety,the incidence of treatment-related adverse events (TRAEs) of any grade in the NAIC group and the NAC group was comparable (96.2％ and 96.2％,respectively).In an exploratory subgroup analysis of tumor pathological regression,the patients with clinicopathological features such as age<65 years,male,stage Ⅲ～Ⅳ A of American Joint Committee on Cancer (AJCC)staging,histological type of adenocarcinoma,high-moderate differentiated,intestinal-type gastric cancer,stage T3～4 of clinical T-staging,and stage N2～3 of clinical N-staging were more likely to benefit from NAIC.Conclusion NAIC results in a higher rate of pathological regression and a comparable incidence of adverse events when compared with chemotherapy alone for patients with local advanced gastric adenocarcinoma.