Objective: To investigate the therapeutic effect of patchouli alcohol on mice with lung-heat syndrome based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)/nuclear factor-kappa B(NF-κB) signaling pathway. Methods: First, network pharmacology was used to predict the potential targets of patchouli alcohol in the treatment of lung-heat syndrome, and a "component-disease-key target" network was constructed for pathway analysis. Then, 40 BALB/c mice were assigned to the normal, lung-heat model, honeysuckle, and low-dose and high-dose patchouli alcohol groups. All groups, except the blank group, were intranasally infected with 50 μL (103 TCID50) of influenza virus solution. After two hours of infection, mice were treated once a day for seven consecutive days. The therapeutic mechanism of patchouli alcohol was explored by measuring pulmonary inflammatory factors, the PI3K/Akt/NF-κB pathway, hypothalamic fever markers (PGE2, cAMP, cGMP levels), rectal temperature, and tissue energy metabolism. Results: Network pharmacology identified 135 target genes related to patchouli alcohol and lung-heat syndrome, with the key targets being STAT3, H1F1A, and NF-κB1. In animal experiments, patchouli alcohol significantly alleviated influenza virus-induced lung inflammatory damage in mice with lung-heat syndrome, inhibited the expression of TNF-α and IL-6 in lung tissues(P<0.01), and suppressed the activation of the PI3K/Akt/NF-κB pathway. It also reduced hypothalamic levels of PGE2 and cAMP(P<0.01), suppressed the increase in rectal temperature, significantly decreased liver glycogen and pyruvate levels(P<0.01), and increased the activities of SDH, LDH, and Na+ -K+ -ATPase in the liver(P<0.01) Conclusion Patchouli alcohol improves the symptoms of lung-heat syndrome in mice by inhibiting the activation of the PI3K/Akt/NF-κB pathway, reducing proinflammatory cytokines and inflammatory damage, and regulating hypothalamic fever markers and energy metabolism.

Objective: To investigate the biological effects of carvacrol on rats with stomach-heat and stomach-cold and its regulation on transient receptor potential(TRP) channels in rats with stomach-heat, and to study the cold and heat properties of carvacrol and its possible mechanism. Methods: According to the random number method, 100 SD rats were divided into stomach-heat blank group, stomach-heat model group, Coptidis Rhizoma group, stomach-heat low-dose and high-dose carvacrol group, stomach-cold blank group, stomach-cold model group, Baked ginger group, stomach-cold low-dose group and high-dose carvacrol group, 10 rats in each group. The rat model of stomach-heat was established by intragastric administration of pepper aqueous solution (0.80 g/kg) and anhydrous ethanol, and the rat model of stomach-cold was established by intragastric administration of water extract of Anemarrhena asphodeloides and sodium hydroxide (10.40 g/kg). On the day of modeling, the rats in the Baked ginger group were given Baked ginger decoction (0.78 g/kg), and the rats in the Coptidis Rhizoma group were given Coptidis Rhizoma decoction (0.43 g/kg).The stomach-cold and stomach-heat low-dose group of carvacrol was given carvacrol emulsion (40 mg/kg), high-dose group was given carvacrol emulsion (80 mg/kg).All rats of the blank and model groups were given the equal volume of emulsion prepared by 5% dimethyl sulfoxide, 1% Tween 80, 1% polyethylene glycol 400, and 93% normal saline, once a day, for 7 days. The general condition of rats was observed and the body mass was recorded. The pathological morphology of gastric tissue was observed by hematoxylin-eosin staining. The changes of material and energy metabolism, cyclic nucleotide (cAMP), thyroid hormone and gastrointestinal hormone in each group were determined by enzyme-linked immunosorbent assay. The expression levels of transient receptor potential vanilloid subtype 1 (TRPV1), transient receptor potential channel M8 (TRPM8) and uncoupling protein-1 (UCP1) in rats with gastric fever were detected by Western blotting. Results: Compared with the stomach-heat blank group, the body mass of rats in the stomach-heat model group decreased at the fifth and seventh day (P<0.05). The contents (or ratio) of hepatic glycogen (HGlyc), total cholesterol (TC), triglyceride (TG), and vasoactive intestinal peptide (VIP) were decreased (P<0.05), and Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, cytochrome C oxidase (COX), NADH dehydrogenase (ND), cyclic adenosine phosphate (cAMP), cAMP/cyclic guanosine phosphate (cGMP), triiodothyronine (T3), thyroxine (T4), gastrin (GAS), motilin (MTL), and α-amylase (α-AMS) all increased (P<0.05). Compared with the stomach-heat model group, the body mass of rats in the Coptidis Rhizoma group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, VIP and α-AMS were increased, and Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and GAS all decreased (P<0.05). The body mass of rats in the stomach-heat low-dose carvacrol group decreased at the seventh day. The contents (or ratio) of HGlyc, TC, and VIP were increased, Na+ -K+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, and MTL all decreased, the expression of TRPV1 and UCP1 in gastric tissue decreased, while TRPM8 increased (P<0.05) in rats of the stomach-heat low-dose and high-dose carvacrol groups. Compared with the stomach-cold blank group, the body mass of rats in the stomach-cold model group decreased at the third, fifth, and seventh day, the contents (or ratio) of HGlyc, TC, TG, α-AMS, and VIP all increased, while Na+ -K+ -ATPase, Ca2+ -Mg2+ -ATPase, COX, ND, cAMP, cAMP/cGMP, T3, T4, GAS, and MTL all decreased (P<0.05). Compared with the stomach-cold model group, the body mass of rats in the Baked ginger group was increased at the seventh day, and the contents (or ratio) of HGlyc, VIP, and α-AMS all decreased, while Na+ -K+ -ATPase, COX, ND, cAMP/cGMP, T3, T4, GAS, and MTL all increased (P<0.05). The contents of HGlyc, cAMP, α-AMS, and VIP of rats in the stomach-cold low and high-dose carvacrol group all decreased (P<0.05). TG in the stomach-cold low-dose carvacrol group was increased. TC, Ca2+ -Mg2+ -ATPase, and cGMP all increased, while cAMP/cGMP decreased (P<0.05) in the high-dose carvacrol group. Conclusion In this study, the rat model of stomach-cold and stomach-heat were successfully established by using cold and heat factors. The result showed that carvacrol had a certain inhibitory effect on body mass, material energy metabolism, cyclic nucleotide level, thyroid hormone and gastrointestinal function in rats with stomach-heat, indicating that the drug was cold. Carvacrol′s cold medicinal property could be biologically explained by TRPV1 activation, UCP1 induction, and TRPM8 suppression.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective To investigate the effect of amygdalin on the permeability increase of microvascular endothelial cells(PMVEC)induced by influenza A virus FM1 and its mechanism.Methods The PMVEC cells were randomly divided into control group,model group(100 TCID50 FM1),amygdalin low-dose group(100 TCID50 FM1+4.0 mg·mL-1 amygdalin),amygdalin medium-dose group(100 TCID50 FM1+8.0 mg·mL-1 amygdalin),amygdalin high-dose group(100 TCID50 FM1+16.0 mg·mL-1 amygdalin)and 740Y-P group(100 TCID50 FM1+16.0 mg·mL-1 amygdalin+50 μmol·L-1 PI3K activator 740Y-P).Methyl thiazolyl tetrazolium(MTT)method,Transwell method,enzyme linked immunosorbent assay(ELISA)method and Western blot method were used to detect cell proliferation,cell permeability,inflammatory factor expression level and protein expression level in each group,respectively.Results Interleukin-6(IL-6)levels in control,model,amygdalin-L,amygdalin-M,amygdalin-H groups were(50.12±3.16),(93.12±5.61),(80.33±6.24),(70.05±5.46)and(61.03±4.68)pg·mL-1,respectively;the levels of tumor necrosis factor-α(TNF-α)in each group were(101.31±9.24),(167.05±10.31),(142.02±10.13),(125.34±9.87)and(112.44±8.05)pg·mL-1,respectively.The cell transepithelial resistance(TER)of control,model,amygdalin-L,amygdalin-M,amygdalin-H and 740Y-P groups were(53.01±4.17),(24.98±2.66),(30.01±3.49),(36.84±3.25),(46.23±4.31),(30.21±3.16)Ω × cm2;phosphorylated phosphatidylinositol-3 hydroxy kinase(p-PI3K)protein levels in each group were 0.34±0.04,1.01±0.09,0.80±0.08,0.61±0.07,0.43±0.05,0.87±0.09,respectively;phosphorylated mammalian target of repamycin(p-mTOR)levels in each group were 0.27±0.03,0.82±0.10,0.60±0.06,0.42±0.03,0.31±0.02 and 1.01±0.12,respectively.Compared model group with control group;compared amygdalinp-L,-M,-H groups with model group;compared amygdalinp-H group with 740Y-P group,the differences of the above indicators were all statistically significant(all P＜0.05).Conclusion Amygdalin may decrease the permeability of PMVEC cells induced by influenza virus FM1 by inhibiting PI3K/AKT/mTOR pathway.

Objective To study the pharmacokinetic characteristics of the test formulation of compound lidocaine cream and reference formulation of lidocaine and prilocaine cream in Chinese healthy subjects and to evaluate whether there is bioequivalence between the two formulations.Methods A single-center,single-dose,randomized,open-label,two-period,two-sequence,crossover design was used.This study included 40 healthy subjects,and in each period,test formulation or reference formulation 60 g was applied to the skin in front of both thighs(200 cm2 each side,a total of 400 cm2)under fasting conditions,and the drug was left on for at least 5 h after application.The concentrations of lidocaine and prilocaine in plasma were determined using liquid chromatography-tandem mass spectrometry(LC-MS/MS)method.Pharmacokinetic parameters were calculated using WinNonlin 8.0 software to evaluate the bioequivalence of the two formulations.Results After the application of the test formulation compound lidocaine cream and the reference formulation lidocaine and prilocaine cream on both thighs of the subjects,the pharmacokinetic parameters of lidocaine in plasma were as follows:Cmax were(167.27±91.33)and(156.13±66.86)ng·mL-1,AUC0-t were(1 651.78±685.09)and(1 636.69±617.23)ng·mL-1·h,AUC0-∞ were(1 669.85±684.65)and(1 654.37±618.30)ng·mL-1·h,the adjusted geometric mean ratios were 104.49％,101.88％and 101.89％,respectively,with 90％confidence intervals of 98.18％-111.20％,97.80％-106.13％and 97.87％-106.07％,all within the range of 80.00％-125.00％.The pharmacokinetic parameters of prilocaine in plasma were as follows:Cmax were(95.66±48.84)and(87.52±39.16)ng·mL-1,AUC0-t were(790.86±263.99)and(774.14±256.42)ng·mL-1·h,AUC0_m were(807.27±264.67)and(792.84±254.06)ng·mL-1 h,the adjusted geometric mean ratios were 107.34％,103.55％and 102.98％,respectively with 90％confidence intervals of 101.69％-113.31％,99.94％-107.30％and 99.65％-106.43％,all within the range of 80.00％-125.00％.Conclusion The test formulation compound lidocaine cream and the reference formulation lidocaine and prilocaine cream are bioequivalent.

Objective:To investigate the association between hyperuricemia and the risk for stroke occurrence, as well as the mediating effect of hypertension on this association.Methods:In this study, the China Chronic Diseases and Nutrition Surveillance system in 2015 was used as baseline data. We identified hospital admissions for stroke using the electronic homepage of inpatient medical records from 2013-2020, and death data were obtained from the 2015-2020 National Mortality Surveillance System. A retrospective cohort was established after matching and linking the database. The Cox proportional hazard regression model was used to analyze the relationship between hyperuricemia and the risk of stroke and its subtypes. Restricted cubic spline analysis was conducted to examine the dose-response relationship between serum uric acid levels and the risk for stroke. Mediation analysis was performed to investigate the mediating effect of hypertension on the association between hyperuricemia and the risk for stroke and its subtypes. Subgroup analyses were conducted based on gender and age groups.Results:A total of 124 352 study subjects were included, with an accumulative follow-up time of 612 911.36 person-years. During the follow-up period, 4 638 cases of stroke were found, including 3 919 cases of ischemic stroke and 689 cases of hemorrhagic stroke. The incidence density of stroke was 756.72 per 100 000 person-years, 641.37 per 100 000 person-years for ischemic stroke, and 114.60 per 100 000 person-years for hemorrhagic stroke. Multivariable Cox proportional hazards regression models showed that after adjusting for covariates, compared to those without hyperuricemia, individuals with hyperuricemia had a 16% higher risk for stroke [hazard ratio ( HR)=1.16, 95% CI: 1.06-1.27], a 12% higher risk of ischemic stroke ( HR=1.12, 95% CI: 1.01-1.24), and a 39% higher risk of hemorrhagic stroke ( HR=1.39, 95% CI: 1.11-1.75). Mediation analysis showed that hypertension partially mediated the associations between hyperuricemia and the risk for stroke, ischemic stroke, and hemorrhagic stroke, with mediation proportions of 36.07%, 39.98%, and 25.34%, respectively. The mediating effect is pronounced in the male population and individuals below 65. Conclusion:Hyperuricemia is a risk factor for stroke, and hypertension partially mediates the effect of hyperuricemia on stroke.

Tricuspid regurgitation(TR)is a common heart valve disease.According to the pathogenesis,TR can be divided into primary(organic)and secondary(functional)regurgitation,of which functional TR accounts for more than 90%.Patients with severe TR have poor prognosis and poor drug treatment,and surgery(valvuloplasty)is the main treatment.At present,transcatheter edge-to-edge tricuspid valve repair(T-TEER)has become an essential program of transcatheter treatment for TR,providing minimally invasive treatment for TR patients who cannot undergo surgery or are at high risk of surgery.T-TEER reduces the degree of regurgitation by clamping leaflets,and is currently in the early stage of research and development exploration and clinical validation,mainly for functional TR.T-TEER devices have also made significant progress(TriClip,PASCAL),and Chinese-made novel-designed T-TEER devices are also undergoing clinical trials(DragonFly-TTM,SQ-Kyrin-TTM,NeoBlazarTM).This paper reviews the current applications and research progress of T-TEER.

We aimed to identify the infectious source of a case of melioidosis,to provide evidence for the prevention and control of melioidosis in Shanxi Province,China.The patient developed repeated fever,fatigue,diarrhea,and other symptoms after being caught in the rain while traveling in Hainan Province.The blood culture was positive,and the bacterial strain was i-dentified as Burkholderia thayensis and sent to the provincial Center for Disease Control and Prevention for further evaluation.MALDI-TOF MS and biochemical identification were used to identify the strain,whole genome sequencing was performed after nucleic acid extraction,MLST type and drug-resistance genes were analyzed,and a phylogenetic tree was constructed.The iso-lated strain was identified as Burkholderia pseudomallei by MALDI-TOF MS and biochemistry,and the MLST type was 366.The whole gene sequencing analysis indicated a close evolutionary relationship with the three isolates in Hainan Province,with high homology.This case of melioidosis was indeed imported from Hainan Province,according to molecular tracing analysis and epidemiological investigation,thus suggesting that medical institutions and disease control departments should strengthen understanding of melioidosis,and improve the diagnosis and treatment ability.

Objective:To understand the whole genome and genetic evolution characteristics of the first epidemic influenza A (H3N2) viruses in Wuxi from 2022-2023.Methods:Real time fluorescence quantitative RT-PCR method was used to perform typing on respiratory samples of influenza cases. Virus isolation was performed on samples with positive nucleic acid of subtype A H3N2 influenza virus detected. After cell culture, nucleic acid was extracted from strains with red blood cell agglutination test (HA) ≥ 1∶8, whole genome sequence was amplified, library was constructed, and computer sequencing was performed using MiSeq sequencer. Using NC_007366.1 as reference strain, the data were analyzed using CLC Genomics Workbench (Version 23) software. The phylogenetic tree was constructed using MEGA 7.0 software, and the N-glycosylation sites were predicted by NetNGlyc 1.0 Server software.Results:The nucleotide homology and amino acid homology among 35 strains of influenza A H3N2 virus from 2022 to 2023 were 96.4%-100% and 95.2%-100%, respectively. The 16 epidemic strains in 2022 belong to the 3C.2a1b.2a.1a evolutionary branch, while the 19 epidemic strains in 2023 belong to the 3C.2a1b.2a.2a.3a.1 evolutionary branch. There are 7 differences in the nucleotide sequence of the HA gene between the 2022 epidemic strain and the corresponding vaccine strain, sharing 15 mutation sites; There are 28 differences in the nucleotide sequence of the HA gene between the 2023 epidemic strain and the corresponding vaccine strain, sharing 17 mutation sites. The HA genes of 35 epidemic strains all lack N-glycosylation site 61: NSS, while in 2023, the HA genes of 19 epidemic strains added N-glycosylation site 110: NSS.Conclusions:The HA and NA genes of influenza A H3N2 virus in 2022 and 2023 belong to two evolutionary branches, respectively, and both show specific amino acid site changes compared to the corresponding vaccine strains. The antigen matching between the 2022 epidemic strain and the vaccine strain is relatively good, while there is a risk of low antigen matching between the 2023 epidemic strain and the vaccine strain.

Objective:To investigate the overall recurrence rate and the pattern of treatment failure in thoracic esophageal cancer (TEC) patients after minimally invasive esophagectomy (MIE), and to evaluate the significance of adjuvant therapy after MIE.Methods:Clinical data of TEC patients who underwent MIE with or without neoadjuvant chemotherapy in the Fourth Hospital of Hebei Medical University between 2016 and 2018 were retrospectively analyzed. The pathology-based lymph node metastasis (LNM) rate, overall recurrence rate, and pattern of treatment failure following MIE were analyzed by SPSS 26.0 statistical software. Cox regression model was used to identify the high-risk factors for recurrent disease. Propensity score matching was performed to compare the survival of patients between the postoperative radiotherapy group and non-radiotherapy group.Results:A total of 443 eligible patients were enrolled in this study, and the pathology-based LNM rate in all groups was 42.0%. The overall recurrence rate was 34.8%. Regional lymphatic metastasis was the most frequent pattern of recurrence (24.2%), followed by distant metastasis (19.4%). Multivariate Cox regression analysis identified pT 3-4 stage and pN + stage as the independent risk factors for recurrence. At the same time, the total number of lymph nodes dissected ≥12 and the number of lymph nodes dissected ≥7 in the neck clavicle and upper mediastinum could reduce the risk of tumor recurrence. The 1-, 3-, and 5-year disease-free survival (DFS) rates in the postoperative radiotherapy group and non-radiotherapy group were 83.5%, 66.8%, 60.7%, and 79.2%, 61.6%, 57.2%, respectively ( χ2=0.13, P=0.715). The 1-, 3-, and 5-year overall survival (OS) rates in two groups were 92.0%, 72.0%, 67.5% and 84.0%, 68.0%, 55.4% , respectively ( χ2=0.43, P=0.513). Conclusions:Regional lymphatic and distant metastases are the main patterns of recurrence for TEC patients after MIE with or without neoadjuvant chemotherapy. pT 3-4 stage, pN + stage, insufficient total number of lymph node dissection and insufficient number of lymph nodes in neck supraclavicular and upper mediastinal dissection are high-risk factors for postoperative recurrence. The survival rate in the postoperative radiotherapy group tends to be higher than that in the non-radiotherapy group. Adjuvant therapy, including postoperative radiotherapy, may remain necessary.