Efficacy and safety of lenalidomide in the treatment of B-cell non-Hodgkin lymphoma.

BACKGROUND: The combination of rituximab and chemotherapy is a first-line treatment for patients with B-cell non-Hodgkin lymphoma. Lenalidomide is an immunomodulatory drug that has shown promising properties and activity in a variety of hematological malignancies. This study evaluated the efficacy and safety of lenalidomide-based regimens in the treatment of B-cell non-Hodgkin lymphoma. METHODS: The PubMed, Science Direct, ClinicalTrials.gov, and Web of Science databases were searched for relevant studies published up to May 2022. Studies with patients diagnosed with non-Hodgkin B-cell lymphoma, who were randomly assigned to a lenalidomide treatment group or a non-lenalidomide control group were considered for inclusion in this review and meta-analysis. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) of the time-to-event outcomes and risk ratios (RRs) with 95% CIs of dichotomous data were estimated. RESULTS: A total of 3593 patients from 10 studies were evaluated. The results of the pooled analysis indicated that the lenalidomide-based regimen was associated with prolonged overall survival (HR, 0.85; 95% CI 0.74-0.97; P = 0.02) and progression-free survival (HR, 0.70; 95% CI 0.57-0.88; P = 0.002). Significant differences were found in the overall response rate (RR, 1.18; 95% CI 1.04-1.33; P = 0.01) and complete response rate (RR, 1.18; 95% CI 1.00-1.39; P = 0.05) between the treatment and control groups. CONCLUSIONS: Lenalidomide appears to be a promising therapeutic agent that offers the possibility of a novel combination of chemotherapy free regimen for patients with B-cell non-Hodgkin lymphoma.

Comparison of the clinical efficacy of bone grafting and bone grafting combined with guided tissue regeneration in periodontal regenerative therapy: a meta-analysis.

OBJECTIVE: This study aims to compare the clinical efficacy of simple bone grafting and bone grafting combined with guided tissue regeneration (GTR) in periodontal regenerative therapy. METHODS: The authors systematically searched PubMed, the Web of Science, The National Library of Medicine, the China National Knowledge Infrastructure database and the Wanfang database and collected randomized controlled trials relating to bone graft co-guided tissue regeneration. The retrieval was conducted between January 1990 and December 2022. This study included relevant literature about the clinical efficacy of bone grafting combined with GTR according to the population, intervention, control and outcomes principle and excluded studies using other materials in addition to bone graft and membrane materials. After independently screening the literature, extracting the data and evaluating the risk of bias in the included studies, data analysis was performed using RevMan 5.3 software.  Results: Eighteen studies met the inclusion criteria, and, after further evaluation, a total of 327 teeth that were featured in 15 articles were finally included for meta-analysis. The meta-analysis showed that there was no significant statistical difference in clinical attachment level, probing depth and bone gain between the test group (bone grafting with GTR) and the control group (bone grafting only) at 6 months after the operation (p > 0.05). In terms of gingival recession (GR), the use of non-resorbable membranes produced more recession in the test group compared with the control group (p < 0.05), whereas the use of resorbable membranes produced less recession (p < 0.05). CONCLUSION: Both simple bone grafting and bone grafting combined with membrane materials have good clinical efficacy in periodontal regenerative therapy, and no significant difference in clinical efficacy is indicated between the two, with the exception of GR.

Meiotic protein SYCP2 confers resistance to DNA-damaging agents through R-loop-mediated DNA repair.

Drugs targeting the DNA damage response (DDR) are widely used in cancer therapy, but resistance to these drugs remains a major clinical challenge. Here, we show that SYCP2, a meiotic protein in the synaptonemal complex, is aberrantly and commonly expressed in breast and ovarian cancers and associated with broad resistance to DDR drugs. Mechanistically, SYCP2 enhances the repair of DNA double-strand breaks (DSBs) through transcription-coupled homologous recombination (TC-HR). SYCP2 promotes R-loop formation at DSBs and facilitates RAD51 recruitment independently of BRCA1. SYCP2 loss impairs RAD51 localization, reduces TC-HR, and renders tumors sensitive to PARP and topoisomerase I (TOP1) inhibitors. Furthermore, our studies of two clinical cohorts find that SYCP2 overexpression correlates with breast cancer resistance to antibody-conjugated TOP1 inhibitor and ovarian cancer resistance to platinum treatment. Collectively, our data suggest that SYCP2 confers cancer cell resistance to DNA-damaging agents by stimulating R-loop-mediated DSB repair, offering opportunities to improve DDR therapy.

Comparison of triplanar chevron osteotomy with chevron osteotomy in hallux valgus treatment for the prevention of transfer metatarsalgia.

Hallux valgus (HV) is often accompanied by metatarsalgia. This study compared the radiological and clinical outcomes of new triplanar chevron osteotomy (TCO) and chevron osteotomy (CO) in the treatment of HV, especially for patients with plantar callosities and metatarsalgia. In this retrospective analysis, 90 patients (45 patients per group) with mild to moderate HV and plantar callosities were treated with TCO and CO from July 2020 to January 2022. In both procedures, the apex was located in the center of the head of the first metatarsal bone, and the CO was oriented towards the fourth MTPJ at a 60° angle. Plantar-oblique chevron osteotomy was defined as chevron osteotomy and a 20° plantar tilt; TCO was defined as plantar-oblique chevron osteotomy-based metatarsal osteotomy with a 10° tilt towards the metatarsal head. Primary outcome measures included preoperative and postoperative hallux valgus angle, 1 to 2 intermetatarsal angle (IMA), distal metatarsal articular angle (DMAA), first metatarsal length (FML), and second metatarsal head height X-ray images; clinical measurements, including visual analogue scale and American Orthopaedic Foot & Ankle Society (AOFAS) scores; changes in callosity grade and area; and changes in the number of people with metatarsalgia. Secondary outcomes included complications, recurrence rates, and cosmetic appearance. The hallux valgus angle, IMA, and DMAA were significantly lower after surgery (P  < .001) in all patients. In the TCO group, the mean FML and second metatarsal head height increased significantly postoperatively (P < .001). The AOFAS and visual analogue scale scores improved postoperatively in both groups (P < .001). All patients experienced satisfactory pain relief and acceptable cosmesis. The plantar callosity areas were smaller postoperatively in both the TCO and CO groups, but the change in the area (Δarea) in the TCO group significantly differed from that in the CO group (P < .001). The number of postoperative patients with metatarsalgia and the plantar callosity grade were both significantly lower in the TCO group than in the CO group after osteotomy (P < .05). TCO prevents dorsal shift of the metatarsal head and preserves and even increases FML, thereby preventing future metatarsalgia in patients. Therefore, compared with CO, TCO has better orthopedic outcomes and is an effective method for treating mild to moderate HV and preventing transfer metatarsalgia.

Heteromeric guanosine (G)-quadruplex derived antenna modules with directional energy transfer.

A heteromeric guanosine (G)-quadruplex centered self-assembly approach is developed to prepare compact light-harvesting antenna modules featuring multiple donor dyes and a single toehold region. Due to the mix-and-match nature of our approach, the number and placement of donor dyes can be readily fine-tuned via quadruplex assembly. Moreover, hybridization of the toehold with an acceptor containing sequence results in directional energy transfer ensembles with effective absorption coefficients in the 105 M-1 cm-1 range. These compact antennas exhibit system efficiencies that are comparable to much larger and elaborate DNA architectures containing numerous DNA strands.

Risk factors and prognosis of interstitial lung disease for primary Sjögren syndrome patients: A retrospective case‒control study.

OBJECTIVE: To determine the prevalence, clinical features, risk factors, and prognosis of interstitial lung disease (ILD) in patients with primary Sjogren's syndrome (pSS). METHODS: Data from 274 pSS patients from August 2013 to August 2022 were reviewed. The clinical features of pSS with ILD were revealed. Logistic regression was used to determine risk factors for ILD in pSS patients. Survival analysis and Cox regression were used to analyse the prognosis and prognostic factors of pSS patients. RESULTS: In pSS patients, the prevalence of ILD was 22.3% (61/274). The pSS patients with ILD were characterized by a late onset and long disease course, with a nonspecific interstitial pneumonia (NSIP) pattern as the predominant high-resolution computed tomography (HRCT) finding. Logistic regression results indicated that an age over 50 years old (OR 4.786, 95% CI 1.602-14.299; P = 0.005), purpuric rash (OR 4.695, 95% CI 1.537-14.339; P = 0.007), AMA-M2 antibody positivity (OR 2.582, 95% CI 1.166-5.722; P = 0.019), and diabetes (OR 2.514, 95% CI 1.025-6.167; P = 0.044) were risk factors for ILD in pSS patients. Cox regression results showed that advanced age (HR 1.240, 95% CI 1.088-1.413; P = 0.001) and cancer history (HR 8.411, 95% CI 1.771-39.934; P = 0.007) were risk factors for pSS patient survival. CONCLUSION: This study showed that pSS patients with ILD tended to have a late onset and long course of pSS. An age over 50 years, purpuric rash, AMA-M2 antibody positivity, and diabetes were risk factors for ILD in pSS patients. Advanced age and cancer history were prognostic factors in pSS patients. Key Points • This study showed that pSS patients with ILD tended to have a late-onset and lengthy course of pSS, with the NSIP pattern as the predominant lung image. • The risk factors for ILD in pSS patients determined in this study were an age over 50 years, purpuric rash, AMA-M2 antibody positivity, and diabetes. • The prognostic risk factors for pSS patients were advanced age and cancer history.

Hydrocarbon Accumulation Periods in the Upper Paleozoic Strata of the Western Ordos Basin, China, Based on Fluid Inclusions and Basin Modeling.

The upper Paleozoic strata in the western part of the Ordos Basin have rich oil and gas resources but low exploration levels. These strata were subjected to multiple tectonic events, such as the Caledonian, Hercynian, Indosinian, and Himalayan movements, which led to a relatively complex process of hydrocarbon accumulation in the study area. These strata also have obvious structural segmentation in the north-south direction. However, the accumulation periods of the upper Paleozoic strata in different structural sections of the western Ordos Basin and their differences are poorly understood. A total of 65 sandstone samples from the upper Paleozoic reservoirs in 16 representative wells were selected for fluid inclusion analyses. The results of fluid inclusion analyses, combined with the burial-thermal histories of representative wells, were used to determine the hydrocarbon accumulation periods of the main layers and summarize their patterns in different structural regions and layers. The results show that the formation of fluid inclusions in the main upper Paleozoic strata can be divided into two stages. The first-stage inclusions mainly occur in secondary quartz edges, and the second-stage inclusions mainly occur in healed microcracks. The inclusion types are dominantly hydrocarbon-bearing, brine, and minor nonhydrocarbon gas inclusions. The hydrocarbon components are mostly CH4 and minor asphaltene, and the nonhydrocarbon gases are dominantly CO2 and minor SO2. The homogenization temperatures of the brine inclusions associated with hydrocarbon inclusions in major layers in the study area have a wide distribution and multiple peaks; the main peaks in the central part of a given tectonic area are slightly lower than those in the eastern part, and the main peaks in a given location tend to increase with decreasing burial depth. Hydrocarbon accumulation in the upper Paleozoic strata in the study area mainly occurred in the Early and Middle Jurassic and Early Cretaceous. The Early and Middle Jurassic were the mature oil and gas accumulation periods, and the Early Cretaceous was the high-maturity natural gas accumulation period and the most critical accumulation period. The accumulation period in the central part of a given structural region occurred earlier than that in the eastern part, and the accumulation period in different layers in a given location gradually shifted at a later time from deep to shallow.

A perspective of immunotherapy for acute myeloid leukemia: Current advances and challenges.

During the last decade, the underlying pathogenic mechanisms of acute myeloid leukemia (AML) have been the subject of extensive study which has considerably increased our understanding of the disease. However, both resistance to chemotherapy and disease relapse remain the principal obstacles to successful treatment. Because of acute and chronic undesirable effects frequently associated with conventional cytotoxic chemotherapy, consolidation chemotherapy is not feasible, especially for elderly patients, which has attracted a growing body of research to attempt to tackle this problem. Immunotherapies for acute myeloid leukemia, including immune checkpoint inhibitors, monoclonal antibodies, dendritic cell (DC) vaccines, together with T-cell therapy based on engineered antigen receptor have been developed recently. Our review presents the recent progress in immunotherapy for the treatment of AML and discusses effective therapies that have the most potential and major challenges.

Efficacy and safety of tofacitinib combined with methotrexate in the treatment of rheumatoid arthritis: A systematic review and meta-analysis.

Objective: To evaluate the efficacy and safety of tofacitinib in combination with methotrexate (MTX) versus MTX monotherapy in patients with active rheumatoid arthritis (RA). Methods: Trials were identified from four electronic databases: PubMed, Web of science, Cochrane Library and EMBASE from inception to April 2022. Two independent reviewers evaluated each database to scan the title, abstract and keywords of each record retrieved. Full articles were further assessed when the information suggested that the study was a randomized clinical trial (RCT) comparing tofacitinib combined with MTX vs. MTX monotherapy in patients with active RA. Data were extracted from the literature, and the methodological quality of the included literature were evaluated and screened by two reviewers independently. The results were analyzed using RevMan5.3 software. The full text of the studies and extracted data were reviewed independently according to PRISMA guidelines. The outcome indicators were ACR 20, ACR 50, ACR 70, Disease activity score 28 (DAS28), erythrocyte sedimentation Rate (ESR) and adverse events (AEs). Results: Of 1152 studies yielded by the search, 4 were retained, totaling 1782 patients (1345 treated with tofacitinib combined with MTX vs 437 received MTX. In the trial of insufficient response to MTX treatment, tofacitinib combined with MTX had significant advantages compared with MTX monotherapy. Numerically higher ACR20, ACR50 and ACR70 response rates were observed in the tofacitinib combined with MTX groups versus MTX monotherapy. ACR20 (odds ratio (OR), 3.62; 95% CI, 2.84-4.61; P < 0.001), ACR50 (OR, 5.17; 95% CI, 3.62-7.38; P < 0.001), and ACR70 (OR, 8.44; 95% CI, 4.34-16.41; P < 0.001), DAS28 (ESR) < 2.6 (OR, 4.71, 95% CI, 2.06-10.77; P < 0.001). The probability of adverse events of tofacitinib combined with MTX was lower than that of MTX monotherapy (OR, 1.42; 95% CI, 1.08-1.88; P = 0.01). The number of cases discontinued due to lack of efficacy or adverse events was similar in both groups (OR, 0.93; 95% CI, 0.52-1.68). The probability of abnormal liver enzymes in the treatment of tofacitinib combined with MTX was significantly lower than that of MTX monotherapy (OR, 1.86; 95% CI, 1.35-2.56). However, there was no significant difference between the two groups in severe adverse reactions, neutropenia, anemia and cardiovascular disease. Conclusions: In terms of ACR20/50/70 and DAS28 (ESR), tofacitinib combined with MTX demonstrated superiority to MTX monotherapy in the treatment of patients with refractory RA. Considering the hepatoprotective and observably therapeutic efficacy, tofacitinib combined with MTX could be effective in treating refractory RA. However, in terms of hepatoprotective, it requires further large-scale and high-quality clinical trials to confirm.

Jiedu-Quyu-Ziyin Fang (JQZF) inhibits the proliferation and activation of B cells in MRL/lpr mice via modulating the AKT/mTOR/c-Myc signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Jiedu-Quyu-Ziyin Fang (JQZF) is a new herbal formula improved based on "Sheng Ma Bie Jia Tang" in the Golden Chamber, has been proved to be effective in the treatment of SLE. The ability of JQZF to prevent lymphocyte growth and survival has been demonstrated in earlier investigations. However, the specific mechanism of JQZF on SLE has not been fully investigated. AIM OF THE STUDY: To reveal the potential mechanisms of JQZF inhibiting B cell proliferation and activation in MRL/lpr mice. MATERIALS AND METHODS: MRL/lpr mice were treated with low-dose, high-dose JQZF and normal saline for 6 weeks. The effect of JQZF on disease improvement in MRL/lpr mice was studied using enzyme-linked immunosorbent assay (ELISA), histopathological staining, serum biochemical parameters and urinary protein levels. The changes of B lymphocyte subsets in the spleen were analyzed by flow cytometry. The contents of ATP and PA in B lymphocytes from the spleens of mice were determined by ATP content assay kit and PA assay kit. Raji cells (a B lymphocyte line) were selected as the cell model in vitro. The effects of JQZF on the proliferation and apoptosis of B cells were detected by flow cytometry and CCK8. The effect of JQZF on the AKT/mTOR/c-Myc signaling pathway in B cells were detected via western blot. RESULTS: JQZF, especially at high dose, significantly improved the disease development of MRL/lpr mice. Flow cytometry results showed that JQZF affected the proliferation and activation of B cells. In addition, JQZF inhibited the production of ATP and PA in B lymphocytes. In vitro cell experiments further confirmed that JQZF can inhibit Raji proliferation and promote cell apoptosis through AKT/mTOR/c-Myc signaling pathway. CONCLUSION: JQZF may affect the proliferation and activation of B cells by inhibiting the AKT/mTOR/c-Myc signaling pathway.

Allogeneic tendons in the treatment of malunited lateral malleolar avulsion fractures with chronic lateral ankle instability.

BACKGROUND: The aim of this study is to report our institution's experience regarding the application of allogeneic tendons for the reconstruction of malunited lateral malleolar avulsion fractures with chronic lateral ankle instability. METHODS: This retrospective study included 34 (34 ankles) patients surgically treated for malunited lateral malleolar avulsion fractures with chronic lateral ankle instability from January 2016 to December 2019. All patients underwent allogeneic tendon reconstruction. The pre- and postoperative American Orthopaedic Foot and Ankle Society (AOFAS) scores、Karlsson Ankle Functional Scores (KAFS) and visual analogue scale (VAS) scores were used to evaluate the functional recovery of the ankle joint. The final follow-up, based on radiographic assessment, including talar tilt and anterior talar translation, was performed to evaluate the stability of the postoperative ankle joints. RESULTS: Thirty-two patients (32 ankles) returned for final clinical and radiologic follow-up at an average of 29 (range 24-35) months and 2 patients (2 ankles) were lost to follow-up. The preoperative talus inclination angle (13.6 ± 1.9°) and anterior displacement (9.6 ± 2.8 mm) were re-examined under X-ray and found to be reduced to 3.4 ± 1.2° and 3.8 ± 1.1 mm, respectively (p＜0.01). The AOFAS scores increased from 58.5 ± 4.0 to 90.9 ± 3.8 and the Karlsson scores improved from 52.2 ± 3.6 to 89.8 ± 4.5, which was obviously better and the difference was statistically significant (P < 0.01). The VAS scores were significantly reduced from a preoperative mean of 6.8 ± 1.0 to 2.8 ± 0.9 postoperatively (p＜0.01). CONCLUSION: In this population and with this follow-up, the application of allogeneic tendons to treat malunited lateral malleolar avulsion fractures combined with chronic lateral ankle instability appeared safe and effective.

Development of a nomogram to predict surgical site infection after open reduction and internal fixation for closed pilon fracture: a prospective single-center study.

BACKGROUND: To explore the risk factors and develop a nomogram in order to predict surgical site infection (SSI) after open reduction and internal fixation (ORIF) for closed pilon fractures (CPF). METHODS: A prospective cohort study with one-year follow-up was carried out in a provincial trauma center. From January 2019 to January 2021, 417 adult patients with CPFs receiving ORIF were enrolled. A Whitney U test or t test, Pearson chi-square test, and multiple logistic regression analyses were gradually used for screening the adjusted factors of SSI. A nomogram model was built to predict the risk of SSI, and the concordance index (C-index), the receiver operating characteristic (ROC) curve, calibration curve and decision curve analysis (DCA) were used for evaluating the prediction performance and consistency of the nomogram model. The bootstrap method was employed to test the validity of the nomogram. RESULTS: The incidence of SSI after ORIF for CPFs was 7.2% (30/417): 4.1% (17/417) of superficial SSIs and 3.1% (13/417) of deep SSIs. The most common pathogenic bacteria were Staphylococcus aureus (36.6%, 11/30). The multivariate analysis showed tourniquet use, longer preoperative stay, lower preoperative albumin (ALB), higher preoperative body mass index (BMI) and hypersensitive C-reactive protein (Hs-CRP) were independent risk factors of SSI. Additionally, the C-index and bootstrap value of the nomogram model were 0.838 and 0.820, respectively. Finally, the calibration curve indicated that the actual diagnosed SSI had good consistency with the predicted probability, and the DCA showed that the nomogram had clinical value. CONCLUSIONS: Tourniquet use, longer preoperative stay, lower preoperative ALB, higher preoperative BMI and Hs-CRP were five independent risk factors of SSI after closed pilon fractures treated by ORIF. These five predictors are shown on the nomogram, with which we may be able to further prevent the CPS patients from SSI. Trial registration NO 2018-026-1, October /24/2018, prospectively registered. The study was registered in October 24, 2018. The study protocol was designed based on the Declaration of Helsinki and admitted by the Institutional Review Board. The ethics committee approved the study on factors related to fracture healing in orthopedic surgery. Data analyzed in the present study were acquired from the patients who underwent open reduction and internal fixation from January 2019 to January 2021.

Unlocking the Potential of Magnetic Refrigeration: Investigating the Compatibility of the Ga-Based Liquid Metal with a La(Fe,Mn,Si)13Hz Magnetocaloric Material for Enhanced Long-Term Stability.

Magnetic refrigeration (MR) is a cutting-edge technology that promises high energy efficiency and eco-friendliness, making it an exciting alternative to traditional refrigeration systems. However, the main challenge to its widespread adoption is cost competitiveness. In this context, the use of liquid metals as heat transfer liquids in the MR has been proposed as a game-changing solution. Unfortunately, the toxicity and flammability of these liquid metals have raised serious concerns, limiting their practical use. In this study, we investigate the compatibility of a nontoxic and nonflammable GaInSn-based liquid metal with a magnetocaloric material, La(Fe,Mn,Si)13Hz, over a 1.5 year period. Our findings reveal nearly a 14% reduction in specific cooling energy and peak-specific isothermal magnetic entropy change for the considered magnetocaloric material. Our study provides valuable insights into the long-term stability of magnetocaloric materials and their compatibility with liquid metals, facilitating the development of more cost-effective and sustainable MR systems.

[Scarf osteotomy combined with soft tissue balance release for severe hallux valgus].

OBJECTIVE: To explore clinical effect of Scarf osteotomy combined with soft tissue balance in treating severe hallux valgus. METHODS: Totally 38 patients(50 feet) with severe hallux valux who underwent Scarf osteotomy combined with soft tissue balance surgery from June 2019 to June 2021 were retrospectively analyzed, aged from 29 to 64 years old with an average of(54.7±6.8) years old; 26 feet on the left side and 24 feet on the right side;the courses of disease ranged from 5 to 23 years with an average of (12.4±3.9) years. Hallux valgus angle (HVA), intermetatarsal angle (IMA), and distal metatarsal articular angle (DMAA) were compared before and after operation, and postoperative complications was observed. American orthopedic foot ankle society(AOFAS) score before operation and final follow-up was used to evaluate recovery of forefoot function, and visual analogue scale (VAS) was used to evaluate pain relief. RESULTS: Thirty-eight patients (50 feet) were followed up from 15 to 23 months with an average of (18.3±3.2) months. Preoperative HVA, IMA and DMAA were (44.61±3.92)°, (18.74±2.51)°, (12.85±2.11)°, and improved to (13.45±2.13)°, (7.83±1.36)°, (7.03±1.39)°at final follow-up, which had statistical differneces(P<0.05). No delayed union or nonunion of osteotomy end, fracture or loosening of internal fixation, hallux varus occurred. VAS and AOFAS score improved from (6.81±2.14), (43.6±8.4)points before operation to (1.97±0.78), (87.6±5.2) points at final follow-up, which had statistical difference(P<0.01). According to AOFAS at final follow-up, 20 feet got excellent result, 28 feet good and 2 feet moderate. CONCLUSION: Scarf osteotomy combined with soft tissue balance release for severe hallux valgus has good stability and corrective effect, but learning curve and postoperative complications should be paid attention.

Randomized, double-blind, noninferiority study of diclofenac diethylamine 2.32% gel applied twice daily versus diclofenac diethylamine 1.16% gel applied four times daily in patients with acute ankle sprain.

BACKGROUND: Diclofenac diethylamine (DDEA) gel has demonstrated efficacy for treatment of ankle sprains in both the 1.16% four-times-daily (QID) and 2.32% twice-daily (BID) formulations. The objective of this study was to compare, for the first time, the efficacy of DDEA 2.32% gel BID and DDEA 1.16% gel QID. METHODS: This was a phase 3, randomized, double-blind, multicenter, active-controlled, parallel-group study conducted in China from October 2019 to November 2020, designed to determine the noninferiority of DDEA 2.32% gel BID relative to DDEA 1.16% gel QID for treatment of grade I-II ankle sprain. At study entry, patients must have had pain on movement (POM) ≥50 mm on a 100-mm visual analogue scale (VAS), and not received any pain medication. The primary efficacy endpoint was the noninferiority of DDEA 2.32% gel BID vs DDEA 1.16% gel QID for POM as assessed by the patient using the 100-mm VAS, conducted on day 5. Secondary endpoints included measures of ankle tenderness, joint function, swelling, and patient-reported pain intensity and pain relief. RESULTS: A total of 302 patients were randomized and 95.4% completed the study. The mean (SD) change in POM from baseline to day 5 using the 100-mm VAS was - 42.8 mm (19.7 mm) with DDEA 2.32% gel BID and - 43.1 mm (18.1 mm) with DDEA 1.16% gel QID for the per-protocol population. The least squares mean difference (DDEA gel 2.32% - DDEA gel 1.16%) at this timepoint was 1.11 mm (95% CI - 3.00, 5.22; P = 0.595), and the upper limit (5.22 mm) of the 95% CI was less than the noninferiority margin of 13 mm, demonstrating that DDEA 2.32% gel BID was noninferior to DDEA 1.16% gel QID. Similar trends were seen for the secondary efficacy endpoints. There was no significant difference in the incidence of treatment-emergent adverse events or adverse events adjudicated as being treatment related. All treatment-related adverse events were dermatological; one patient discontinued from the DDEA 2.32% gel BID arm due to application-site inflammation. CONCLUSIONS: DDEA 2.32% gel BID offers a convenient alternative to DDEA 1.16% gel QID, with similar pain reduction and relief, anti-inflammatory effects, and tolerability. TRIAL REGISTRATION: NCT04052620.

Risk factors for deep surgical site infection following surgically treated peri-ankle fractures: a case-control study based on propensity score matching.

AIMS: This study aims to identify the risk factors for deep surgical site infection (DSSI) following surgically treated peri-ankle fractures. METHODS: We performed a retrospective case-control study using the propensity score matching (PSM) method in 1:2 ratio, based on the 6 baseline variables, including age, gender, living area, insurance type, fracture location and surgical date. Data on patients who underwent surgical treatment of peri-ankle fractures were collected by inquiring their hospitalization medical records and operative records, as well as the laboratory reports. Conditional logistic regression analysis was performed to identify the risk factors for DSSI. RESULTS: A total of 2147 patients were eligibly included and 74 had a DSSI, indicating an incidence rate of 3.4%. After PSM, 70 cases of DSSI and 140 controls without DSSI were matched, constituting the study cohort. The univariate analyses showed significant differences between groups in terms of history of any surgery, time to operation, surgical wound classification, smoking, alcohol drinking, RBC count, hemoglobin concentration and hematocrit (%). The conditional logistic regression analysis showed time to operation of < 4 or > 9 (vs 4-9 days); unclean wound, current smoking, high-energy injury mechanism and lower hematocrit were independent risk factors for DSSI. CONCLUSIONS: Timely modification of smoking and hematocrit (%), and limiting operation within a rational time frame for an optimized soft tissue condition, may provide potential clinical benefits for SSI prevention.

Comparative transcriptomic reveals the molecular mechanism of maize hybrid Zhengdan538 in response to water deficit.

Heterosis, known as one of the most successful strategies for increasing grain yield and abiotic/biotic stress tolerance, has been widely exploited in maize breeding. However, the underlying molecular processes are still to be elucidated. The maize hybrid "Zhengdan538" shows high tolerance to drought stress. The transcriptomes of the seedling leaves of its parents, "ZhengA88" and "ZhengT22" and their reciprocal F1 hybrid under well-watered and water deficit conditions, were analyzed by RNA sequencing (RNA-Seq). Transcriptome profiling of the reciprocal hybrid revealed 2994-4692 differentially expressed genes (DEGs) under well-watered and water-deficit conditions, which were identified by comparing with their parents. The reciprocal hybrid was more closely related to the parental line "ZhengT22" than to the parental line "ZhengA88" in terms of gene expression patterns under water-deficit condition. Furthermore, genes showed expression level dominance (ELD), especially the high-parental ELD (Class 3 and 5), accounted for the largest proportion of DEGs between the reciprocal F1 hybrid and their parental lines under water deficit. These ELD genes mainly participated in photosynthesis, energy biosynthesis, and metabolism processes. The results indicated that ELD genes played important roles in hybrid tolerance to water deficit. Moreover, a set of important drought-responsive transcription factors were found to be encoded by the identified ELD genes and are thought to function in improving drought tolerance in maize hybrid plants. Our results provide a better understanding of the molecular mechanism of drought tolerance in hybrid maize.

TKIs combined with chemotherapy followed by allo-HSCT in Philadelphia chromosome-positive myelodysplastic syndrome: A case report and literature review.

INTRODUCTION: Philadelphia chromosome (Ph) positive myelodysplastic syndrome (MDS) is a very rare disease. At present, the specific role of Ph in MDS is not clear, but such patients seem to have a poor prognosis, so the disease deserves attention. Here, we describe the history of a woman with Ph-positive MDS and perform a systematic review of related literature. PATIENT CONCERNS AND DIAGNOSIS: We report a 38-year-old woman with Ph-positive MDS. INTERVENTIONS AND OUTCOMES: She received chemotherapy with decitabine, cytarabine, aclarubicin, and granulocyte colony-stimulating factor (DCAG) combined with imatinib mesylate and achieved a bone marrow remission. She then underwent an allogeneic hematopoietic stem cell transplant. The condition is good and no recurrence of the disease has been observed. CONCLUSION: Ph-positive MDS is a very rare disease. Ph may aid in the malignant progression of MDS leaving such patients with a very poor prognosis. Tyrosine kinase inhibitors (TKIs) plus chemotherapy followed by allogeneic hematopoietic stem cell transplantation has provided these patients with satisfactory outcomes.

Triptolide in the treatment of systemic lupus erythematosus - regulatory effects on miR-146a in B cell TLR7 signaling pathway in mice.

Objective: To clarify the mechanism of triptolide (TP) in alleviating the conditions underlying SLE. Methods: Eight-week-old MRL/lpr mice were randomly divided into a model group (n = 5), low-dose TP (TP-L) group (n = 5), and high-dose TP (TP-H) group (n = 5). Mice in these groups were gavaged with normal saline, low-dose TP solution, and high-dose TP solution for 8 weeks, respectively. The expression levels of anti-dsDNA, IgG, IgM, IgA, C3, C4, and CREA, BUN, ALT, AST, ALB, and ALP indexes in the serum of mice were detected. The proportion of CD19+CD138+B220- cells in the spleen and the pathological changes of kidney tissue in the mice were also evaluated. The possible signaling pathways and microRNA (miRNA) targets of TP in the treatment of SLE were analyzed using network pharmacology. The expressions of TLR7 mRNA and miR-146a in Raji cells (a B lymphocyte line) were detected using qPCR before and after intervention with a miR-146a inhibitor. The protein expression levels of TLR7, MyD88, p-IRAK1, and p-NF-κBp65 were detected using western blot analysis. Results: TP could significantly decrease the levels of ds-DNA and IgG, alleviate pathological injury in renal tissue, and upregulate miR-146a expression in the B cells of MRL/lpr mice without obvious liver and kidney toxicity. Network pharmacology analysis showed that TP could mainly regulate the Toll-like receptor signaling pathway, and NF-κB signaling pathway, among others. miRNA target prediction suggested that TP could regulate miRNAs such as miR-146a. In vitro cell experiments further confirmed that TP could significantly upregulate miR-146a expression and downregulate the expression of TLR7 mRNA and protein levels TLR7, MyD88, p-IRAK1, and p-NF-κBp65. After intervention with a miR-146a inhibitor, TP had no obvious inhibitory effects on TLR7, MyD88, p-IRAK1, and p-NF-κBp65 expression. Conclusion: TP may exert therapeutic effects on SLE by regulating miR-146a expression, inhibiting the TLR7/NF-κB signaling pathway, and affecting B cell activation.

Molecular mapping of quantitative trait loci for 3 husk traits using genotyping by sequencing in maize (Zea mays L.).

The maize (Zea mays L.) husk consists of multiple leaf layers and plays an important role in grain growth and development. Despite significant achievements in physiological and morphological research, few studies have focused on the detection of genetic loci underlying husk-related traits due to the lack of efficient tools. In this study, we constructed an ultra-high-density linkage map using genotyping by sequencing based on a recombinant inbred line population to estimate the genetic variance and heritability of 3 husk traits, i.e. husk length, husk width, and husk layer number in 3 field environments and the combined environment. The 3 husk traits showed broad phenotypic variation and high heritability; the broad-sense heritability (H2) was 0.92, 0.84, and 0.86. Twenty quantitative trait loci were consistently detected more than 1 environment, including 9 for husk length, 6 for husk width, and 5 for husk layer number. These loci were considered as stable quantitative trait loci. Based on the quantitative trait loci mapping in the recombinant inbred line population, qHL6 and qHN4 were detected across all environments and inferred to be reliable and major-effect quantitative trait loci for husk length and husk layer number, respectively. In addition, several predicted candidate genes were identified in the region of qHL6 and qHN4, of which 17 candidate genes potentially play a role in biological processes related to development process and energy metabolism. These results will be as a useful resource for performing functional studies aimed at understanding the molecular pathways involved in husk growth and development.