Objective To understand the clinical distribution characteristics and drug-resistance genotypes of carbapenem-resistant Pseudomonas aeruginosa(CRPA)in a tertiary hospital in Shanghai,so as to guide the rational use of antibiotics,reduce bacterial resistance and control nosocomial infections.Methods A total of 94 consecutive and non-redundant CRPA strains isolated from clinical specimens were collected in The First Affiliated Hospital of Naval Medical University between Jan.1,and Dec.31,2019.The distribution of CRPA across departments and sample sources were analyzed.Antimicrobial susceptibility testing against 13 antibiotics was determined using the VITEK 2 Compact automated microbiology analyzer and the Kirby-Bauer disk diffusion method.Polymerase chain reaction(PCR)was employed to detect genes encoding extended-spectrum β-lactamase resistance gene,carbapenemase resistance gene,and porin resistance gene.Homology analysis of selected isolates was performed using kSNP3,a k-mer-based software,for single nucleotide polymorphism(SNP)analysis.An evolutionary tree was constructed to assess genetic relationships.Additionally,multilocus sequence typing(MLST)was performed using the Pseudomonas aeruginosa typing scheme from the PubMLST database.Results Among the 94 CRPA isolates,high resistance rates were observed for carbapenems,including imipenem(92.6%,87 strains)and meropenem(87.2%,82 strains).In contrast,low resistance rates were detected for aminoglycosides,such as amikacin(10.6%,10 strains),gentamicin(20.2%,19 strains),and tobramycin(20.2%,19 strains).The top 3 departments in terms of isolate distribution were the Emergency Intensive Care Unit(9.6%,9 strains),Department of Cerebrovascular Surgery(8.5%,8 strains),and Department of Respiratory Medicine(8.5%,8 strains).PCR analysis of 94 CRPA strains detected outer membrane protein D2(OprD2)gene deletion in 47(50.0%)strains,13(13.8%)strains were positive for blaKPC,4(4.3%)strains for blaVIM,2(2.1%)strains for blaIMP,1(1.1%)strain for blaNDM,12(12.8%)strains for blaTEM,4(4.3%)strains for blaPER,and 2(2.1%)strains for blaGES,while blaOXA-48,blaBIC,blaSIM,blaVEB,and blaSHV were not detected.MLST identified 36 different sequence types(STs),with ST463 and ST274 being the most common,and 2 new ST(ST4023 and ST4024)were identified for the first time.Conclusion CRPA strains carry multiple resistance genes and exhibit concurrent resistance to several commonly used clinical antibiotics.The resistance is primarily associated with the presence of blaKPC,blaVIM and blaTEM genes and the deletion of OprD2 gene.Clinical monitoring of CRPA should be strengthened,and rational use of antimicrobial agents is essential to control its spread within the hospital.

Objective:To investigate the different expression levels of programmed cell death 1 ligand 1 (PD-L1) in non-small cell carcinoma (NSCLC) of distribution characteristics of TCM constitutions and prognosis.Methods:The clinical data of 355 NSCLC patients who had been treated with immune checkpoint inhibitors (ICIs) from January 2019 to June 2023 in the Cancer Medical Center of the First Affiliated Hospital of Hunan University of Chinese Medicine were retrospectively analyzed, and their TCM constitutions were determined. According to the expression level of PD-L1, they were divided into three groups: low expression group (TPS≤1%), medium expression group (1% < TPS < 49%) and high expression group (TPS≥50%). Overall survival (OS) of patients was followed up, and the median OS were compared. Kaplan-Meier method was used to draw survival curves, and Log-rank test was used to compare the difference of survival curves. The independent risk factors of OS were analyzed by COX regression.Results:The distribution of different TCM constitutions showed statistical significance across the three groups ( P<0.05). The median OS for the medium and high expression groups were 21.082 months and 25.714 months, respectively, both significantly higher than the 14.437 months for the low expression group ( P<0.05). The survival curve of TCM constitutions showed that the constitutions significantly correlated with the prognosis of ICIs treatment were qi deficiency, phlegm dampness, and blood stasis ( P<0.05 or P<0.01). The median OS from high to low was 44.971 months for phlegm-dampness constitution, 23.297 months for qi-deficiency constitution, and 11.763 months for blood-stasis constitution. COX regression analysis indicated that medium PD-L1 expression ( HR=0.622, 95% CI=0.459,0.844, P=0.002), high PD-L1 expression ( HR=0.509, 95% CI=0.361,0.718, P<0.001), phlegm-dampness constitution ( HR=0.556, 95% CI=0.335,0.924, P=0.024), and blood-stasis constitution ( HR=2.952, 95% CI=1.929,4.518, P<0.001) were independent prognostic factors. Conclusions:The higher the expression level of PD-L1 in NSCLC patients, the better the prognosis of ICIs treatment. The prognosis of ICIs treatment is better for people with phlegm-dampness constitution and poor for those with blood stasis constitution.

BACKGROUND:Careful regulation of bone immune response during repair of bone scaffold is important for bone regeneration. OBJECTIVE:To review the influence of bone immune response on bone repair and the design of bone tissue engineering scaffold with regulating bone immune function and its application in bone repair. METHODS:Relevant articles published from 1973 to 2023 were retrieved from Science Direct,PubMed,Web of Science,and CNKI databases.English search terms were"osteoimmunology,macrophages,bone repair materials,bone scaffold,bone defects,bone regeneration".Chinese search terms were"bone immunity,macrophages,bone repair material,bone stent,bone defect,bone regeneration".Totally 80 articles of the latest research progress in this field were summarized and analyzed. RESULTS AND CONCLUSION:(1)A detailed review was conducted on the important time points in the origin and development process of bone immunity,and it was explained that macrophages,as important members of the bone immune regulatory system,can be divided into two phenotypes:M1(pro-inflammatory)and M2(anti-inflammatory),and play a key role in different stages of bone regeneration.During the inflammatory phase,M1 type macrophages can activate osteoclasts,initiate tissue repair processes,and participate in the reconstruction of bone microvascular networks.On the other hand,during the bone tissue regeneration process in the later stages of inflammation,sustained high expression of M1 type macrophages can hinder the formation of new bones.During the repair phase,M2 macrophages can secrete osteogenic cytokines,stimulate osteogenic differentiation and mineralization of bone marrow mesenchymal stem cells,and promote bone formation.On the other hand,long-term activation of M2 macrophages can increase the secretion of fibrogenic molecules,leading to excessive formation of scar tissue and delaying the healing process.Therefore,regulating macrophages to undergo phenotype transformation at appropriate stages and constructing an immune microenvironment beneficial for osteogenesis has great significance for bone regeneration.(2)In the process of designing bone scaffolds with bone immune regulation characteristics,the physical and chemical properties such as scaffold roughness,pore structure,stiffness,hydrophilicity,surface charge,and surface functional groups can be changed to affect non-specific protein and cell adhesion,thereby affecting the interaction between bone scaffolds and the immune system.By designing surface functional coatings of bioactive substances such as hydroxyapatite,bioactive glass,metal ions,extracellular matrix,drugs,cytokines,and exosomes,the immune microenvironment can be actively regulated by releasing bioactive substances after implantation into the body,affecting macrophage polarization and crosstalk between macrophages and bone cells,and promoting more M2 polarization of macrophages,so as to build a bone immune microenvironment that is conducive to bone regeneration.(3)Based on the research and development of bone tissue engineering scaffolds,in addition to focusing on the direct regulatory factors of stem cell osteogenic differentiation,this article also proposes that attention should be paid to the management of the immune microenvironment of stem cell differentiation.By regulating the appropriate bone immune microenvironment,more stem cell osteogenic differentiation can be induced;the osteogenic efficiency of the scaffold can be enhanced,and the concept of"bone immune regulatory characteristics"can be condensed;deeply elucidated the multi-directional regulatory role of the bone immune microenvironment and introduced the existing strategies for changing the physicochemical properties and surface functional coating of scaffolds to endow them with bone immune regulatory potential,providing new ideas for guiding the development of a new generation of bone tissue engineering scaffolds with bone immune regulatory characteristics.However,the bone immune microenvironment is a dynamic equilibrium state,and most of the existing regulatory strategies do not consider the dynamic matching of regulation.Therefore,the research and development of intelligent bone immune regulatory scaffolds with efficient and targeted regulation of the immune microenvironment will be a key focus of attention for scholars in future.

Objective: To uncover the underlying mechanisms of action of the Yinlai decoction on high-calorie diet-induced pneumonia through proteomics analysis. Methods: Based on the Gene Expression Omnibus (GEO) database, lung tissue samples from normal and high-fat diet (HFD) fed mice in the GSE16377 dataset were selected as test cohorts to identify differentially expressed genes and conduct bioinformatics analyses. In the animal experiments, mice were randomly divided into the control (N), high-calorie diet pneumonia (M), and Yinlai decoction treatment (Y) groups. Mice in the M group received high-calorie feed and a 0.5 mg/mL lipopolysaccharide solution spray for 30 min for 3 d. The mice in the Y group were intragastrically administered 2 mL/10 g Yinlai decoction twice daily for 3 d. Pathological evaluation of the lung tissue was performed. Differentially expressed proteins (DEPs) in the lung tissue were identified using quantitative proteomics and bioinformatics analyses. The drug-target relationships between Yinlai decoction and core DEPs in the lung tissue were verified using AutoDock Vina and Molecular Graphics Laboratory (MGL) Tools. DEPs were verified by western blot. Results: GEO data mining showed that an HFD altered oxidative phosphorylation in mouse lung tissue. The Yinlai decoction alleviated pathological damage to lung tissue and pneumonia in mice that were fed a high-calorie diet. A total of 47 DEPs were identified between the Y and M groups. Enrichment analysis revealed their association with energy metabolism pathways such as the tricarboxylic acid cycle (TCA) and oxidative phosphorylation. The protein-protein interaction network revealed that Atp5a1, Pdha1, and Sdha were the target proteins mediating the therapeutic effects of Yinlai decoction. Molecular docking results suggested that the mechanism of the therapeutic effect of Yinlai decoction involves the binding of brassinolide, praeruptorin B, chrysoeriol, and other components in Yinlai decoction to Atp5a1. Conclusion The Yinlai decoction alleviated lung tissue damage and pneumonia in mice that were fed a high-calorie diet by regulating the TCA and oxidative phosphorylation. Our study highlights the importance of a healthy diet for patients with pneumonia and provides a scientific basis for the prevention and treatment of pneumonia through dietary adjustments.

Objective:To evaluate the practical value of ultrasound, ultrasound new technologies (ultrasound elastography, contrast enhanced ultrasound) and computed tomography (CT) examination alone or the combination of both of the four in the clinical diagnosis of lymph node metastasis of thyroid cancer by meta-analysis system.Methods:This study screened relevant literature on ultrasound, new ultrasound technologies, and CT in the diagnosis of lymph node metastasis of thyroid cancer by searching Chinese and English databases from January 2006 to August 2023. Two scholars independently assessed the quality of the literatures and scored them using the QUADAS scale. Then, the diagnostic ratio of single and combined examinations was analyzed by Meta-Disc software, and the heterogeneity test and meta-analysis were performed to calculate the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic ratio, accuracy, and area under curve (AUC). Finally, the diagnostic efficacies of different diagnostic techniques and their combination in identifying lymph node metastasis of thyroid cancer were assessed by calculating OR and P values by two-by-two comparisons. Results:Sixty-nine diagnostic studies totaling 30, 666 lesions were finally included. The meta-analysis study showed that contrast enhanced ultrasound had the highest sensitivity[0.83(0.77-0.87)], ultrasound specificity was the highest [0.84(0.79-0.88)], the highest AUC was for contrast enhanced ultrasound (0.90), and contrast enhanced ultrasound and ultrasound elastography had high accuracies (0.81, 0.80, respectively) both of them were higher than those of ultrasound (0.77) and CT (0.69). Contrast enhanced ultrasound and ultrasound elastography were both more sensitive than CT, with statistically significant differences between them ( P<0.01); contrast enhanced ultrasound + ultrasound elastography had the highest accuracy, while ultrasound + contrast enhanced ultrasound and contrast enhanced ultrasound + ultrasound elastography were both more sensitive, with no statistically significant differences between them ( P>0.05), but the latter had the highest specificity [0.90(0.88-0.92)], which were statistically significantly different from each other ( P<0.05), ultrasound+ contrast enhanced ultrasound and contrast enhanced ultrasound+ ultrasound elastography had higher sensitivities than ultrasound+ CT, which were statistically different from each other ( P<0.05), and ultrasound+ CT had the lowest specificity [0.76(0.70-0.81)]. Conclusions:The diagnostic efficacy of thyroid cancer lymph node metastasis is highest with contrast enhanced ultrasound. The new ultrasound technique for diagnosing thyroid cancer lymph node metastasis has a higher diagnostic value than CT, and it can be used as a complementary examination to conventional ultrasound.When the two techniques are used in combination, contrast enhanced ultrasound + ultrasound elastography has the highest accuracy, contrast enhanced ultrasound + ultrasound elastography and ultrasound + contrast enhanced ultrasound both have high sensitivity and specificity, and the diagnostic performance of both is higher than that of ultrasound + ultrasound elastography and ultrasound + CT, and in actual clinical practice when ultrasound elastography combined with contrast enhanced ultrasound is limited in the examination, ultrasound combined with contrast enhanced ultrasound can effectively serve as an alternative means to provide a good diagnostic support.

This paper introduces Professor HUANG Jinchang's experience in treating low anterior resection syndrome (LARS) of rectal cancer. Based on the clinical experience in treating fecal incontinence after rectal cancer surgery, Professor HUANG Jinchang proposes that the primary pathogenesis of LARS is spleen-kidney yang deficiency with internal obstruction of damp turbidity. The treatment approach should focus on strengthening the spleen, warming the kidney, and eliminating turbidity. The Baliao acupoints are specifically selected to eliminate turbidity, promote yang , facilitate the qi flow of the viscera, and regulate the opening and closing of the anus. Emphasis is placed on deep needling at the Baliao acupoints, with flexible acupoint selection based on accompanying symptoms. Additionally, moxibustion and bloodletting cupping are used to restore regular bowel movements and improve the quality of life for patients who have undergone anus-preserving surgery for rectal cancer.
Humans ; Rectal Neoplasms/therapy* ; Acupuncture Points ; Electroacupuncture ; Male ; Female ; Fecal Incontinence/etiology* ; Postoperative Complications/etiology* ; Middle Aged ; Yang Deficiency/therapy* ; Low Anterior Resection Syndrome

Objective:To analyze the expression and clinical significance of SHC SH2-binding protein 1(SHCBP1)in lung adenocarcinoma(LUAD).Methods:Oncomine,TIMER,UALCAN,GEPIA,Kaplan-Meier plotter and STRING databases were used to explore the effect of SHCBP1 on progression and immune infiltration of LUAD.Results:Expression of SHCBP1 mRNA in LUAD tissue was significantly higher than that in normal lung tissue(P<0.05).Expression of SHCBP1 mRNA was significantly increased in LUAD patients with smoking history,nodal metastasis,late clinical stage and TP53 mutation(P<0.05).Survival analysis by GEPIA and Kaplan-Meier plotter databases showed that LUAD patients with high SHCBP1 mRNA expression had a lower overall survival rate(P<0.05).SHCBP1 mRNA was correlated with immune cell infiltration,immune cell markers and immune checkpoint expression in LUAD.Conclusion:High expression of SHCBP1 is related to poor prognosis and tumor immune infiltration of LUAD patients.

Objective: To evaluate the development trajectory of sugar-sweetened beverage (SSB) intake in childhood, and to explore the influence of different SSB intake patterns on childhood obesity. Methods: In 2016, a follow-up cohort study was carried out in two primary schools in Bengbu, Anhui Province. Three annual follow-ups were conducted in 1 263 children at baseline, and 997 children were included in the final analysis. Parental and student questionnaires were used to obtain basic information related to the children s consumption of SSBs. A group-based trajectory model (GBTM) was applied to classify the development trajectory of SSB intake patterns in childhood. Multiple linear regression analyses were performed to assess the correlation between different SSB intake patterns and childhood obesity. Results: GBTM identified four childhood SSB intake patterns, namely, the "persistently-low group (n=822), “decreasing-after-increasing” group (n=20), “gradually-decreasing” group (n=106), and “increasing” group (n=49). In the decreasing-after-increasing group and the gradually-decreasing group, baseline BMI levels and BMI levels obtained at the three follow-ups were significantly higher than those observed in the persistently-low group (F=6.26, 5.90, 5.99, 5.87, P<0.01). There were sex differences in the association between SSB intake patterns and the children s BMI levels. Among girls, after adjusting for confounding factors, the gradually decreasing group increased by 1.20 kg/m 2(B=1.20，95%CI=0.25-2.15, P=0.01) when compared with the persistently low group at the third follow-up. Among boys, no statistically significant association was found between SSB intake patterns and BMI levels (P>0.05). Conclusion Sex differences were observed with respect to the association between SSB intake patterns and obesity in children. Girls with a higher SSB intake had a significantly increased risk of obesity. Further studies are needed to explore the physiological mechanisms underlying sex differences, to provide the theoretical basis for developing intervention programs to prevent childhood obesity.

Objective:To investigate the distribution and drug resistance of pathogens causing blood stream infection in patients with pancreatic neoplasms.Methods:Clinical data of patients with pancreatic neoplasms complicated with bloodstream infection with confirmed pathological evidence admitted in the First Affiliated Hospital of Naval Medical University from January 2016 to June 2019 were collected. Bacteria were isolated from blood culture, and microbial sensitivity tests were analyzed by minimum inhibitory concentration and Kirby-Bauer methods. The distribution and drug resistance of pathogens causing blood stream infection in patients with pancreatic neoplasms were analyzed.Results:There were 116 cases (8.5%) with bloodstream infection in 1 372 patients with pancreatic neoplasms. A total of 156 bacterial strains were isolated from blood culture, of which 127 strains (81.4%) were gram negative aerobic bacteria, mainly including Escherichia coli (42 strains), Klebsiella pneumoniae (34 strains), Pseudomonas aeruginosa (12 strains), and 25 strains (16.0%) were gram positive aerobic bacteria, mainly including Enterococcus faecium (11 strains), Enterococcus faecalis (3 strains), Streptococcus angina (3 strains). 4 strains (2.6%) were anaerobic bacteria. The results of antibiotic susceptibility showed that the resistance rate of Escherichia coli to ampicillin was 90.5%, and to cefoperazone-sulbactam was 2.4%. The resistance rate of Klebsiella pneumoniae to piperacillin was 20.6%, and to cefoperazone-sulbactam was 5.9%. The resistance rate of Pseudomonas aeruginosa to imipenem was 41.7%, and no resistant strain was found to cefoperazone-sulbactam. The resistance rate of Enterococcus and Streptococcus pharyngitis to erythromycin were 85.7% and 33.3%, and no strains were resistant to vancomycin.Conclusions:The rate of blood stream infection in patients with pancreatic neoplasms was relatively high. In clinical practice, the distribution of pathogenic bacteria should be understood, the drug resistance should be monitored and antibiotics should be reasonably used, in order to maximally prevent and interfere with the occurrence of blood stream infection.

OBJECTIVE:To prepare Dexzopiclone orally disintegrating tablets (DODT),and to optimize its formulation.METHODS:Direct powder compression method was used to prepare DODT.Using repose angle of material,disintegration time and taste evaluation as indexes,single factor test was used to screen the types or amount of bulking agent,disintegrating agent,glidant and flavoring agent;using disintegration time as index,orthogonal experiment was applied to optimize the proportion of bulking agent,the amount of disintegrating agent,glidant and flavoring agent.Then the hardness and main component contents of DODT prepared by optimal formulation were determined.RESULTS:The optimal formulation was as follows as the ratio of mannitol-MCC 1 ∶ 4,the amount of disintegrating agent PVPP was 15％,the amount of glidant magnesium stearate was 1.0％,the amount of flavoring agent stevia was 3.0％.Three batches of prepared DODT were smooth in surface and good in taste;their disintegration time were(26.7 ± 1.2),(26.7 ± 0.6),(27.6 ± 0.9)s,hardness were (3.59 ± 0.19),(3.49 ± 0.18),(3.27 ± 0.16) kg,and contents were (99.47 ± 0.15) ％,(99.53 ± 0.05)％,(99.46 ± 0.20) ％,respectively (all RSDs≤0.87％,n=3).CONCLUSIONS:Prepared DODT are all in line with the quality requirements of orally disintegrating tablets.