ObjectiveThis study aimed to elucidate the mechanistic role of Staphylococcus aureus in the pathogenesis of atopic dermatitis (AD), a chronic inflammatory skin disorder characterized by pruritus and barrier dysfunction. A key focus was screening traditional Chinese medicine (TCM) active components with dual antibacterial and antipruritic efficacy, followed by systematic evaluation of their in vitro antibacterial activity. Additionally, a novel drug delivery system was constructed to enable localized efficient drug delivery, inhibiting S. aureus proliferation and alleviating its induced pruritus, thereby providing new strategies for targeted AD therapy. MethodsMale C57BL/6J mice aged 6-8 weeks (body weight 18-22 g) were used to establish an AD model via repeated oxazolone sensitization. On day 14, microbial samples were collected from the lesional area (1 cm²) using sterile cotton swabs, followed by vortex mixing, serial dilution, and plating on 5% sheep blood agar plates (incubated at 37°C for 24 h). Single colonies with complete transparent β-hemolytic zones were isolated and identified as vancomycin-intermediate S. aureus (VISA) via 16S rRNA sequencing. An S. aureus mono-infection animal model was then established by applying gauze saturated with bacterial suspension (McFarland turbidity 0.1) to the nape and back skin of mice. The pruritic phenotype and inflammatory cell infiltration induced by S. aureus were evaluated using comprehensive approaches including behavioral assays (e.g., scratching frequency recording), hematoxylin-eosin (HE) staining, and toluidine blue staining. The in vitro antibacterial efficacy of the TCM monomer pseudolaric acid B (PAB) and double network hydrogel (DN) was separately assessed by disk diffusion assay, while the minimum inhibitory concentration (MIC) of PAB was determined via broth dilution method. Further validation of the pharmacodynamic characteristics of the composite system (PAB@DN, composed of PAB and DN) was conducted through behavioral assays, HE staining, and dermatitis scoring, with its drug release profile evaluated by mass spectrometry analysis. Based on scratching behavioral analysis and dermatitis scoring, the optimal ratio and concentration of PAB@DN were optimized. ResultsThe S. aureus load in AD lesional tissues was significantly higher than in normal skin ((5.3±0.33)×10⁶ CFU vs. (3.6±0.26)×10⁷ CFU, P<0.001). In the S. aureus mono-infection group, mice exhibited a 6.7-fold increase in scratching frequency compared to the control group. HE staining revealed marked epidermal thickening ((10.4±2.39) μm vs. (85.6±1.95) μm, P<0.000 1), and toluidine blue staining showed a 23-fold increase in mast cell degranulation. Pseudolaric acid B exhibited a significant concentration-dependent inhibitory effect onS. aureus growth, with its in vitro antibacterial effect being 57% that of the antibiotic cefepime (inhibition zone diameter: PAB (1.885±0.036) cm vs. cefepime (3.636±0.005) cm, P<0.000 1) and a minimum inhibitory concentration (MIC) of 1 g/L. The carrier double network hydrogel (DN) itself lacked direct antibacterial activity (no significant difference in inhibition zone diameter compared to the control) but effectively ameliorated the dry symptoms of AD-like lesions. The PAB@DN composite system demonstrated a synergistic effect compared to individual components, resulting in a 50% reduction in scratching behavior, an 86% decrease in dermatitis score, and a 60% reduction in epidermal thickening. It also reduced the S. aureus load in mouse skin by approximately 34%, with the optimal effective formulation being PAB at 1 g/L loaded onto DN. ConclusionS. aureus colonization plays a critical driving role in the onset and progression of AD. Using an S. aureus infection model, this study confirmed that the pseudolaric acidB-hydrogel composite delivery system (PAB@DN) can effectively alleviate S. aureus-induced pruritus and skin damage, providing experimental evidence for microbiota-targeted therapy of AD.

Glucagon-like peptide-1 （GLP-1） receptor agonists are a novel class of antidiabetic drugs that also possess lipid- lowering and cardiovascular protective effects， with liraglutide and semaglutide being their representative medications. Based on a systematic literature search， this review summarizes the lipid-lowering mechanisms by which liraglutide and semaglutide exert direct effects on the liver and kidney （regulating autophagy， key lipid metabolism pathways， reverse cholesterol transport， etc.）， direct actions on adipose tissue （affecting adipocyte proliferation and differentiation， expression of lipid metabolism proteins， and gene transcription）， activation of sympathetic pathways through the central nervous system， and modulation of the gut microbiota. Additionally， it summarizes the clinical evidence of their lipid-lowering effects in populations with type 2 diabetes mellitus， overweight individuals， and others. These findings indicate that GLP-1 receptor agonists exert lipid-lowering effects by acting on multiple tissues or systems， providing crucial evidence for further elucidating the molecular mechanisms of these drugs in lipid regulation and exploring potential new ideas for their clinical applications.

AIM:To elucidate the intervention and mechanism of 4'-hydroxychalcone(4-HC)in colitis mice through the regulation of Th17/Treg homeostasis.METHODS:Using a dextran sodium sulfate(DSS)-induced colitis model in mice,we meticulously observed the pathological characteristics of colon tissue via HE staining.Additionally,we employed immunohistochemical analysis and Western blot techniques to assess the expression levels of proteins associated with the JAK/STAT signaling pathway,as well as the specific content of tight junction proteins such as ZO-1 and occludin.The differentiation of Th17 and Treg cells was analyzed through flow cytometry.RESULTS:Compared to the normal group,the DSS group exhibited a consistent decline in body weight,coupled with symptoms of diarrhea and hematochezia,an increase in the DAI score,and a notable reduction in colon length.In contrast,the body weight of the 4-HC group dis-played an upward trend following an initial decrease,with improvements in diarrhea and hematochezia symptoms,a reduc-tion in the DAI score,and a restoration of colon length relative to the model group.The integrity of colon tissue in the 4-HC group was significantly better than that in the DSS group,evidenced by a marked increase in the number of goblet cells and an enhancement in crypt integrity,while the average histology score showed a decrease.Western blot analysis re-vealed substantial increase in ZO-1 and occludin expression after 4-HC treatment.Flow cytometry results indicated a dra-matic decrease in the differentiation rate of Th17 cells in spleen lymphocytes and mesenteric lymph nodes,while the dif-ferentiation rate of Treg cells was significantly elevated.Immunohistochemical and Western blot analyses demonstrated that 4-HC markedly reduced the phosphorylation of STAT1 and STAT3,while up-regulating the phosphorylation of STAT6,suggesting that 4-HC modulates CD4+T cell activity through the JAK-STAT pathway.CONCLUSION:The 4-HC may enhance the course of DSS-induced colitis in mice,alleviate colonic tissue damage,and modulate the balance be-tween Th17 and Treg cells,potentially involving the JAK/STAT signaling pathway.

Artificial intelligence （AI） and population pharmacokinetics （PPK） technologies have demonstrated significant potential in the personalized medication of immunosuppressants after organ transplantation, enabling precise prediction of drug dosages. This article provides a comprehensive review of the application status of AI and PPK in the individualized administration of immunosuppressants after organ transplantation， focuses on monitoring blood drug concentration， predicting efficacy/adverse reactions， and establishing individualized dosing models for organ transplant recipients after immunosuppressant administration， and analyzes and compares the application characteristics of different methods in different organ transplant patients as well as the integration and future development of AI and PPK technologies. AI and PPK technologies can not only significantly reduce the dependence on human resources， but also greatly improve the level of individualized treatment of immunosuppressants after organ transplantation， and reduce the discomfort and burden caused by frequent blood concentration monitoring to patients.

Objective To explore the early clinical manifestations,random cortisol levels,and management of late-onset circulatory collapse(LCC)in preterm infants.Methods Preterm infants with LCC from October to December 2023 at the Affiliated Suzhou Hospital of Nanjing Medical University were included.Maternal perinatal factors and infants'early clinical symptoms,signs,random serum cortisol levels,treatment,and outcomes were retrospectively analyzed.Results Seven preterm infants with LCC were included,with gestational ages of 25 weeks+2 days to 29 weeks and birth weights of 800-1 150 g.At 3 weeks of age,abnormal weight gain[gain rate:21-28.5 g/(kg·d)],generalized edema,low serum sodium(129.5-135.2 mmol/L),and decreased random serum cortisol concentrations(13.6-44.6 nmol/L)were observed.After 1-2 weeks of hydrocortisone treatment,edema subsided and serum sodium increased.Conclusions In clinically stable preterm infants,early manifestations of LCC include abnormal weight gain,generalized edema,recurrent hyponatremia,and decreased random serum cortisol concentrations.Hydrocortisone treatment effectively improves symptoms.

Objective To explore the early clinical manifestations,random cortisol levels,and management of late-onset circulatory collapse(LCC)in preterm infants.Methods Preterm infants with LCC from October to December 2023 at the Affiliated Suzhou Hospital of Nanjing Medical University were included.Maternal perinatal factors and infants'early clinical symptoms,signs,random serum cortisol levels,treatment,and outcomes were retrospectively analyzed.Results Seven preterm infants with LCC were included,with gestational ages of 25 weeks+2 days to 29 weeks and birth weights of 800-1 150 g.At 3 weeks of age,abnormal weight gain[gain rate:21-28.5 g/(kg·d)],generalized edema,low serum sodium(129.5-135.2 mmol/L),and decreased random serum cortisol concentrations(13.6-44.6 nmol/L)were observed.After 1-2 weeks of hydrocortisone treatment,edema subsided and serum sodium increased.Conclusions In clinically stable preterm infants,early manifestations of LCC include abnormal weight gain,generalized edema,recurrent hyponatremia,and decreased random serum cortisol concentrations.Hydrocortisone treatment effectively improves symptoms.

AIM:To elucidate the intervention and mechanism of 4'-hydroxychalcone(4-HC)in colitis mice through the regulation of Th17/Treg homeostasis.METHODS:Using a dextran sodium sulfate(DSS)-induced colitis model in mice,we meticulously observed the pathological characteristics of colon tissue via HE staining.Additionally,we employed immunohistochemical analysis and Western blot techniques to assess the expression levels of proteins associated with the JAK/STAT signaling pathway,as well as the specific content of tight junction proteins such as ZO-1 and occludin.The differentiation of Th17 and Treg cells was analyzed through flow cytometry.RESULTS:Compared to the normal group,the DSS group exhibited a consistent decline in body weight,coupled with symptoms of diarrhea and hematochezia,an increase in the DAI score,and a notable reduction in colon length.In contrast,the body weight of the 4-HC group dis-played an upward trend following an initial decrease,with improvements in diarrhea and hematochezia symptoms,a reduc-tion in the DAI score,and a restoration of colon length relative to the model group.The integrity of colon tissue in the 4-HC group was significantly better than that in the DSS group,evidenced by a marked increase in the number of goblet cells and an enhancement in crypt integrity,while the average histology score showed a decrease.Western blot analysis re-vealed substantial increase in ZO-1 and occludin expression after 4-HC treatment.Flow cytometry results indicated a dra-matic decrease in the differentiation rate of Th17 cells in spleen lymphocytes and mesenteric lymph nodes,while the dif-ferentiation rate of Treg cells was significantly elevated.Immunohistochemical and Western blot analyses demonstrated that 4-HC markedly reduced the phosphorylation of STAT1 and STAT3,while up-regulating the phosphorylation of STAT6,suggesting that 4-HC modulates CD4+T cell activity through the JAK-STAT pathway.CONCLUSION:The 4-HC may enhance the course of DSS-induced colitis in mice,alleviate colonic tissue damage,and modulate the balance be-tween Th17 and Treg cells,potentially involving the JAK/STAT signaling pathway.

Objective:To investigate the risk factors affecting the prognosis of penile cancer after surgery.Methods:We retrospectively analyzed the clinical data on 112 cases of penile cancer treated in Weifang People's Hospital from January 2013 to De-cember 2023.Using the Kaplan-Meier survival curve,χ2 test,Fisher's exact test,and univariate and multivariate Cox risk regression analyses,we compared the clinical characteristics among different groups,and determined the independent prognostic risk factors for cancer-specific survival(CSS)of the patients.Results:The 1-,3-and 5-year CSS rates of the penile cancer patients were 78.2%,66.1% and 63.7%,respectively.Kaplan-Meier analysis indicated a significant correlation of a higher neutrophil-to-lymphocyte ratio(NLR)with a lower CSS rate(P<0.001).Multivariate Cox regression analysis showed high NLR(HR=2.6;95% CI:1.031-6.558;P=0.043)to be an independent risk factor for CSS.Conclusion:Preoperative NLR is an independent risk factor for the prognosis of penile cancer.In addition,older age,farmer or worker occupation,lower education,preoperative lymphocyte-to-monocyte ratio(LMR)≤2.81,preoperative fibrinogen(FIB)≥3.41 g/L,advanced tumor stage and tumor differentiation are associated with the poor prognosis the malignancy.

Objective To observe the effects of moxibustion on myocardial pathological morphology,α-smooth muscle actin(α-SMA)and chromosome 10 deletion phosphatase and tensin homologous protein(PTEN)/mammalian target of rapamycin(mTOR)signalling pathway in rats with chronic heart failure(CHF),and to explore the possible mechanism of moxibustion in attenuating myocardial fibrosis in rats with CHF.Methods According to the random number table method,60 male SD rats were divided into the normal group(n=10)and the surgery group(n=50),and the rats in the surgery group were ligated the left coronary artery to replicate the CHF model.According to the random number table method,40 successfully modelled rats were divided into the model group,the moxibustion group,the bpV(phen)group,and the moxibustion+bpV(phen)group,with 10 rats in each group.The normal and model groups were not given any intervention;in the moxibustion group,customized moxa sticks were used to moxibrate the bilateral"Feishu"(BL13)and"Xinshu"(BL15)on the back of the rats for 30 min at each point once a day;the bpV(phen)group was injected intraperitoneally with the bpV(phen)solution(0.15 mg/kg)twice a week;the moxibustion+bpV(phen)group was based on the bpV(phen)group,and moxibustion was applied according to the moxibustion group.The intervention was carried out for 4 weeks.The general conditions of rats,such as feeding and activity were observed;HE staining was used to detect morphological changes of the cardiomyocytes;Masson staining was used to detect myocardial fibrosis;the cardiac echocardiography was used to detect ejection fraction(EF)and fractional shortening(FS);real-time PCR was used to detect the mRNA expressions of PTEN and mTOR in the cardiac muscle tissues;protein expressions of PTEN,mTOR,α-SMA in rat myocardial tissue were detected by Western blotting.Results Compared with the normal group,rats in the model group had altered cardiomyocyte morphology,severe damage to myocardial fiber structure,significantly lower EF,FS,and mTOR mRNA and protein expressions,and significantly higher PTEN,α-SMA protein expressions and PTEN mRNA expression(P<0.05).Compared with the model group,myocardial ultrastructural damage was attenuated in the moxibustion group,bpV(phen)group,and moxibustion+ bpV(phen)group,and EF,FS,and mRNA and protein expressions of mTOR were significantly higher,α-SMA protein expression was significantly lower,and mRNA and protein expressions of PTEN were significantly lower(P<0.05).Compared with the moxibustion+bpV(phen)group,myocardial ultrastructural damage was worsen in the moxibustion and bpV(phen)groups,with significantly lower EF,FS,and mRNA and protein expressions of mTOR,significantly higher α-SMA protein expression,and significantly higher mRNA and protein expressions of PTEN(P<0.05).Conclusion Moxibustion can improve the pathological morphology and function of cardiomyocytes and attenuate myocardial fibrosis in rats with CHF,and its mechanism may be related to the down-regulation of PTEN expression,and then the up-regulation of mTOR expression.

OBJECTIVE: To investigate the efficacy of posterior three-columns osteotomy in the treatment of severe tuberculous angular kyphosis. METHODS: Total of 33 patients with severe tuberculous angular kyphosis were treated with posterior three-columns osteotomy from January 2006 to January 2019 including 24 males and 9 females with an average age of (40.6±23.3) years old ranging from 15 to 62 years old and an average disease duration of (23.5±15.5) years ranging from 4 to 40 years. The Cobb's angle of kyphosis was (118.65±28.82)°. Interradicular bone-disc-bone osteotomy(BDBO), posterior-only vertebral column resection (PVCR) and posterior multilevel vertebral osteotomy (PMVO) were performed to correct spinal deformity individually. The visual analogue scale (VAS), Oswestry disability index (ODI), sagittal vertical axis (SVA), ASIA spinal cord functional classification and motor function score, and deformity correction rate were measured and statistically analyzed before, after and at the final follow-up. RESULTS: Total of 33 patients were followed up from 15 to 96 months with an average of (38.00±6.38) months. The last follow-up of kyphosis Cobb angle (23.88±5.45)° showed no significant loss from postoperative 12 months (20.40±9.13)°, P>0.05. The SVA, VAS, ODI and ASIA spinal cord functional classification and motor function score were significantly improved at 1 year and last follow-up after operation(P<0.01). The fusion time of the osteotomy site was (18.50±5.16) months. The ASIA classification of 15 patients with spinal cord injury were improved by at least 2 grades after operation, and their daily life and work ability were various levels of restored. Postoperative complications of spinal cord injury occurred in 3 cases. CONCLUSION Posterior three-columns osteotomy is the most effective method for the treatment of angular kyphosis of spinal tuberculosis.Careful preoperative design and individualized osteotomy can not only correct the deformity, but also a successful decompression to the spinal cord and promote the recovery of spinal cord function.
Humans ; Male ; Female ; Osteotomy/methods* ; Kyphosis/surgery* ; Adult ; Adolescent ; Middle Aged ; Young Adult ; Tuberculosis, Spinal/complications* ; Treatment Outcome