At present, research on the efficacy of local physical cooling devices is mainly based on clinical observation, but there is relatively little research on evaluating the effectiveness of local cold therapy cooling and the penetration depth. This study is based on the research of the structure and morphology of local muscle tissue in the human body, as well as the heat transfer characteristics and mechanisms of the human body. A simulation phantom of human muscle tissue under temperature cycling was created, and the differences in evaluating the effectiveness of local cold therapy between the human body and the simulation phantom were compared. This provides a new evaluation method for evaluating the cooling effectiveness of local physical cooling equipment.
Humans ; Phantoms, Imaging ; Hypothermia, Induced/methods*

Myocardial fibrosis is a serious cause of heart failure and even sudden cardiac death. However, the mechanisms underlying myocardial ischemia-induced cardiac fibrosis remain unclear. Here, we identified that the expression of sterile alpha and TIR motif containing 1 (SARM1), was increased significantly in the ischemic cardiomyopathy patients, dilated cardiomyopathy patients (GSE116250) and fibrotic heart tissues of mice. Additionally, inhibition or knockdown of SARM1 can improve myocardial fibrosis and cardiac function of myocardial infarction (MI) mice. Moreover, SARM1 fibroblasts-specific knock-in mice had increased deposition of extracellular matrix and impaired cardiac function. Mechanically, elevated expression of SARM1 promotes the deposition of extracellular matrix by directly modulating P4HA1. Notably, by using the Click-iT reaction, we identified that the increased expression of ZDHHC17 promotes the palmitoylation levels of SARM1, thereby accelerating the fibrosis process. Based on the fibrosis-promoting effect of SARM1, we screened several drugs with anti-myocardial fibrosis activity. In conclusion, we have unveiled that palmitoylated SARM1 targeting P4HA1 promotes collagen deposition and myocardial fibrosis. Inhibition of SARM1 is a potential strategy for the treatment of myocardial fibrosis. The sites where SARM1 interacts with P4HA1 and the palmitoylation modification sites of SARM1 may be the active targets for anti-fibrosis drugs.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective To investigate the expression level of serum tRNA derived tRF-17-79MP9PP(tRF-17)in patients with breast cancer and evaluate its correlation with the prognostic of the patients.Methods The serum samples were collected from 70 patients with breast cancer admitted to Jiangsu Cancer Hospital during June 2016 and December 2019 and 25 age-matched healthy women,and the clinical data of the patients were recorded.The expression level of serum tRF-17 was detected by real-time fluorescence quantitative PCR(qRT-PCR).The receiver operating characteristics(ROC)curve was used to evaluate the diagnosis value of tRF-17 in breast cancer patients.The correlations of tRF-17 with blood inflammatory indicators and tumor markers were analyzed by Spearman correlation analysis.The deadline for follow-up was April 2023.The factors influencing the prognosis of breast cancer were analyzed by the univari-ate and multivariate COX regression analysis.Results The expression levels of serum tRF-17 in breast cancer patients(3.99[0.70,10.46])were significantly lower than that in healthy controls(14.09[5.14,21.34],Z=-3.575,P＜0.01).The area under the ROC curve of tRF-17 for diagnosing breast cancer was 0.742(95％CI:0.635-0.849,P＜0.01).The average survival time of patients with high expression of tRF-17 was significantly higher than that of patients with low expression(75.97 months vs 56.06 months,log-rank P＜0.01).The COX proportional hazards model analysis showed that lymph node metastasis and the expression level of serum tRF-17 were independent risk factors affecting the prognosis of the patients(HR=1.723,95％Cl:1.084-2.739,P＜0.05;HR=0.189,95％CI:0.041-0.862,P＜0.05).Conclusion Serum tRF-17 is low expressed in breast cancer patients,and its expression level is an inde-pendent risk factor affecting the prognosis of breast cancer patients,which may be used as a biomarker to evaluate the prognosis of the patients.

Objective:This study aimed to overview the typical practies made by Europe on rare diseases cooperative researches and provide reference for the construction of rare disease research system in China.Methods:Through literature reviews and official website information, this study systematically summarized the contributions and outputs made by the framework of Europe cooperation in rare disease field.Results:Focusing on the needs of patients, the aim of international cooperation was to improve the ability of ″diagnosis, treatment, research and education″. inclnding multi-sourced special funding and project topic screening, expert networks setup and patient impower, research network construction and mutual promotion, information system modernization, etc.Conclusions:The eco-system of rare disease research in China is still under-construction. It is recommended to combine the characteristics of China′s healthcare system, optimize input strategies, empower patients, innovate mechanism, and speed up bioinformation technology.

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a^-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a^-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

Objective:In this study, the role of IL-17 in the pathogenesis of idiopathic myositis (IIM) was preliminarily investigated by detecting the expression of IL-17 in the muscle tissues of patients with idiopathic inflammatory myositis (IIM) and normal controls.Methods:Twenty-eight patients (20 in DM group with dermatomyositis and 8 in ASS group with anti-synthase syndrome) who were diagnosed with IIM after muscle biopsy and autoantibody detection in our hospital for the first time from October 2019 to August 2021 were included. Twelve cases with normal muscle tissue matched for age and sex were included as the control group. Western blot and immunohistochemical techniques were used to detect the expression level of IL-17 in muscle tissue, and enzyme-linked immunosorbent assay (ELISA) was used to detect serum IL-6. Mann-Whitney U rank sum test was used to compare the difference of IL-17 expression in muscle tissue between the two groups, and non-parametric test was used for comparison between multiple groups. Chi-square test and Spearman rank correlation analysis were used, and P<0.05 was considered statistically significant. Results:① The expression level of IL-17 in IIM muscle tissue[1.63(1.30, 2.05)pg/ml was higher than that in control group[1.00(0.96, 1.00)pg/ml, and the difference was statistically significant ( Z=-3.52, P<0.001). The difference be-tween DM[1.94(1.58, 2.14)pg/ml] and ASS[1.22(1.04,1.55)pg/ml was statistically significant ( Z=-3.20, P=0.001). ② Compared with healthy control group [4.08(3.01, 5.67)pg/ml, the expression of IL-6 in ⅡM serum[8.88(4.93, 13.64) was high ( Z=-3.01, P=0.003), which was positively correlated with the expression of IL-17 ( r=0.42, P=0.027). ③ The ex-pression of IL-17 in muscle tissue was higher in IIM associated with muscle weakness[1.91(1.56, 2.14) pg/ml vs 1.50(1.04, 2.00)pg/ml] ( Z=-1.38, P=0.020), dysphagia [2.06(1.99, 2.14)pg/ml vs 1.62(1.52, 2.04)pg/ml] ( Z=-2.74, P=0.010) and skin involvement[1.98(1.57, 2.14)pg/ml vs 1.04(0.86, 1.61)pg/ml] ( Z=-3.20, P<0.010), and the differences were statistically significant ( P<0.05). ④IL-17 was positively correlated with Myoact-total activity ( r=0.51, P=0.006), Myoact-muscle symptom ( r=0.45, P=0.016), erythrocyte sedimen tation ( r=0.48, P=0.020), and myoenzyme increase ( r=0.56, P=0.002). Conclusion:IL-17 and IL-6 are synergistically involved in the pathogenesis of IIM, suggesting that IL-17 is the therapeutic target of IIM.

Objective:To analyze the influencing factors of the public hospital′s WeChat official accountcommunication effect, for references for improving the public hospital′s WeChat official account′s public opinion guidance in health dissemination field.Methods:The communication data of all the tweets on the official account of a tertiary hospital from 2018 to 2021 were obtained, taking the tweets reading times as the evaluation index of the communication effect of the WeChat official account. The number of sharing times, the number of title words, punctuation points, the first launch platform and content type were took as factors that may affect comounication effectiveness for single factor analysis and multiple linear regression analysis.Results:A total of 1 102 tweets were included, with an average reading times of 10 670, and an average sharing times of 411. The top 10 tweets in terms of reading times were mainly about the treatment of major diseases, emergencies, common misconceptions and health popular science. The sharing times and the hand-painted entries were positively correlated with the reading times( P<0.05), while the number of title words and punctuation was negatively correlated with the reading times( P<0.05). The reading times of tweets varied with different title sentence structures, initial platforms, source departments, and content types, and the differenceswere statistically significant( P<0.05). The sharing times, hand-painted entries, title sentence structures and content typeswere the influencing factors of the public hospital′s WeChat official account communication effect( P<0.05). Conclusions:The tweets of a public hospital′s WeChat official account with high reading times focused on the hot issues that people pay attention to, and there were many factors influencing the communication effect. The author suggested that the WeChat official account of public hospitals should focus on the needs of the people, promote the construction of high-quality content, and further strengthen the design level of copywriting to improve its audience and communication power.

Objective:To investigate the efficacy and safety of anlotinib combined with whole brain radiation therapy in the treatment of driver gene mutation-negative non-small cell lung cancer (NSCLC) patients with multiple brain metastases.Methods:Forty-two driver gene mutation-negative NSCLC patients with multiple brain metastases who were admitted to Shaoxing People's Hospital from March 2018 to March 2022 were included. Among them, 21 patients in the anlotinib combined with whole brain radiation therapy group were enrolled from a prospective single-arm study (clinical trial registration number: ChiCTR1900027769), and the patients in the whole brain radiation therapy-alone group were enrolled from a concurrent retrospective study, and after 1∶1 propensity score matching, a total of 21 patients were finally included. The intracranial objective response rate (iORR), intracranial disease control rate (iDCR), intracranial progression-free survival (iPFS), overall survival (OS), and adverse events were compared between the two groups.Results:Among 21 patients in the arotinib combined with whole brain radiation therapy group, there were 1 case (4.8%) of complete remission (CR), 13 cases (61.9%) of partial remission (PR), 6 cases (28.6%) of stable disease (SD), and 1 case (4.8%) of progressive disease (PD). Among 21 patients in the whole brain radiation therapy-alone group, there were 0 case of CR, 10 cases (47.6%) of PR, 7 cases (33.3%) of SD, and 4 cases (19.0%) of PD. The iORR was 66.7% (14/21) and 47.6% (10/21) in the anlotinib combined with whole brain radiation therapy group and whole brain radiation therapy-alone group, respectively ( P = 0.212), and the iDCR was 95.2% (20/21) and 81.0% (17/21), respectively ( P = 0.343). The median iPFS time was 10.4 and 5.3 months in the anrotinib combined with whole brain radiation therapy group and the whole brain radiation therapy-alone group, respectively, and the difference in iPFS between the two groups was statistically significant ( P = 0.049); the 1-year OS rate was 50.5% and 39.5%, and the 2-year OS rate was 29.9% and 26.3%, respectively, with the median OS time of 13.4 and 6.6 months, respectively. The difference in OS between the two groups was not statistically significant ( P = 0.452). The most common treatment-related adverse effects in the anlotinib combined with whole brain radiation therapy group were loss of appetite (13/21, 61.9%), hypertension (11/21, 52.4%), fatigue (10/21, 47.6%), diarrhea (6/21, 28.6%), vomiting (6/21, 28.6%), dizziness (9/21, 42.9%), and headache (8/21, 38.1%). No ≥grade 4 adverse effects were observed, and there were no significant differences in adverse effects between the two groups (all P > 0.05). Conclusions:Anlotinib combined with whole brain radiation therapy can prolong the iPFS time of driver gene mutation-negative NSCLC patients with multiple brain metastases, and it is well-tolerated in terms of safety.

Objective:To evaluate the efficacy and safety of mitoxantrone hydrochloride liposome injection in the treatment of peripheral T-cell lymphoma (PTCL) in a real-world setting.Methods:This was a real-world ambispective cohort study (MOMENT study) (Chinese clinical trial registry number: ChiCTR2200062067). Clinical data were collected from 198 patients who received mitoxantrone hydrochloride liposome injection as monotherapy or combination therapy at 37 hospitals from January 2022 to January 2023, including 166 patients in the retrospective cohort and 32 patients in the prospective cohort; 10 patients in the treatment-na?ve group and 188 patients in the relapsed/refractory group. Clinical characteristics, efficacy and adverse events were summarized, and the overall survival (OS) and progression-free survival (PFS) were analyzed.Results:All 198 patients were treated with mitoxantrone hydrochloride liposome injection for a median of 3 cycles (range 1-7 cycles); 28 cases were treated with mitoxantrone hydrochloride liposome injection as monotherapy, and 170 cases were treated with the combination regimen. Among 188 relapsed/refractory patients, 45 cases (23.9%) were in complete remission (CR), 82 cases (43.6%) were in partial remission (PR), and 28 cases (14.9%) were in disease stabilization (SD), and 33 cases (17.6%) were in disease progression (PD), with an objective remission rate (ORR) of 67.6% (127/188). Among 10 treatment-na?ve patients, 4 cases (40.0%) were in CR, 5 cases (50.0%) were in PR, and 1 case (10.0%) was in PD, with an ORR of 90.0% (9/10). The median follow-up time was 2.9 months (95% CI 2.4-3.7 months), and the median PFS and OS of patients in relapsed/refractory and treatment-na?ve groups were not reached. In relapsed/refractory patients, the difference in ORR between patients with different number of treatment lines of mitoxantrone hydrochloride liposome injection [ORR of the second-line, the third-line and ≥the forth-line treatment was 74.4% (67/90), 73.9% (34/46) and 50.0% (26/52)] was statistically significant ( P = 0.008). Of the 198 PTCL patients, 182 cases (91.9%) experienced at least 1 time of treatment-related adverse events, and the incidence rate of ≥grade 3 adverse events was 66.7% (132/198), which was mainly characterized by hematologic adverse events. The ≥ grade 3 hematologic adverse events mainly included decreased lymphocyte count, decreased neutrophil count, decreased white blood cell count, and anemia; non-hematologic adverse events were mostly grade 1-2, mainly including pigmentation disorders and upper respiratory tract infection. Conclusions:The use of mitoxantrone hydrochloride liposome injection-containing regimen in the treatment of PTCL has definite efficacy and is well tolerated, and it is a new therapeutic option for PTCL patients.