Octapeptin has strong antibacterial activity against Gram-negative bacteria such as Escherichia coli, Klebsiella pneumoniae and Acinetobacter baumannii, while it also has activity against some Gram-positive bacteria. This study used natural octapeptin A3 and B3 as lead compounds for structural modification. Twenty-one peptide derivatives (including A3 and B3) containing eight amino acid residues were prepared by solid-phase synthesis, and evaluated for antibacterial activity and renal cytotoxicity. Among them, three compounds 6, 7 and 17 exhibited broad-spectrum antibacterial activity and significantly enhanced the activity for Gram-positive bacteria while maintaining the activity of Gram-negative bacteria. Several compounds improved the activity for Pseudomonas aeruginosa. Compound 7 was active against all test strains and had relatively low renal cytotoxicity. The results provide a basis for the further development of novel polypeptide antibiotics.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in healthcare facilities in major regions of China in 2023.Methods Clinical isolates collected from 73 hospitals across China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2023 Clinical & Laboratory Standards Institute (CLSI) breakpoints.Results A total of 445199 clinical isolates were collected in 2023,of which 29.0％ were gram-positive and 71.0％ were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species (excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi) (MRSA,MRSE and MRCNS) was 29.6％,81.9％ and 78.5％,respectively.Methicillin-resistant strains showed significantly higher resistance rates to most antimicrobial agents than methicillin-susceptible strains (MSSA,MSSE and MSCNS).Overall,92.9％ of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 91.4％ of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis had significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 93.1％ in the isolates from children and and 95.9％ in the isolates from adults.The resistance rate to carbapenems was lower than 15.0％ for most Enterobacterales species except for Klebsiella,22.5％ and 23.6％ of which were resistant to imipenem and meropenem,respectively .Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.6％ to 10.0％.The resistance rate to imipenem and meropenem was 21.9％ and 17.4％ for Pseudomonas aeruginosa,respectively,and 67.5％ and 68.1％ for Acinetobacter baumannii,respectively.Conclusions Increasing resistance to the commonly used antimicrobial agents is still observed in clinical bacterial isolates.However,the prevalence of important crabapenem-resistant organisms such as crabapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a slightly decreasing trend.This finding suggests that strengthening bacterial resistance surveillance and multidisciplinary linkage are important for preventing the occurrence and development of bacterial resistance.

Objective: To analyze the correlation between loss of smell/taste and the number of real confirmed cases of coronavirus disease 2019 (COVID-19) worldwide based on Google Trends data, and to explore the guiding role of smell/taste loss for the COVID-19 prevention and control. Methods: "Loss of smell" and "loss of taste" related keywords were searched in the Google Trends platform, the data were obtained from Jan. 1 2019 to Jul. 11 2021. The daily and newly confirmed COVID-19 case number were collected from World Health Organization (WHO) since Dec. 30 2019. All data were statistically analyzed by SPSS 23.0 software. The correlation was finally tested by Spearman correlation analysis. Results: A total of data from 80 weeks were collected. The retrospective analysis was performed on the new trend of COVID-19 confirmed cases in a total of 186 292 441 cases worldwide. Since the epidemic of COVID-19 was recorded on the WHO website, the relative searches related to loss of smell/taste in the Google Trends platform had been increasing globally. The global relative search volumes of "loss of smell" and "loss of taste" on Google Trends was 10.23±2.58 and 16.33±2.47 before the record of epidemic while 80.25±39.81 and 80.45±40.04 after (t value was 8.67, 14.43, respectively, both P<0.001). In the United States and India, the relative searches for "loss of smell" and "loss of taste" after the record of epidemic were also much higher than before (all P<0.001). The correlation coefficients between the trend of weekly new COVID-19 cases and the Google Trends of "loss of smell" in the global, United States, and India was 0.53, 0.76, and 0.82 respectively (all P<0.001), the correlation coefficients with Google Trends of "loss of taste" was 0.54, 0.78, and 0.82 respectively (all P<0.001). The lowest and highest point of loss of smell/taste search curves of Google Trends in different periods appeared 7 to 14 days earlier than that of the weekly newly COVID-19 confirmed cases curves, respectively. Conclusions: There is a significant positive correlation between the number of newly confirmed cases of COVID-19 worldwide and the amount of keywords, such as "loss of smell" and "loss of taste", retrieved in Google Trends. The trend of big data based on Google Trends might predict the outbreak trend of COVID-19 in advance.
Ageusia ; Big Data ; COVID-19 ; Disease Outbreaks ; Humans ; Internet ; Retrospective Studies ; Smell ; United States

Objective     To analyze the perioperative outcomes of uniportal thoracoscopic lobectomy compared with three-port thoracoscopic lobectomy. Methods     Data were extracted from the Western China Lung Cancer Database, a prospectively maintained database at the Department of Thoracic Surgery, West China Hospital, Sichuan University. Perioperative outcomes of the patients who underwent uniportal or three-port thoracoscopic lobectomy for lung cancer during January 2014 through April 2021 were analyzed by using propensity score matching. Altogether 5 817 lung cancer patients were enrolled who underwent thoracoscopic lobectomy (uniportal: 530 patients; three-port: 5 287 patients). After matching, 529 patients of uniportal and 1 583 patients of three-port were included. There were 529 patients with 320 males and 209 females at median age of 58 (51, 65) years in the uniportal group and 1 583 patients with 915 males and 668 females at median age of 58 (51, 65) years in the three-port group. Results     Uniportal thoracoscopic lobectomy was associated with less intraoperative blood loss (20 mL vs. 30 mL, P<0.001), longer operative time (115 min vs. 105 min, P<0.001) than three-port thoracoscopic lobectomy. No significant difference was found between the two groups regarding the number of lymph node dissected, rate of conversion to thoracotomy, incidence of postoperative complication, postoperative pain score within 3 postoperative days, length of hospital stay, or hospitalization expenses. Conclusion     Uniportal video-assisted thoracoscopic lobectomy is safe and effective, and the overall perioperative outcomes are comparable between uniportal and three-port strategies, although the two groups show differences in intraoperative blood loss.

Objective     To identify the risk factors for postoperative recurrence of peripheral solid small-nodule lung cancer (PSSNLC) (T≤2 cm), and to explore the effects of surgery types on prognosis. Methods     We extracted data from Western China Lung Cancer Database (WCLCD), a prospectively maintained database at the Department of Thoracic Surgery, West China Hospital, Sichuan University, and Surveillance, Epidemiology, and End Results (SEER)  database for peripheral solid small-nodule lung cancer patients (T≤2 cm N0M0, stageⅠ) who underwent surgery between 2005 and 2016. We used univariable and multivariable logistic regression to analyze risk factors for recurrence of PSSNLC. We applied propensity-score matching to compare the long-term results of segmentectomy and lobectomy, as well as the survival of patients from WCLCD and SEER. We finally included 4 800 patients with PSSNLC (T≤2 cm N0M0)(WCLCD: SEER=354∶4 446). We matched 103 segmentectomies and 350 lobectomies in T≤1 cm, and 280 segmentectomies and 1 067 lobectomies in 1 cm

Objective: To analyze the current adherence to imatinib in patients with gastrointestinal stromal tumors (GIST) in China and its influencing factors. Methods: A cross-sectional survey was conducted. Study period: from October 1, 2020 to November 31, 2020. Study subjects: GIST patients taking imatinib who were diagnosed and treated in public tertiary level A general hospitals or oncology hospitals; those who had not been pathologically diagnosed, those who never received imatinib, or those who had taken imatinib in the past but stopped afterwards were excluded. The Questionnaire Star online surgery platform was used to design a questionnaire about the adherence to adjuvant imatinib therapy of Chinese GIST patients. The link of questionnaire was sent through WeChat. The questionnaire contained basic information of patients, medication status and Morisky Medication Adherence Scale. Results: A total of 2162 questionnaires from 31 provinces, autonomous regions, and municipalities were collected, of which 2005 were valid questionnaires, with an effective rate of 92.7%. The survey subjects included 1104 males and 901 females, with a median age of 56 (22-91) years old. Working status: 609 cases (30.4%) in the work unit, 729 cases (36.4%) of retirement, 667 cases of flexible employment or unemployment (33.3%). Education level: 477 cases (23.8%) with bachelor degree or above, 658 cases (32.8%) of high school, 782 cases (39.0%) of elementary or junior high school, 88 cases (4.4%) without education. Marital status: 1789 cases (89.2%) were married, 179 cases (8.9%) divorced or widowed, 37 cases (1.8%) unmarried. Two hundred and ninety-four patients (14.7%) had metastasis when they were first diagnosed, including 203 liver metastases, 52 peritoneal metastases, and 39 other metastases. One thousand eight hundred and sixty-nine patients underwent surgical treatment, of whom 1642 (81.9%) achieved complete resection. The median time of taking imatinib was 25 (1-200) months. Common adverse reactions of imatinib included 1701 cases (84.8%) of periorbital edema, 1031 cases (51.4%) of leukopenia, 948 cases (47.3%) of fatigue, 781 cases (39.0%) of nausea and vomiting, 709 cases (35.4%) of rash, and 670 cases (33.4%) of lower extremity edema. The score of the Morisky Medication Adherence Scale showed that 392 cases (19.6%) had poor adherence, 1023 cases (51.0%) had moderate adherence, and 590 cases (29.4%) had good adherence. Univariate analysis showed that gender, age, work status, economic income, residence, education level, marriage, the duration of taking medication and adverse reactions were associated with adherence to adjuvant imatinib therapy (all P<0.05). Multivariate analysis showed that female (OR=1.264, P=0.009), non-retirement (OR=1.454, P=0.001), monthly income ≤4000 yuan (OR=1.280, P=0.036), township residents (OR=1.332, P=0.005), unmarried or divorced or widowed (OR=1.362, P=0.026), the duration of imatinib medication >36 months (OR=1.478, P<0.001) and adverse reactions (OR=1.719, P=0.048) were independent risk factors for poor adherence to adjuvant imatinib. Among patients undergoing complete resection, 324 (19.7%) had poor adherence, 836 (50.9%) had moderate adherence, and 482 (29.4%) had good adherence. Meanwhile, 55 patients with good adherence (11.4%) developed recurrence after surgery, 121 patients with moderate adherence (14.5%) developed recurrence, 61 patients with poor adherence (18.8%) developed recurrence, and the difference was statistically significant (P=0.017). Conclusions: The adherence to adjuvant therapy with imatinib in Chinese GIST patients is relatively poor. Females, non-retirement, monthly income ≤4000 yuan, township residents, unmarried or divorced or widowed, the duration of imatinib medication >36 months, and adverse reactions are independently associated with poor adherence of GIST patients. Those with poor adherence have a higher risk of recurrence after surgery. Positive interventions based on the above risk factors are advocated to improve the prognosis of patients with GIST.
Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use* ; Chemotherapy, Adjuvant ; Cross-Sectional Studies ; Female ; Gastrointestinal Stromal Tumors/drug therapy* ; Humans ; Imatinib Mesylate/therapeutic use* ; Male ; Middle Aged ; Neoplasm Recurrence, Local/drug therapy*

Objective To observe the immune effect of PD-1 (programmed death-1) antibody in the treatment of patients with advanced cancer .Methods From October 2015 to March 2016 ,18 patients with advanced tumor were selected to receive the PD-1 antibody treatment in Eastern Hepatobiliary Surgical Hospital .Clinical efficacy ,adverse reactions and progression free survival time were monitored .The quality of life were compared before and after the treatment .Results Among 18 cases , PR 5 cases ,SD 7 cases and PD 6 cases .The KPS scores for quality of life was significantly increased (P<0 .05) after treat-ment .At the end of follow-up ,5 patients died ,2 patients were lost in follow-up ,11 patients survived .The median progression free survival was 2 .6 months (95% CI:1 .8-3 .3 months) .No serious adverse reactions and abnormal laboratory results were reported .Conclusion PD-1 antibody is a safe and effective treatment for advanced tumors .It is well tolerated and has less ad-verse reactions .The randomized control studies with larger samples are needed to further confirm our conclusions .

Sheng-Mai-San (SMS), a well-known Chinese medicinal plant formula, is widely used for the treatment of cardiac diseases characterized by deficiency of Qi and Yin syndrome. A mouse chronic intermittent hypoxia (CIH) model was established to mimic the primary clinical features of deficiency of Qi and Yin syndrome. Mice experienced CIH for 28 days (nadir 7% to peak 8% oxygen, 20 min per day), resulting in left ventricle (LV) dysfunction and structure abnormalities. After administration of SMS (0.55, 1.1, and 5.5 g·kg(-1)·d(-1)) for four weeks, improved cardiac function was observed, as indicated by the increase in the ejection fraction from the LV on echocardiography. SMS also preserved the structural integrity of the LV against eccentric hypotrophy, tissue vacuolization, and mitochondrial injury as measured by histology, electron microscopy, and ultrasound assessments. Mechanistically, the antioxidant effects of SMS were demonstrated; SMS was able to suppress mitochondrial apoptosis as indicated by the reduction of several pro-apoptotic factors (Bax, cytochrome c, and cleaved caspase-3) and up-regulation of the anti-apoptosis factor Bcl-2. In conclusion, these results demonstrate that SMS treatment can protect the structure and function of the LV and that the protective effects of this formula are associated with the regulation of the mitochondrial apoptosis pathway.
Animals ; Antioxidants ; pharmacology ; therapeutic use ; Apoptosis ; Cardiomyopathies ; drug therapy ; etiology ; Caspase 3 ; metabolism ; Cytochromes c ; metabolism ; Disease Models, Animal ; Drug Combinations ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Heart Ventricles ; drug effects ; pathology ; physiopathology ; Hypoxia ; Male ; Mice, Inbred ICR ; Mitochondria ; drug effects ; metabolism ; Myocardium ; pathology ; Oxygen ; metabolism ; Phytotherapy ; Qi ; Up-Regulation ; Ventricular Dysfunction, Left ; drug therapy ; etiology ; bcl-2-Associated X Protein ; metabolism

The present study was designed to investigate the chemical constituents and bioactivities of the roots of Liriope muscari (Decne.) L.H. Bailey. The compounds were isolated through various chromatography techniques, including silica gel, Sephadex LH-20, and semi-preparative HPLC. The structures were elucidated by infrared (IR), mass spectrometric (MS), 1D- and 2D-NMR analyses in comparison with reference data. In addition, the cytotoxicity of these compounds against human breast cancer MDA-MB-435 cells was evaluated by the MTT assay. Two new steroidal glycosides, 25(R, S)-ruscogenin-1-O-[β-D-fucopyranosyl (1→2)]-[β-D-xylopyranosyl(1→3)]β-D-glucopyranoside (Liriopem I, 1) and 25(R, S)- ruscogenin-1-O-[β-D-fucopyranosyl (1→2)]-[β-D-xylopyranosyl(1→4)]-β-D-fucopyranoside (Liriopem II, 2 and two known compounds LM-S6 (3) and DT-13 (4) were isolated and identified. Liriopem I(1), liriopem II(2) and DT-13 (4) showed remarkable cytotoxicity with IC50 values being (0.58 ± 0.08), (0.05 ± 0.10), and (0.15 ± 0.09) μg·mL(-1), respectively. In summary, compounds 1 and 2 identified in the present study exerted cytotoxicity against breast cancer cells, providing a basis for future development of these compounds as novel anticancer agents.
Cell Line, Tumor ; Cell Survival ; drug effects ; Drugs, Chinese Herbal ; chemistry ; isolation & purification ; toxicity ; Glycosides ; chemistry ; isolation & purification ; toxicity ; Humans ; Liriope Plant ; chemistry ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Plant Roots ; chemistry