OBJECTIVE: To assess the association of microribonucleic acid (miRNA) gene polymorphisms with the risk and clinicopathological characteristics of Crohn's disease (CD) and the influence of miRNA gene variants on the response to ustekinumab (UST) treatment among CD patients. METHODS: From January 2018 to February 2025, 312 patients diagnosed with CD and 527 gender- and age-matched normal controls were selected as the study subjects at the Department of Gastroenterology of the Second Affiliated Hospital of Wenzhou Medical University. Genotypes of miR-155 (rs767649), miR-21 (rs13137), miR-124 (rs531564) and miR-146a (rs57095329, rs2431697) were determined with multiplex polymerase chain reaction-ligase detection reaction (PCR-LDR) technique. The patients were divided into different subgroups according to the Montreal Classification Criteria for CD. Harvey-Bradshaw index (HBI) and simplified endoscopic score for CD were respectively applied to assess the clinical and endoscopic disease activity of CD. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between the two groups, as well as their influence on the clinicopathological characteristics of CD patients. Among them, 185 CD patients received first-line UST treatment, with the first sufficient dose of UST (6 mg/kg) administered intravenously. Based on the changes in HBI at week 8, the response of patients to UST treatment was evaluated. Unconditional logistic regression model was employed to analyze the distribution of miRNA gene polymorphisms between clinically responsive group (the decline of HBI ≥ 3 scores compared to week 0) and non-responsive group. All of the P values were adjusted by Bonferroni correction. This study has been approved by the Medical Ethics Committee of the Second Affiliated Hospital of Wenzhou Medical University (Ethics No.: 2025-K-12-01). RESULTS: No significant difference was found in the distribution of miRNA gene polymorphisms between the two groups (all P > 0.05). The variant genotype (TC+CC) of rs2431697 was more common among patients with terminal ileal-type and ileocolic-type CD than those with the colonic-type CD (OR = 4.98, 95%CI: 1.49~16.68, P = 0.009, adjusted P = 0.045). However, the opposite conclusion was drawn for the homozygous variant genotype (TT) of rs13137 and variant genotype (GC+CC) of rs531564 (OR = 0.37, 95%CI: 0.18~0.76, P = 0.007, adjusted P = 0.035; OR = 0.36, 95%CI: 0.18~0.73, P = 0.004, adjusted P = 0.020). Compared to patients with non-stricturing and penetrating CD, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common in those with stricturing and penetrating CD (OR = 4.06, 95%CI: 2.46~6.71, P < 0.001, adjusted P < 0.005; OR = 3.12, 95%CI: 2.06~4.73, P < 0.001, adjusted P < 0.005). However, the frequencies of variant genotype (AT+TT) and variant allele (T) of rs13137 were lower among patients with stricturing and penetrating CD than in those without (OR = 0.25, 95%CI: 0.15~0.41, P < 0.001, adjusted P < 0.005; OR = 0.45, 95%CI: 0.33~0.63, P < 0.001, adjusted P < 0.005). Additionally, the variant genotype (AG+GG) and variant allele (G) of rs57095329 were more common among those with moderately to severely endoscopic activity than those with mildly endoscopic activity (OR = 2.01, 95%CI: 1.19~3.42, P = 0.009, adjusted P = 0.045; OR = 2.04, 95%CI: 1.28~3.25, P = 0.003, adjusted P = 0.015). In total 117 cases had shown clinical response by week 8, while 68 cases showed no response. Compared with t he clinically non-responsive group, the variant genotype (TC+CC) and variant allele (C) of rs2431697 were more common in the clinically responsive group (OR = 3.86, 95%CI: 1.80~8.32, P = 0.001, adjusted P = 0.005; OR = 2.60, 95%CI: 1.34~5.06, P = 0.005, adjusted P = 0.025). However, the variant genotype (TA+AA) of rs767649 was less frequent in the clinically responsive group than the non-responsive group (OR = 0.40, 95%CI: 0.21~0.74, P = 0.004, adjusted P = 0.020). The same conclusion was drawn for the variant genotype (AT+TT) and variant allele (T) of rs13137 when the clinically responsive group was compared with the non-responsive group (OR = 0.30, 95%CI: 0.14~0.63, P = 0.002, adjusted P = 0.010; OR = 0.54, 95%CI: 0.35~0.82, P = 0.005, adjusted P = 0.025). CONCLUSION Genetic polymorphisms of miRNAs are not associated with the risk of developing CD. The miR-146a (rs57095329) variant may increase the endoscopic activity of CD and the risk for stenosis or penetration. However, the miR-146a (rs2431697) variant may increase the risk of ileal involvement. The miR-21 (rs13137) variant may reduce the risk of ileal involvement and the risk of stenosis or penetration. The miR-124 (rs531564) variant may reduce the risk of ileal involvement. Among patients receiving UST treatment, the miR-146a (rs2431697) variant may increase the clinical response by week 8. However, both the miR-155 (rs767649) and miR-21 (rs13137) variants may decrease the clinical response by week 8.
Humans ; MicroRNAs/genetics* ; Crohn Disease/pathology* ; Male ; Female ; Adult ; Polymorphism, Single Nucleotide ; Middle Aged ; Asian People/genetics* ; Genetic Predisposition to Disease ; Genotype ; Young Adult ; Case-Control Studies ; Adolescent ; East Asian People

Atopic dermatitis （AD） is a common pruritic and chronic inflammatory dermatosis in clinical practice and is one of the diseases responding specifically to traditional Chinese medicine （TCM）. With the launch of biological agents and small molecule drugs and the development and implementation of guidelines of diagnosis and treatment， clinical pathways of treatment of moderate to severe AD， and consensus on the whole-process management of AD， the clinical efficacy of moderate to severe AD has been significantly improved. However， there are still many unmet clinical needs that require more effective methods to meet. In response to the Opinions of the CPC Central Committee and the State Council on Facilitating the Inheritance， Innovation， and Development of Traditional Chinese Medicine and the spirit of the National Conference on TCM， the China Association of Chinese Medicine organized more than 20 experts in TCM dermatology， Western medicine dermatology， interdisciplinary fields， and industries to discuss the difficulties and advantages of TCM in the treatment of AD. TCM treatment for AD can not only improve rash and relieve itching but also solve many concomitant syndromes. The abundant external treatment methods of TCM have advantages for different special populations and rash characteristics. The concept of treating disease before its onset in TCM is in line with the chronic disease management mode of prevention and treatment of atopic march and prevention of recurrence. In addition， TCM therapy can reduce the use of topical glucocorticoids and has good safety. Regarding the comorbidity of AD， equal emphasis on TCM and Western medicine and multidisciplinary joint treatment should be advocated to achieve maximum benefit for patients. The exchange of TCM and Western medicine has clarified the positioning and advantages of TCM intervention in AD， providing guidance for clinical and scientific research.

Objective:To analyze the incidence and risk factors of malignant tumors among HIV-infected patients in Taizhou, Zhejiang Province.Methods:The data were collected from the China Information System for Disease Control and Prevention and the Taizhou Chronic Disease Information Management System. A retrospective cohort study design was used. The subjects were HIV-infected patients who had their household registration in Taizhou from 2005 to 2023 and participated in the follow-up. The observation period was until December 31, 2024. The standardized incidence ratios (SIR) of malignant tumors among HIV-infected patients were analyzed. Cox proportional hazards regression model was used to analyze the influencing factors of malignant tumor incidence.Results:A total of 3 593 HIV-infected patients were included, of whom 292 had malignant tumors. The proportions of AIDS-defining malignancies and non-AIDS-defining malignancies were 12.33% (36/292) and 87.67% (256/292), respectively. The proportion of malignant tumors before and after AIDS confirmation was 43.49% (127/292) and 56.51% (165/292), respectively. 3 466 HIV-infected patients were included in the follow-up cohort, with a total follow-up of 24 968.59 person-years. The incidence rate of malignant tumors in patients with HIV infection was 658.46 per 100 000 (SIR=1.89, 95% CI: 1.61-2.20). The SIR of malignant tumors showed an upward trend with the increase of time. The results of Cox proportional hazards regression model analysis showed that HIV-infected patients in the age groups of 45-59 and ≥60 years (a HR=2.58, 95% CI: 1.26-5.28; a HR=5.00, 95% CI: 2.38-10.51) were more likely to develop malignant tumors. HIV-infected patients with an educational level of senior high school or above (a HR=0.52, 95% CI: 0.29-0.95) and those in the first CD4 +T lymphocyte/CD8 +T lymphocyte count ratio ≥0.5 (a HR=0.52, 95% CI: 0.28-0.97) were less likely to develop malignant tumors. Conclusions:From 2005 to 2023, the incidence of malignant tumors among HIV-infected people in Taizhou was higher than that of the general population, and most of them were non-AIDS-defining malignancies. It is necessary to strengthen the early screening and diagnosis of malignant tumors among HIV-infected patients.

Objective:To explore the predictive value of procalcitonin-to-albumin ratio (PAR) in the short-term prognosis of sequential treatment with butylphthalide for acute cerebral infarction (ACI) after interventional surgery.Methods:The clinical data of ACI patients admitted to 970th Hospital of the Joint Logistics Support Force of the People′s Liberation Army of China from January 2020 to June 2022 were retrospectively included. According to the prognosis of sequential treatment of butylphthalide after interventional therapy, 80 patients with poor prognosis were included in the poor group, and 80 patients with good prognosis were included in the good group. The detection data of procalcitonin, albumin and other laboratory indexes of the two groups of patients on admission were collected, the PAR value was calculated, and the predictive value of PAR on the short-term prognosis of butylphthalide sequential therapy after ACI intervention was analyzed.Results:The levels of procalcitonin (PCT), PAR, D-dimer (D-D), and low density lipoprotein cholesterol (LDL-C) in the poor group were higher than those in the good group: (24.74 ± 5.37) ng/L vs. (20.96 ± 4.11) ng/L, 0.91 ± 0.35 vs. 0.62 ± 0.19, (0.75 ± 0.22) mg/L vs. (0.56 ± 0.17) mg/L, (3.28 ± 0.43) mmol/L vs. (3.03 ± 0.45) mmol/L, while the levels of albumin (ALB) were lower than those in the good group: (29.43 ± 4.25) g/L vs. (33.71 ± 4.53) g/L, with a statistical significant difference ( P<0.05). Multivariate Logistic regression analysis showed that PCT, ALB, PAR, D-D, and LDL-C were all factors influencing the short-term prognosis of sequential treatment with butylphthalide after ACI intervention ( P<0.05). The results of receiver operating characteristic curve (ROC) showed that PCT, ALB, PAR, D-D and LDL-C had certain predictive value for the short-term prognosis of butylphthalide sequential therapy after ACI intervention, and PAR had the best predictive value. Conclusions:PAR is an influential factor for the sequential short-term prognosis of butylphthalide after ACI intervention, and it has certain predictive value for the short-term prognosis of patients.

Objective:To identify and validate secreted effector proteins of Chlamydia psittaci ( C. psittaci) through bioinformatic prediction and experimental verification, and to characterize their subcellular localization in host cells. Methods:Potential effector proteins were predicted using bioinformatics tools. Candidate effectors were fused to β-lactamase through the constructed expression vectors, and these vectors were transformed into C. psittaci. The secretion of these candidate effectors was evaluated by β-lactamase translocation assays. Eukaryotic expression vectors of confirmed effectors were transfected into host cells to determine their intracellular localization patterns. Results:Bioinformatic analysis identified 29 candidate effector proteins. Experimental validation confirmed the secretion of five effectors, with four exhibiting cytoplasmic localization and one displaying nuclear localization in host cells.Conclusion:This study characterizes five novel C. psittaci secreted effector proteins, providing critical insights for investigating the molecular pathogenesis of psittacosis.

OBJECTIVE: To investigate the biological effect of medical recombinant human-derived collagen functional dressings in wound healing. METHODS: MTT assay and RTCA assay were used to detect cell toxicity and proliferation. Scratch assay and Transwell cell migration assay were used to detect cell motility and migration ability. Enzyme-linked immunosorbent assay was used to detect the contents of vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and platelet-endothelial cell adhesion molecule (CD31) in the supernatant of four types of cells. After animal surgery, the surgical wound was taken at 1 week, 4 weeks and 13 weeks, respectively, for hematoxylin eosin (HE) staining and immunohistochemistry to observe the inflammatory response and CD31 expression of the wound. RESULTS: Medical recombinant human-derived collagen functional dressing promotes cell proliferation and migration, enhances wound angiogenesis by upregulating the expression of VEGF, FGF, and CD31 in human dermal vascular endothelial cells (HDVEC) and human vascular endothelial cells (HVEC), thereby improving local blood supply to the wound, regulating the inflammatory response of the wound, and accelerating wound healing. CONCLUSION Recombinant type Ⅲ humanized collagen plays an important role in wound healing.
Humans ; Wound Healing/drug effects* ; Recombinant Proteins/pharmacology* ; Animals ; Cell Proliferation ; Cell Movement ; Collagen/pharmacology* ; Vascular Endothelial Growth Factor A/metabolism* ; Bandages ; Platelet Endothelial Cell Adhesion Molecule-1/metabolism* ; Endothelial Cells ; Fibroblast Growth Factors/metabolism*

Peri-implant keratinized mucosa (PIKM) augmentation refers to surgical procedures aimed at increasing the width of PIKM. Consensus reports emphasize the necessity of maintaining a minimum width of PIKM to ensure long-term peri-implant health. Currently, several surgical techniques have been validated for their effectiveness in increasing PIKM. However, the selection and application of PIKM augmentation methods may present challenges for dental practitioners due to heterogeneity in surgical techniques, variations in clinical scenarios, and anatomical differences. Therefore, clear guidelines and considerations for PIKM augmentation are needed. This expert consensus focuses on the commonly employed surgical techniques for PIKM augmentation and the factors influencing their selection at second-stage surgery. It aims to establish a standardized framework for assessing, planning, and executing PIKM augmentation procedures, with the goal of offering evidence-based guidance to enhance the predictability and success of PIKM augmentation.
Humans ; Consensus ; Dental Implants ; Mouth Mucosa/surgery* ; Keratins

The study explores the traditional Chinese medicine （TCM） diagnostic and treatment approach to coronary microvascular disease （CMVD） from the perspective of "disharmony of blood collaterals and dysfunction of qi transformation". It is proposed that the core pathogenesis of CMVD lies in these two mechanisms. From an integrative medicine perspective， different CMVD types are analyzed based on their specific pathogenesis. Through clinical practice， four targeted treatment methods， i.e. warming， unblocking， tonifying， and activating， are formulated. CMVD caused by atherosclerosis is primarily associated with myocardial ischemia， myocardial infarction， and coronary revascularization， with corresponding pathological mechanisms of latent pathogenic obstruction， toxic accumulation in the collaterals， and deficiency with collateral stasis. The disease progression exhibits characteristics of correlation， staging， and transformation. Accordingly， treatment principles include warming to assist qi transformation， unblocking obstruction and dispelling turbidity， activating to disperse toxic stasis and invigorate collaterals， and tonifying to eliminate stasis and nourish collaterals. For CMVD unrelated to atherosclerosis， attention should be paid to the underlying disease， analyzing the main syndromes of blood and collateral disharmony. An approach combining disease-syndrome differentiation with blood and collateral regulation is emphasized for precise treatment.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.

ObjectiveTo unveil the mechanism of Jianpi Huogu prescription （JPHGP） in ameliorating the dyslipidemia of steroid-induced osteonecrosis of the femur head （SONFH） by oxylipidomics combined with transcriptomics. MethodsSixty SD rats were assigned into normal， model， low-， medium-， and high-dose （2.5， 5， 10 g·kg^-1， respectively） JPHGP， and Jiangushengwan （1.53 g·kg^-1） groups. Lipopolysaccharide was injected into the tail vein at a dose of 20 μg·kg^-1 on days 1 and 2， and methylprednisolone sodium succinate was injected at a dose of 40 mg·kg^-1 into the buttock muscle on days 3 to 5. The normal group received an equal volume of normal saline. Drug administration by gavage began 4 weeks after the last injection， and samples were taken after administration for 8 weeks. Hematoxylin-eosin staining was conducted to reveal the histopathological changes of the femoral head， and the number of adipocytes， the rate of empty bone lacunae， and the trabecular area were calculated. Micro-computed tomography was used for revealing the histological and histomorphometrical changes of the femoral head. Enzyme-linked immunosorbent assay was employed to measure the serum levels of triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein （LDL）， high-density lipoprotein （HDL）， apolipoprotein A1 （ApoA1）， and apolipoprotein B （ApoB）. At the same time， the femoral head was collected for oxylipidomic and transcriptomic detection. The differential metabolites and differential genes were enriched and analyzed， and the target genes regulating lipid metabolism were predicted. The predicted target proteins were further verified by molecular docking， immunohistochemistry， and Western blot. ResultsCompared with the normal group， the model group showcased thinning of the femoral head， trabecular fracture， karyopyknosis， subchondral cystic degeneration， increases in the number of adipocytes and the rate of empty bone lacunae （P<0.01）， a reduction in the trabecular area （P<0.01）， decreases in BMD， Tb.Th， Tb.N， and BV/TV， and increases in Tb.Sp and BS/BV （P<0.01）. Compared with the model group， the JPHGP groups showed no obvious thinning of the femoral head or subchondroidal cystic degeneration. The high- and medium-dose JPHGP groups presented declines in the number of adipocytes and the rate of empty bone lacunae， an increase in the trabecular area （P<0.05， P<0.01）， rises in BMD， Tb.Th， Tb.N， and BV/TV， and decreases in Tb.Sp and BS/BV （P<0.05， P<0.01）. Compared with the normal group， the model group showcased raised serum levels of TG， TC， LDL， and ApoB and lowered serum levels of HDL and ApoA1 （P<0.01）. Compared with the model group， the JPHGP groups had lowered serum levels of TG， TC， LDL， and ApoB （P<0.05， P<0.01） and a risen serum level of ApoA1 （P<0.05， P<0.01）. Moreover， the serum level of HDL in the high-dose JPHGP group increased （P<0.01）. A total of 19 different metabolites of disease set and drug set were screened out by oxylipidomics of the femoral head， and 119 core genes with restored expression were detected by transcriptomics. The enriched pathways were mainly concentrated in inflammation， lipids， apoptosis， and osteoclast differentiation. Molecular docking， immunohistochemistry， and Western blot results showed that compared with the normal group， the model group displayed increased content of 5-lipoxygenase （5-LO） and peroxisome proliferator-activated receptor γ （PPARγ） in the femoral head （P<0.01）. Compared with the model group， medium- and high-dose JPHGP reduced the content of 5-LO and PPARγ （P<0.05， P<0.01）. ConclusionJPHGP can restore the levels of oxidized lipid metabolites by regulating the 5-LO-PPARγ axis to treat SONFH in rats. Relevant studies provide experimental evidence for the efficacy mechanism of JPHGP in the treatment of SONFH.