MiR-122-5p regulates erastin-induced ferroptosis via CS in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is a tumor that occurs in the nasopharynx. Although advances in detection and treatment have improved the prognosis of NPC the treatment of advanced NPC remains challenging. Here, we explored the effect of microRNA (miR)-122-5p on erastin-induced ferroptosis in NPC cells and the role of ferroptosis in the development of NPC. The effect of miR-122-5p silencing and overexpression and the effect of citrate synthase on erastin-induced lipid peroxidation in NPC cells was analyzed by measuring the amounts of malondialdehyde, Fe2+, glutathione, and reactive oxygen species and the morphological alterations of mitochondria. The malignant biological behavior of NPC cells was examined by cell counting kit-8, EDU, colony formation, Transwell, and wound healing assays. The effects of miR-122-5p on cell proliferation and migration associated with ferroptosis were examined in vivo in a mouse model of NPC generated by subcutaneous injection of NPC cells. We found that erastin induced ferroptosis in NPC cells. miR-122-5p overexpression inhibited CS, thereby promoting erastin-induced ferroptosis in NPC cells and decreasing NPC cell proliferation, migration, and invasion.

Arthroscopic inferior leaf meniscectomy of the involved anterior horn in the lateral meniscus horizontal tear via an accessary extreme far anteromedial portal.

BACKGROUND: An accessory extreme far anteromedial portal can improve visualisation and ease inferior leaf meniscectomy in patients with lateral meniscal anterior horn horizontal tears. However, the therapeutic outcomes of adding an accessory extreme far anteromedial portal remain unclear. This study aimed to evaluate the clinical efficacy of adding an accessory extreme far anteromedial portal for treating lateral meniscal horizontal tears involving the anterior horns. METHODS: This retrospective study included 101 patients with anterior horn involvement in lateral meniscal horizontal tears who underwent arthroscopic unstable inferior leaf meniscectomy between January 2016 and December 2020. The pathologies were diagnosed using physical examinations and magnetic resonance imaging. The anterior horn involved in the lateral meniscal horizontal tears was treated using inferior leaf meniscectomy. The primary endpoints were changes in the visual analogue scale, Lysholm, International Knee Documentation Committee, and Tegner scores at the final follow-up. The secondary endpoint was meniscal cure rate at 3 months postoperatively. The preoperative and postoperative functional scores were compared. The occurrence of complications was recorded. RESULTS: All patients were followed up for an average of 4.9 ± 1.2 years (range 2.3-7.5 years). After 4 months, none of the patients experienced pain, weakness, instability, or tenderness in the lateral joint line, achieving an imaging cure rate of 98%. At the final follow-up, significant postoperative improvements were observed in the average values of the visual analogue scale score (3.5 ± 0.7 vs. 0.7 ± 0.6), Lysholm score (62.7 ± 4.4 vs. 91.8 ± 3.1), International Knee Documentation Committee score (61.9 ± 3.7 vs. 91.7 ± 9.5), and Tegner score (2.0 ± 0.7 vs. 6.1 ± 0.7). Excellent Lysholm scores were obtained in 81 patients, and good outcomes were obtained in 18 patients, with an excellent-to-good rate of 98.0%. CONCLUSIONS: Inferior leaf resection via the accessory far anteromedial portal is a safe treatment option for the involved anterior horn in lateral meniscal horizontal tears. This approach enhances visibility and facilitates surgical procedures, with minimal complications.

Clinical outcomes following direct anterior approach during total hip arthroplasty without hip extension: a retrospective comparative study.

BACKGROUND: Traditional total hip arthroplasty (THA) using the direct anterior approach (DAA) requires a hip extension. This study aimed to compare the clinical outcomes of patients undergoing THA with DAA using either the no hip extension (NHE) or the traditional hip extension (THE) strategy. METHODS: A retrospective analysis of demographics, clinical and radiological outcomes, and occurrence of complications was performed using data from 123 patients treated between January 2020 and November 2021. The patients were categorised into two groups: NHE (84 patients) and THE (39 patients). RESULTS: The NHE group exhibited shorter operative time and had more male participants with higher ages. Comparable outcomes were observed in the visual analogue scale, Harris Hip, and Oxford Hip scores at the final follow-up. Furthermore, complications were observed in the NHE and THE groups, including two and one greater trochanteric fractures and three and one transfusions, respectively. CONCLUSIONS: Compared to the THE, employing the NHE strategy during THA with DAA in elderly and young female patients resulted in comparable clinical outcomes with several advantages, such as favourable surgical time. The NHE method also exhibited good safety and effectiveness. Therefore, the NHE strategy may be a favourable option for elderly and young female patients.

[Research on Runx2 gene induced differentiation of human amniotic mesenchymal stem cells into ligament fibroblasts in vitro and promotion of tendon-bone healing in rabbits].

Objective: To investigate whether the Runx2 gene can induce the differentiation of human amniotic mesenchymal stem cells (hAMSCs) to ligament fibroblasts in vitro and promote the tendon-bone healing in rabbits. Methods: hAMSCs were isolated from the placentas voluntarily donated from healthy parturients and passaged, and then identified by flow cytometric identification. Adenoviral vectors carrying Runx2 gene (Ad-Runx2) and empty vector adenovirus (Ad-NC) were constructed and viral titer assay; then, the 3rd generation hAMSCs were transfected with Ad-Runx2 (Ad-Runx2 group) or Ad-NC (Ad-NC group). The real-time fluorescence quantitative PCR and Western blot were used to detect Runx2 gene and protein expression to verify the effectiveness of Ad-Runx2 transfection of hAMSCs; and at 3 and 7 days after transfection, real-time fluorescence quantitative PCR was further used to detect the expressions of ligament fibroblast-related genes [vascular endothelial growth factor (VEGF), collagen type Ⅰ, Fibronectin, and Tenascin-C]. The hAMSCs were used as a blank control group. The hAMSCs, hAMSCs transfected with Ad-NC, and hAMSCs were mixed with Matrigel according to the ratio of 1 : 1 and 1 : 2 to construct the cell-scaffold compound. Cell proliferation was detected by cell counting kit 8 (CCK-8) assay, and the corresponding cell-scaffold compound with better proliferation were taken for subsequent animal experiments. Twelve New Zealand white rabbits were randomly divided into 4 groups of sham operation group (Sham group), anterior cruciate ligament reconstruction group (ACLR group), anterior cruciate ligament reconstruction+hAMSCs transfected with Ad-NC-scaffold compound group (Ad-NC group), and anterior cruciate ligament reconstruction+hAMSCs transfected with Ad-Runx2-scaffold compound group (Ad-Runx2 group), with 3 rabbits in each group. After preparing the ACL reconstruction model, the Ad-NC group and the Ad-Runx2 group injected the optimal hAMSCs-Matrigel compunds into the bone channel correspondingly. The samples were taken for gross, histological (HE staining and sirius red staining), and immunofluorescence staining observation at 1 month after operation to evaluate the inflammatory cell infiltration as well as collagen and Tenascin-C content in the ligament tissues. Results: Flow cytometric identification of the isolated cells conformed to the phenotypic characteristics of MSCs. The Runx2 gene was successfully transfected into hAMSCs. Compared with the Ad-NC group, the relative expressions of VEGF and collagen type Ⅰ genes in the Ad-Runx2 group significantly increased at 3 and 7 days after transfection ( P<0.05), Fibronectin significantly increased at 3 days ( P<0.05), and Tenascin-C significantly increased at 3 days and decreased at 7 days ( P<0.05). CCK-8 detection showed that there was no significant difference ( P>0.05) in the cell proliferation between groups and between different time points after mixed culture of two ratios. So the cell-scaffold compound constructed in the ratio of 1∶1 was selected for subsequent experiments. Animal experiments showed that at 1 month after operation, the continuity of the grafted tendon was complete in all groups; HE staining showed that the tissue repair in the Ad-Runx2 group was better and there were fewer inflammatory cells when compared with the ACLR group and the Ad-NC group; sirius red staining and immunofluorescence staining showed that the Ad-Runx2 group had more collagen typeⅠ and Ⅲ fibers, tending to form a normal ACL structure. However, the fluorescence intensity of Tenascin-C protein was weakening when compared to the ACLR and Ad-NC groups. Conclusion: Runx2 gene transfection of hAMSCs induces directed differentiation to ligament fibroblasts and promotes tendon-bone healing in reconstructed anterior cruciate ligament in rabbits.

Extrachromosomal DNA (ecDNA): Unveiling its role in cancer progression and implications for early detection.

Extrachromosomal DNA (ecDNA) is a special class of circular DNA in eukaryotes, which is independent of conventional chromosomes. These circular molecules play important roles in biology, especially in cancer biology. The emergence of sequencing technologies such as CCDA-seq and Amplicon Architect has led to a progressive unraveling of the mystery of ecDNA. Consequently, insights into its function and potential applications have begun to surface. Among these studies, the most noteworthy research pertains to cancer-related investigations into ecDNA. Numerous studies have underscored the significance of ecDNA in the pathogenesis of cancer and its role in accelerating cancer evolution. This review provides an overview of the source, structure, and function of ecDNA, while compiling recent advancements in ecDNA in the field of cancer. Nonetheless, further research is imperative to determine its effectiveness and specificity as a biomarker for early cancer detection.

Why Treg should be the focus of cancer immunotherapy: The latest thought.

Regulatory T cells are a subgroup of T cells with immunomodulatory functions. Different from most cytotoxic T cells and helper T cells, they play a supporting role in the immune system. What's more, regulatory T cells often play an immunosuppressive role, which mainly plays a role in maintaining the stability of the immune system and regulating the immune response in the body. However, recent studies have shown that not only playing a role in autoimmune diseases, organ transplantation, and other aspects, regulatory T cells can also play a role in the immune escape of tumors in the body, through various mechanisms to help tumor cells escape from the demic immune system, weakening the anti-cancer effect in the body. For a better understanding of the role that regulatory T cells can play in cancer, and to be able to use regulatory T cells for tumor immunotherapy more quickly. This review focuses on the research progress of various mechanisms of regulatory T cells in the tumor environment, the related research of tumor cells acting on regulatory T cells, and the existing various therapeutic methods acting on regulatory T cells.

The Keto-Switched Photocatalysis of Reconstructed Covalent Organic Frameworks for Efficient Hydrogen Evolution.

The keto-switched photocatalysis of covalent organic frameworks (COFs) for efficient H2 evolution was reported for the first time by engineering, at a molecular level, the local structure and component of the skeletal building blocks. A series of imine-linked BT-COFs were synthesized by the Schiff-base reaction of 1, 3, 5-benzenetrialdehyde with diamines to demonstrate the structural reconstruction of enol to keto configurations by alkaline catalysis. The keto groups of the skeletal building blocks served as active injectors, where hot π-electrons were provided to Pt nanoparticles (NPs) across a polyvinylpyrrolidone (PVP) insulting layer. The characterization results, together with density functional theory calculations, indicated clearly that the formation of keto-injectors not only made the conduction band level more negative, but also led to an inhomogeneous charge distribution in the donor-acceptor molecular building blocks to form a strong intramolecular built-in electric field. As a result, visible-light photocatalysis of TP-COFs-1 with one keto group in the skeletal building blocks was successfully enabled and achieved an impressive H2 evolution rate as high as 0.96 mmol g-1 h-1 . Also, the photocatalytic H2 evolution rates of the reconstructed BT-COFs-2 and -3 with two and three keto-injectors were significantly enhanced by alkaline post-treatment.

Unravelling the dynamics of soil microbial communities under the environmental selection and range shift process in afforestation ecosystems.

The process of forest range shift not only affects the vegetation aboveground but also influences the dynamics of belowground microbial communities. To investigate the changes in soil under forest range shift, we examined the natural forest soil microbiome along with its corresponding physicochemical properties, as well as the afforestation of natural forest by seedlings and sowing. By utilizing natural forests and employing different afforestation methods, we simulated the three stages of forest range shift: the staging stage, regeneration, and colonization. We employed network analysis and phylogenetic assemblages to examine the structure of soil microbial communities during these three stages in a macro-environmental change context. Ordination and regression analyses were also used to explore the correlation between microorganisms, environmental factors, and changes in their niches. The findings revealed that different afforestation (range shift) types led to distinct microbial compositions. Seedling afforestation exhibited similarities to mature forests, suggesting a significant influence on below-ground microorganisms. In contrast, sowing-based afforestation resulted in small changes in soil microbes, indicating a legacy effect on grassland soils. The impact of the rhizosphere on microbial composition remained consistent across the three forest types. Overall, this study underscores the significance of forest range shift in shaping soil microbial communities and emphasizes the need to consider these dynamics in forest management and restoration endeavours.

Hip effusion/synovitis influences results after multiple drilling core decompression for bone marrow edema syndrome of hip.

BACKGROUND: At present, it is not known whether hip effusion/synovitis affects the therapeutic effect of multiple drilling core decompression (MDCD) in patients with bone marrow edema syndrome of hip (BMESH). The aims were to assess hip effusion/synovitis and its relationship with results of MDCD in patients with BMESH. METHODS: The data of undergoing arthroscopic-assisted MDCD for treatment of BMESH with hip effusion/synovitis by one surgeon were retrospectively reviewed from the associated medical records at the Affiliated Hospital of Zunyi Medical University (2016-2019). Seven patients (9 hips) participated in this study. Patients were followed up at 1, 2, 3, 6, 12 and 24 months. Data included demographics and clinical outcomes. The pre- and postoperative pain and functional outcomes were measured with the visual analogue scale (VAS), Harris Hip Score (HHS), Hip Outcome Score Activities of Daily Living subscale (HOS-ADL), International Hip Outcome Tool-12 (iHOT-12) and range of motion (ROM). RESULTS: Seven patients (9 hips) were followed up. Disappearance of hip pain immediately obtained at rest after surgery. All of 7 patients returned to their former activity level at postoperative 3 months, bone marrow edema had disappeared on Magnetic Resonance Imaging (MRI). The VAS, HHS, HOS-ADL, iHOT-12, and ROM at postoperative 1 month had a significant difference (P < 0.05) compared with preoperative. It was also statistically significant (P < 0.05) when compared with other time points. At the final follow-up, all patients had no limited ROM, which was symmetrical with the contralateral of hip joint. Hip effusion/synovitis were observed in 9 hips. Labral tears, cartilage fissure, and loose bodies were observed in 1 hip, respectively. Kirschner wire tracks bleeding occurred in 1 hip. No other complications occurred. CONCLUSIONS: Hip effusion/synovitis could affect the clinical outcomes after MDCD in patients with BMESH. Arthroscopic procedure of hip effusion/synovitis can shorten postoperative pain relief time, disappearance time of bone marrow edema on MRI. It can simultaneously diagnose and treat other concomitant intraarticular pathologies, and be a safe operation with fewer complications.

Effect of different pre-hospital first aid methods on the efficacy and prognosis of acute myocardial infarction with left heart failure: a systematic review and meta-analysis.

Background: Pre-hospital first aid for acute myocardial infarction (AMI) is an important way to save patients. However, there are still some disputes about the way of pre-hospital first aid. Therefore, this paper provides a Meta-analysis to evaluate the efficacy and prognosis of different prehospital care for AMI with left heart failure. Methods: By searching the published studies in the databases, the literature related to the pre-hospital first aid for patients with AMI and left heart failure was screened out. The quality of the literature was evaluated according to the Newcastle-Ottawa scale (NOS), and the corresponding data were extracted for meta-analysis. Meta-analysis was performed on 7 outcome indicators (clinical effect of patients after treatment, respiratory rate, heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), survival status, and incidence of complications). A funnel plot and Egger's test were used to test risk of bias. Results: A total of 16 articles were finally included, comprising a total of 1,465 patients. The literature quality evaluation found that 8 literatures were rated as low risk of bias, and 8 literatures were rated as medium risk of bias. The meta-analysis results showed that the clinical effect of the first aid and then transportation group was better than that of the transportation and then first aid group [risk ratio (RR) =1.35, 95% confidence interval (CI): 1.27 to 1.45, P<0.01]; the respiratory rate decreased [mean difference (MD) =-4.84, 95% CI: -6.50 to -3.18, P<0.01]; the heart rate decreased (MD =-11.34, 95% CI: -12.69 to -9.99, P<0.01); SBP decreased (MD =-6.00, 95% CI: -10.00 to -2.00, P<0.01); the DBP decreased (MD =-3.54, 95% CI: -4.45 to -2.64, P<0.01); the survival status of the patients improved (RR =1.29, 95% CI: 1.18 to 1.41, P<0.01); the incidence of complications was reduced (RR =0.31, 95% CI: 0.20 to 0.48, P<0.01). Conclusions: Pre-hospital first aid and then transportation can significantly improve the clinical treatment effect of patients. However, considering that the literatures included in this paper are non-randomized controlled studies and the overall quality of the included literatures is not high and the number of studies is limited, further exploration is needed.

A Nomogram for Early Diagnosis of Community-Acquired Pneumonia Based on Bronchoalveolar Lavage Fluid Metabolomics.

Purpose: There is a high disease burden associated with community-acquired pneumonia (CAP) around the world. A timely and correct diagnosis of CAP can facilitate early treatment and prevent illness progression. The present study aimed to find some novel biomarkers of CAP by metabolic analysis and construct a nomogram model for precise diagnosis and individualized treatment of CAP patients. Patients and Methods: 42 CAP patients and 20 controls were enrolled in this study. The metabolic profiles of bronchoalveolar lavage fluid (BALF) samples were identified by untargeted LC-MS/MS analysis. With a VIP score ≥ 1 in OPLS-DA analysis and P < 0.05, the significantly dysregulated metabolites were estimated as potential biomarkers of CAP, which were further included in the construction of the diagnostic prediction model along with laboratory inflammatory indexes via stepwise backward regression analysis. Discrimination, calibration, and clinical applicability of the nomogram were evaluated by the C-index, the calibration curve, and the decision curve analysis (DCA) estimated by bootstrap resampling. Results: The metabolic profiles differed obviously between CAP patients and healthy controls, as shown by PCA and OPLS-DA plots. Seven metabolites significantly dysregulated in CAP were established: dimethyl disulfide, oleic acid (d5), N-acetyl-a-neuraminic acid, pyrimidine, choline, LPC (12:0/0:0) and PA (20:4/2:0). Multivariate logistic regression revealed that the expression levels of PA (20:4/2:0), N-acetyl-a-neuraminic acid, and CRP were associated with CAP. After being validated by bootstrap resampling, this model showed satisfactory diagnostic performance. Conclusion: A novel nomogram prediction model containing metabolic potential biomarkers in BALF that was developed for the early diagnosis of CAP offers insights into the pathogenesis and host response in CAP.

MiR-223-3p regulates the eosinophil degranulation and enhances the inflammation in allergic rhinitis by targeting FBXW7.

OBJECTIVES: MiR-223-3p is a multifunctional microRNA regulated by multiple transcription factors and plays a critical role in inflammation. This paper was designed to investigate the regulatory role and mechanism of miR-223-3p in eosinophils degranulation and allergic rhinitis (AR) inflammation. METHODS: OVA sensitized AR mouse model and EOL-1 cells model were established. RT-qPCR and FISH were performed to detect the miR-223-3p expression. ELISA and WB were utilized to evaluate mRNA and protein expression. HE staining and transmission electron microscopy were applied to observe the morphological changes in nasal mucosa. Flow cytometry and immunofluorescence staining were performed to measure the proportion of eosinophils and eosinophilic major basic protein expression. The targeting relationship between miR-223-3p and FBXW7 was verified by bioinformatic analysis and dual-luciferase reporter gene assay. The expression of FBXW7 was detected by immunohistochemistry. RESULTS: The level of miR-223-3p in nasal mucosa was significantly up-regulated in AR group. The expression of miR-223-3p, ECP, MBP, and EPO were increased in EOL-1 cells, further increasing the miR-223-3p level could promote the ECP and EPO mRNA expression. Upregulation of miR-223-3p increased eosinophils granule protein expression, aggravated mucosal destruction and enhanced AR inflammation. Luciferase assay verified miR-223-3p directly target the 3'-UTR of FBXW7. In vitro, overexpression of FBXW7 could reverse the increase in MBP expression caused by the up-regulation of miR-223-3p. In vivo, knockdown of FBXW7 could reverse the down-regulation in granule protein level caused by the down-regulation of miR-223-3p, thereby aggravating AR inflammation. CONCLUSION: Collected evidence elucidated that miR-223-3p could regulate the eosinophil degranulation and enhances the inflammation in AR by targeting FBXW7. The miR-223-3p/FBXW7 axis may provide a novel approach for AR treatment.

Pyomelanin production via heterologous expression of 4-hydroxyphenylpyruvate dioxygenase (HPPD) and construction of HPPD inhibitor screening model.

Melanin has an increasing market demand in cosmetics, food, medicine as well as aerospace due to its unique properties. Heterologous expression of 4-hydroxyphenylpyruvate dioxygenase (HPPD) from the melanin-producing strain Streptomyces fungicidicus NW-EN1 in Escherichia coli shortened the fermentation cycle of melanin. HPPD catalyzed 4-hydrophenylpyruvate (HPP) to form homologous acid (HGA) and finally form melanin. The purified melanin had the highest absorption peak at 460 nm. Fourier transform infrared spectroscopy and scanning electron microscope scanning showed that the pigment had universal characteristic peaks. The presence of HGA, a predictor of pyomelanin, was identified by high-performance liquid chromatography analysis. The recombinant E. coli produced 804.4 ± 5.9 mg/L pyomelanin within 48 h. Metal ions had a great influence on the production of pyomelanin. Pyomelanin was stable in response to light intensity and had a protective effect against bacteria under UV irradiation. Meanwhile, we utilized the chromogenic effect after whole-cell catalysis to reflect the inhibition of the HPPD inhibitors (mesotrione and isoxaflutole) on HPPD by observing the color change. As a rapid method to test the action of inhibitors, this method is expected to be useful for the development of HPPD-inhibiting herbicides.

[Short-term effectiveness of modified arthroscopic Latarjet procedure with double EndoButtons for recurrent anterior shoulder dislocation].

Objective: To evaluate the short-term effectiveness of modified arthroscopic Latarjet procedure with double EndoButtons for recurrent anterior shoulder dislocation. Methods: Between January 2019 and November 2020, 36 patients with recurrent anterior shoulder dislocation were treated by modified arthroscopic Latarjet procedure with double EndoButtons. There were 26 males and 10 females, with an average age of 27.8 years (range, 18-36 years). The number of shoulder dislocations ranged from 3 to 12 times, with an average of 6.5 times. The disease duration ranged from 5 to 36 months, with an average of 16.2 months. Preoperative shoulder fear test was positive, and the Beighton score of joint relaxation was 0-4, with an average of 1.3. Imaging examination showed that the defect width of the ipsilateral glenoid bone was 16%-28%, with an average of 21.5%. Postoperative complications, recurrent dislocation, subluxation, and instability of shoulder joint were recorded. Shoulder range of motion was examined, including forward flexion, external rotation at side, external rotation at 90° abduction, and internal rotation. Shoulder joint function was evaluated by Walch-Duplay score, American Association for Shoulder and Elbow Surgery Score (ASES), and ROWE score. X-ray film and CT images were taken to observe the shaping of coracoid process graft. Results: All incisions healed by first intention, and no vascular or nerve injury occurred. All patients were followed up 12-28 months, with an average of 19.9 months. During follow-up, no shoulder dislocation recurred, and shoulder fear test was negative. At last follow-up, there was no significant difference in shoulder forward flexion, external rotation at side, external rotation at 90° abduction, and internal rotation when compared with preoperative values (P>0.05). The Walch-Duplay score, ASES score, and ROWE score of shoulder function significantly improved (P<0.05). Postoperative imaging examination showed that coracoid process graft was at the same level with the glenoid in 33 cases (91.7%), medial in 1 case (2.8%), and lateral in 2 cases (5.6%); the center of coracoid process graft was mainly located between 3 to 5 o'clock in 33 cases (91.7%), higher than 3 o'clock in 1 case (2.8%), and lower than 5 o'clock in 2 cases (5.6%). There was no obvious glenohumeral joint degeneration during follow-up, and the coracoid process graft gradually formed concentric circles with the humeral head. Conclusion: The modified arthroscopic Latarjet procedure with double EndoButtons can effectively treat recurrent anterior shoulder dislocation, and the short-term effectiveness is satisfactory, and the position of coracoid process graft is accurate.

[Short-term effectiveness of high tibial osteotomy combined with arthroscopic surgery for knee varus arthritis and the results of secondary arthroscopic exploration].

Objective: To investigate the effectiveness of high tibial osteotomy (HTO) combined with arthroscopic surgery to treat medial compartment knee osteoarthritis (KOA) and secondary arthroscopic exploration to evaluate the outcome of cartilage and meniscus. Methods: A clinical data of 57 patients with medial compartment KOA with varus deformity of lower extremities admitted between August 2014 and October 2018 were retrospectively analyzed. There were 23 males and 34 females with an average age of 51.2 years (range, 41-63 years). The disease duration ranged from 2 to 8 years, with an average of 4.7 years. The preoperative femorotibial angle was (179.86±4.69)°, the relative position of the lower limb mechanical axis passing through the tibial plateau was 24.21%±6.98%, and the posterior slope of the tibial plateau was (5.23±1.45)°. The Kellgren-Lawrence grade of knee joint was grade Ⅱ in 22 cases and grade Ⅲ in 35 cases. The preoperative Hospital for Special Surgery (HSS) score, Lysholm score, and visual analogue scale (VAS) score were 59.1±7.3, 48.8±7.6, and 6.2±1.1, respectively. Arthroscopic exploration was performed during the operation to record the articular cartilage degeneration in the weight-bearing area of the medial compartment (Outerbridge grade Ⅰ in 18 cases, grade Ⅱ in 30 cases, and grade Ⅲ in 9 cases) and the condition of the medial meniscus injury, and the corresponding treatment was performed. The coronal force line was adjusted according to the preoperative Kellgren-Lawrence grade of the knee joint during the operation. After operation, the relative position of the lower limb mechanical axis passing through the tibial plateau, the femorotibial angle, and the posterior slope of the tibial plateau were measured; the Kellgren-Lawrence grade of the knee joint was recorded; the Outerbridge grade of articular cartilage degeneration and the meniscus outcome were evaluated by combining with the MRI of the knee joint at 1 year after operation and the second arthroscopic exploration when the internal fixator was removed. The function and pain of the knee were evaluated by Lysholm score, HSS score, and VAS score. Results: All the 57 patients were followed up 36-58 months with an average of 42.1 months. Incisions healed by first intention, and no neurovascular injury, intraarticular or hinge fractures occurred during operation, and no postoperative complications such as deep vein thrombosis of lower limbs and internal fixation failure occurred. All the osteotomy sites healed at 3 months after operation. At 1 year after operation, the internal fixator was removed, and the second arthroscopic exploration showed that there were 15 cases of Outerbridge grade Ⅰ, 31 cases of grade Ⅱ, and 11 cases of grade Ⅲ in the weight-bearing area of the medial compartment, and there was no significant difference when compared with preoperative grade ( Z=31.992, P=0.997); there was no cartilage degeneration in other compartments. Meniscus healing was seen in the injured meniscus, and no injury was seen in the normal meniscus. At last follow-up, there were 19 cases of Kellgren-Lawrence grade Ⅱ and 38 cases of grade Ⅲ, and there was no significant difference when compared with preoperative grade ( Z=49.049, P=0.764). The relative position of the lower limb mechanical axis passing through the tibial plateau was 59.16%±2.87%, and the femorotibial angle was (171.54±3.39)°, which significantly improved when compared with those before operation ( P<0.001). The posterior slope of the tibial plateau was (5.65±1.22)°, which was not significantly different from that before operation ( t=-1.673, P=0.096). The HSS score, Lysholm score, and VAS score were 82.3±7.7, 83.4±6.4, and 1.6±1.1 respectively, which were significantly different from those before operation ( P<0.001). Conclusion: HTO combined with arthroscopic surgery for medial compartment KOA with varus deformity of lower extremities can effectively improve the force line of lower extremities, relieve pain symptoms, and improve joint function, with satisfactory short-term effectiveness, and without significant progress in articular cartilage or meniscus injury after operation.

Identification of Conservation Priority Areas and a Protection Network for the Siberian Musk Deer (Moschus moschiferus L.) in Northeast China.

Species conservation actions are guided by available information on the biogeography of the protected species. In this study, we integrated the occurrence data of Siberian musk deer (Moschus moschiferus L.) collected from 2019 to 2021 with species distribution models to estimate the species' potential distribution in Northeast China. We then identified conservation priority areas using a core-area zonation algorithm. In addition, we analyzed core patch fragmentation using FRAGSTATS. Lastly, we identified potential connectivity corridors and constructed a potential protection network based on the least-cost path and the circuit theory. The results showed concentrations of M. moschiferus in the northern Greater Khingan Mountains, the southeastern Lesser Khingan Mountains, and the eastern Changbai Mountains, with a potential distribution area of 127,442.14 km2. Conservation priority areas included 41 core patches with an area of 106,306.43 km2. Patch fragmentation mainly occurred in the Changbai Mountains and the Lesser Khingan Mountains. We constructed an ecological network composed of 41 core patches and 69 linkages for M. moschiferus in Northeast China. The results suggest that the Greater Khingan Mountains represent the most suitable area to maintain the stability of M. moschiferus populations in Northeast China. Considering the high habitat quality requirements of M. moschiferus and its endangered status, we propose that the Chinese government accelerates the construction of the Greater Khingan Mountains National Park and the Lesser Khingan Mountains National Park and enlarges the Northeast China Tiger and Leopard National Park to address the fragmentation of protected areas and the habitat of M. moschiferus.

Epstein Barr virus-positive B-cell lymphoma is highly vulnerable to MDM2 inhibitors in vivo.

Epstein-Barr virus-positive (EBV-positive) B-cell lymphomas are common in immunocompromised patients and remain an unmet medical need. Here we report that MDM2 inhibitors (MDM2is) navtemadlin and idasanutlin have potent in vivo activity in EBV-positive B-cell lymphoma established in immunocompromised mice. Tumor regression was observed in all 5 EBV-positive xenograft-associated B-cell lymphomas treated with navtemadlin or idasanutlin. Molecular characterization showed that treatment with MDM2is resulted in activation of p53 pathways and downregulation of cell cycle effectors in human lymphoma cell lines that were either EBV-positive or had undetectable expression of BCL6, a transcriptional inhibitor of the TP53 gene. Moreover, treatment with navtemadlin resulted in tumor regression and prevented systemic dissemination of EBV-positive lymphoma derived from 2 juvenile patients with posttransplant lymphoproliferative diseases, including 1 whose tumor was resistant to virus-specific T-cell therapy. These results provide proof-of-concept for targeted therapy of EBV-positive lymphoma with MDM2is and the feasibility of using EBV infection or loss of BCL6 expression to identify responders to MDM2is.

Second Primary Malignancy in Patients with Hypopharyngeal Carcinoma: A SEER-Based Study.

BACKGROUND: A population-based analysis of the risk of secondary primary malignancy (SPM) in patients with hypopharyngeal carcinoma (HPC) has been lacking in the literature. Therefore, we conducted this study to determine the risk factors and assess the effects of SPM on the overall survival (OS) and cancer-specific survival (CSS) of patients with HPC. METHODS: Data on selected patients diagnosed with HPC from the Surveillance, Epidemiology and End Results (SEER) database between 1973 and 2015 were examined through logistic regression, Cox regression and nomogram methods. RESULTS: The overall risk of SPM in patients with HPC was higher than that in the general population (SIR: 2.77; P < 0.05). The specific-site, including the oral cavity, pharynx, digestive system, respiratory system and endocrine system, had a relatively higher risk of SPM. The overall risks of the subgroup of people 55-75 years of age and all subgroups of sex, race and latency were significantly elevated. In addition, patients with HPC were more likely to have been diagnosed in 2010-2015 (vs 2004-2009; P = 0.002), to be unmarried (vs married; P = 0.008), to have distant metastasis (vs no metastasis; P = 0.016) and to have had no surgery for the first tumor (vs surgery for the first tumor; P = 0.021), and these aspects were associated with a significantly elevated risk of developing SPM. SPM was independently associated with better OS and CSS. The OS and CSS in patients with HPC with SPM were better than those in patients without SPM (log rank P < 0.0001). The C indexes of the nomogram constructed with ten influencing factors including SPM were 0.681:0.699 for OS and 0.705:0.724 for CSS (training cohort:validation cohort). CONCLUSION: Although the overall risk of SPM in patients with HPC was elevated, SPM did not decrease the OS and CSS in patients with HPC. This finding is inconsistent with clinical observations and thus requires further research and exploration. It possibly because HPC might have a shorter survival time, or the follow-up time was not long enough.

Three-Phase Equilibrium Calculations of Water/Hydrocarbon/Nonhydrocarbon Systems Based on the Equation of State (EOS) in Thermal Processes.

A simple and novel approach is proposed to represent the mutual solubility of water and hydrocarbon components based on equations of state at high temperatures in thermal recovery processes. Sϕreide and Whitson modifications are applied to the Peng-Robinson (PR) equation of state (EOS) so that all components, including the water component, can exist in all phases, reasonably representing gas solubility in water and water solubility in hydrocarbon phases. We propose an algorithm to assign binary interaction parameters (BIPs) for aqueous and nonaqueous phases. The water vapor pressure helps select initial K-values for stability analysis so that the aqueous phase can be split out first if present. The algorithm is tested by a wide range of variations in pressure, temperature, and composition. The results show the robustness of the algorithm and the effects of temperature and overall water mole fraction on phase behaviors in steam flooding processes.

MicroRNA-155-5p regulates the Th1/Th2 cytokines expression and the apoptosis of group 2 innate lymphoid cells via targeting TP53INP1 in allergic rhinitis.

As a key component of innate immunity, group 2 innate lymphoid cells (ILC2s) play a key role in Allergic rhinitis (AR). We previously demonstrated that both miR-155-5p and ILC2s are overexpressed in the nasal mucosa of AR patients, but the underlying mechanism remains unclear. At present study, we revealed that miR-155-5p was highly expressed in ILC2s of AR patients. Moreover, miR-155-5p promoted the secretion of Th2 cytokines of ILC2s, while inhibited the secretion of Th1 cytokines and the apoptosis of ILC2s. Meanwhile, the TP53INP1 expression was poorly expressed in ILC2s of AR patients. A dual luciferase reporter assay demonstrated that TP53INP1 was a direct target of miR-155-5p, and its expression was inversely associated with miR-155-5p in ILC2s. Furthermore, TP53INP1 inhibited the secretion of Th2 cytokines of ILC2s, while promoted the secretion of Th1 cytokines and the apoptosis of ILC2s. Notably, rescue experiments demonstrated that overexpression of TP53INP1 could partially reverse the effect of miR-155-5p on ILC2s. Taken together, these findings suggested that miR-155-5p aggravated the inflammatory response of AR dominated by ILC2s via targeting TP53INP1, which may aid in the development of novel therapeutic agents for AR.