The problem of drug resistance resulting from the long-term use of antimicrobials is a serious threat to global health,and the emergence of multidrug-resistant bacteria,in particular,has greatly limited therapeutic op-tions.Therefore,the development of new or alternative antimicrobial agents has become an urgent need.Antimi-crobial peptides(AMPs)have been regarded as good alternatives to antibacterial drugs due to their strong antibac-terial activity and unique mechanism of action.At present,some AMPs have completed preclinical studies on drug-resistant bacterial infections and entered the clinical trial stage,while their stability and targeting have been signifi-cantly improved through the optimisation of amino acid modification,nano-delivery system and other technolo-gies,which have gradually become a research hotspot in this field.Therefore,this paper discusses the importance of AMPs in bacterial drug resistance from the biological properties of AMPs,the mechanism of regulating bacteri-al drug resistance and the application of AMPs in the treatment of drug-resistant bacterial infections,with a view to providing a reference for the development of drugs against drug-resistant bacteria and clinical application.

The problem of drug resistance resulting from the long-term use of antimicrobials is a serious threat to global health,and the emergence of multidrug-resistant bacteria,in particular,has greatly limited therapeutic op-tions.Therefore,the development of new or alternative antimicrobial agents has become an urgent need.Antimi-crobial peptides(AMPs)have been regarded as good alternatives to antibacterial drugs due to their strong antibac-terial activity and unique mechanism of action.At present,some AMPs have completed preclinical studies on drug-resistant bacterial infections and entered the clinical trial stage,while their stability and targeting have been signifi-cantly improved through the optimisation of amino acid modification,nano-delivery system and other technolo-gies,which have gradually become a research hotspot in this field.Therefore,this paper discusses the importance of AMPs in bacterial drug resistance from the biological properties of AMPs,the mechanism of regulating bacteri-al drug resistance and the application of AMPs in the treatment of drug-resistant bacterial infections,with a view to providing a reference for the development of drugs against drug-resistant bacteria and clinical application.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

OBJECTIVE: Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery. METHODS: We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated. RESULTS: A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery. CONCLUSION These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.
Female ; Humans ; Male ; Middle Aged ; Brucellosis ; COVID-19 ; Retrospective Studies ; SARS-CoV-2 ; Treatment Outcome ; Case Reports as Topic

ObjectiveTo explore the differences in response to bakuchiol-induced hepatotoxicity between Institute of Cancer Research （ICR） mice and Kunming （KM） mice. MethodThe objective manifestations of bakuchiol-induced hepatotoxicity in mice were confirmed by acute and subacute toxicity animal experiments， and enrichment pathways of differential genes between normal ICR mice and KM mice were compared by transcriptomics. The real-time quantitative polymerase chain reaction （real-time qPCR） assay was used to verify the mRNA expression of key genes in the related pathways to confirm the species differences of bakuchiol-induced liver injury. ResultIn the subacute toxicity experiment， compared with the normal mice， the ICR mice showed increased serum content of alkaline phosphatase （ALP）， and 5′-nucleotidase （5′-NT）， without significant difference， and no manifest change was observed in KM mice. Pathological results showed that hepatocyte hypertrophy was the main pathological feature in ICR mice and hepatocyte steatosis in KM mice. In the acute toxicity experiment， KM mice showed erect hair， mental malaise， and near-death 3 days after administration. The levels of serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in KM mice （400 mg·kg^-1） significantly increased（P<0.01）， and the activity of total reactive oxygen species （SOD） in liver significantly decreased（P<0.01）compared with those in normal mice， while the serum content of 5′-NT and cholinesterase （CHE） in ICR mice （400 mg·kg^-1） were significantly elevated （P<0.01）. The liver/brain ratio in ICR mice increased by 20.34% and that in KM mice increased by 29.14% （P<0.01）. The main pathological manifestation of the liver in ICR mice was hepatocyte hypertrophy， while those in KM mice were focal inflammation， hepatocyte hypertrophy， and hepatocyte steatosis. Kyoto Encyclopedia of Genes and Genomes（KEGG）and Reactome pathway enrichment analyses showed that the differential gene expression between ICR mice and KM mice was mainly involved in oxidative phosphorylation， bile secretion， bile acid and bile salts synthesis， and metabolism pathway. CYP7A1 was up-regulated in all groups with drug intervention （P<0.01） and MRP2 was reduced in all groups with drug intervention of KM mice （P<0.01） and elevated in all groups with drug intervention of ICR mice （P<0.01） compared with those in the normal group. The expression of BSEP was lowered in ICR mice with acute liver injury （400 mg·kg^-1） （P<0.05）. SHP1 was highly expressed in KM mice with acute liver injury （400 mg·kg^-1）. The expression of FXR was diminished in ICR mice with subacute liver injury （200 mg·kg^-1） （P<0.01）. SOD1， CAT， and NFR2 significantly decreased in KM mice with acute liver injury （400 mg·kg^-1）， and CAT dwindled in KM mice with subacute liver injury （200 mg·kg^-1） （P<0.01）. GSTA1 and GPX1 significantly increased in KM mice with acute liver injury （400 mg·kg^-1） （P<0.01） and SOD1， CAT， NRF2， and GSTA1 significantly increased in ICR mice with subacute liver injury （200 mg·kg^-1） （P<0.01）. CAT and NRF2 significantly increased in ICR mice with acute liver injury （400 mg·kg^-1） （P<0.01）. ConclusionWith the increase in the dosage of bakuchiol， the liver injury induced by oxidative stress in KM mice was gradually aggravated， and ICR mice showed stronger antioxidant capacity. The comparison of responses to bakuchiol-induced hepatotoxicity between ICR mice and KM mice reveals that ICR mice are more suitable for the investigation of the mechanisms related to bile secretion and bile acid metabolism in the research on bakuchiol-induced hepatotoxicity in mice. KM mice are more prone to liver injury caused by oxidative stress.

OBJECTIVE: To explore whether acupuncture combined with moxibustion could inhibit epithelialmesenchymal transition in Crohn's disease by affecting the transforming growth factor β 1 (TGF- β 1)/Smad3/Snail pathway. METHODS: Sixty-three patients with Crohn's disease were randomly divided into an observation group (31 cases) receiving moxibustion at 43 °C combined with acupuncture, and a control group (32 cases) receiving moxibustion at 37 °C combined with sham acupuncture using a random number table. Patients were treated for 12 weeks. Crohn's Disease Activity Index (CDAI) was used to evaluate disease activity. Hematoxylin-eosin staining and transmission electron microscopy were utilized to observe the morphological and ultrastructural changes. Immunohistochemistry was used to detect the expression of transforming growth factor β 1 (TGF-β 1), T β R1, T β R2, Smad3, Snail, E-cadherin and fibronectin in intestinal mucosal tissues. RESULTS: The decrease of the CDAI score, morphological and ultrastructural changes were more significant in observation group. The expression levels of TGF- β 1, Tβ R2, Smad3, and Snail in the observation group were significantly lower than those before the treatment (P<0.05 or P<0.01). After treatment, the expression levels of TGF-β 1, TβR2, and Snail in the observation group were significantly lower than those in the control group (all P<0.05); compared with the control group, the expression of fibronectin in the observation group was significantly decreased, and the expression of E-cadherin was significantly increased (all P<0.05). CONCLUSIONS Moxibustion at 43 °C combined with acupuncture may suppress TGF-β 1/Smad3/Snail pathway-mediated epithelial-mesenchymal transition of intestinal epithelial cells in Crohn's disease patients by inhibiting the expression levels of TGF-β 1, Tβ R2, Smad3, and Snail. (Registration No. ChiCTR-IIR-16007751).
Acupuncture Therapy ; Cadherins/metabolism* ; Crohn Disease/therapy* ; Epithelial-Mesenchymal Transition ; Fibronectins/metabolism* ; Humans ; Moxibustion ; Smad3 Protein/metabolism* ; Snail Family Transcription Factors/metabolism* ; Transforming Growth Factor beta1/metabolism*

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Objective To investigate the expression of semaphorin 3A (Sema3A) and its receptor neuropilin-1 (NRP-1) in gastric cancer and its correlation with microvessel density (MVD), and then to explore the effect of recombinant human Sema3A on angiogenesis of gastric cancer and the associated mechanisms. Methods Forty cases of gastric cancer tissues and its corresponding adjacent normal tissues were used to detecte the expression of Sema3A, NRP-1 and MVD in tissues by immunohistochemistry method . The expression level of Sema3A in serum of gastric cancer patient group and normal control group were measured by Enzyme-linked immuno-sorbent assay (ELISA). Western blotting was used to detect the expression of Sema3A and NRP-1 in five gastric cancer cell lines (MGC-803,HGC-27,MKN-28,SGC-7901,MKN-45) and human gastric mucosal epithelial cell (GES-1). Transwell chamber was used to construct non-contact in vitro co-culture system, in which the effects of different concentrations of recombinant human Sema3A on angiogenesis in gastric cancer were analyzed by tube formation assay preliminarily. The expression levels of vascular endothelial growth factor receptor 2 (VEGFR2) and NRP-1 in co-culture system were detected by Western blotting. Results The expression levels of Sema3A in gastric cancer tissues, cell lines and patient serum were significantly lower than that in the control group(P<0. 05), while the expression of NRP-1 in gastric cancer tissues and MKN-28 cells was significantly increased, and both of them were associated with TNM staging of gastric cancer (P < 0. 05) . In vitro co-culture system, The tube forming abilities of human umbilical vein endothelial cell (HUVEC) were decreased in recombinant human Sema3A treated group, and this phenomenon was concentration dependent. The expression of VEGFR2 protein was down-regulated by recombinant human Sema3A. Conclusion The expression of Sema3A was decreased in gastric cancer tissues, cell lines and patient serum, and negatively correlated with microvessel density. The recombinant human Sema3A could inhibit the angiogenesis of gastric cancer in vitro, which may be related to down-regulation of VEGFR2 protein expression.

OBJECTIVETo evaluate the impact of Jinlongshe Granule (, JLSG) on quality of life (QOL) of stage IV gastric cancer patients.

METHODSThis randomized, double-blind and placebo-controlled clinical trial included 50 patients with advanced gastric cancer. They were equally randomized into a JLSG group and a placebo group. Patients in both groups received routine Chinese herbal decoctions according to Chinese medicine (CM) treatment based on syndrome differentiation. Patients in JLSG group received additional JLSG, and those in the placebo group received an additional placebo. In the JLSG group, 19 patients who completed the study were used for analysis. In the placebo group, finally the data of 20 patients who completed the study were used for analysis. The treatment course was at least 3 months, and the follow-up duration was at least 6 months in 5 interviews. Repeated measurements of the subscale items and individual items in European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30) obtained at the 5 interviews were compared using different patient groups, changes over time and changes within one group over time independently to observe the tendency of changes in the scores.

RESULTSUsing time as the variant, there was signifificant difference in 4 functional scales (physical, role, emotional and social, P<0.05), 3 symptom scales (fatigue, nausea and vomiting and pain,P<0.05) and a global health status/QOL scale (P<0.05) and 6 single symptoms dyspnoea (P>0.05), insomnia (P<0.05), appetite loss (P<0.05), constipation (P<0.05), diarrhea (P>0.05) and financial difficulties (P<0.05). There was also signifificant difference in these items between the two groups when the placebo group and group over time were used as variants (P<0.05 or P<0.01).

CONCLUSIONAdditional use of JLSG on the basis of routine CM treatment could improve the somatic function, role function, emotional function, social function, cognitive function and general QOL of patients with advanced gastric cancer, and relieve the symptoms of fatigue, nausea and vomiting, pain, loss of appetite and constipation.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; Double-Blind Method ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Middle Aged ; Placebos ; Quality of Life ; Stomach Neoplasms ; drug therapy ; physiopathology ; Young Adult