ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

Objective To investigate the mechanism by which angiotensin Ⅱ type 1 receptor autoantibody(AT1-AA)promotes phenotypic switch of vascular smooth muscle cells(VSMCs)and vascular fibrosis through abnormal expression of circadian clock protein BMAL1.Methods Twelve male SD rats(6～8 weeks old,weighing 180～220 g)were randomly divided into(n=6)a control group and an AT1-AA-positive group[established by active immunization of SD rats with AT1R extracellular loop Ⅱ peptide(AT1R-ECLⅡ)].HE and Masson stainings were used to observe structural changes and fibrosis in the thoracic aorta(n=3).Western blotting was performed to detect the expression of Collagen I,phenotypic switch-related proteins(SM22,α-SMA,OPN and MMP2)in vascular tissues and primary VSMCs(n=4),as well as the expression of BMAL1 at CT0,CT4,CT8,CT12,CT16,and CT20.Transwell and scratch assays were used to assess the proliferation and migration of VSMCs(n=3).si-RNA was employed to knock down Bmal1,followed by detection of BMAL1,Collagen I,and phenotypic conversion-related protein expression(n=3).Additionally,AT1-AA-positive AT1R-knockout(AT1R-KO)rats were constructed to measure BMAL1 expression in thoracic aortic tissues(n=4).Results The AT1-AA-positive rats had significantly thickened thoracic aortic vessel wall[(140±9)%vs(120±5)%,P<0.05],badly arranged VSMCs,obvious blue Masson staining,and up-regulated Collagen I expression(P<0.05).In the thoracic aorta of AT1-AA-positive rats and AT1-AA-treated VSMCs,the expression of contractile phenotype-related proteins(α-SMA,SM22)was decreased(P<0.05),while the expression of synthetic phenotype-related proteins(OPN,MMP2)was increased(P<0.05).AT1-AA enhanced the scratch healing ability and migration ability of VSMCs.Furthermore,both mRNA and protein levels of Bmal1 were significantly up-regulated at CT12(P<0.05),and the rhythmicity of Bmal1 was lost.Knockdown of Bmal1 partially ameliorated AT1-AA-induced phenotypic switch of VSMCs.Compared with AT1-AA-positive WT rats,AT1-AA-positive AT1R-KO rats showed significantly reduced BMAL1 expression in the thoracic aorta(1.35±0.06 vs 0.86±0.07,P<0.001).At the cellular level,AT1-AA-induced phenotypic switch and high Collagen I expression in VSMCs were partially improved in AT1R-KO VSMCs.Conclusion AT1-AA promotes VSMCs phenotypic conversion and vascular fibrosis through the AT1R-Bmal1 axis.

Alzheimer's disease(AD)is a progressive neurodegenerative disease with hidden onset.Recent researches have shown that apolipoprotein E4(APOE4)is a high-risk genetic factor of AD,and the clinical symptoms in APOE4 genotype AD patients are closely related to metabolic disorders.This paper reviewed the role of APOE4 in the pathogenesis of AD,and it is indicated that APOE4 contributes to the injury of the cerebral blood-brain barrier,is associated with the disorder of cerebral glucose and lipid metabolism,and leads to the damage of the scavenging ability of microglia.Moreover,this paper explored the approach of early intervention of AD with traditional Chinese medicine(TCM)based on the APOE4 pathogenesis.Based on the pathogenesis of AD being deficiency in origin and excess in superficiality,and under the guidance of the principle of prevention before illness in TCM,it is proposed that early TCM intervention for APOE4 genotype AD patients with metabolic disorders can be performed through improving the phlegm-dampness constitution,by focusing on insulin resistance-related indicators,and with traditional Chinese drug therapy based on syndrome differentiation alone or together with comprehensive management of exercises,diet control and drug interventions,thus to reduce or delay the onset of APOE4 genotype AD.

OBJECTIVE: To explore the feasibility and effectiveness of repairing surgical defect in pharyngo-laryngeal malignant tumor with free rectus femoris flap. METHODS: The clinical data of 34 patients with surgical defects in pharyngo-laryngeal malignant tumor who met the selection criteria between July 2014 and August 2024 were retrospectively analyzed. There were 25 males and 9 females, aged 25-82 years, with a median age of 54 years. The disease duration ranged from 2 months to 2 years, with a median of 7 months. The tumor locations included the oropharynx, hypopharynx, cervical esophagus, and larynx. Pathological types included squamous cell carcinoma (29 cases), myoepithelial carcinoma (2 cases), adenoid cystic carcinoma (1 case), and diffuse large B-cell lymphoma (2 cases). TNM staging: 16 cases of T ₄N ₁M ₀, 3 cases of T ₄N ₂M ₀, 3 cases of T ₄N ₀M ₀, 10 cases of T ₃N ₁M ₀, and 2 cases of T ₃N ₀M ₀. The 2017 American Joint Committee on Cancer (AJCC) staging was stage Ⅲ in 2 cases and stage Ⅳ in 32 cases. The blood supply of the proximal rectus femoris muscle was observed by enhanced CT of the lower limb vessels before operation, and the surgical defects ranged from 3.0 cm×2.0 cm to 12.0 cm×8.5 cm. The blood supply and perforators of rectus femoris muscle were explored during operation, and the free rectus femoris flap pedicled with the direct vascular stem of rectus femoris muscle was used to repair the defect. For the patients with pharyngeal fistula or obvious neck swelling after operation, the blood supply of the flap was analyzed by vascular enhanced CT to determine the corresponding strategies of nutritional support, anti-infection, dressing change and drainage. Radiotherapy and chemotherapy were supplemented in 27 patients with lymph node metastasis after operation. RESULTS: All the 34 patients were followed up 1-10 years, with an average of 3 years. The flap was found to be necrotic by fibrolaryngoscopy at 1 week after operation in 2 cases, and the incision healed after dressing change and nutritional support, and no reoperation was performed. The flap was in good condition at 1 week after operation in 4 cases, and the signs of gradual necrosis of the flap were found within 1 month after operation, of which 2 cases were healed after dressing change, 1 case was removed the necrotic tissue by reoperation, and 1 case was healed after pectoralis major myocutaneous flap was used to repair the pharyngeal tissue defect. The flaps survived in 28 cases, including 4 cases of pharyngeal fistula, which healed by dressing change. Twenty-two cases achieved satisfactory results in swallowing or phonation. Two patients with total laryngectomy and voice reconstruction underwent reoperation to seal the voice tube because of postoperative aspiration. During the follow-up, 1 case had tracheal stomal recurrence, 2 cases had bone metastasis, and 1 case had bone and lung metastasis. CONCLUSION The free rectus femoris flap has good flexibility, the volume of the flap is easy to adjust, and the incision of the donor site is concealed, which is expected to become a new choice for the repair of the surgical defect in pharyngo-laryngeal malignant tumor.
Humans ; Male ; Middle Aged ; Female ; Aged ; Adult ; Plastic Surgery Procedures/methods* ; Retrospective Studies ; Laryngeal Neoplasms/pathology* ; Aged, 80 and over ; Pharyngeal Neoplasms/pathology* ; Free Tissue Flaps/blood supply* ; Quadriceps Muscle/transplantation* ; Surgical Wound/surgery* ; Treatment Outcome

Abstract Tumor immune escape represents a pivotal determinant of cancer immunotherapy failure. It's mechanistically linked to immunosuppressive tumor microenvironment(TME). The TME comprises tumor cells, immune cells, stromal components and extracellular matrix. These components interact synergistically to suppress antitumor immunity through multiple pathways, thereby promoting immune evasion. As crucial chromosomal stability regulators, centromere proteins(CENPs) remodel the TME via multifaceted mechanisms to potentiate immune evasion. This review synthesizes current knowledge on CENPs' role in tumor immune evasion, offering novel insights for cancer diagnostics and immunotherapy.

Objective:To observe the clinical effect of Shenfu injection in preventing septic cardiomyopathy (SIC) in septic patients.Methods:From June 2022 to January 2023, patients with sepsis or septic shock who did not develop SIC were randomly divided into treatment group and control group according to the ratio of 1:1. In the treatment group, Shenfu injection (50 mL) was pumped intravenously once every 12 hours for 5 days. In the control group, 50 mL of normal saline was pumped intravenously once every 12 hours, and the course of treatment was 5 days. The primary end point was the incidence of SIC in the first 5 days. The secondary end points were the application time of vasoactive drugs, fluid balance in the previous week, hospitalization time in ICU, total ventilation time and 28-day mortality.Results:112 patients were randomly divided into two groups. Seven patients in the treatment group were excluded twice, and finally 49 patients were included in the analysis, while six patients in the control group were excluded twice and 50 patients included in the analysis. The total incidence of SIC in the treatment group within 5 days was significantly lower than that in the control group (42.9% vs. 64.0%, P = 0.035). Among them, the left ventricular systolic dysfunction in the treatment group was significantly lower than that in the control group (24.5% vs 52.0%, P=0.005), and there was no significant difference in the incidence of left ventricular diastolic dysfunction between the two groups. The incidence of right ventricular dysfunction in the control group was 28.0%, which was significantly higher than 10.2% in the treatment group ( P = 0.025). The duration of using vasoconstrictors in the treatment group was 75(48, 97) hours, which was significantly lower than 97(66, 28) hours in the control group ( P = 0.039). The duration of inotropic drugs use in the treatment group was 32(18, 49) h, which was also significantly shorter than 44(25, 61) h in the control group ( P=0.046). The fluid balance of the control group in the first week was (1 260±850) mL, which was significantly higher than (450±520) mL in the treatment group ( P=0.008). There was no statistical difference in ICU stay, total ventilation time and 28-day mortality between the two groups (all P > 0.05). Conclusion:Early application of Shenfu injection can significantly reduce the incidence of SIC, accompanied by less use of vasoactive drugs and positive fluid balance, which has a good clinical application prospect.

Objective To evaluate the therapeutic effect of poloxamer hydrogel loaded with exosomes derived from human dental pulp stem cells genetically modified with human hepatocyte growth factor against radiation skin injuries.Methods Human dental pulp stem cells derived exosomes(DPSC-Exo)and hepatocyte growth factor modified DPSC-Exo(HGF-DPSC-Exo)were extracted via ultracentrifugation separation,identified in terms of particle size and morphology,and analyzed separately by means of nanoparticle tracking analysis and scanning electron microscopy(SEM),while exosome marker proteins were determined by Western blot.Then,the effect of exosomes on radiation-damaged skin cells was assessed.The poloxamer hydrogel was prepared and its safety was evaluated with CCK-8.A mouse model of injury combined with radiation injury was established,and the therapeutic effect of hydrogel loaded with exosomes was determined based on wound size,HE and Masson staining.Furthermore,the underlining therapeutic mechanism was explored with Tunnel assay,malondialdehyde content and peroxidase activity.Results The diameter exosomes ranged from 30 to 150 nm and their morphology was a disc-shaped vesicle under SEM.Moreover,CD9,CD63 and TSG101 were expressed.The results of cellular experiments showed that exosomes significantly promoted the proliferation and migration of radiation-damaged skin keratinocytes and fibroblasts,and reduced their apoptosis.HGF modification enhanced the healing effect of exosomes.Poloxamer hydrogel showed good temperature-sensitive properties and biocompatibility.The results of animal experiments showed that exosomes significantly accelerated the healing of radiation-combined injuries in mice,inhibited inflammatory infiltration and mitigated collagen deposition in the wound.Interestingly,the healing effect in the group treated with hydrogel loaded with exosomes was the best.The underlining mechanism was possibly related to promotion of cell proliferation and inhibition of apoptosis and oxidative stress.Conclusion A novel poloxamer hydrogel loaded HGF-DPSC-Exo has been prepared and its therapeutic effect against radiation combined injury has been proved,thus providing a new strategy for the treatment of radiation skin injury in clinic.

The human gastrointestinal tract is the largest reservoir of bacteria in the body,inhabiting a very complex and active microbial community.Under normal circumstances,the interaction between the intestinal flora and the host maintains a dynamic balance.Spleen deficiency syndrome is a common classic syndrome type in TCM clinical practice.A large number of studies have shown that spleen deficiency syndrome is closely related to intestinal microorganisms,and the balance of intestinal flora is the basis for the normal functioning of the spleen's main transportation and transformation functions.Intestinal flora imbalance can lead to a series of manifestations of spleen deficiency.In addition,intestinal flora is an important medium for the metabolism of polysaccharide components and the effectiveness of traditional Chinese medicine for invigorating the spleen,and traditional Chinese medicine for invigorating the spleen can also play a therapeutic role by regulating the structure and quantity of intestinal flora.This article summarizes the relationship between intestinal flora and spleen deficiency syndrome in physiology,pathology,and the efficacy of traditional Chinese medicine for invigorating the spleen.Based on intestinal flora,the study of spleen deficiency syndrome aims to provide some thoughts and suggestions for revealing the connotation of spleen deficiency syndrome in traditional Chinese medicine.

Objective To investigate the genetic causal relationship between rheumatoid arthritis (RA) and its serological antibody levels with pre-eclampsia (PE) based on Mendelian randomization (MR). Methods Single nucleotide polymorphism (SNP) with significant differences were screened as instrumental variables,and the five MR analytic method with the inverse variance weighting (IVW) as the main analytical method were applied to comprehensively assess the causal cc relationship between OA,serum antibody levels PE.The MR-Egger intercept method,MR pleiotropy residual and outlier (MR-PRESSO) method,Cochrane's Q-test were applied to explore the horizontal pleiotropy and heterogeneity of SNP,and the leave-one-out meth-od was used to explore the effect of individual SNPs on MR results.Results The IVW result indicated that RA (OR=1.098,95％CI:1.036-1.164,P=0.002) and seropositive RA (OR=1.088,95％CI:1.026-1.153,P=0.005) were the PE risk factors,whereas seronegative RA (OR=1.036,95％CI:0.971-1.104, P=0.282) did not have a significant causal relationship with PE.No significant level pleiotropy or heteroge-neity was found in the SNPs used in MR analyses of the 3 exposure factors.rs34434863 played a decisive role in the causal relationship of RA and seropositive RA with PE.Conclusion Based on MR analysis,there is a significant positive causal relationship between RA and seropositive RA with PE,whereas there was no signifi-cant causal relationship between seronegative RA and PE.

OBJECTIVE To investigate the mechanisms by which the NPY-Y1 signalling pathway regulates eosinophilic inflammation in the nasal mucosa of rats with eosinophilic chronic rhinosinusitis(ECRS).METHODS Seventy-two rats were divided into 6 groups according to the random grouping method of body weight.There were 12 rats in each group,including the control group,ECRS group,no-loading group,neuropeptide Y(NPY)interference group,low antagonist group and high antagonist group.Except for the control group,the ECRS rat model was constructed using the ovalbumin sensitisation+bacterial toxin method in the other five groups.The no-loading group and NPY-interfering group were intervened by tail vein injection of siNC and NPY siRNA plasmid,respectively,and the low and high antagonist groups were intervened by intraperitoneal injection of 20 and 50 μg of BIBO 3304,respectively.The rats were executed at the end of the final stimulation,and the nasal mucosal tissues were taken for HE staining and eosinophil(Eos)counting.NPY,IL-4,IL-5,IL-13 mRNA expression in nasal mucosa was detected by RT-PCT.Nuclear factor κB p65(NF-κB p65),NF-κB p50 protein expression was detected by Western blot method.NPY,NPY1 receptor(Y1R)expression was detected by immunohistochemistry.RESULTS HE staining results showed that the tissue structure of the nasal mucosa in the control group was complete and orderly.In the ECRS group and the airborne group,the cell arrangement was disordered and a large number of inflammatory cell infiltration appeared.In the low antagonist group,the cell structure was improved and the inflammatory cell infiltration was reduced.Compared with the low antagonist group,the improvement of cell structure and inflammatory cell infiltration was more significant in the NPY interference group and high antagonist group.Compared with the control group,the Eos count of nasal mucosa,NPY,IL-4,IL-5,IL-13 mRNA,NF-κB p65,NF-κB p50 protein and the relative intensity values of NPY and Y1R cell staining were significantly higher in both the ECRS group and the no-loading group(all P<0.05).Compared with the ECRS group and the no-loading group,the above indexes were reduced in the NPY interference group,the low antagonist group and the high antagonist group,and the NPY interference group and the high antagonist group were lower than that of the low antagonist group(all P<0.05).There was no statistically significant difference in the above indicators between the ECRS group and the no-loading group,the NPY interference group and the high antagonist group(all P>0.05).CONCLUSION ECRS rats have an abnormal infiltrative inflammatory response to Eos in the nasal mucosa,the mechanism of which may be related to the NPY-Y1 signalling pathway through activation of the NF-κB signalling pathway and effector protein expression.