ObjectiveTo evaluate the clinical efficacy and safety of acupuncture in treating severe Bell's palsy and to explore its potential mechanism by investigating the effect on serum levels of glial cell line-derived neurotrophic factor （GDNF） and nerve growth factor （NGF）. MethodsA randomized， subject-blinded， sham-acupuncture controlled trial was conducted. A total of 130 patients with severe Bell's palsy were randomly allocated into a treatment group or a control group at a 1∶1 ratio. Both groups received conventional western medicine. In addition， the treatment group received acupuncture， while the control group received sham acupuncture， with each session lasting 30 minutes. The treatment course lasted 8 weeks for both groups， followed by a follow-up assessment at week 12. The primary outcome was the proportion of patients achieving House-Brackmann （H-B） grade Ⅱ or lower at week 8. Secondary outcomes included Sunnybrook facial grading system scores at week 0， 4， 8， and 12， the time to satisfactory recovery（the time required to achieve H-B grade≤Ⅱ）， distribution of H-B grades and facial disability index （FDI） scores including the physical function subscale （FDIP） and social/well-being function subscale （FDIS） scores at week 0， 4， 8， and 12， and serum GDNF and NGF levels at week 0， 4， and 8. Adverse events and participants' self-assessments of treatment efficacy were also recorded. ResultsA total of 122 participants completed the study， including 62 in the treatment group and 60 in the control group. An intention-to-treat （ITT） analysis was performed， and missing data were handled using the last observation carried forward （LOCF） method. The proportion of patients achieving H-B grade ≤grade Ⅱ at week 8 was 78.5% （51/65） in the treatment group， significantly higher than 49.2% （32/65） in the control group （P＜0.05）. The Sunnybrook scores， FDIP and FDIS scores increased， while H-B grades decreased at week 4， 8， and 12 in both groups compared to week 0； moreover， improvements in all outcome measures were significantly greater in the treatment group than in the control group （P＜0.05）. The median time to satisfactory recovery was 6 weeks （95%CI： 5.697-6.303） in the treatment group， significantly shorter than 12 weeks （95%CI： 8.314-15.686） in the control group （P＜0.05）. Serum levels of GDNF and NGF were significantly higher in the treatment group at weeks 4 and 8 （P＜0.05）. No serious acupuncture-related adverse events occurred in either group. Adverse events were reported in 5 patients （7.69%） in the treatment group and 4 patients （6.15%） in the control group， with no statistically significant difference between groups （P＞0.05）. Patients' self-assessment of treatment efficacy after 8 weeks treatment was significantly better in the treatment group （P＜0.05）. ConclusionAcupuncture can effectively improve facial nerve function and shorten recovery time in patients with severe Bell's palsy， with a favorable safety profile. The therapeutic mechanism may be associated with the upregulation of serum GDNF and NGF levels.

Objective To optimize the extraction process of Xuetong capsules and establish its quality control method. Methods The extraction process was optimized by orthogonal experiment using ethanol reflux method to investigate the effects of different factors on diphenylstilbene, aloin and extraction yield. The content of 5 anthraquinone compounds in Xuetong capsule was determined by HPLC. Results The optimal extraction process was to add 10 times ethanol, with an ethanol concentration of 70%, and extract 3 times, each time for 1 h; 5 components had a good linear relationship with peak area within a certain concentration range, r>0.999 7; The range of sample recovery rate was 93.66%-96.85%, RSD range of 1.48%-1.66%. The content determination results of the 5 components in three batches of Xuetong capsules were （0.632-0.641）, （0.660-0.681）, （1.968-1.991）, （2.547-2.580）, and （1.076-1.101） mg/g. Conclusion The method was accurate, reproducible, and highly feasible, which could be references for producing and improving the quality control standards of Xuetong capsules.

Objective:To discuss the differential expression of microRNA(miR)-125a-5p in peripheral blood mononuclear cells(PBMCs)of the patients with mycobacterium tuberculosis(MTB)infection and its effect on macrophage polarization,and to clarify its clinical significance.Methods:A total of 40 patients with active tuberculosis(ATB)(ATB group),35 patients with latent tuberculosis infection(LTBI)(LTBI group),and 40 healthy physical examinees(control group)clinically diagnosed from July 2022 to June 2023 were selected.The fasting blood samples of the subjects in three groups were collected next morning after 12 h of fasting,and then serum was separated.Enzyme-linked immunosorbent assay(ELISA)method was used to detect the levels of inflammatory factors in the serum of the subjects in various groups.Simultaneously,the PBMCs were extracted from the subjects in various groups;flow cytometry was used to detect the expression levels of CD80 and CD206 proteins in the PBMCs of the subjects in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of microRNA(miR)-125a-5p and interleukin-6(IL-6)mRNA in PBMCs of the subjects in various groups.Results:There were no statistically significant differences in the general information of the subjects among three groups(P>0.05).Compared with control group,the erythrocyte sedimentation rate(ESR),percentages of monocytes(MONO),tumor necrosis factor-α(TNF-α)levels,and interleukin-10(IL-10)levels in serum of the patients in ATB group and LTBI group were significantly increased(P<0.05),and the percentages of lymphocytes(LY)were significantly decreased(P<0.05);compared with ATB group,the ESR and level of IL-10 in serum of the patients in LTBI group were significantly decreased(P<0.05),and the percentage of LY was significantly increased(P<0.05);there were statistically significant differences in the counts of white blood cell(WBC)of the subjects among various groups(P>0.05).The flow cytometry results showed that compared with control group,the expression levels of CD80 and CD206 proteins in PBMCs of the patients in ATB group and LTBI group were significantly increased(P<0.05).Compared with ATB group,the expression level of CD206 protein in the PBMCs of the patients in LTBI group was significantly increased(P<0.05),and the expression level of CD80 protein was significantly decreased(P<0.05).The RT-qPCR results showed that compared with control group,the expression levels of miR-125a-5p and IL-6 mRNA in the PBMCs of the patients in ATB group and LTBI group were significantly increased(P<0.05);compared with ATB group,the expression levels of miR-125a-5p and IL-6 mRNA in PBMCs of the patients in LTBI group were significantly increased(P<0.05).The correlation analysis results showed that the miR-125a-5p expression level was positively correlated with the TNF-α level and IL-6 mRNA expression level(r=0.406,P<0.05;r=0.351,P<0.05),and negatively correlated with the IL-10 level(r=-0.368,P<0.05).The area under the receiver operating characteristic(ROC)curve(AUC)value of miR-125a-5p expression level for diagnosing LTBI patients was 0.89(P<0.01),with a sensitivity of 0.85 and a specificity of 0.88.Conclusion:The expression level of miR-125a-5p in PBMCs of the patients in LTBI group is significantly increased,and it can affect the macrophage polarization to M1,promote the inflammatory response process of macrophages and participate in the occurrence and development of pulmonary tuberculosis.

The development of blood purification materials has progressed from cellulose membranes to high-strength polymer membranes, but the blood compatibility of the membranes remains a major challenge for their clinical applications. In this review, blood purification materials were categorized according to the commonly used material surface modification strategies, including surface grafting of anticoagulant groups, surface coating of materials and electrostatic layer-by-layer self-assembly, covalent attachment of superhydrophilic hydrogels, and blending method. Anticoagulant properties such as clotting time and surface hydrophilicity of various blood purification materials were also discussed to further analyze the value and challenges of blood purification materials in clinical practice.

Objective To explore the inhibitory effect of guggulsterone(GS)on diethylnitrosamine(DEN)-induced liver fibrosis in rats and its mechanism.Methods DEN-induced liver fibrosis model was established in SD rats.The successful model rats were randomly divided into model group(n=6),GS group(n=6,50 mg/kg,intraperitoneal injection for 4 weeks),GS+SRI group(n=6,50 mg/kg+30 mg/kg,intraperitoneal injection for 4 weeks),and control group(n=6,without DEN-induced).Rats in the control group and the model group were injected with the same amount of normal saline.The pathological changes of the liver were detected by HE staining.Serum liver function indexes including alanine aminotransferase(ALT),aspartate aminotransferase(AST),albumin(ALB)and alkaline phosphatase(ALP)were detected by automatic biochemical analyzer.The serum levels of pro-collagen Ⅲ(PC-Ⅲ),collagen Ⅳ(Ⅳ-C),hyaluronidase(HA),laminin(LN),malondialdehyde(MDA),reduced glutathione(GSH),superoxide dismutase(SOD),and catalase(CAT)were detected by ELISA assay.The mRNA and protein expression of TGF-β1,Smad2,and p-Smad3/Smad3 were detected by Real-time PCR and Western blotting.Results Compared with the control group,the model group showed typical pathological changes of liver fibrosis;the serum ALB,GSH,SOD and CAT levels were significantly decreased(P＜0.05);the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA,LN and the mRNA expression of TGF-β1,Smad3 and protein expression of TGF-β1,p-Smad3 in liver tissues were significantly increased(P＜0.05).Compared with the model group,the pathological changes of liver fibrosis in the GS group were alleviated,and the serum levels of ALB,GSH,SOD and CAT were significantly increased(P＜0.05),the serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN,the mRNA expression of TGF-β1 and Smad3,and protein expression of TGF-β1 and p-Smad3 in liver tissues were significantly decreased(P＜0.05).In addition,after the administration of SRI,TGF-β1 signaling pathway activator,compared with the GS group,the GS+SRI group showed significantly decreased serum ALB,GSH,SOD and CAT levels(P＜0.05),but significantly increased serum levels of ALT,AST,ALP,MDA,PC-Ⅲ,Ⅳ-C,HA and LN as well as the mRNA expression of TGF-β1 and Smad3 and protein expression of TGF-β1 and p-Smad3 in liver tissues(P＜0.05).Therefore,SRI attenuated the anti-fibrotic effect of GS on rats with liver fibrosis.Conclusion GS has certain inhibitory effect on DEN-induced liver fibrosis in rats,and its mechanism may be related to the reduction of oxidative stress level and the inhibition of the activation of TGF-β1/Smad3 signaling pathway.

Objective To explore the correlation between the ratio of free triiodothyronine/free thyroxine(FT3/FT4)and the early-phase insulin secretion index(ΔI30/ΔG30)in type 2 diabetes mellitus(T2DM)patients with normal thyroid function.Methods 200 patients with T2DM with normal thyroid function in Hebei General Hospital from September 2019 to June 2021 were selected and divided into the Q1 group with FT3/FT4≤0.26(n=67),the Q2 group with 0.27≤FT3/FT4≤0.29(n=67),and the Q3 group with FT3/FT4≥0.30(n=66)according to the tertiles of the FT3/FT4.The general data,biochemical indicators and islet functions of the three groups were compared,and the relationship between the FT3/FT4 ratio and the ΔI30/ΔG30 as well as the islet β cell function was analyzed.Results The fasting insulin(FIns),2 h postprandial insulin(2 hIns),homeostatic model assessment of islet β cell(HOMA-β)and area under the curve of insulin(AUCI)in Q3 group were higher than those in Q1 and Q2 groups(P<0.05),2 h postprandial blood glucose(2 hPG)in Q3 group was lower than those in Q1 and Q2 groups(P<0.05).Systolic blood pressure in Q2 group was higher than those in Q1 group(P<0.05).Compared with Q1 group,diastolic blood pressure,body mass index(BMI),alanine aminotransferase(ALT),fasting C-peptide(FC-P),area under curve of C-P(AUCC),2 h postprandial C-peptide(2 hC-P)and ΔI30/ΔG30 in Q3 group were significantly higher(P<0.05),and HbA1c was significantly lower(P<0.05).Spearman correlation analysis showed that Δ I30/Δ G30,HOMA-β,AUCI,AUCC and HOMA-IR were positively correlated with BMI,ALT,FC-P,2 hC-P,FIns,2 hIns and FT3/FT4(P<0.05),it was negatively correlated with HbA1c and 2 hPG(P<0.05).Linear regression analysis showed that ΔI30/ΔG30,HOMA-β,AUCI and AUCC were the influencing factors of FT3/FT4 after adjusting for confounding factors.Conclusions ΔI30/ΔG30,HOMA-β,AUCI and AUCC are the influencing factors of FT3/FT4 in T2DM patients with normal thyroid function,suggesting that FT3/FT4 is higher in patients with better islet β cell secretion function.

AIM:To investigate the mechanism by which muscle segment homeobox 2(Msx2)regulates the differentiation of outer enamel epithelial cells in the enamel organ.METHODS:Tissue paraffin sections were prepared and subjected to hematoxylin-eosin(HE)staining to analyze the effect of Msx2 deficiency on the differentiation status of epithelial cells in the enamel organ at the morphological level.At the ultrastructural level,alterations in cell structure were analyzed.The intermediate steps mediating cell differentiation were identified.Transcriptome sequencing analysis was performed to validate the molecular mechanisms underlying the observed phenomena.RESULTS:Msx2 deficiency was innovatively found to induce severe squamous epithelial hyperplasia in outer enamel epithelial cells of enamel organ,accompanied by dynamic restructuring of the cell cytoskeleton and alterations in cell adhesion at the ultrastructure level.As a transcriptional repressor,the loss of Msx2 expression results in significant increases(P＜0.05 or P＜0.01)in the mRNA expression levels of integrin β2(Itgβ2),ItgαM,Itgα4,Rac family small GTPase 2(Rac2),Rac/Cdc42 guanine nucleo-tide exchange factor 6(Arhgef6)and protein tyrosine phosphatase receptor type C(Ptprc).CONCLUSION:Msx2 regu-lates cytoskeleton structure and cell-cell interaction through the Rho GTPases signaling pathway,thereby influencing the differentiation state of outer enamel epithelial cells.This study reveals the mechanism through which Msx2 regulates the differentiation of outer enamel epithelial cells,providing a theoretical foundation for the prevention and treatment of enam-el-related clinical dental diseases.

T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

The persistent high prevalence and poor survival outcomes of lung cancer underscore the urgent need for innovative therapeutic modalities. Here, we present a novel multifunctional delivery platform for the synergistic treatment of lung malignancies, combining in situ-triggerable photodynamic therapy (PDT) with radiotherapy. The new platform CLL was developed by loading a new reactive oxygen species (ROS)-triggerable photosensitizer, luminol-conjugated chlorin e6 (Ce6), into liposomes. CLL can be activated through the bioluminescence resonance energy transfer effect under oxidative stress, thereby producing singlet oxygen for targeted tumor treatment without external irradiation. In vitro studies showed significant cytotoxic effects of CLL in both 4T1 and A549 tumor cells. Furthermore, a PDT-radiopharmaceutical combination nanotherapy CLL-¹⁷⁷Lu was engineered by incorporating the radionuclide ¹⁷⁷Lu into CLL. CLL-¹⁷⁷Lu demonstrated synergistic antitumor effects in 4T1 and A549 tumor cells, as well as in mouse models of 4T1 breast cancer lung metastasis or A549 tumor xenografts. Mechanistically, CLL-¹⁷⁷Lu can induce singlet oxygen/ROS generation, enhance tumor cell apoptosis, and promote M1 macrophage-mediated immunotherapy. Preliminary assessments showed a favorable profile for CLL-¹⁷⁷Lu, highlighting its potential as a promising nanotherapy for cancer treatment. Additionally, CLL can serve as a versatile platform for delivering a range of therapies to achieve synergistic antitumor effects.

Objectives:To observe the efficacy of minimally invasive transforaminal lumbar interbody fusion(MIS-TLIF)under microscope via fixed channel in the treatment of patients with double segment lumbar spondylolisthesis,and analyze its impact on lumbar stability and complications.Methods:108 patients with bilateral lumbar spondylolisthesis admitted and treated in our hospital from January 2022 to January 2024 were selected as the study subjects in this prospective study.Using a random number table,the patients were divided into two groups:conventional group(n=53,29 males and 24 females,53.23±4.30 years old)and microscope group(n=55,28 males and 27 females,53.45±4.28 years old).The patients in the conventional group underwent MIS-TLIF via fixed channel through conventional approach,and patients in the microscope group received MIS-TLIF via fixed channel under microscope.There was no significant difference between the two groups in baseline data(P＞0.05).The drainage volume and bleeding volume,fluoroscopy frequency,operative time and the occurrence of complications of the two groups of patients were recorded and compared.The clinical efficacy was evaluated using the modified MacNab scoring standard 6 months after operation.X-ray examinations were performed before operation,3 months and 6 months after operation,and the height of intervertebral space and spondylolisthesis angle were measured and compared to evaluate the stability of the lumbar spine;During the same period,Japanese Orthopaedic Association(JOA)score and Oswestry disability index(ODI)were used to evaluate and compare the lumbar dysfunction of the two groups of patients.The levels of C-reactive protein(CRP),tumor necrosis factor-α(TNF-α),and creatine kinase(CK)in the two groups of patients were detected and compared by enzyme-linked immunosorbent assay(ELISA)before operation,3d,and 6d after operation to evaluate inflammatory factors.Results:Compared with the conventional group,the total excellent and good rate of the microscope group was higher(78.18％vs 60.38％,P＜0.05),and the drainage and bleeding volume were less(98.03±9.77mL vs 120.73±13.52mL and 113.42±11.03mL vs 142.69±15.72mL,P＜0.05),fluoroscopy frequency was fewer(6.71±0.58 vs 8.36±0.72,P＜0.05),operative time was shorter(123.59±13.58min vs 157.42±16.89min,P＜0.05),and complication rate were lower(3.64％vs 16.98％,P＜0.05).Before operation,the intervertebral space height,slip angle,JOA score,and ODI were comparable between the two groups(P＞0.05).At 3 and 6 months after operation,the intervertebral space height and JOA score increased,and the microscope group was higher(Postoperative 3 months:8.03±0.80mm vs 6.12±0.72mm,15.28±1.24 points vs 11.14±1.02 points;Postoperative 6 months,11.02±1.27mm vs 9.23±0.95mm,21.72±2.14 points vs 18.03±1.60 points,P＜0.05),while the slip angle and ODI score decreased,and the microscope group was lower(Postoperative 3 months:2.41°±0.28° vs 3.01°±0.32°,32.14±2.96 points vs 36.01±3.14 points;Postoperative 6 months:1.60°±0.16° vs 2.03°±0.25°,24.77±2.15 points vs 28.01±2.60 points,P＜0.05).Before operation and on 6d after operation,the levels of CRP,TNF-α,and CK were comparable between the two groups(P＞0.05);3d after operation,the levels of CRP,TNF-cc and CK in the microscope group were lower(6.01±0.75mg/L vs 8.23±0.93mg/L,23.01±2.01 pg/mL vs 29.36±2.57pg/mL,170.43±19.01U/L vs 205.72±30.89U/L,P＜0.05).Conclusions:Microscopically-assisted MIS-TLIF demonstrates excellent short-term efficacy in treating two-segment lumbar spondylolisthesis,which can significantly reduce complication risks.It effectively enhances postoperative lumbar stability,promotes functional recovery,and suppresses early inflammatory responses,making it a clinically valuable treatment option.