ObjectiveTo explore the mechanism of Huanglian Wendantang on damp-heat type diabetes enteropathy rats based on the G protein coupled bile acid receptor 5/glucagon like peptide-1 （TGR5/GLP-1） signaling pathway and intestinal flora. MethodsA total of 72 male Sprague Dawley （SD） rats were adaptively fed for one week. Twelve SD rats were randomly selected as a blank group and fed with an ordinary diet. The rest of the SD rats were fasted for 12 hours without water. A rat model with damp-heat type diabetes enteropathy was made by left intraperitoneal injection of streptozotocin （55 mg·kg^-1） and high sugar and high fat diet （20% sucrose solution + high fat diet） in a humid and hot environment （artificial climate box： temperature 30-34 ℃， relative humidity： 85%-95%）. After successful modeling， the rats were randomly divided into a model group， a metformin group （200 mg·kg^-1）， low-dose， medium-dose， and high-dose Huanglian Wendantang groups （7.10， 14.20， 28.39 g·kg^-1）， with 12 rats in each group. The normal group and the model group were orally administered with physiological saline once a day for 6 consecutive weeks. During the observation period， the weight and blood glucose levels of rats were measured and recorded weekly. After the administration， fresh feces were collected from rats， and 16S rRNA sequencing technology was used to study the differences and changes in intestinal flora among different groups. The levels of tumor necrosis factor-α （TNF-α） and interleukin-6 （IL-6） in the serum of rats were detected by enzyme-linked immunosorbent assay （ELISA）， and the pathological morphological changes of colon tissue were examined. The expression of TGR5 and GLP-1 in colon tissue was detected by immunohistochemistry， and the expression of TGR5 and GLP-1 proteins in colon tissue was measured by Western blot. ResultsCompared with the blank group， the model group showed a decrease in body weight， an increase in blood glucose， and significant damp-heat symptoms. The levels of IL-6 and TNF-α in serum were significantly increased （P<0.01）. The expression of TGR5 and GLP-1 was decreased （P<0.01）， and the pathogenic bacteria were increased. Compared with the model group， the treatment groups exhibited improvements in body weight， blood glucose levels， and damp-heat syndrome in rats. Among them， the high-dose group of Huanglian Wendantang displayed the most significant improvement effect， with significantly reduced inflammation levels （P<0.01） and elevated expression of TGR5 and GLP-1 （P<0.01）. Colonic pathological sections showed that Huanglian Wendantang could effectively ameliorate colonic pathological changes. The 16S rRNA sequencing result indicated a significant increase in beneficial bacteria in the treatment groups. ConclusionHuanglian Wendantang can effectively ameliorate the damp-heat symptoms and blood glucose levels in rats with damp-heat type diabetes enteropathy， and it may exert an effect by regulating the TGR5/GLP-1 signaling pathway and intestinal flora disorder.

Metformin has been demonstrated to attenuate hyperglycaemia by modulating the gut microbiota. However, the mechanisms through which the microbiome mediates metformin monotherapy failure (MMF) are unclear. Herein, in a prospective clinical cohort study of newly diagnosed type 2 diabetes mellitus (T2DM) patients treated with metformin monotherapy, metagenomic sequencing of faecal samples revealed that Phocaeicola vulgatus abundance was approximately 12 times higher in nonresponders than in responders. P. vulgatus rapidly hydrolysed taurine-conjugated bile acids, leading to ceramide accumulation and reversing the improvements in glucose intolerance conferred by metformin in high-fat diet-fed mice. Interestingly, C22:0 ceramide bound to mitochondrial fission factor to induce mitochondrial fragmentation and impair hepatic oxidative phosphorylation in P. vulgatus-colonized hyperglycaemic mice, which could be exacerbated by metformin. This work suggests that metformin may be unsuitable for P. vulgatus-rich T2DM patients and that clinicians should be aware of metformin toxicity to mitochondria. Suppressing P. vulgatus growth with cefaclor or improving mitochondrial function using adenosylcobalamin may represent simple, safe, effective therapeutic strategies for addressing MMF.

ObjectiveTo understand the current drug resistance status and bacterial multilocus sequence typing （MLST） of human and avian Campylobacter jejuni in Jinshan District， Shanghai. MethodsFecal samples were collected from diarrhea patients in the annuity mountainous area from 2021 to 2022， and poultry and related samples were collected from 2 poultry farms in the Jinshan area for detection of C. jejuni. Minimal inhibitory concentration （MIC） drug sensitivity test was performed on the detected C. jejuni， and some strains were selected for whole genome sequencing and MLST analysis. ResultsA total of 823 samples of diarrhea disease were collected， and 32 strains of C. jejuni were detected， with a detection rate of 3.89%. Out of 600 poultry related samples， 62 strains of C. jejuni were detected， with a detection rate of 10.33%. Human multidrug resistance reached 93.75% （30/32）， while avian multidrug resistance reached 100.00%（62/62）. The top four drug resistance rates of human and avian C. jejuni were azithromycin （100.00% from humans and 100.00% from birds）， naphthoic acid （93.75% from humans and 87.10% from birds）， ciprofloxacin （90.63% from humans and 98.39% from birds）， and tetracycline （84.38% from humans and 98.39% from birds）. The relatively low resistance strains of human derived C. were erythromycin， chloramphenicol， and thalithromycin. The relatively low resistance strains of avian C. jejuni were erythromycin， clindamycin， and flufenicol. MLST analysis showed that the selected 16 strains of bacteria were divided into 9 ST types， among which the evolutionary relationship of avian C. jejuni was relatively concentrated， while human C. jejuni was relatively dispersed. It was found that one strain of avian C. jejuni was closely related to two strains of human C. jejuni. ConclusionsC. jejuni infection is severe in patients with diarrhea in this region， with a detection rate second only to salmonella and Vibrio parahaemolyticus. C. jejuni infection in poultry is relatively common， and both are highly resistant. Therefore， monitoring and control should be strengthened. MLST analysis shows new ST types in both avian and human sources of C. jejuni， indicating the emergence of new mutations that require continuous monitoring to avoid the epidemics caused by new strains. The isolated strains with close genetic relationships between avian and human sources reveal the evidence of the spread of C. jejuni from poultry to humans. Therefore it is necessary to strengthen the monitoring of C. jejuni in relevant samples from breeding farms.

ObjectiveTo determine the drug sensitivity and molecular typing characteristics of Klebsiella pneumoniae isolated from meat and diarrhea samples in a local area. MethodsSeventy-one strains of K.pneumoniae were isolated from 118 meat food （chicken and pork） randomly sampled in the markets in Jinshan District， Shanghai， 2020‒2021， and 1 499 diarrhea samples from outpatient diarrhoea patients in hospitals in the same district. Then drug susceptibility testing was conducted by micro-broth dilution method， and sequence identity was determined by pulsed field gel electrophoresis（PFGE）. ResultsThe overall detection rate of K.pneumoniae in meat was 11.86% （14/118）， with detection rate 20.93% （9/43） in chicken and 6.67% （5/75） in pork. The difference in detection between meats was statistically significant （χ²=5.317，P<0.05）. The detection rate of K.pneumoniae in diarrhea samples was 3.80% （57/1 499）. Furthermore， the isolated strains showed the highest resistance to ampicillin at 76.06%. The multi-drug resistant strains included 5 of human origin （8.77%） and 2 of foodborne origin （14.28%）. Additionally， 1 foodborne imipenem-resistant strain was detected. A total of 71 strains of K.pneumoniae were found to have 70 banding types， with similarity ranging from 39.4% to 100%， suggesting genetic diversity. ConclusionK.pneumoniae isolated from foodborne and diarrhea samples showed multi-drug resistance in Jinshan District， . with scattered PFGE banding patterns. It is recommended to strengthen the monitoring of this pathogen in the population and animal food， and be alert to the emerging multi-drug resistant strains and risk of food chain transmission.

Objective:To conduct the clinical effect achieved by the combination of axillary flap trimming and scraping through small axillary incisions in treating bromhidrosis.Methods:From June 2021 to December 2022, a study was conducted on patients with bilateral bromhidrosis in the Department of Plastic Surgery, Jining First People’s Hospital. The study used a self-control method, with one side undergoing axillary flap trimming combined with scraping through small axillary incisions (designated as Group A), while the other side underwent direct axillary flap trimming through central axillary incisions (designated as Group B). Randomization was achieved using a number table method for both sides. In Group A, two short incision lines of 0.5-1.0 cm were designed on both sides of the armpit. These incisions separated all layers of the skin, and excised the sweat glands and fat tissue. Additionally, two drainage openings were left in the surgical area to maintain two drainage tubes through the surgical incision. In Group B, the incision lines of 2-3 cm were designed in the central axillary area. After incision and dissection, four drainage tubes were retained in the operation area. The efficacy evaluation consisted of three aspects: the surgical outcome one month post-operation, categorized as cure, effective, or ineffective; the recurrence of bromhidrosis six months post-operation; and the occurrence of surgical complications. SPSS 25.0 software was used for data analysis, and chi-square test was applied for the comparisons between the two groups in terms of response rate, recurrence rate, and complication rate. A statistically significant difference was determined at the P<0.05 level. Results:A study was conducted on 62 patients, aged between 16 and 35 years, with bilateral bromhidrosis, including 38 males and 24 females. In Group A, 55 patients achieved complete cure, while 7 patients experienced significant improvement, resulting in an overall effectiveness rate of 100%. However, 5 cases of recurrence were observed, with a recurrence rate of 8.1%. Additionally, there were 1 case of subflap hematoma, 2 cases of flap erosion, and 1 case of scar hypertrophy, resulting in a complication rate of 6.5%. In Group B, 58 patients achieved complete cure, while 4 patients experienced improvement, resulting in an overall effectiveness rate of 100%. Three cases of recurrence were reported within 6 months, with a recurrence rate of 4.8%. Furthermore, there were 4 cases of subflap hematoma, 4 cases of flap erosion, 2 cases of flap necrosis, and 4 cases of scar hypertrophy, resulting in a complication rate of 22.6%. Statistical analysis showed no significant difference in treatment response rate ( χ2=0.34, P=0.559) or postoperative recurrence rate ( χ2=0.53, P=1.000) between the two groups. However, the complication rate in Group A was significantly lower than that in Group B ( χ2=6.50, P=0.011). Conclusion:The clinical outcome is satisfactory, achieving a high rate of effectiveness by the combination of axillary flap trimming and scraping through small axillary incisions in treating bromhidrosis. And the complications are fewer compared to the direct axillary flap trimming through central axillary incisions.

Background::Thoracic aortic aneurysm (TAA) is a fatal cardiovascular disease, the pathogenesis of which has not yet been clarified. This study aimed to identify and validate the diagnostic markers of TAA to provide a strong theoretical basis for developing new methods to prevent and treat this disease.Methods::Gene expression profiles of the GSE9106, GSE26155, and GSE155468 datasets were acquired from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified using the "limma" package in R. Least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), random forest, and binary logistic regression analyses were used to screen the diagnostic marker genes. Single-sample gene set enrichment analysis (ssGSEA) was used to estimate immune cell infiltration in TAA.Results::A total of 16 DEGs were identified. The enrichment and functional correlation analyses showed that DEGs were mainly associated with inflammatory response pathways and collagen-related diseases. Collagen type I alpha 1 chain ( COL1A1) and synaptotagmin like 2 ( SYTL2) were identified as diagnostic marker genes with a high diagnostic value for TAA. The expression of COL1A1 and SYTL2 was considerably higher in TAA vascular wall tissues than in the corresponding normal tissues, and there were significant differences in the infiltration of immune cells between TAA and normal vascular wall tissues. Additionally, COL1A1 and SYTL2 expression were associated with the infiltration of immune cells in the vascular wall tissue. Single-cell analysis showed that COL1A1 in TAA was mainly derived from fibroblasts and SYTL2 mainly from cluster of differentiation (CD)8 + T cells. In addition, single-cell analysis indicated that fibroblasts and CD8 + T cells in TAA were significantly higher than those in normal arterial wall tissue. Conclusions::COL1A1 and SYTL2 may serve as diagnostic marker genes for TAA. The upregulation of SYTL2 and COL1A1 may be involved in the inflammatory infiltration of the vessel wall and poor extracellular matrix remodeling, promoting the progression of TAA.

Objective:To conduct the clinical effect achieved by the combination of axillary flap trimming and scraping through small axillary incisions in treating bromhidrosis.Methods:From June 2021 to December 2022, a study was conducted on patients with bilateral bromhidrosis in the Department of Plastic Surgery, Jining First People’s Hospital. The study used a self-control method, with one side undergoing axillary flap trimming combined with scraping through small axillary incisions (designated as Group A), while the other side underwent direct axillary flap trimming through central axillary incisions (designated as Group B). Randomization was achieved using a number table method for both sides. In Group A, two short incision lines of 0.5-1.0 cm were designed on both sides of the armpit. These incisions separated all layers of the skin, and excised the sweat glands and fat tissue. Additionally, two drainage openings were left in the surgical area to maintain two drainage tubes through the surgical incision. In Group B, the incision lines of 2-3 cm were designed in the central axillary area. After incision and dissection, four drainage tubes were retained in the operation area. The efficacy evaluation consisted of three aspects: the surgical outcome one month post-operation, categorized as cure, effective, or ineffective; the recurrence of bromhidrosis six months post-operation; and the occurrence of surgical complications. SPSS 25.0 software was used for data analysis, and chi-square test was applied for the comparisons between the two groups in terms of response rate, recurrence rate, and complication rate. A statistically significant difference was determined at the P<0.05 level. Results:A study was conducted on 62 patients, aged between 16 and 35 years, with bilateral bromhidrosis, including 38 males and 24 females. In Group A, 55 patients achieved complete cure, while 7 patients experienced significant improvement, resulting in an overall effectiveness rate of 100%. However, 5 cases of recurrence were observed, with a recurrence rate of 8.1%. Additionally, there were 1 case of subflap hematoma, 2 cases of flap erosion, and 1 case of scar hypertrophy, resulting in a complication rate of 6.5%. In Group B, 58 patients achieved complete cure, while 4 patients experienced improvement, resulting in an overall effectiveness rate of 100%. Three cases of recurrence were reported within 6 months, with a recurrence rate of 4.8%. Furthermore, there were 4 cases of subflap hematoma, 4 cases of flap erosion, 2 cases of flap necrosis, and 4 cases of scar hypertrophy, resulting in a complication rate of 22.6%. Statistical analysis showed no significant difference in treatment response rate ( χ2=0.34, P=0.559) or postoperative recurrence rate ( χ2=0.53, P=1.000) between the two groups. However, the complication rate in Group A was significantly lower than that in Group B ( χ2=6.50, P=0.011). Conclusion:The clinical outcome is satisfactory, achieving a high rate of effectiveness by the combination of axillary flap trimming and scraping through small axillary incisions in treating bromhidrosis. And the complications are fewer compared to the direct axillary flap trimming through central axillary incisions.

The neurovascular unit (NVU) is highly responsible for cerebral homeostasis and its dysfunction emerges as a critical contributor to Alzheimer's disease (AD) pathology. Hence, rescuing NVU dysfunction might be a viable approach to AD treatments. Here, we fabricated a self-regulated muti-functional nano-modulator (siR/PIO@RP) that can intelligently navigate to damaged blood-brain barrier and release therapeutical cargoes for synergetic AD therapy. The resulting siR/PIO@RP enables self-regulation of its distribution in accordance with the physio/pathological state (low/high RAGE expression) of the target site via a feedback loop. siR/PIO@RP is capable of performing intricate tasks and goes beyond the capabilities of single-target therapeutic agents utilized in AD therapy, such as reducing cerebral Aβ load, relieving neuroinflammation, and alleviating the dysfunction of NVU. Overall, the current study provides proof of concept that normalizing NVU holds promise as a means of alleviating AD symptoms.

In carbohydrate chemistry, the stereoselective synthesis of 1,2-cis-glycosides remains a formidable challenge. This complexity is comparable to the synthesis of 1,2-cis-β-D-mannosides, primarily due to the adverse anomeric and Δ-2 effects. Over the past decades, to attain β-stereoselectivity in D-rhamnosylation, researchers have devised numerous direct and indirect methodologies, including the hydrogen-bond-mediated aglycone delivery (HAD) method, the synthesis of β-D-mannoside paired with C6 deoxygenation, and the combined approach of 1,2-trans-glycosylation and C2 epimerization. This review elaborates on the advancements in β-D-rhamnosylation and its implications for the total synthesis of tiacumicin B and other physiologically relevant glycans.
Glycosides ; Mannosides ; Glycosylation ; Stereoisomerism