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 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 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 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 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

This study was aimed to quantify plasma circulating DNA level in patients with acute myeloid leukemia (AML) and to evaluate its clinical significance. 66 AML patients and 100 controls (60 healthy subjects for health examination, 20 cases of benign hematopathy, and 20 cases of solid tumors) were enrolled in this study. Blood samples were collected from AML patients at different status of disease and control groups. Circulating DNA were drew by using the BILATEST DNA Kit. The level of plasma DNA was determined by using duplex real-time quantitative PCR. The results showed that the median value of plasma DNA level in AML patients at diagnosis was 168.5 (73.4 - 245.1) ng/ml, significantly higher than those in three control groups, and the median level in male patients was significantly higher than that in female patients (P = 0.019). No significant difference was found in plasma DNA level of the patients at different ages and with different FAB subtypes. Compared with level before chemotherapy, the plasma DNA levels in complete remission patients and partial remission patients decreased significantly, and with no statistical difference from level of healthy controls, but was significantly different from level of non-remission patients (P < 0.05). Following up of 31 remission patients showed that the plasma DNA level increased in 5 out of 6 (83.3%) relapsed patients, but no increase was found in 22 out of 25 (88.0%) non-relapsed patients. It is concluded that the quantification of plasma DNA may be useful for evaluating therapeutic effects and monitoring relapse in AML patients.
Adolescent ; Adult ; Aged ; Case-Control Studies ; DNA ; blood ; Female ; Humans ; Leukemia, Myeloid, Acute ; blood ; pathology ; Male ; Middle Aged ; Prognosis ; Young Adult

Objective To probe into effective surgical methods to reduce post-operational recurrence rate of nodular goiter.Methods One hundred and fifty-seven patients with nodular goiter who were admitted and had operations in our hospitals between Jan,2007 and June,2011 were assigned to one of the following 4 groups:total thyroidectomy(TT),nearly total thyroidectomy (NTT),subtotal thyroidectomy (STT),removal of lesion only or partial thyroidectomy (also termed as local removal,LR).Postsurgical recurrences and complications were compared among these groups.Results The recurrences were statistically analysed.There was a highly significant difference between TF and STT、TT and LR、NTT and LR; no difference was observed between TT and NTT,STT and STT + E,STT and LR.A statistical analysis was also carried out on the postsurgical compications in these patients.highly significant differnce was found between TT and STT,TT and NTT,TT and LR.There was a significant diffrence between STT and NTT.There was no difference between STT and LR,NTT and LR.Conclusion TT,STT,NTT are all effective operations for nodular goiter and should be advocated.Satisfactory efficacy may be obtained with oral thyroxine or euthyrox for postsurgical lifetime.However,LR or partial thyroidectomy should be adopted cautiously.