Most cancers are currently incurable, partly due to abnormal post-translational modifications (PTMs). In this study, we initially used multiple myeloma (MM) as a working model and found that SUMOylation activating enzyme subunit 1 (SAE1) promotes the malignancy of MM. Through proteome microarray analysis, SAE1 was identified as a potential target for bioactive colcemid or its derivative colchicine. Elevated levels of SAE1 were associated with poor clinical survival and increased MM proliferation in vitro and in vivo. Additionally, SAE1 directly SUMOylated and upregulated the total protein expression of p27, leading to LLPS-mediated nuclear export of p27. Our study also demonstrated the involvement of SAE1 in other types of cancer cells, and provided the first monomer crystal structure of SAE1 and its key binding model with colchicine. Colchicine also showed promising results in the Patient-Derived Tumor Xenograft (PDX) model. Furthermore, a controlled clinical trial with 56 MM patients demonstrated the clinical efficacy of colchicine. Our findings reveal a novel mechanism by which tumor cells evade p27-induced cellular growth arrest through p27 SUMOylation-mediated nuclear export. SAE1 may serve as a promising therapeutic target, and colchicine may be a potential treatment option for multiple types of cancer in clinical settings.

Humans ; Nutrition Assessment ; Prognosis ; Silicosis/prevention & control* ; Occupational Diseases ; China/epidemiology* ; Occupational Exposure ; Silicon Dioxide

Renal outer medullary potassium (ROMK) channel is an important K⁺ excretion channel in the body, and K⁺ secreted by the ROMK channels is most or all source of urinary potassium. Previous studies focused on the ROMK channels of thick ascending limb (TAL) and collecting duct (CD), while there were few studies on the involvement of ROMK channels of the late distal convoluted tubule (DCT2) in K⁺ excretion. The purpose of the present study was mainly to record the ROMK channels current in renal DCT2 and observe the effect of high potassium diet on the ROMK channels by using single channel and whole-cell patch-clamp techniques. The results showed that a small conductance channel current with a conductance of 39 pS could be recorded in the apical membrane of renal DCT2, and it could be blocked by Tertiapin-Q (TPNQ), a ROMK channel inhibitor. The high potassium diet significantly increased the probability of ROMK channel current occurrence in the apical membrane of renal DCT2, and enhanced the activity of ROMK channel, compared to normal potassium diet (P < 0.01). Western blot results also demonstrated that the high potassium diet significantly up-regulated the protein expression levels of ROMK channels and epithelial sodium channel (ENaC), and down-regulated the protein expression level of Na⁺-Cl^- cotransporter (NCC). Moreover, the high potassium diet significantly increased urinary potassium excretion. These results suggest that the high potassium diet may activate the ROMK channels in the apical membrane of renal DCT2 and increase the urinary potassium excretion by up-regulating the expression of renal ROMK channels.
Potassium Channels, Inwardly Rectifying/metabolism* ; Kidney Tubules, Distal/metabolism* ; Potassium/metabolism* ; Epithelial Sodium Channels/metabolism* ; Diet

Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.

OBJECTIVE: To investigate the efficacy and safety of daratumumab in treatment of multiple myeloma (MM) patients with renal impairment (RI). METHODS: The clinical data of 15 MM patients with RI who received daratumumab-based regimen from January 2021 to March 2022 in three centers were retrospectively analyzed. Patients were treated with daratumumab or daratumumab combined with dexamethasone or daratumumab combined with bortezomib and dexamethasone and the curative effect and survival were analyzed. RESULTS: The median age of 15 patients was 64 (ranged 54-82) years old. Six patients were IgG-MM, 2 were IgA-MM,1 was IgD-MM and 6 were light chain MM. Median estinated glomerular filtration rate (eGFR) was 22.48 ml/(min·1.73 M₂). Overall response rate of 11 patients with MM was 91% (≥MR), including 1 case of stringent complete response (sCR), 2 cases of very good partial response (VGPR), 3 cases of partial response (PR) and 4 cases of minor response (MR). The rate of renal response was 60%(9/15), including 4 cases of complete response (CR), 1 case of PR and 4 cases of MR. A median time of optimal renal response was 21 (ranged 7-56) days. With a median follow-up of 3 months, the median progression-free survival and overall survival of all patients were not reached. After treatment with daratumumab-based regimen, grade 1-2 neutropenia was the most common hematological adverse reaction. Non-hematological adverse reactions were mainly infusion-related adverse reactions and infections. CONCLUSION Daratumumab-based regimens have good short-term efficacy and safety in the treatment of multiple myeloma patients with renal impairment.
Humans ; Middle Aged ; Aged ; Aged, 80 and over ; Multiple Myeloma/drug therapy* ; Retrospective Studies ; Dexamethasone/therapeutic use* ; Antibodies, Monoclonal/therapeutic use* ; Bortezomib/therapeutic use* ; Renal Insufficiency/drug therapy* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use*

Background::To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.Methods::This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.Results::A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%-48.1%; P = 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151-3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350-67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression. Conclusions::SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.Trial registration::Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term= NCT04260594&draw=2&rank=1

To investigate the prevalence of diabetes mellitus (DM) among residents in Chongchuan district, Nantong city in 2012 and 2018, and evaluate the effectiveness of community comprehensive management of DM. Based on the data of 17 780 and 13 382 residents in the cross-sectional surveys of the " National Demonstration Area for Comprehensive Prevention and Control of Chronic Diseases " project in Chongchuan District of Nantong City, Jiangsu Province in 2012 and 2018, 4 583 and 3 996 DM-related information were obtained. The population of Jiangsu Province in 2012 and 2018 was used as the reference for standardization. The rates of prevalence and management (including awareness, treatment, treatment of patients who knew their diabetic situation, control and control of patients under treatment) of DM in the two surveys were compared using chi-square test. The results showed that in 2012 and 2018, the prevalence rates of DM were 12.0% and 15.7% (χ²=24.25, P<0.05), and the standardized rates were 10.1% and 10.8% (χ²=1.05, P=0.306). The incidence rates were 5.7% and 2.3%, respectively (χ²=55.60, P<0.05). The standardized prevalence rates in the two surveys were 9.7% and 11.6% for males (χ²=3.66, P=0.056) and 10.5% and 9.9% for females (χ²=0.50, P=0.481), 7.2% and 6.5% (χ²=0.85, P=0.357) for people aged 18-59 years old and 20.6% and 21.9% (χ²=0.91, P=0.339) for people aged 60 years and over, respectively. The standardized rates of awareness, treatment, treatment of patients who knew their diabetic situation, control, and control of patients under treatment in 2018 were 84.4%, 80.3%, 95.2%, 58.4%, and 70.2%, respectively, higher than 47.2%, 23.4%, 44.8%, 30.4% and 59.4% in 2012 (χ²=183.33, χ²=380.65, χ²=282.99, χ²=93.24, χ²=6.22, all P<0.05). Among men, the standardized rates of awareness, treatment, treatment of patients who knew their diabetic situation, and control in 2018 were 85.8%, 78.8%, 91.8% and 62.7%, higher than 50.5%, 37.5%, 72.3% and 32.6% in 2012 (χ²=78.40, χ²=96.17, χ²=27.55, χ²=48.96, all P<0.05). Similarly, the standardized management rates in 2018 were 83.0%, 81.7%, 98.5%, 54.1% and 65.1%, higher than 44.0%, 10.0%, 18.3%, 28.2% and 48.8% in 2012 among women (χ²=105.52, χ²=326.36, χ²=317.22, χ²=43.34, χ²=3.87, all P<0.05). The standardized rates of awareness, treatment, treatment of patients who knew their diabetic situation, and control of people aged 18-59 and 60 years and over were 82.9%, 79.7%, 96.1%, 55.0% and 88.0%, 81.8%, 93.0% and 67.2%, higher than 42.6%, 19.8%, 42.2%, 27.5% and 63.9%, 36.8%, 53.9%, 40.8% in 2012 (χ²=44.51, χ²=102.17, χ²=57.78, χ²=21.65, all P<0.05; χ²=71.18, χ²=181.55, χ²=146.26, χ²=59.23, all P<0.05). The comprehensive prevention and control system of chronic diseases, which comprehensively covered the life of community residents, had good management effect on DM, and effectively promoted health education and health promotion.
Adolescent ; Adult ; Aged ; Cross-Sectional Studies ; Diabetes Mellitus/prevention & control* ; Female ; Humans ; Incidence ; Male ; Middle Aged ; Prevalence ; Rural Population ; Young Adult

OBJECTIVE: To investigate the surgical skills and clinical curative results of arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome. METHODS: From February 2019 to August 2020, 13 patients with ankle instability combined with anteromedial impingement were retrospectively analyzed. There were 10 males and 3 females with age of (40.0±15.1) years old. The course of disease was(44.1±33.2) months. All patients had history of ankle sprain. MRI showed the injury of anterior talofibular ligament. All patients had anteromedial pain and pressing pain when ankle dorsiflexion. All patients were treated with ankle debridement and Brostr?m-Gould surgery under ankle arthroscopic. Postoperative results were evaluated by VAS(visual analogue scale) and AOFAS-AH(American Orthopaedic Foot and Ankle Society Ankle-Hindfoot scale, AOFAS-AH). RESULTS: All 13 patients completed the surgery successfully with an operative time of 60 to 90 minutes. All the surgical incisions healed by first intention, and no complications such as incision infection, skin necrosis and neurovascular injury. Follow-up time was (18.1±4.7) months. At the latest follow-up, the VAS score was 1.2±1.1, which was significantly lower than the preoperative score 4.8±1.5 (P<0.05);the AOFAS-AH score 94.2±5.1 was significantly higher than the preoperative score 65.5±11.5 (P<0.05). The AOFAS-AH score at the final follow-up ranged from 84 to 100. All patients walked with normal gait without ankle instability or impingement recurrence. CONCLUSION Ankle anteromedial impingement syndrome combined with ankle instability is easy to be ignored clinically. Such kind of anteromedial impingement syndrome is mostly related to osteophyte at dorsal medial talar neck. Arthroscopic treatment of ankle instability combined with anteromedial impingement syndrome has satisfactory curative effect with safety and minimal injury.
Adult ; Ankle ; Arthroscopy/methods* ; Female ; Humans ; Joint Instability/surgery* ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

OBJECTIVE: To explore early efficacy of minimally invasive Chevron Akin(MICA) osteotomy for the treatment of mild to moderate hallux valgus. METHODS: From June 2019 to April 2021, a total of 26 patients (29 feet) with mild to moderate hallux valgus, including 1 male and 25 females aged from 19 to 78 years old with an average of(38.3±19.5) years old, were treated with MICA. Preoperative and postoperative hallux valgus angle(HVA), intermetatarsal angle(IMA) and shortening of the first metatarsal were observed and compared. American Orthopedic Foot and Ankle Society (AOFAS) forefoot scoring system and visual analogue scale (VAS) were applied to evaluate clinical outcome at the final follow-up, and complications were also recorded. RESULTS: All patients obtained followed up from 12 to 33 months with an average of(19.6±5.1) months. HVA and IMA was improved from (32.3±6.6)° and (11.7±3.2)° pre-operatively to (13.0±5.3)° and (6.1±3.2)° post-operatively, respectively, which had a significant difference (P<0.01). The average shortening of the first metatarsal was (2.7±1.1) mm. AOFAS and VAS was improved from (55.7±7.4) and (6.5±1.5) preoperatively and to (88.5±7.9) and (0.7±0.4) respectively at the final follow-up, which also had a significant difference(P<0.01). According to AOFAS score, 15 feet achieved an excellent result, 11 good and 3 moderate. CONCLUSION MICA osteotomy is a safe and reliable surgical technique for mild to moderate hallux valgus with advantages of minimally invasive, rapid recovery, low complication rate and an effect improvement of hallux valgus deformity.
Adolescent ; Adult ; Aged ; Bunion ; Female ; Hallux Valgus/surgery* ; Humans ; Male ; Metatarsal Bones/surgery* ; Middle Aged ; Osteotomy/methods* ; Treatment Outcome ; Young Adult

Objective: To investigate the clinicopathological characteristics and prognosis of high-grade B-cell lymphoma (HGBL) involving combined rearrangements of MYC, bcl-2 and bcl-6. Methods: A total of 1 138 cases of large B cell lymphoma (LBL) that were treated at the Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2017 to September 2020 were analyzed using fluorescence in situ hybridization (FISH) with probes against MYC, bcl-2 and bcl-6. The clinical and pathological data of the 45 patients with HGBL that had rearrangements of MYC and bcl-2 and/or bcl-6 were collected and retrospectively analyzed. Results: Among the 1 138 LBL, 45 (4.0%) cases had combined rearrangements of MYC, bcl-2 and/or bcl-6 that included 6 HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, 14 HGBL cases with MYC and bcl-2 rearrangements, and 25 HGBL cases with MYC and bcl-6 rearrangements. Of these 45 patients, 29 patients were male, and 16 patients were female, aged 29 to 83 years. HGBL with MYC, bcl-2 and bcl-6 rearrangements and HGBL with MYC and bcl-2 rearrangement were reclassified as the germinal center B-cell (GCB) subtype using the Hans algorithm. HGBL with MYC and bcl-6 rearrangement were reclassified as the GCB subtype (68.0%) and the non-GCB subtype (32.0%). The vast majority of HGBL cases had a high Ki-67 proliferation index. Most HGBL patients had advanced stage disease with a high IPI score and an increased LDH level. Also, some patients had clinical features including elevated plasma β2-microglobulin levels, B symptoms, and bone marrow involvement. The IPI scores and LDH levels were significantly different between the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements and the HGBL cases with MYC and bcl-6 rearrangements (P<0.05). Compared with the HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the HGBL cases with MYC and bcl-2 or bcl-6 rearrangements had a lower incidence of bone marrow involvement (P<0.05). There were no significant differences in the prognosis among HGBL cases with MYC, bcl-2 and bcl-6 rearrangements, the cases with MYC and bcl-2 rearrangements, and the cases with MYC and bcl-6 rearrangements (P>0.05). Conclusions: HGBL with MYC, bcl-2 and/or bcl-6 rearrangements are rare types of B-cell lymphoma with high degree of malignancy and have a short overall survival. To reduce misdiagnosis and improve diagnostic accuracy, it is necessary to assess the patients' clinical features and conduct histopathological, immunohistochemical and FISH analyses.
Adult ; Aged ; Aged, 80 and over ; China ; Female ; Gene Rearrangement ; Humans ; In Situ Hybridization, Fluorescence ; Lymphoma, Large B-Cell, Diffuse/genetics* ; Male ; Middle Aged ; Prognosis ; Proto-Oncogene Proteins c-bcl-2/genetics* ; Proto-Oncogene Proteins c-bcl-6/genetics* ; Proto-Oncogene Proteins c-myc/genetics* ; Retrospective Studies