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.

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.

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: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.

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 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 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.

OBJECTI VE To establish the high performan ce liquid c hromatography（HPLC）fingerprint of carotenoid in Lycium barbarum，and to investigate the spectrum-effect relationship between its common peak and antioxidant activity. METHODS HPLC method was adopted. The fingerprints of carotenoid in 34 batches of L. barbarum from different producing areas were established by Similarity Evaluation System of TCM Fingerprint （2012 edition），and similarity evaluation and common peak identification were carried out. Taking scavenging rate of DPPH free radical as index ，in vitro antioxidant activity of carotenoid in L. barbarum was investigated. The spectrum-effect relationship between the common peaks of carotenoids in L. barbarum and antioxidant activity was analyzed by grey correlation method. RESULTS There were 4 common peaks in the fingerprints of carotenoids in 34 batches of L. barbarum ，and the similarity was not less than 0.903. Peak 1 was identified as zeaxanthin ，and peak 4 as zeaxanthin dipalmitate. The scavenging rates of them to DPPH free radical were 1.792％-3.160％. The common peaks of carotenoids in L. barbarum were positively correlated with scavenging rate of DPPH free radical ，and the correlation degree was greater than 0.6；the correlation degree of peak 2 and peak 4（zeaxanthin dipalmitate ）with scavenging rate of DPPH free radical was greater than 0.8. According to the correlation degree ，the contribution of each common peak to scavenging rate of DPPH free radical was determined as peak 2＞ peak 4（zeaxanthin dipalmitate ）＞peak 1（zeaxanthin）＞peak 3. CONCLUSIONS In this study ，HPLC fingerprint of carotenoid in L. barbarum is successfully established ，and two common peaks are identified. The chemical components represented by peak 2 and zeaxanthin palmitate may be the material basis of antioxidant activity of carotenoid in L. barbarum .

Humans ; Lymphoma, T-Cell, Cutaneous/complications* ; Neuroglia ; Pruritus/pathology* ; Skin Neoplasms/complications* ; Spinal Cord/pathology* ; Sympathetic Nervous System

Objective:To analyze the efficacy and safety of Daratumumab for the treatment of primary AL light chain systemic amyloidosis.Methods:Twenty one patients who were diagnosed as primary AL light chain systemic amyloidosis and treated with Daratumumab from 7 centers were retrospectively analyzed. Daratumumab was administrated as first line therapy in seven patients and 14 patients with relapsed settings. Hematological response, safety and survival were analyzed.Results:All 7 patients achieved very good partial response (VGPR) or better with first-line application of daratumumab. Three patients died, and the other four achieved organ remission. Among 14 relapsed patients, 2 patients had a difference of free light chain (dFLC) less than 20 mg/L before treatment, and 9 with a dFLC of more than 50 mg/L. All patients reached partial response (PR) or better, including 4 patients with complete response (CR), 3 with VGPR and 2 with PR. The response rate was 100% in 3 patients with dFLC 20-50 mg/L at baseline. The organ remission rate was 50% in patients with heart involvement and 58.3% in patients with kidney impairment. The overall median follow-up period was 5.3 months, and 11 months in surviving patients. One patient died of severe infection and disseminated intravascular coagulation (DIC) with stable amyloidosis. One patient switched to other regimens because dFLC elevated but did not fulfill progressive disease after 2 year application. As to safety, no grade 3/4 infusion reaction developed, and grade 1 infusion reaction occurred in 3 cases during the first infusion. Lymphocytopenia was seen in 75% patients including grade 3 or more in 30% patients.Conclusion:Daratumumab is effective to eliminate serum free light chain in both newly diagnosed and relapsed patients with systemic amyloidosis.