The Janus kinase/signal transducers and activators of transcription (JAK-STAT) control natural killer (NK) cells development and cytotoxic functions, however, whether long non-coding RNAs (lncRNAs) are involved in this pathway remains unknown. We found that miR155HG was elevated in activated NK cells and promoted their proliferation and effector functions in both NK92 and induced-pluripotent stem cells (iPSCs)-derived NK (iPSC-NK) cells, without reliance on its derived miR-155 and micropeptide P155. Mechanistically, miR155HG bound to miR-6756 and relieved its repression of JAK3 expression, thereby promoting the JAK-STAT pathway and enhancing NK cell proliferation and function. Further investigations disclosed that upon cytokine stimulation, STAT3 directly interacts with miR155HG promoter and induces miR155HG transcription. Collectively, we identify a miR155HG-mediated positive feedback loop of the JAK-STAT signaling. Our study will also provide a power target regarding miR155HG for improving NK cell generation and effector function in the field of NK cell adoptive transfer therapy against cancer, especially iPSC-derived NK cells.

Objective:To investigate the characteristics of hand dysfunction and its associated factors in patients with rheumatoid arthritis (RA).Methods:A cross-sectional study. Patients with RA were recruited from January 2019 to April 2024 at the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Demographic and clinical data were collected, including age, gender, active smoking, disease duration, time of morning stiffness, rheumatoid factor and anti-cyclic citrullinated peptide antibody, disease activity, radiographic indicators, and hand function assessment. Hand function was assessed by grip strength measures and self-reported items related to hand function in the Stanford Health Assessment Questionnaire. Factors related to hand function were analyzed by logistic regression analyses.Results:A total of 1 079 RA patients were recruited [mean age: (53.0±12.6) years]. Overall, 72.6% (783/1 079) patients experienced a decrease in grip strength, 57.2% (617/1 079) patients experienced a decreased grip strength in both hands, with the average grip strength of the left and right hands decreasing by 16.3% and 14.1%, respectively, compared to normal values; 39.9% (430/1 079) patients had self-reported hand dysfunction. There were 185 (17.1%) older RA patients (age ≥65 years). The proportion of older RA patients with decreased grip strength [89.7% (166/185) vs. 69.0% (617/894)] and degree of decrease in grip strength compared to normal values (left hand:-35.3%±30.6% vs. -12.3%±38.6%; right hand:-32.6%±32.3% vs. -10.3%±42.1%) were significantly higher than that in young patients, and the proportion of older patients with self-reported hand dysfunction was also significantly higher [53.0% (98/185) vs. 37.1% (332/894), all P<0.001]. Multivariate logistic regression analysis showed that pain visual analogue scale ( OR=1.375, 95% CI 1.020-1.854) was independently associated with grip strength decrease in older RA patients, while the 28-joint tender joint count ( OR=1.151, 95% CI 1.063-1.246) and provider global assessment of disease activity ( OR=1.381, 95% CI 1.171-1.628) were associated with self-reported hand dysfunction. Conclusions:Hand dysfunction is common in RA patients, especially among older RA patients, which is related to pain, joint tenderness and provider global assessment of disease activity. This result implies the importance of pain management in RA patients.

Objective:To investigate the characteristics of hand dysfunction and its associated factors in patients with rheumatoid arthritis (RA).Methods:A cross-sectional study. Patients with RA were recruited from January 2019 to April 2024 at the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University. Demographic and clinical data were collected, including age, gender, active smoking, disease duration, time of morning stiffness, rheumatoid factor and anti-cyclic citrullinated peptide antibody, disease activity, radiographic indicators, and hand function assessment. Hand function was assessed by grip strength measures and self-reported items related to hand function in the Stanford Health Assessment Questionnaire. Factors related to hand function were analyzed by logistic regression analyses.Results:A total of 1 079 RA patients were recruited [mean age: (53.0±12.6) years]. Overall, 72.6% (783/1 079) patients experienced a decrease in grip strength, 57.2% (617/1 079) patients experienced a decreased grip strength in both hands, with the average grip strength of the left and right hands decreasing by 16.3% and 14.1%, respectively, compared to normal values; 39.9% (430/1 079) patients had self-reported hand dysfunction. There were 185 (17.1%) older RA patients (age ≥65 years). The proportion of older RA patients with decreased grip strength [89.7% (166/185) vs. 69.0% (617/894)] and degree of decrease in grip strength compared to normal values (left hand:-35.3%±30.6% vs. -12.3%±38.6%; right hand:-32.6%±32.3% vs. -10.3%±42.1%) were significantly higher than that in young patients, and the proportion of older patients with self-reported hand dysfunction was also significantly higher [53.0% (98/185) vs. 37.1% (332/894), all P<0.001]. Multivariate logistic regression analysis showed that pain visual analogue scale ( OR=1.375, 95% CI 1.020-1.854) was independently associated with grip strength decrease in older RA patients, while the 28-joint tender joint count ( OR=1.151, 95% CI 1.063-1.246) and provider global assessment of disease activity ( OR=1.381, 95% CI 1.171-1.628) were associated with self-reported hand dysfunction. Conclusions:Hand dysfunction is common in RA patients, especially among older RA patients, which is related to pain, joint tenderness and provider global assessment of disease activity. This result implies the importance of pain management in RA patients.

Objective:To measure and analyze the occlusal force and contact in children with mixed dentition,and to preliminarily provide baseline data on the occlusion of individual normal occlusion children with mixed dentition.Methods:A cross-sectional study was conducted,including 20 children with mixed dentition and individual normal occlusion,consisting of 12 boys and 8 girls,aged 6.5-9.8 years.The Dental Prescale Ⅱ occlusal analysis system was used to measure the occlusal force and contact at the intercuspal position,including the maximum occlusal force(N)and the occlusal contact area(mm2)of the entire dentition,and the left and right sides,average occlusal pressure(MPa),maximum occlusal pressure(MPa),and to determine the position of the center of occlusal force.The gender differences in maximum occlusal force,average occlusal pressure,and occlusal contact area were ana-lyzed,the bilateral symmetry of occlusion in children with mixed dentition and individual normal occlu-sion was compared,and the correlation between occlusal data and age,height,weight,and body mass index(BMI)was analyzed.Results:(1)The average maximum occlusal force of the entire dentition in the 20 children with mixed dentition at the intercuspal position was(869.18±106.64)N,the average occlusal contact area was(25.19±2.89)mm2,the average occlusal pressure was(34.37±5.98)MPa,and the maximum occlusal pressure M(P25,P75)was 120(120,120)MPa;(2)There was no statistically significant difference in the maximum occlusal force,average occlusal pressure,maximum occlusal pressure,and occlusal contact area between the left and right sides(P＞0.05);(3)At the intercuspal position,the average occlusal contact area for 12 boys and 8 girls was(26.71±3.91)mm2and(21.62±3.08)mm2 respectively,and the average maximum occlusal force was(911.92±145.05)N and(769.47±116.45)N respectively,with statistically significant differences(P＜0.05),while there was no statistically significant difference in the average occlusal pressure between boys and girls(P＞0.05);(4)The maximum occlusal force at the intercuspal position was weakly correlated with age(r=0.219,P=0.046),and strongly positively correlated with the occlusal contact area(r=0.949,P＜0.001),while the average occlusal pressure,maximum occlusal pressure,and occlusal contact area were not correlated with age,height,weight,or BMI;(5)The center of occlusal force in the 20 children with mixed dentition and individual normal occlusion was located in the molar region,with 7 children having the maximum occlusal pressure point only in the first permanent molar region,10 children having it in both the deciduous molar region and the first permanent molar region,and 3 children having it only in the deciduous molar region.Conclusion:In children with mixed dentition and individual normal occlusion,the maximum occlusal force,occlusal contact area,average occlusal pressure,and maximum occlusal pressure at the intercuspal position show good bilateral symmetry;there are gender differences in the maximum occlusal force and occlusal contact area,with boys having greater values than girls;the maxi-mum occlusal force is positively correlated with the occlusal contact area.

Objective: To investigate the effects of long-term hyperglycemia on renal pathology of type 1 diabetic mellitus(T1DM) cynomolgus monkeys by establishing streptozotocin(STZ)-induced T1DM. Methods: Eight 4-year-old male cynomolgus monkeys were randomly divided into control and model groups. Four cynomolgus monkeys were used in the control group, and four cynomolgus monkeys were injected with streptozotocin to create a T1DM model. Hematoxylin-eosin(HE) staining and periodic acid-Schiff(PAS) staining were used to observe renal pathological changes.The histological characteristics and changes were observed under transmission electron microscope. Morphometric measurements were used to analyze the glomerular area, the thickness of the glomerular basement membrane, the proportion of glomerular podocyte foot processes and the average area of foot processes. Results: In comparison to the control group, the model group showed pathological changes in the kidneys, including increased glomerular area(P<0.01), thickened basement membrane, capillary loop compression, disordered arrangement of endothelial cell fenestrations, proliferation of mesangial cells, mesangial expansion, accumulation of mesangial matrix glycoproteins, a decrease in the number of foot processes(P<0.001), a decrease in the average size of the foot processes(P<0.05), widened podocyte slit diaphragm, and an increase in the number of fused foot processes(P<0.001). Conclusion Cynomolgus monkeys with T1DM suffer from renal pathological changes due to long-term hyperglycemia.

During the carcinoma transformation of colitis， the imbalance of “metabolic-immune interaction” resulted from abnormal energy and metabolic substrates flow and direction was the key process， which caused by intercellular metabolic competition. Based on traditional Chinese medicine （TCM） theory and clinical research， we found that “fire failing to warm earth” is the key pathogenesis of colon-cancer transformation. “Fire” was a synonym for TCM to understand the energy metabolism， combined modern medical research findings， we thought energy metabolism disorders was a microcosmic manifestation of the “fire decline”， while abnormal immune function was the biological basis of “earth deficiency”. The imbalance between “metabolism-immune interaction” and the “fire failing to warm earth” pathogenesis of colitis-cancer transformation demonstrated the different understanding of the same pathological mechanism between western medicine and TCM. For treatment， it could be effectivce to delay the transformation of colitis-cancer by synergistically regulated the energy metabolism - “replenish fire” and enhanced the immune function - “nourish earth”， which was called the methods of replenishing fire to nourish earth.

Despite the availability of direct-acting antivirals (DAAs) for chronic hepatitis C virus (HCV) infection in Korea, need remains for pangenotypic regimens that can be used in the presence of hepatic impairment, comorbidities, or prior treatment failure. We investigated the efficacy and safety of sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir for 12 weeks in HCV-infected Korean adults. Methods: This Phase 3b, multicenter, open-label study included 2 cohorts. In Cohort 1, participants with HCV genotype 1 or 2 and who were treatment-naive or treatment-experienced with interferon-based treatments, received sofosbuvir–velpatasvir 400/100 mg/day. In Cohort 2, HCV genotype 1 infected individuals who previously received an NS5A inhibitor-containing regimen ≥ 4 weeks received sofosbuvir–velpatasvir–voxilaprevir 400/100/100 mg/day. Decompensated cirrhosis was an exclusion criterion. The primary endpoint was SVR12, defined as HCV RNA < 15 IU/mL 12 weeks following treatment. Results: Of 53 participants receiving sofosbuvir–velpatasvir, 52 (98.1%) achieved SVR12. The single participant who did not achieve SVR12 experienced an asymptomatic Grade 3 ASL/ALT elevation on day 15 and discontinued treatment. The event resolved without intervention. All 33 participants (100%) treated with sofosbuvir–velpatasvir–voxilaprevir achieved SVR 12. Overall, sofosbuvir–velpatasvir and sofosbuvir–velpatasvir–voxilaprevir were safe and well tolerated. Three participants (5.6%) in Cohort 1 and 1 participant (3.0%) in Cohort 2 had serious adverse events, but none were considered treatment-related. No deaths or grade 4 laboratory abnormalities were reported. Conclusions: Treatment with sofosbuvir–velpatasvir or sofosbuvir–velpatasvir–voxilaprevir was safe and resulted in high SVR12 rates in Korean HCV patients.

With in-depth research and development of dermoscopy, the dermoscopic features including perifollicular pigments, perilesional pigments, pigment network structure, satellite phenomenon and "tapioca sago" appearance, micro-Koebner phenomenon and comet tail-like phenomenon have provided a basis for the evaluation of vitiligo activity. This review summarizes progress in the evaluation of vitiligo activity with dermoscopy in recent years, aiming to promote the application of dermoscopy in the assessment of vitiligo activity.

Objective:To study the prognostic impact of prognostic nutritional index (PNI) before radiotherapy in clinical stage Ⅲ esophageal cancer patients.Methods:We retrospectively reviewed 125 esophageal cancer patients with clinical stage Ⅲ undergoing definitive radiotherapy in Fourth Hospital of Hebei Medical University from 2013 to 2017. The PNI and nutritional risk index (NRI) were calculated before radiotherapy. The optimal cutoff value of PNI was determined by time-dependent receiver operating characteristics (ROC) at 49.925.The patients were divided into low PNI group(PNI<49.925) and high PNI group (PNI≥49.925). Based on NRI, the patients were divided into normal NRI group (NRI≥100) and abnormal NRI group (NRI<100). Kaplan-Meier method was used to calculate the overall survival (OS) and progression-free survival (PFS) and to perform univariate analysis. The mutlivariate analysis was performed by Cox regression model.Results:PNI was positively correlated with hemoglobin ( r=0.505, P<0.001) and NRI ( r=0.594, P<0.001). The 1-, 3- and 5-year OS rates in the low PNI group were significantly lower than those of the high PNI group (67.5%, 27.3%, 11.4% vs. 85.4%, 45.8%, 27.4%, respectively, χ2=8.569, P<0.05). Moreover, the 1-, 3- and 5-year PFS rates in the low PNI group were obviously higher than those in the high PNI group (59.7%, 23.2%, 4.9% vs. 79.2%, 35.4%, 24.9%, respectively, χ2=6.715, P<0.05). Univariate analysis showed that GTV, radiotherapy dose, chemotherapy, albumin, NRI and PNI were significantly correlated with OS and PFS (OS: χ2=6.822, 4.326, 4.474, 13.123, 8.846, 8.569, P<0.05: PFS: χ2=7.869, 4.636, 5.874, 10.911, 8.544, 6.715, P<0.05). Multivariate analysis showed that GTV, radiotherapy dose and PNI were independent prognostic factors for OS ( P<0.05). And GTV, radiotherapy dose, chemotherapy and PNI were independent prognostic factors for PFS ( P<0.05). Conclusions:The PNI before radiotherapy is a significant and independent predictor for survival of clinical stage Ⅲ esophageal cancer patients. Based on simple and inexpensive standard laboratory measurements, PNI could be a promising prognostic biomarker for esophageal cancer patients.

Red blood cell (RBC) transfusion is a clinically effective therapy in anemia, for example in patients with malignancies (Shander et al., 2020), bleeding (Odutayo et al., 2017), and preoperative anemia (Padmanabhan et al., 2019). The past few decades have witnessed a shortage of blood for transfusion due to limited health insurance coverage for blood use and the rapid expansion of hospitals (Chen et al., 2011; Shi et al., 2014). Blood donation levels may easily be affected by general changes in the environment, policy, major events such as disasters, and public sentiment (Hu et al., 2019). Meanwhile, the transfusion of allogeneic RBC is a double-edged sword, increasing the possibility of infectious and immunological complications, and also leading to higher morbidity and mortality after transfusion (Frank et al., 2012). Considering that the continual shortfall has been increasingly prominent, identifying the factors associated with RBC transfusion could help blood transfusion departments to improve their supply of blood products as well as their inventory management (O'Donnell et al., 2018).