OBJECTIVE: To assess the safety and topical efficacy of prim-O-glucosylcimifugin (POG) and investigate the molecular mechanisms of its therapeutic effects in atopic dermatitis (AD). METHODS: The effects of POG on human keratinocyte cell viability and its anti-inflammatory properties were evaluated using cell counting kit-8 assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Subsequently, the impact of POG on the differentiation of cluster of differentiation (CD) 4⁺ T cell subsets, including T-helper type (Th) 1, Th2, Th17, and regulatory T (Treg), was examined through in vitro experiments. Network pharmacology analysis was used to elucidate POG's therapeutic mechanisms. Furthermore, the therapeutic potential of topically applied POG was further evaluated in a calcipotriol-induced mouse model of AD. The protein and transcript levels of inflammatory markers, including cytokines, lymphocyte-specific protein tyrosine kinase (Lck) mRNA, and LCK phosphorylation (p-LCK), were quantified using immunohistochemistry, RT-qPCR, and Western blot analysis. RESULTS: POG was able to suppress cell proliferation and downregulate the transcription of interleukin 4 (Il4) and Il13 mRNA. In vitro experiments indicated that POG significantly inhibited the differentiation of Th2 cells, whereas it exerted negligible influence on the differentiation of Th1, Th17 and Treg cells. Network pharmacology identified LCK as a key therapeutic target of POG. Moreover, the topical application of POG effectively alleviated skin lesions in the calcipotriol-induced AD mouse models without causing pathological changes in the liver, kidney or spleen tissues. POG significantly reduced the levels of Il4, Il5, Il13, and thymic stromal lymphopoietin (Tslp) mRNA in the AD mice. Concurrently, POG enhanced the expression of p-LCK protein and Lck mRNA. CONCLUSION Our research revealed that POG inhibits Th2 cell differentiation by promoting p-LCK protein expression and hence effectively alleviates AD-related skin inflammation. Please cite this article as: Zhao H, Ma X, Wang H, Ding XJ, Kuai L, Song JK, Zhang Z, Yang D, Gao CJ, Li B, Zhou M. Prim-O-glucosylcimifugin mitigates atopic dermatitis by inhibiting Th2 differentiation through LCK phosphorylation modulation. J Integr Med. 2025; 23(3): 309-319.
Dermatitis, Atopic/drug therapy* ; Animals ; Humans ; Cell Differentiation/drug effects* ; Phosphorylation/drug effects* ; Mice ; Th2 Cells/drug effects* ; Keratinocytes/drug effects* ; Disease Models, Animal ; Mice, Inbred BALB C ; Calcitriol/analogs & derivatives*

Objective:To evaluate the efficacy and safety of traditional Chinese medicine(TCM)in the treatment of male im-mune infertility(MII)by meta-analysis.Methods:We retrieved randomized controlled trial(RCT)on the treatment of male im-mune infertility with traditional Chinese medicine from the databases of WanFang,Chinese Biomedical Literature,Cochrane Library,Weipu,PubMed and CNKI,and performed methodological quality assessment of the RCTs identified and statistical analysis and evalua-tion of the publication bias using the RevMan5.4 software.Results:Totally,25 RCTs(2 563 cases)were included in this study.Compared with Western medicine alone in the treatment of MII,TCM achieved a significantly higher total effectiveness rate(OR=6.35,95% CI:4.96-8.13,P<0.000 01),negative conversion rate of seminal plasma anti-sperm antibodies(OR=4.52,95% CI:2.72-7.51,P<0.000 01),negative rate of serum anti-sperm antibodies(OR=2.98,95% CI:2.23-3.96,P<0.000 01),sperm concentration(MD=15.56,95% CI:11.32-19.79,P<0.000 01),grade a sperm motility(MD=3.85,95% CI:1.91-5.79,P=0.000 01),grade a+b sperm motility(MD=13.77,95% CI:7.06-20.48,P<0.000 1),sperm viability(MD=10.32,95% CI:6.78-13.86,P<0.000 01)and pregnancy rate(OR=3.53,95% CI:2.68-4.63,P<0.000 01),but a lower rate of adverse reactions(OR=0.06,95% CI:0.01-0.23,P<0.000 01).There was no statistically significant difference in the percentage of morphologically abnormal sperm between TCM and Western medicine alone in the treatment of MII(MD=-7.53,95% CI:-15.50-0.44,P=0.06).Conclusion:TCM has a definite effectiveness and high safe in the treatment of male immune infertility.

Pentacyclic triterpenoids are a class of widespread natural compounds containing six isoprene structures with a wide range of pharmacological activities, including antibacterial, anti-inflammatory, antiviral, antitumor, immune regulation, etc. The structural modifications of pentacyclic triterpenoid natural products and the drug development have always been a hot research topic. This article reviews the recent progresses in the structural modifications, pharmacological effects, and clinical studies of different kinds of pentacyclic triterpenoid natural products.

Inflammatory bowel disease (IBD) is characterized by chronic relapsing intestinal inflammation and encompasses ulcerative colitis (UC) and Crohn's disease (CD). IBD has emerged as a global healthcare problem. Clinically efficacious therapeutic agents are deficient. This study concentrates on models of ulcerative colitis with the objective of discovering novel therapeutic strategies. Previous investigations have established that schisandrin A demonstrates anti-inflammatory effects in vitro, concurrently enhancing the transcriptional activity of farnesoid X receptor (FXR). FXR inversely modulates the transcriptional activity of NF-κB, which has an important role in regulating inflammatory responses. Consequently, the current study was to explore the safeguarding influence of schisandrin A on ulcerative colitis and delineate the mechanism by which it regulates this effect through the FXR signaling pathway. The effect of schisandrin A on the mRNA levels of inflammatory factors was evaluated in RAW264.7 cells. The dual luciferase reporter gene assay was used to verify the relationship between schisandrin A and FXR targeting. The animal experiments were performed in accordance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (approval No. PZSHUTCM2304250005). Acute ulcerative colitis was induced in wild-type or FXR knockout C57BL/6 mice by drinking 3% dextran sodium sulfate (DSS) for 7 days, and schisandrin A was administered via gavage for a continuous treatment period of 7 days. The body weight and faecal were monitored daily. The mRNA levels of inflammatory factors in colon tissue and FXR target genes were measured by RT-qPCR. The findings revealed that schisandrin A, in vitro, impeded the lipopolysaccharide (LPS)-induced elevation in mRNA levels of inflammatory factors and schisandrin A could augment transcriptional activity of FXR. In wild-type mice, schisandrin A significantly improved weight loss, colon shortening, loose stools and blood in stools in mice with acute ulcerative colitis, and schisandrin A significantly reduced the expression of pro-inflammatory factors genes and significantly increased the expression of FXR target genes in colon tissues. In FXR knockout mice, the administration of schisandrin A failed to yield ameliorative effect on acute ulcerative colitis in mice. In conclusion, schisandrin A can reduce intestinal inflammation through the FXR signaling pathway to alleviate acute ulcerative colitis in mice. Implications arise that Schisandra lignans could serve as lead compounds for drug development aimed at inflammatory bowel disease.

Objective To explore the predictive value of soluble fms-like tyrosine kinase-1(sFlt-1)and leukotriene B4(LTB4)in patients with intracranial aneurysms for cerebral vasospasm(CVS)after interventional embolization.Methods A total of 98 patients with intracranial aneurysms admitted to our hospital from January 2019 to September 2023 were regarded as the observation group,and were divided into the CVS group(32 cases)and the non CVS group(66 cases)according to whether CVS occurred or not within 3 to 5 days after surgery;102 healthy examinees in our hospital were selected as the control group.Enzyme-linked immunosorbent assay was used to detect serum levels of sFlt-1 and LTB4;the influencing factors for CVS after interventional embolization of intracranial aneurysms were analyzed by Logistic regression analysis;the predictive value of serum sFlt-1 and LTB4 levels for the occurrence of CVS after interventional embolization of intracranial aneurysms was analyzed by receiver operating characteristic(ROC)curve.Results The serum levels of sFlt-1 and LTB4 of patients in the observation group were obviously higher than those in the control group,and the differences were statistically significant(P<0.05).The serum levels of sFlt-1 and LTB4,and the proportions of patients with postoperative blood pressure fluctuation range≥30 mmHg and Hunt-Hess grade Ⅲ in the CVS group were obviously higher than those in the non CVS group,and the differences were statistically significant(P<0.05).SFlt-1(OR:2.985;95%CI:1.684 to 5.291)and LTB4(OR:2.868;95%CI:1.581 to 5.204)were the independent risk factors for CVS after interventional embolization of intracranial aneurysms(P<0.05).The area under the curve(AUC)of sFlt-1 and LTB4 alone and in combination for predicting the occurrence of CVS after interventional embolization of intracranial aneurysms were 0.839,0.825,and 0.915,respectively,with sensitivity of 84.44%,87.59%,and 81.36%,and specificity of 74.26%,75.87%,and 90.98%,respectively.The AUC of the combination of the two was higher than those of sFlt-1 and LTB4 alone,and the differences were statistically significant(Z=2.150,2.546,P<0.05).Conclusion The serum levels of sFlt-1 and LTB4 in patients with CVS after interventional embolization of intracranial aneurysms are increased,and the combination of the two can serve as the important indicators for predicting CVS.

Objective To observe the effect of dapagliflozin on Klotho protein and renal function in elderly patients with diabetic kidney disease(DKD),and explore the related factors affecting the level of Klotho protein.Methods A total of 88 elderly DKD patients admitted to the Affiliated Hospital of Xuzhou Medical University from January 2021 to November 2021 were randomly divided into dapagli-flozin group and control group.The patients were treated for 12 weeks.The body weight,blood pressure,blood glucose,Klotho protein,renal function,urinary albumin/creatinine(UACR)were estimated before and after treatment,respectively,and adverse reactions were recorded.Results After treatment,the decrease degree of body weight,body mass index,systolic blood pressure,diastolic blood pres-sure,blood urea nitrogen(BUN),serum uric acid,cystatin C,UACR and the increase degree of Klotho protein were greater in dapagli-flozin group than those in the control group(P＜0.001).Multiple linear regression analysis showed that age,BUN and UACR were inde-pendent related factors affecting the level of Klotho protein.There was no significant difference in adverse events between the two groups(P＞0.05).Conclusion Dapagliflozin treatment can reduce body weight,blood pressure,improve renal function and increase the level of Klotho protein.The regulatory effect of dapagliflozin on Klotho protein may be one of the important mechanisms of its renal protection.

Objective:To analyze the impact of transcervical resection of adhesion (TCRA) on obstetric complications in patients after frozen-thawed embryo transfer (FET) and its associated factors.Methods:A retrospective cohort study was conducted by collecting clinical data from patients who underwent autologous oocyte FET treatment and gave birth to at least one live newborn at the Reproductive Medicine Center of Nanjing Women and Children's Healthcare Hospital from April 2015 to May 2022. Based on the uterine condition, patients were divided into three groups: control group with normal uterine morphology (712 cases); the intrauterine adhesion (IUA) group consisting of IUA patients who did not undergo TCRA surgery (45 cases); the TCRA group, which included IUA patients who received TCRA treatment (51 cases). The relationship between uterine conditions and obstetric complications among the three groups was investigated using propensity score matching (PSM). Multivariate logistic regression analysis was applied to identify risk factors associated with obstetric complications related to TCRA. The performance of the constructed multivariate logistic regression model was evaluated using calibration curves and receiver operating characteristic (ROC) curves.Results:1) Before PSM, statistically significant differences were observed among the three groups regarding endometrial thickness, the presence of a scarred uterus, numbers of pregnancies, deliveries, miscarriages, induced abortions, and transferred embryos (all P<0.05). After PSM, baseline characteristics were balanced across the groups. The rates of placenta accreta spectrum disorders (PAS) in the TCRA group [48.8% (20/41)] and the IUA group [45.2% (19/42)] were significantly higher than those in control group [24.7% (18/73), P=0.016; 22.8% (18/79), P=0.019]. 2) Multivariable logistic regression analysis revealed that endometrial thickness ( OR=0.79, 95% CI: 0.69-0.90, P<0.001], number of pregnancies (2 times, OR=2.25, 95% CI: 1.33-3.82, P=0.003), endometrial preparation protocol (gonadotropin-releasing hormone agonist plus hormone replacement therapy, OR=2.29, 95% CI: 1.16-4.52, P=0.017), the presence of a scarred uterus ( OR=2.19, 95% CI: 1.39-3.45, P<0.001), and uterine cavity conditions (IUA and TCRA, OR=2.11, 95% CI: 1.07-4.17, P=0.031; OR=2.70, 95% CI: 1.37-5.31, P=0.004) were independent predictors of PAS occurrence. 3) The area under the ROC curve for this model was 0.732 (95% CI: 0.686-0.778). Calibration curve results, after internal validation, showed good consistency between predicted risks and actual outcomes, demonstrating good discriminative ability and calibration ( P=0.540). Conclusion:The incidence of obstetric complications such as placenta previa, postpartum hemorrhage, and premature rupture of membranes in patients who underwent TCRA surgery was comparable to that of patients with a normal uterine morphology. However, TCRA significantly increased the risk of PAS in patients with IUA undergoing FET assisted reproductive treatment.

Objective:To analyze the impact of transcervical resection of adhesion (TCRA) on obstetric complications in patients after frozen-thawed embryo transfer (FET) and its associated factors.Methods:A retrospective cohort study was conducted by collecting clinical data from patients who underwent autologous oocyte FET treatment and gave birth to at least one live newborn at the Reproductive Medicine Center of Nanjing Women and Children's Healthcare Hospital from April 2015 to May 2022. Based on the uterine condition, patients were divided into three groups: control group with normal uterine morphology (712 cases); the intrauterine adhesion (IUA) group consisting of IUA patients who did not undergo TCRA surgery (45 cases); the TCRA group, which included IUA patients who received TCRA treatment (51 cases). The relationship between uterine conditions and obstetric complications among the three groups was investigated using propensity score matching (PSM). Multivariate logistic regression analysis was applied to identify risk factors associated with obstetric complications related to TCRA. The performance of the constructed multivariate logistic regression model was evaluated using calibration curves and receiver operating characteristic (ROC) curves.Results:1) Before PSM, statistically significant differences were observed among the three groups regarding endometrial thickness, the presence of a scarred uterus, numbers of pregnancies, deliveries, miscarriages, induced abortions, and transferred embryos (all P<0.05). After PSM, baseline characteristics were balanced across the groups. The rates of placenta accreta spectrum disorders (PAS) in the TCRA group [48.8% (20/41)] and the IUA group [45.2% (19/42)] were significantly higher than those in control group [24.7% (18/73), P=0.016; 22.8% (18/79), P=0.019]. 2) Multivariable logistic regression analysis revealed that endometrial thickness ( OR=0.79, 95% CI: 0.69-0.90, P<0.001], number of pregnancies (2 times, OR=2.25, 95% CI: 1.33-3.82, P=0.003), endometrial preparation protocol (gonadotropin-releasing hormone agonist plus hormone replacement therapy, OR=2.29, 95% CI: 1.16-4.52, P=0.017), the presence of a scarred uterus ( OR=2.19, 95% CI: 1.39-3.45, P<0.001), and uterine cavity conditions (IUA and TCRA, OR=2.11, 95% CI: 1.07-4.17, P=0.031; OR=2.70, 95% CI: 1.37-5.31, P=0.004) were independent predictors of PAS occurrence. 3) The area under the ROC curve for this model was 0.732 (95% CI: 0.686-0.778). Calibration curve results, after internal validation, showed good consistency between predicted risks and actual outcomes, demonstrating good discriminative ability and calibration ( P=0.540). Conclusion:The incidence of obstetric complications such as placenta previa, postpartum hemorrhage, and premature rupture of membranes in patients who underwent TCRA surgery was comparable to that of patients with a normal uterine morphology. However, TCRA significantly increased the risk of PAS in patients with IUA undergoing FET assisted reproductive treatment.

AIM To prepare bergenin nanostructured lipid carriers,and to investigate their in vivo pharmacokinetics.METHODS The nanostructured lipid carriers were prepared by melting method.With solid lipid type,liquid lipid type,solid-liquid lipid ratio,lipid-drug ratio and poloxamer 188 concentration as influecing factors,encapsulation efficiency,drug loading and particle size as evaluation indices,the formulation was optimized by single factor test,after which the in vitro drug release was investigated,the stability was determined,and crystalline form analysis was performed.Eighteen rats were randomly assigned into three groups and given intragastric administration of the 0.5%CMC-Na suspensions of bergenin,physical mixture and bergenin solid dispersions(60 mg/kg),respectively,after which blood collection was made at 0.25,0.5,1,2,3,4,5,6,8,10,12 h,HPLC was adopted in the plasma concentration determination of bergenin,and main pharmacokinetic parameters were calculated.RESULTS The optimal formulation was determined to be glyceryl behenate as solid lipid,oleic acid as liquid lipid,4 ∶ 1 for solid-liquid lipid ratio,10 ∶ 1 as lipid-drug ratio 2.0%for poloxamer 188 concentration,the average concentration,drug loading,particle size and Zeta potential were(84.16±1.57)%,(7.73±0.27)%and(215.53±18.04)nm and-(37.56±2.03)mV,respectively.The nanostructured lipid carriers demonstrated the accumulative release rate of less than 50%within 240 min in simulated gastric fluid,which was 71.04%within 36 h in simulated intestinal fluid,along with good stability within 12 h in the latter.Bergenin existed in the nanostructured lipid carriers in an amorphous state.Compared with raw medicine and physical mixture,the nanostructured lipid carriers displayed prolonged tmax and t1/2(P<0.01),and increased Cmax,AUC0-t,AUC0-∞(P<0.01),whose relative bioavailability was enhanced to 6.08 times as compared with that of raw medicine.CONCLUSION Nanostructured lipid carriers can improve the stability and oral bioavailability of bergenin.

Objective: To examine the application value of 3D Slicer software assisted domestic frameless stereotactic robot in biopsy of intracranial lesions. Methods: A retrospective analysis was performed on 80 patients who admitted consecutively and underwent intracerebral lesions biopsy with the domestic frameless stereotactic robot at Department of Neurosurgery, Aerospace Central Hospital from January 2019 to December 2021. There were 36 males and 44 females, with a mean age of (38.5±18.0) years (range: 6 to 71 years). Before surgery only enhanced T1-weighted three-dimensional magnetization prepared gradient echo sequences and diffusion tensor imaging scans were performed. Self-reconstruction of intracranial lesions, cerebral cortex and blood vessels was carried out using 3D Slicer software system after the DICOM format imaging data of 80 patients were collected. These imaging data were merged to the workstation of the domestic frameless stereotactic robot for preoperative surgical planning and the surgical puncture path was designed to avoid blood vessels in the brain functional area, cerebral cortex and sulcus. Results: All frameless stereotactic biopsy were successfully performed. Postoperative pathological diagnosis included 50 cases of diffuse astrocytic and oligodendroglioma, 15 cases of lymphoma, 5 cases of metastatic tumors, 5 cases of inflammatory demyelinating disease, 2 cases of inflammatory granuloma, 1 case of hemangioma, 1 case of acute lymphoblastic leukemia intracranial invasion and 1 case of seminoma. The positive diagnosis rate was 100% (80/80). Postoperative imaging confirmed that the puncture path and target were accurately implemented according to the preoperative planning, and the target error was (1.32±0.44) mm (range: 0.55 to 1.99 mm). One case of puncture-related bleeding occurred at the target after surgery and improved after treatment. Conclusion: The three-dimensional multimodal images reconstructed by the 3D Slicer software before operation could help the surgeons make the preoperative planning and reduce the risk of stereotactic brain biopsy.
Male ; Female ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Brain Neoplasms/pathology* ; Diffusion Tensor Imaging ; Retrospective Studies ; Robotics ; Biopsy ; Software ; Stereotaxic Techniques