OBJECTIVE: To review the latest research advancements in surgical techniques for the treatment of limb lymphedema. METHODS: The relevant literature at home and abroad in recent years was extensively reviewed, and the research on the treatment of limb lymphedema by surgical techniques were summarized and analyzed. RESULTS: Lymphovenous anastomosis has demonstrated good effectiveness for early to mid-stage limb lymphedema, however its long-term effectiveness and applicability for late-stage limb lymphedema still require further validation. Autologous lymphatic/venous grafting has shown clinical feasibility in the treatment of secondary limb lymphedema. Research on tissue-engineered lymphatic scaffolds remains insufficient, primarily due to the complexity of lymphatic anatomical structures and the technical challenges involved. Nevertheless, its potential application is promising. Vascularized lymph node flap transplantation has shown significant effectiveness in treating limb lymphedema, particularly yielding good outcomes in upper limb cases. However, it can not guarantee a complete cure for the condition. Charles' operation is the most effective treatment option for patients with late-stage limb lymphedema, but its extensive incision and severe postoperative complications limit its application. Liposuction has the advantages such as minimal invasiveness, high safety, and repeatability. It is suitable for patients with late-stage limb lymphedema who have failed conservative treatment or developed adiposity. However, its effectiveness is limited in patients with significant limb fibrosis. CONCLUSION Current treatments for limb lymphedema require further improvement, and there is considerable debate regarding treatment strategies for different stages of the condition. Future high-quality, multi-system combined treatment approaches are anticipated to guide clinical practice.
Humans ; Lymphedema/surgery* ; Surgical Flaps/blood supply* ; Lymphatic Vessels/surgery* ; Anastomosis, Surgical/methods* ; Lymph Nodes/transplantation* ; Lipectomy/methods* ; Extremities/surgery* ; Treatment Outcome ; Tissue Engineering ; Tissue Scaffolds ; Veins/transplantation*

Objective The study aims to investigate the immunological functions of the nucleocapsid (N) protein of the novel coronavirus Omicron (BA.1, BA.2) and evaluate the differences among different N proteins of mutant strains in immunogenicity. Methods By aligning sequences, the mutation sites of the Omicron (BA.1, BA.2) N protein relative to prototype strain of the novel coronavirus (Wuhan-Hu-1) were determined. The pET-28a-N-Wuhan-Hu-1 plasmid was used as template to construct pET-28a-BA.1/BA.2-N through single point mutation or homologous recombination. The three kinds of N protein were expressed in prokaryotic system, purified through Ni-NTA affinity chromatography, and then immunized into mice. The titer and reactivity of the polyclonal antibody, as well as the expression level of IL-1β and IFN-γ in mouse spleen cells, were detected using indirect ELISA and Western blot assay. Results The constructed prokaryotic expression plasmids were successfully used to express the Wuhan-Hu-1 N, BA.1 N, and BA.2 N proteins in E.coli BL21(DE3) at 37 DegreesCelsius for 4 hours. The indirect ELISA test showed that the titers of polyclonal antibody prepared by three N proteins were all 1:51 200. All three N proteins can increase the expression of IFN-γ and IL-1β cytokines, but the effect of Omicron N protein in activing two cytokines was more obvious than that of Wuhan-Hu-1 N protein. Conclusion The study obtained three new coronavirus N proteins and polyclonal antibodies, and confirmed that mutations in the amino acid sites of the N protein can affect its immunogenicity. This provides a basis for developing rapid diagnostic methods targeting N protein of different novel coronavirus variants.
Animals ; Mice ; SARS-CoV-2/genetics* ; Coronavirus Nucleocapsid Proteins/immunology* ; Nucleocapsid Proteins/isolation & purification* ; COVID-19/immunology* ; Antibodies, Viral/immunology* ; Mice, Inbred BALB C ; Interferon-gamma/metabolism* ; Interleukin-1beta/metabolism* ; Female ; Escherichia coli/metabolism* ; Mutation ; Humans

Objective:To investigate the mechanism of ursolic acid regulating HMGB1/TLR4 pathway in reducing intestinal barrier injury in a rat model of ulcerative colitis(UC).Methods:Rats were randomly divided into control group,model group,glycyr-rhizic acid(HMGB1 inhibitor)group,ursolic acid group and glycyrrhizic acid+ursolic acid group,with 12 rats in each group.UC rat model was induced by tritrobenzene sulfonate enema.After drug administration,body weight and disease activity index(DAI)score were performed of rats in each group;pathological morphology of colonic mucosa was detected by HE staining,the thickness of mucosa and height of villi were compared;levels of catalase(CAT),superoxide dismutase(SOD),malondialdehyde(MDA)in colon tissue,levels of serum diamine oxidase(DAO),and intestinal fatty acid binding protein(I-FABP),TNF-α,IL-18,IL-6 were detected by kits;expression levels of tight junction proteins(Claudin-1,ZO-1,Occludin)and HMGB1/TLR4 pathway proteins(HMGB1,TLR4,MyD88)in colon tissues were detected by Western blotting.Expression levels of HMGB1,TLR4 and MyD88 in colonic tissue were detected by immunohistochemistry.Results:Compared with control group,colonic mucosal tissue of model group had severe pathological injury,the body weight,mucosal thickness,villus height,CAT,SOD,Claudin-1,ZO-1 and Occludin levels in colon tis-sue were significantly reduced,while DAI score,serum DAO,I-FABP,TNF-α,IL-18 and IL-6 levels,colon tissue MDA,HMGB1,TLR4 and MyD88 levels were significantly increased(P<0.05);compared with model group,pathological injury of colonic mucosal tissue of rats in ursolic acid group,glycyrrhizic acid group and glycyrrhizic acid+ursolic acid group were reduced,body weight,muco-sal thickness,villus height,colon tissue CAT,SOD,Claudin-1,ZO-1 and Occludin levels were significantly increased,while DAI score,serum DAO,I-FABP,TNF-α,IL-18 and IL-6 levels,colon tissue MDA,HMGB1,TLR4 and MyD88 levels were significantly reduced(P<0.05);combined intervention of glycyrrhizic acid and ursolic acid could enhance the influence of ursolic acid on the above indexes(P<0.05).Conclusion:Ursolic acid can inhibit inflammation,reduce the level of oxidative stress,reduce the colonic mucosal injury of UC rats,repair the intestinal mucosal barrier function,and improve the clinical symptoms of rats,which may be achieved by down-regulating the HMGB1/TLR4 pathway.

Objective To study the influence of stent and balloon shape on hemodynamics in tapered vessels with multiple stenosis.Methods The hemodynamic model was established after the implantation of vascular stent in tapered vessel with multiple stenosis.The numerical simulation method was used to study the effect of the combination of different shaped stents and balloons on postoperative hemodynamics.Results When the cylindrical stent was expanded using the cylindrical balloon and tapered balloon respectively,compared with cylindrical balloon expansion,the proportion of low-speed blood flow area generated by tapered balloon expansion was reduced by 0.58％,and the proportion of low time-averaged wall shear stress(TAWSS)area was reduced by 3.22％.The use of tapered balloon for expansion could produce less low-speed blood flow and low TAWSS area.When tapered balloon was used to expand the cylindrical stent and tapered stent respectively,compared with expanding tapered stent,the proportion of low-speed blood flow area generated by expanding cylindrical stent decreased by 1.35％,and the proportion of low TAWSS area decreased by 9.73％.Conclusions The hemodynamic environment of tapered vessel with multiple stenosis was influenced by the shape of stent and balloon.The use of tapered balloon to expand the cylindrical stent in tapered vessels with multiple stenosis can achieve favorable hemodynamic environment and reduce the risk of ISR occurence.This study can provide a scientific basis for the rational formulation of clinical intervention scheme.

Objective:Using Mendelian randomization analysis to investigate the unidirectional causal effects of gut microbiota on gout and serum uric acid levels.Methods:The Mendelian randomization analysis was conducted using summary statistics from genome-wide association studies (GWAS). The gut microbiota was used as the exposure factor, with gout and serum uric acid levels as the outcomes, utilizing the MiBioGen Consortium, FinnGen GWAS, and CKDGen Consortium meta-analysis databases. The analysis was performed using inverse variance weighted (IVW) method, MR-Egger, and weighted median (WM) approach. Additionally, sensitivity analysis was conducted by excluding heterogeneity and horizontal pleiotropy. This study used RStudio 4.3.1 software for analysis.Results:The IVW results confirmed that 17 microbiota taxa were associated with gout, including class Verrucomicrobiaceae [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], family Verrucomicrobiaceae [ OR(95% CI)=1.161(1.004, 1.344), P=0.044], genus Akkermansia [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], genus Collinsella [ OR(95% CI)=1.257(1.043, 1.516), P=0.016], genus Eubacterium hallii group [ OR(95% CI)=1.226(1.022, 1.471), P=0.027], genus Howardella [ OR(95% CI)=1.094(1.001, 1.195), P=0.046], genus Ruminococcaceae UCG010 [ OR(95% CI)=1.317(1.089, 1.593), P=0.004], order Clostridiales [ OR(95% CI)=1.182(1.007,1.387), P=0.041], order Verrucomicrobiales [ OR(95% CI)=1.162(1.004, 1.344), P=0.044], class Melainabacteria [ OR(95% CI)=0.894(0.804, 0.994), P=0.038], family Streptococcaceae [ OR(95% CI)=0.851(0.727, 0.996), P=0.044], unknown family [ OR(95% CI)=0.890(0.800, 0.989), P=0.030], genus Streptococcus [ OR(95% CI)=0.836(0.710, 0.983), P=0.030], unknown genus [ OR(95% CI)=0.890(0.800, 0.989), P=0.030], genus Victivallis [ OR(95% CI)=0.857(0.736, 0.998), P=0.046], order Gastranaerophilales [ OR(95% CI)=0.890(0.800,0.989), P=0.030], and phylum Bacteroidetes [ OR(95% CI)=0.827(0.692, 0.989), P=0.037]. Additionally, 5 microbiota taxa were associated with serum uric acid levels: phylum Actinobacteria [ OR(95% CI)=0.963(0.925, 0.992), P=0.027], family ⅩⅢ [ OR(95% CI)=0.965(0.932, 1.008), P=0.035], genus Escherichia Shigella [ OR(95% CI)=1.047(1.005,1.089), P=0.034], genus Lachnospiraceae FCS020 group [ OR(95% CI)=0.974(0.941, 1.003), P=0.028], and genus Lachnospiraceae NC2004 group [ OR(95% CI)=0.966(0.943, 0.995), P=0.018]. No abnormalities in SNPs were found in the sensitivity analysis. Conclusion:An increase in the levels of class Verrucomicrobiae, family Verrucomicrobiaceae, genus Akkermansia, and genus Escherichia Shigella is associated with an increased risk of gout or serum uric acid levels, while an increase in the levels of class Melainabacteria, family Streptococcaceae, unknown family, phylum Actinobacteria, and family ⅩⅢ is associated with a decreased risk of gout or serum uric acid levels.

Objective:To investigate whether neoadjuvant therapy can improve the prognosis of patients with pancreatic cancer.Methods:A retrospective case-control study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database on 12, 103 patients who underwent surgical treatment between January 1, 2010, and December 31, 2021. Patients were divided into the neoadjuvant therapy group ( n=3 276) and the upfront surgery group ( n=8 827) based on whether they received neoadjuvant treatment. The neoadjuvant therapy group included 2 342 patients receiving neoadjuvant chemotherapy and 934 patients receiving neoadjuvant chemoradiotherapy. The upfront surgery group consisted of 4 335 patients receiving adjuvant chemotherapy, 1 987 patients receiving adjuvant chemoradiotherapy, 63 patients receiving adjuvant radiotherapy, and 2 442 patients undergoing surgery alone. Propensity score matching was used to eliminate group differences and create a cohort with no statistical differences in other clinicopathological features except for the grouping variable. Variables such as age, gender, tumor location, race, population of residence, tumor diameter, household income, TNM stage, and information on radiotherapy and chemotherapy were used for 1∶1 case matching. T stage, N stage, and the use of radiotherapy or chemotherapy were matched exactly. After matching, 1 182 patients were included in each group: the neoadjuvant therapy group contained 1 155 patients receiving neoadjuvant chemoradiotherapy and 27 receiving neoadjuvant chemotherapy, while the upfront surgery group comprised 848 patients receiving adjuvant chemotherapy and 334 receiving adjuvant chemoradiotherapy. TNM staging was reported according to the 7th edition of the AJCC guidelines. The primary outcome was overall survival. Measurement data with skewed distributions were expressed as M( Q1, Q3), and intergroup comparisons were conducted using the Wilcoxon rank-sum test. Categorical data were compared using the chi-square test or the Fisher′s exact test. The Log-rank test and subgroup analyses to assess interactions between neoadjuvant therapy and subgroup in COX regression models were used to compare survival benefits across variables. Landmark analysis was performed to create segmented survival curves, studying the impact of neoadjuvant therapy on prognosis during different follow-up periods. Results:The neoadjuvant therapy group had a higher proportion of T 4 tumor involving celiac axis, superior mesenteric artery, and/or common hepatic artery compared to the upfront surgery group (14.7% vs 2.8%, P<0.001). Additionally, significant differences were observed between groups in terms of race, location, population of residence, age, tumor diameter, tumor stage, and adjuvant therapy regimen ( P<0.05). The median overall survival time in the neoadjuvant therapy group was 30 months, compared to 22 months in the upfront surgery group ( P<0.001). In the neoadjuvant therapy group, the median survival was 30 months for both neoadjuvant chemotherapy and chemoradiotherapy patients; in the upfront surgery group, it was 26 months for both adjuvant chemotherapy and chemoradiotherapy patients, 17 months for adjuvant radiotherapy patients, and 12 months for surgery-only patients. After propensity score matching, there were no differences in the distribution of clinical characteristics between groups ( P>0.05), and all patients in the matched cohort had received chemotherapy. The matched neoadjuvant therapy group had a longer median overall survival compared to the upfront surgery group (30 months vs 27 months, P<0.001). Subgroup interaction analysis revealed that T stage had a significant interaction with neoadjuvant therapy, both before (T 4 stage: HR=0.382, 95% CI: 0.319-0.458; T 2-T 3 stages: HR=0.696, 95% CI: 0.656-0.738; T 1 stage: HR=1.199, 95% CI: 0.867-1.657; interaction P<0.001) and after matching (T 4 stage: HR=0.581, 95% CI: 0.414-0.814; T 2-T 3 stages: HR=0.827, 95% CI: 0.734-0.931; T 1 stage: HR=1.320, 95% CI: 0.716-2.433; interaction P=0.043). Subgroup interaction analysis indicated that T 1 patients did not benefit from neoadjuvant therapy; survival curves plotted for matched T 1 patients showed no difference in survival between the neoadjuvant therapy group and the upfront surgery group ( P=0.323). Conversely, non-T 1 (T 2-T 4) stage patients showed significant survival benefits in both unmatched and matched cohorts ( P<0.001). Landmark analysis showing that the survival benefits occurred mainly in the early postoperative period of up to 3 years ( P<0.001), but there was no difference in overall survival between the neoadjuvant therapy group and the upfront surgery group of >3 years ( P>0.05). Patients with Arterial invasion (T 4 stage compared to T 1-T 3 stages) showed a similarly significant interaction with the benefit of neoadjuvant therapy in both the pre-matching cohort (interaction P<0.001) and the post-matching cohort (interaction P=0.037). Patients with T 4 stage disease in the neoadjuvant therapy group had longer overall survival compared to the upfront surgery group (median overall survival in pre-matching cohort: 30 months vs 13 months, P<0.001; median overall survival in post-matching cohort: 28 months vs 18 months, P=0.001). Among T 4 stage patients in the post-matching cohort, neoadjuvant therapy provided significant survival benefits during the early postoperative period of up to 3 years ( P=0.001). However, there was no difference in overall survival between the neoadjuvant therapy group and the direct surgery group beyond 3 years( P=0.729). Conclusions:The prognosis in the neoadjuvant therapy group was better than in the upfront surgery group. Propensity score matching and subgroup interaction analysis showed that non-T 1 and T 4 stage patients benefited more from neoadjuvant therapy, with benefits mainly seen in the early postoperative period (≤3 years).

Objective:To investigate the mechanism of ursolic acid regulating HMGB1/TLR4 pathway in reducing intestinal barrier injury in a rat model of ulcerative colitis(UC).Methods:Rats were randomly divided into control group,model group,glycyr-rhizic acid(HMGB1 inhibitor)group,ursolic acid group and glycyrrhizic acid+ursolic acid group,with 12 rats in each group.UC rat model was induced by tritrobenzene sulfonate enema.After drug administration,body weight and disease activity index(DAI)score were performed of rats in each group;pathological morphology of colonic mucosa was detected by HE staining,the thickness of mucosa and height of villi were compared;levels of catalase(CAT),superoxide dismutase(SOD),malondialdehyde(MDA)in colon tissue,levels of serum diamine oxidase(DAO),and intestinal fatty acid binding protein(I-FABP),TNF-α,IL-18,IL-6 were detected by kits;expression levels of tight junction proteins(Claudin-1,ZO-1,Occludin)and HMGB1/TLR4 pathway proteins(HMGB1,TLR4,MyD88)in colon tissues were detected by Western blotting.Expression levels of HMGB1,TLR4 and MyD88 in colonic tissue were detected by immunohistochemistry.Results:Compared with control group,colonic mucosal tissue of model group had severe pathological injury,the body weight,mucosal thickness,villus height,CAT,SOD,Claudin-1,ZO-1 and Occludin levels in colon tis-sue were significantly reduced,while DAI score,serum DAO,I-FABP,TNF-α,IL-18 and IL-6 levels,colon tissue MDA,HMGB1,TLR4 and MyD88 levels were significantly increased(P<0.05);compared with model group,pathological injury of colonic mucosal tissue of rats in ursolic acid group,glycyrrhizic acid group and glycyrrhizic acid+ursolic acid group were reduced,body weight,muco-sal thickness,villus height,colon tissue CAT,SOD,Claudin-1,ZO-1 and Occludin levels were significantly increased,while DAI score,serum DAO,I-FABP,TNF-α,IL-18 and IL-6 levels,colon tissue MDA,HMGB1,TLR4 and MyD88 levels were significantly reduced(P<0.05);combined intervention of glycyrrhizic acid and ursolic acid could enhance the influence of ursolic acid on the above indexes(P<0.05).Conclusion:Ursolic acid can inhibit inflammation,reduce the level of oxidative stress,reduce the colonic mucosal injury of UC rats,repair the intestinal mucosal barrier function,and improve the clinical symptoms of rats,which may be achieved by down-regulating the HMGB1/TLR4 pathway.

Objective To explore the value of MRI quantitative parameters and free/total prostate-specific antigen ratio(f/tPSA)for diagnosing prostate imaging reporting and data system(PI-RADS)3-point clinically significant prostate cancer(csPCa).Methods Totally 57 patients with PI-RADS 3-point prostate lesions were retrospectively enrolled,including 18 prostate cancer(PCa)(PCa group)and 39 benign hyperplasia with chronic prostatitis(non-PCa group).The former included 12 cases of csPCa and 6 cases of clinically insignificant PCa(ciPCa).Taken non-PCa and ciPCa into non-csPCa group(n=45),laboratory and MRI parameters(apparent diffusion coefficient[ADC],T1,T2,proton density[PD]values)were compared between PCa and non-PCa groups,also between csPCa and non-csPCa groups.Based on laboratory and MRI parameters being statistically different between groups according to univariate analysis,combined models were established using logistic regression.The efficacy of laboratory,MRI parameters and combined models for differentiating PCa and non-PCa as well as csPCa and non-csPCa were evaluated.Results ADC,T1,T2,PD values in PCa group were all lower those in non-PCa group(all P＜0.05),and f/tPSA,ADC,T1,T2 and PD values in csPCa group were all lower than those in non-csPCa group(all P＜0.05).AUC of ADC,T1,T2 and PD values for differentiating PCa from non-PCa was 0.662,0.755,0.793 and 0.729 respectively,while of ADC-T1-T2-PD combined model was 0.839,higher than that of ADC alone(P＜0.05)but not significantly different with T1,T2 and PD values alone(all P＞0.05).AUC of f/tPSA,ADC,T1,T2 and PD values for differentiating csPCa from non-csPCa was 0.692,0.759,0.741,0.805 and 0.737,respectively,while of ADC-T1-T2-PD combined model was 0.889,higher than that of f/tPSA,ADC and T1 values alone(all P＜0.05)but not significantly different with that of T2 and PD value alone(both P＞0.05).AUC of f/tPSA-ADC-T1-T2-PD combined model was 0.898,higher than that of f/tPSA,ADC,T1 and PD values alone(all P＜0.05)but not significantly different with T2 value and ADC-T1-T2-PD combined model(both P＞0.05).Conclusion MRI quantitative parameters combined with f/tPSA could effectively diagnose PI-RADS 3-point csPCa.

Objective To study the influence of stent and balloon shape on hemodynamics in tapered vessels with multiple stenosis.Methods The hemodynamic model was established after the implantation of vascular stent in tapered vessel with multiple stenosis.The numerical simulation method was used to study the effect of the combination of different shaped stents and balloons on postoperative hemodynamics.Results When the cylindrical stent was expanded using the cylindrical balloon and tapered balloon respectively,compared with cylindrical balloon expansion,the proportion of low-speed blood flow area generated by tapered balloon expansion was reduced by 0.58％,and the proportion of low time-averaged wall shear stress(TAWSS)area was reduced by 3.22％.The use of tapered balloon for expansion could produce less low-speed blood flow and low TAWSS area.When tapered balloon was used to expand the cylindrical stent and tapered stent respectively,compared with expanding tapered stent,the proportion of low-speed blood flow area generated by expanding cylindrical stent decreased by 1.35％,and the proportion of low TAWSS area decreased by 9.73％.Conclusions The hemodynamic environment of tapered vessel with multiple stenosis was influenced by the shape of stent and balloon.The use of tapered balloon to expand the cylindrical stent in tapered vessels with multiple stenosis can achieve favorable hemodynamic environment and reduce the risk of ISR occurence.This study can provide a scientific basis for the rational formulation of clinical intervention scheme.

Objective To explore the value of MRI quantitative parameters and free/total prostate-specific antigen ratio(f/tPSA)for diagnosing prostate imaging reporting and data system(PI-RADS)3-point clinically significant prostate cancer(csPCa).Methods Totally 57 patients with PI-RADS 3-point prostate lesions were retrospectively enrolled,including 18 prostate cancer(PCa)(PCa group)and 39 benign hyperplasia with chronic prostatitis(non-PCa group).The former included 12 cases of csPCa and 6 cases of clinically insignificant PCa(ciPCa).Taken non-PCa and ciPCa into non-csPCa group(n=45),laboratory and MRI parameters(apparent diffusion coefficient[ADC],T1,T2,proton density[PD]values)were compared between PCa and non-PCa groups,also between csPCa and non-csPCa groups.Based on laboratory and MRI parameters being statistically different between groups according to univariate analysis,combined models were established using logistic regression.The efficacy of laboratory,MRI parameters and combined models for differentiating PCa and non-PCa as well as csPCa and non-csPCa were evaluated.Results ADC,T1,T2,PD values in PCa group were all lower those in non-PCa group(all P＜0.05),and f/tPSA,ADC,T1,T2 and PD values in csPCa group were all lower than those in non-csPCa group(all P＜0.05).AUC of ADC,T1,T2 and PD values for differentiating PCa from non-PCa was 0.662,0.755,0.793 and 0.729 respectively,while of ADC-T1-T2-PD combined model was 0.839,higher than that of ADC alone(P＜0.05)but not significantly different with T1,T2 and PD values alone(all P＞0.05).AUC of f/tPSA,ADC,T1,T2 and PD values for differentiating csPCa from non-csPCa was 0.692,0.759,0.741,0.805 and 0.737,respectively,while of ADC-T1-T2-PD combined model was 0.889,higher than that of f/tPSA,ADC and T1 values alone(all P＜0.05)but not significantly different with that of T2 and PD value alone(both P＞0.05).AUC of f/tPSA-ADC-T1-T2-PD combined model was 0.898,higher than that of f/tPSA,ADC,T1 and PD values alone(all P＜0.05)but not significantly different with T2 value and ADC-T1-T2-PD combined model(both P＞0.05).Conclusion MRI quantitative parameters combined with f/tPSA could effectively diagnose PI-RADS 3-point csPCa.