OBJECTIVE: Cigarette smoking exacerbates the progression of pulmonary tuberculosis (TB). The role of tertiary lymphoid structures (TLS) in chronic lung diseases has gained attention; however, it remains unclear whether smoking-exacerbated lung damage in TB is associated with TLS. This study aimed to analyze the characteristics of pulmonary TLS in smokers with TB and to explore the possible role of TLS in smoking-related lung injury in TB. METHODS: Lung tissues from 36 male patients (18 smokers and 18 non-smokers) who underwent surgical resection for pulmonary TB were included in this study. Pathological and immunohistological analyses were conducted to evaluate the quantity of TLS, and chest computed tomography (CT) was used to assess the severity of lung lesions. The correlation between the TLS quantity and TB lesion severity scores was analyzed. The immune cells and chemokines involved in TLS formation were also evaluated and compared between smokers and non-smokers. RESULTS: Smoker patients with TB had significantly higher TLS than non-smokers ( P < 0.001). The TLS quantity in both the lung parenchyma and peribronchial regions correlated with TB lesion severity on chest CT (parenchyma: r = 0.5767; peribronchial: r = 0.7373; both P < 0.001). Immunohistochemical analysis showed increased B cells, T cells, and C-X-C motif chemokine ligand 13 (CXCL13) expression in smoker patients with TB ( P < 0.001). CONCLUSION Smoker TB patients exhibited increased pulmonary TLS, which was associated with exacerbated lung lesions on chest CT, suggesting that cigarette smoking may exacerbate lung damage by promoting TLS formation.
Humans ; Male ; Tuberculosis, Pulmonary/immunology* ; Middle Aged ; Tertiary Lymphoid Structures/pathology* ; Adult ; Lung/pathology* ; Smoking/adverse effects* ; Smokers ; Aged ; Tomography, X-Ray Computed

Objective To investigate the effect of Ophiopogonin D on lipopolysaccharide(LPS)-induced apoptosis of alveolar epithelial cells by regulating the interleukin-6(IL-6)/Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)signaling pathway.Methods A549 AT Ⅱ cells cultured in vitro were randomly divided into four groups:control group,LPS group,LPS+Ophiopogonin D group,LPS+Ophiopogonin D+colivelin(JAK2/STAT3 signal activator)group,except for the control group,and cells in all other groups were established injury models while being grouped with Ophiopogonin D and colivelin for treatment.Cell counting kit-8(CCK-8)experiment and flow cytometry were applied to detect cell proliferation and apoptosis in each group;Western blotting was applied to detect the expression of IL-6/JAK2/STAT3 signaling pathway proteins of cells in each group.Results The apoptosis rates of A549 cells in control group,LPS group,LPS+Ophiopogonin D group and LPS+Ophiopogonin D+colivelin group were(2.52±0.73)％,(52.43±4.14)％,(1.67±0.52)％and(47.94±3.43)％;IL-6 protein levels were 0.14±0.03,0.49±0.05,0.17±0.04 and 0.45±0.06,and p-JAK2/JAK2 protein levels were 0.17±0.04,0.64±0.08,0.19±0.06 and 0.61±0.07;p-STAT3/STAT3 protein levels were 0.20±0.06,0.69±0.10,0.22±0.07 and 0.65±0.09;the apoptosis rates of AT Ⅱ cells were(3.01±0.69)％,(55.16±3.94)％,(2.35±0.71)％and(50.28±3.78)％;the levels of IL-6 protein were 0.11±0.03,0.87±0.13,0.19±0.04 and 0.84±0.12;the p-JAK2/JAK2 protein levels were 0.13±0.04,0.56±0.08,0.15±0.03 and 0.53±0.07;p-STAT3/STAT3 protein levels were 0.30±0.08,0.79±0.14,0.33±0.09 and 0.75±0.13.The above indexes:control group,LPS+Ophiopogonin D group compared with LPS group,LPS+Ophiopogonin D+colivelin group compared with LPS+Ophiopogonin D group,the differences were statistically significant(all P＜0.05).Conclusion Ophiopogonin D can reduce LPS induced inflammation and oxidative stress levels by inhibiting the activation of IL-6/JAK2/STAT3 signaling pathway,ultimately reducing LPS-induced apoptosis of alveolar epithelial cells.

This study aims to identify the main chemical compounds, investigate the effects of different drying methods on the quality, and determine the appropriate drying method of Callicarpae Nudiflorae Folium. UPLC-UV-Q-TOF-MS was employed to characterize and identify 35 main compounds, including phenylethanoid glycosides, flavonoids, and iridoids in Callicarpae Nudiflorae Folium. A method for the simultaneous determination of 8 compounds with strong UV absorption and high content was established to evaluate the quality of Callicarpae Nudiflorae Folium dried by different methods. UPLC-UV-Q-TOF-MS combined with principal component analysis(PCA) was employed to compare the Callicarpae Nudiflorae Folium samples treated by microwave drying at different power(119, 231, and 385 W), drying in the shade, sun drying, and oven drying at different temperatures(50, 60, 70, 80, 90, and 100 ℃). The total content of decaffeoyl acteoside, picroside Ⅲ, galuteolin, forsythin B, acteoside, isoacteoside, 6-hydroxyluteolin-7-glucoside, and caffeic acid in Callicarpae Nudiflorae Folium, as well as the content of most compounds, decreased with the rise in drying temperature and with the decrease in microwave power. Considering the content of compounds, low carbon, and energy saving, microwave drying at 231 W, low-temperature drying, or natural drying is recommended for the production of Callicarpae Nudiflorae Folium. This study provides a scientific basis for the selection of drying methods for Callicarpae Nudiflorae Folium at the place of origin and for the improvement of quality standards.
Desiccation/methods* ; Drugs, Chinese Herbal/chemistry* ; Callicarpa/chemistry* ; Plant Leaves/chemistry* ; Chromatography, High Pressure Liquid ; Flavonoids/analysis* ; Microwaves ; Mass Spectrometry

BACKGROUND: Carbapenemase-producing Klebsiella pneumoniae (CP-Kp) poses distinct clinical challenges due to extensively drug resistant (XDR) phenotype, and sequence type (ST) 11 is the most dominant blaKPC-2-bearing CP-Kp clone in China. The purpose of this current retrospective study was to explore the genetic factors associated with the success of XDR CP-Kp ST11 strains circulated in the intensive care unit (ICU) of a Chinese tertiary hospital. METHODS: Six ST11 XDR CP-Kp strains were identified between May and December 2014 and validated by minimum inhibitory concentration examination, polymerase chain reaction, and pyrosequencing. The six ST11 XDR CP-Kp, as well as three multi-drug resistant (MDR) and four susceptible strains, were sequenced using single-molecule real-time method. Comprehensively structural and functional analysis based on comparative genomics was performed to identify genomic characteristics of the XDR ST11 CP-Kp strains. RESULTS: We found that ST11 XDR blaKPC-2-bearing CP-Kp strains isolated from inpatients spread in the ICU of the hospital. Functionally, genes associated with information storage and processing of the ST11 XDR CP-Kp strains were more abundant than those of MDR and susceptible strains, especially genes correlative with mobile genetic elements (MGEs) such as transposons and prophages. Structurally, eleven large-scale genetic regions taken for the unique genome in these ST11 XDR CP-Kp strains were identified as MGEs including transposons, integrons, prophages, genomic islands, and integrative and conjugative elements. Three of them were located on plasmids and eight on chromosomes; five of them were with antimicrobial resistance genes and eight with adaptation associated genes. Notably, a new blaKPC-2-bearing ΔΔTn1721-blaKPC-2 transposon, probably transposed and truncated from ΔTn1721-blaKPC-2 by IS903D and ISKpn8, was identified in all six ST11 XDR CP-Kp strains. CONCLUSION Our findings suggested that together with clonal spread, MGEs identified uniquely in the ST11 XDR CP-Kp strains might contribute to their formidable adaptability, which facilitated their widespread dissemination in hospital.
Anti-Bacterial Agents ; Bacterial Proteins ; China ; Electrophoresis, Gel, Pulsed-Field ; Hospitals ; Humans ; Klebsiella Infections/drug therapy* ; Klebsiella pneumoniae/genetics* ; Microbial Sensitivity Tests ; Multilocus Sequence Typing ; Pharmaceutical Preparations ; Retrospective Studies ; beta-Lactamases/genetics*

Objective To establish a HPLC method for determining the concentration of voriconazole (VRC) in human plasma.Methods The analysis was conducted using a ZORBAX Eclipse Plus C18 column and the column temperature was 40 ℃.The mobile phase consisted of methanol and water (55∶45).The flow rate was 1 mL · min-1 and the detection was performed at 254 nm.And the internal standard substance was p-Chloroacetanilide.The specificity,lower limit of quantitation (LLOQ),standard curve,precision,accuracy,recovery and stability were investigated.Results Endogenous impurities did not interfere with the determination of the samples in plasma.The standard curve was linear in the range of 0.1-10.0 μg · mL-1 (r =0.999 2),LLOQ was 0.1 μg · mL-1.The RSDs of inter-day and intra-day were all less than 10％ in the plasma and the extraction recovery was 89％-92％.Conclusion This method was simple,sensitive,accurate,efficient and suitable for routine determination of the concentration of VRC in human plasma.

In this paper,the potential climate factors affecting the Pairs polyphylla var. yunnanensis distribution in China at rational scales were selected from related literatures, using the sampling point geographic information from of P. polyphylla var. yunnanensis, combine the maximum entropy model (MaxEnt) with spatial analyst function of ArcGIS software, to study the climate suitability of P. polyphylla var. yunnanensis cultivating region in China and the leading climate factors. The results showed that, average rainfall in August, average rainfall in October, coefficient of variation of seasonal precipitation, the average temperature of the dry season, isothermal characteristic, average temperature in July were the leading climate factors affecting the potential distribution of P. polyphylla var. yunnanensis cultivating region in China, with their cumulative contribution rate reached 97.2% of all candidate climate factors. Existence probability of the region to be predicted of P. polyphylla var. yunnanensis through the constructed model, the climate unsuitable region, low, medium and high region of P. polyphylla var. yunnanensis in China were clarified and the threshold of climatic factors were gave and clarified the climate characteristics of the cultivating region in each climatic suitability division. The results of research can provide reference for production layout and introduction of P. polyphylla var. yunnanensis.

Objective To develop an analytical method for analyzing the unbound concentration of antofloxacin in human plasma .Methods A HPLC method was developed to determine the unbound concentration of antofloxacin in human plasma using ultra -centrifugation.The column was Alltima C18 (150 mm ×4.6 mm,5μm) with room temperature as the column temperature .The mobile phase was composed of 13:87 acetoni-trile-0.05 mol · L-1 phosphate buffer ( pH 3.0 ) with detection wave-length set at 293 nm, and the flow rate was 1.0 mL · min-1 .The method was validated for specificity , precision and accuracy , recovery as well as stability.Results The calibration curves were linear over the range of 0.08-5.49 μg· mL-1 .The intra-day and inter-day preci-sion evaluated at lower limit of quantification and quality control levels were within 2.78%-10.03%.The recoveries calculated for the anto-floxacin were within 92.09%-108.96%from spiked plasma ultrafiltrate samples.Conclusion The analytical method is quick , precise and accuracy and could be used in the analysis of unbound concentration of antofloxacin in plasma.

OBJECTIVETo investigate the clinical value of Paroxetine combined with mid-frequency electrical pulse acupoint stimulation (EPAS) in the treatment of premature ejaculation (PE).

METHODSTotally 69 PE patients were equally assigned to receive oral Paroxetine 20 mg/d, mid-frequency EPAS, or oral Paroxetine 10 mg/d combined with mid-frequency EPAS (P + EPAS) , all for 8 weeks. We obtained the intravaginal ejaculation latency time (IELT) and Chinese Index of Premature Ejaculation (CIPE-5) scores of the patients before and after treatment, and compared adverse reactions among the three groups of patients.

RESULTSOne patient of the Paroxetine group gave up treatment because of abdominal pain and nausea. Compared with the baseline, the patients in the Paroxetine, EPAS, and P + EPAS groups all showed markedly increased IELT ([0.92 ± 0.11] vs [4.07 ± 0.11] min, P < 0.01; [0.92 ± 0.12] VS [2.78 ± 0.17] min P < 0.05; [0.91 ± 0.09] vs [5.31 ± 0.13], P < 0.01) and decreased CIPE-5 scores (12.5 ± 3.0 vs 22.0 ± 2.1, P < 0.01; 12.8 ± 2.9 vs 19.5 ± 1.9, P > 0.05; 13.1 ± 2.8 vs 25.2 ± 2.1, P 0.01), with statistically significant differences between the P + EPAS group and the other two (P < 0.05). The total effectiveness rate was 95.7% in the P + EPAS group, remarkably higher than in the Paroxetine (72.7%, P < 0.05) and the EPAS group (47.8, P < 0.01).

CONCLUSIONOral Paroxetine combined with mid-frequency EPAS has a higher safety and efficacy than either Paroxetine or EPAS alone in the treatment of PE.

Acupuncture Points ; Aged ; Combined Modality Therapy ; methods ; Ejaculation ; Electroacupuncture ; methods ; Humans ; Male ; Paroxetine ; therapeutic use ; Premature Ejaculation ; therapy ; Serotonin Uptake Inhibitors ; therapeutic use ; Treatment Outcome

Objective To evaluate the pharmacokinetics of multiple doses of ampiroxicam tablets in Chinese healthy subjects .Methods A randomized, open study was conducted.Twelve subjects were orally administrated with 27 mg ampiroxicam tablets, once a day for 11 days. The blood samples were collected on the 8th , 9th , and 10th day before ad-ministration.On the 11 th day, the blood and urine samples were collected at different time points after administration , and the concentrations of am-piroxicam in serum and urine were determinated by HPLC method . Results One subject exited on the 7th day.The main pharmacokinetics parameters of 11 subjects after oral doses for 11 days were as follows:Cmax were(8.14 ±2.81) mg? L-1; t1 /2β was (50.10 ±18.10 ) h; tmax was (5.60 ±4.10) h; AUC0 -∞ was (837.05 ±441.47 ) mg? h? L respectively.Urinary recovery rate was (0.55 ±0.51 )% from zero to 192 hours, respectively.Conclusion After multiple dosing, there was a very high trough concentration before dosing because of a very long half -life of ampiroxicam.Blood concentration and pharmacokinetic parameters are individually different, and little drug is excreted by kidney.

BACKGROUNDA new fluroquinolone antibacterial agent, antofloxacin hydrochloride, developed in China, is an 8-NH(2) derivant of levofloxacin. The purpose of the study was to evaluate the pharmacokinetic characteristics of single and multiple oral doses of antofloxacin hydrochloride in Chinese healthy male volunteers.

METHODSAn open-label, non-randomized, single and multiple dose clinical trial was conducted. In single dose study, 12 subjects took 200 mg antofloxacin hydrochloride. In multiple dose study, 12 subjects took antofloxacin hydrochloride 400 mg once on day 1 and 200 mg once daily from day 2 to day 7. HPLC was used to assay the serum and urinary concentrations of antofloxacin.

RESULTSIn single dose study, the maximum concentration of drug in serum (C(max)), the time to reach C(max) (T(max)), and the area under the serum concentration-time curve (AUC (0-∞)) of antofloxacin were (1.89 ± 0.65) mg/L, (1.29 ± 0.26) hours, and (25.24 ± 7.26) mg×h(-1)×L(-1), respectively. Accumulating elimination rate of antoflocaxin from urine within 120 hours was 39.1%. In multiple dose study, blood concentration of antofloxiacin achieved stable state on day 2 after dosing. The minimum concentration drug in serum (C(min)), AUCss, mean concentration of drug in serum (C(av)), and degree of fluctuation (DF) were (0.73 ± 0.18) mg/L, (47.59 ± 7.85) mg×h(-1)×L(-1), (1.98 ± 0.33) mg/L, and 1.74 ± 0.60, respectively. On day 7 after dosing, T(max), C(max), and AUC (0-∞) was (1.14 ± 0.50) hours, (2.52 ± 0.38) mg/L, and (48.77 ± 8.44) mg×h(-1)×L(-1), respectively. Accumulating elimination rate of antofloxaxin from urine within 120 hours after the last dosing was 60.06%.

CONCLUSIONSThe regimen of 400 mg loading dose given on the first treatment day and then 200 mg dose once daily results in satisfactory serum drug concentration.

Administration, Oral ; Adolescent ; Adult ; Anti-Bacterial Agents ; administration & dosage ; blood ; pharmacokinetics ; urine ; Chromatography, High Pressure Liquid ; Humans ; Levofloxacin ; Male ; Ofloxacin ; administration & dosage ; analogs & derivatives ; blood ; pharmacokinetics ; urine ; Young Adult