Objective Given that the PI3K/AKT/mTOR signaling pathway is associated with the progression of knee osteoarthritis(KOA),this study aims to investigate whether the polarization induction of synovial macrophages mediated by the PI3K/AKT/mTOR signaling axis is the cause of KOA progression.Methods The synovial fluid of KOA KL-Ⅱ and KL-Ⅲ patients and normal individuals was collected,and the percentage of M1 macrophages(CD80,CD86)and M2 macrophages(CD163,CD206)in the synovial fluid(M1/M2 ratio)was measured to e-valuate the polarization of macrophage cytokines such as IL-1,IL-6,IL-10,and tumor necrosis factor(TNF)-α,transforming growth factor(TGF)-β Expression in KOA synovial fluid,and detect and analyze of key molecules PI3K/AKT/mTOR signaling axis PI3K,AKT3,mTORC1,and inducible nitric oxide synthase(iONS)in KOA synovial fluid.Results Compared with the synovial fluid of normal individuals,the percentage of M1 macrophages(CD80,CD86)in KOA patients increased(P<0.01),and the M1/M2 ratio increased(P<0.001);The ex-pression of IL-1,IL-6,and TNF-α in the synovial fluid of the KOA group was also higher than that of the control group(P<0.01),while the expression of IL-10 and TGF-β in the KOA group was significantly reduced(P<0.01);The key proteins PI3K,AKT3,mTORC1,and downstream inflammatory factor iONS in the PI3K/AKT/mTOR signaling pathway in the synovial fluid of the KOA group were higher than those in the control group(P<0.01).Conclusion In KOA synovial fluid,M1 macrophage polarization plays a dominant role,and the inflam-matory response mediated by M1 macrophage polarization may be the cause of synovitis.At the same time,the PI3K/AKT/mTOR signaling pathway may mediate the polarization of M1 macrophages involved in KOA inflammato-ry response.

Objective:To investigate the clinical efficacy of reconstruction with the hallux tissue flap for the fingertip defects of thumb and fingers based on the concept and technique of full reconstruction.Methods:From September 2022 to February 2023, the patients with thumb and fingertip defects who were reconstructed using the concept and technology of full reconstruction in Xuzhou Renci Hospital were respective analysised. Based on the degree of defect in the nail bed, bone, and soft tissue of the hand, a hallux osteo-onychocutaneous flap or hallux nail flap was designed and harvested from the same side of the toe, and free transplantation was performed to reconstruct the damaged fingertip. The wounds in the donor site that could not be sutured primarily were treated with dressing change. The surgical complications, the appearance of the reconstructed finger and donor site, Semmes-Weinstein monofilament (SWM) examination, 2-point discrimination (2PD) measurement, and patient satisfaction were regularly recorded. According to the functional evaluation criteria for thumb and finger reconstruction issued by the Hand Surgery of the Chinese Medical Association, the function of the reconstructed fingers was evaluated as excellent (13-15 points), good (9-12 points), fair (5-8 points), and poor (≤4 points). The patients were investigated whether they were satisfied with the outcomes.Results:A total of 8 patients (9 fingers) including 5 males and 3 females were enrolled. The average age was 32.4 years (range, 22-46 years). There were 1 thumb, 2 index fingers, 5 middle fingers, and 1 ring finger. 7 cases (8 fingers) were repaired with the hallux osteo-onychocutaneous flap, and 1 case (1 finger) was repaired with the hallux nail flap. All the reconstructed fingers survived uneventfully, and the recipient site healed primarily, and the donor site healed after dressing change, without infection and other complications. All the 8 patients (9 fingers) were followed up for 3-7 months. The nail plate of the donor site naturally grew and recovered nearly normal. Depression formation was observed at part of the deck junction of the recipient site, and scars were left in the pulp and fibular side of the hallux. At the final follow-up, the reconstructed fingers recovered protective sensation and tactile sense, and the 2PD of the reconstructed fingers was 9 mm and 10 mm in two cases. The SWM score was 3.60-4.31, mean 3.96. The results were the monofilament specifications and indicating the protective sensation was diminished. Functional evaluation of reconstructed fingers: 9 fingers in 8 cases scored 13-14 points, all reaching an excellent level. All patients were satisfied with the surgical results.Conclusion:Based on the concept and technology of full reconstruction, the fingertip defects of the thumb and finger can recover close to normal with the hallux tissue flap in the short-term, while ensuring the overall shape and function of the hallux donor area, achieving a balance between the donor and recipient areas, and achieving satisfactory clinical results.

Objective:To investigate the clinical efficacy of reconstruction with the hallux tissue flap for the fingertip defects of thumb and fingers based on the concept and technique of full reconstruction.Methods:From September 2022 to February 2023, the patients with thumb and fingertip defects who were reconstructed using the concept and technology of full reconstruction in Xuzhou Renci Hospital were respective analysised. Based on the degree of defect in the nail bed, bone, and soft tissue of the hand, a hallux osteo-onychocutaneous flap or hallux nail flap was designed and harvested from the same side of the toe, and free transplantation was performed to reconstruct the damaged fingertip. The wounds in the donor site that could not be sutured primarily were treated with dressing change. The surgical complications, the appearance of the reconstructed finger and donor site, Semmes-Weinstein monofilament (SWM) examination, 2-point discrimination (2PD) measurement, and patient satisfaction were regularly recorded. According to the functional evaluation criteria for thumb and finger reconstruction issued by the Hand Surgery of the Chinese Medical Association, the function of the reconstructed fingers was evaluated as excellent (13-15 points), good (9-12 points), fair (5-8 points), and poor (≤4 points). The patients were investigated whether they were satisfied with the outcomes.Results:A total of 8 patients (9 fingers) including 5 males and 3 females were enrolled. The average age was 32.4 years (range, 22-46 years). There were 1 thumb, 2 index fingers, 5 middle fingers, and 1 ring finger. 7 cases (8 fingers) were repaired with the hallux osteo-onychocutaneous flap, and 1 case (1 finger) was repaired with the hallux nail flap. All the reconstructed fingers survived uneventfully, and the recipient site healed primarily, and the donor site healed after dressing change, without infection and other complications. All the 8 patients (9 fingers) were followed up for 3-7 months. The nail plate of the donor site naturally grew and recovered nearly normal. Depression formation was observed at part of the deck junction of the recipient site, and scars were left in the pulp and fibular side of the hallux. At the final follow-up, the reconstructed fingers recovered protective sensation and tactile sense, and the 2PD of the reconstructed fingers was 9 mm and 10 mm in two cases. The SWM score was 3.60-4.31, mean 3.96. The results were the monofilament specifications and indicating the protective sensation was diminished. Functional evaluation of reconstructed fingers: 9 fingers in 8 cases scored 13-14 points, all reaching an excellent level. All patients were satisfied with the surgical results.Conclusion:Based on the concept and technology of full reconstruction, the fingertip defects of the thumb and finger can recover close to normal with the hallux tissue flap in the short-term, while ensuring the overall shape and function of the hallux donor area, achieving a balance between the donor and recipient areas, and achieving satisfactory clinical results.

Background: Red blood cell distribution width/platelet count ratio (RPR) is a reliable prognostic assessment indicator for numerous diseases. However, no studies to date have examined the relationship between RPR and the prognosis of diffuse large B-cell lymphoma (DLBCL).Therefore, this study aimed to investigate the correlation between RPR and the clinical characteristics and prognosis of patients with diffuse large B-cell lymphoma. Methods: We retrospectively studied 143 patients with newly diagnosed DLBCL and used the median value as the RPR threshold. We also investigated the correlation of pretreatment RPR level with clinical characteristics and its impact on DLBCL prognosis. Results: Using the median value as the cut-off, patients with DLBCL were divided into a low RPR group (＜0.0549) and a high RPR group (≥0.0549). Patients in the high RPR group were older, had a later Ann Arbor stage, were prone to bone marrow invasion, and had a higher National Comprehensive Cancer Network International Prognostic Index score (P ＜ 0.05). A survival analysis showed that progression-free survival (PFS) (P =0.003) and overall survival (OS) (P ＜0.0001) were significantly shorter in the high versus low RPR group. A multifactorial Cox analysis showed that bone marrow invasion and elevated lactate dehydrogenase (LDH) were separate risk factors for PFS (P ＜0.05), while an RPR ≥0.0549 and elevated LDH were separate risk factors for OS (P ＜0.05). Conclusion A high RPR (≥0.0549) in patients with newly diagnosed DLBCL is an independent risk factor for a poor prognosis.

Objective: To observe the effects of the tofacitinib on interstitial lung disease( ILD) by regulating the JAK⁃STAT signaling pathway. Methods: Wistar rats were randomly divided into 4 groups:normal group , ILD group ,prednisone acetate group , and tofacitinib group. Except for the normal group , the other three groups were given 3mg/ml bleomycin solution for modeling. After 28 days of intragastric administration , the lung tissues of all rats were collected for hematoxylin⁃eosin staining ( HE) and Western blot ( WB) to detect the protein levels of JAK1 and STAT1;Enzyme⁃linked immunosorbent assay(ELISA) was used to detect tumor necrosis factor in rat serum (TNF) Ⅳ α , interleukin (IL) Ⅳ6 , IL⁃10 , IL⁃1β . Results : HE staining of lung tissue in ILD ,prednisone acetate group and tofacitinib group showed alveolar tissue thickening , alveolar wall capillary congestion , bronchial luminal epithelial cells shedding, and inflammatory cell exudation. The results of WB showed that JAK1 and STAT1 significantly increased in ILD group , and decreased in different degrees compared with ILD group , tofacitinib group and prednisone acetate group (P < 0. 05) . The ELISA results showed that the expressions of serum TNF⁃α , IL⁃6 and IL⁃1β in the ILD group were significantly higher than those in the normal group (P < 0. 01) . The expression of pine group decreased (P < 0. 05) , and the expression of IL⁃10 was the opposite. Conclusion Tofacitinib reduces lung tissue damage and the inflammatory response in the treatment of ILD by inhibiting the JAK⁃STAT pathway and down⁃regulating the expression of inflammatory factors TNF⁃α , IL⁃6 , IL⁃1β and up⁃regulating the anti⁃inflammatory factor IL⁃10.

Brain size abnormality is correlated with an increased frequency of autism spectrum disorder (ASD) in offspring. Genetic analysis indicates that heterozygous mutations of the WD repeat domain 62 (WDR62) are associated with ASD. However, biological evidence is still lacking. Our study showed that Wdr62 knockout (KO) led to reduced brain size with impaired learning and memory, as well as ASD-like behaviors in mice. Interestingly, Wdr62 Nex-cKO mice (depletion of WDR62 in differentiated neurons) had a largely normal brain size but with aberrant social interactions and repetitive behaviors. WDR62 regulated dendritic spinogenesis and excitatory synaptic transmission in cortical pyramidal neurons. Finally, we revealed that retinoic acid gavages significantly alleviated ASD-like behaviors in mice with WDR62 haploinsufficiency, probably by complementing the expression of ASD and synapse-related genes. Our findings provide a new perspective on the relationship between the microcephaly gene WDR62 and ASD etiology that will benefit clinical diagnosis and intervention of ASD.
Mice ; Animals ; Microcephaly/genetics* ; Autistic Disorder/metabolism* ; Autism Spectrum Disorder/metabolism* ; Nerve Tissue Proteins/metabolism* ; Brain/metabolism* ; Mice, Knockout ; Cell Cycle Proteins/metabolism*

Objective Tostudy the influence of pipe structures on the mixing uniformity of airborne effluents from nuclear power plant chimneys. Methods We used the computational fluid dynamics (CFD) method to simulate the velocity distribution and gas mixing in long straight pipes (I type) with square section and circular section, 90° single-bend pipes (L type) with square section and circular section, and 90° double-bend pipes (S type and U type) with square section and circular section. Results For the long straight pipe, due to the lack of flow disturbance caused by structural changes, the mixing effect was not good; when the pipe section was circular, it might take mixing distance 20 times the hydraulic diameter to achieve the uniformity index required by the relevant standard; for the square pipe, the distance might be longer. In the single bend pipe with square section, the velocity uniformity was improved more greatly after the bend, and the tracer gas met the mixing uniformity at a shorter distance (11 times the hydraulic diameter), as compared with the single bend pipe with circular section. For the S-type double-bend pipe, the tracer gas appeared uniformly mixed after a distance 6 times the hydraulic diameter in the square pipe, and 7 times the hydraulic diameter in the circular pipe. For the U-type double-bend pipe, the gas in the square pipe also achieved uniform mixing ata shorter distance downstream, and the airflow showed greater disturbance when passing through the bend. Conclusion The CFD method can make an accurate prediction for the change patterns of gas mixing uniformity in pipes with different structures, and can partially replace physical experiments to study the factors affecting the mixing uniformity of airborne effluents from the chimney of nuclear power plants.

Objective:To explore effects of targeted nursing combined with positive psychological intervention on prognosis of patients with acute mastitis during lactation under the focused solution model.Methods:A total of 180 patients with acute mastitis during lactation who were admitted to the Fifth Affiliated Hospital of Zhengzhou University from June 2018 to January 2020 were randomly divided into the observation group ( n=92) and the control group ( n=88) . Patients in both groups were given routine nursing intervention for lactation acute mastitis. The control group was given positive psychological intervention on this basis, and the observation group was given targeted nursing based on focused solution mode on the basis of the control group. The differences in prognostic effects of patients were compared between the two groups. State-Trait Anxiety Inventory (STAI) and Edinburgh Postnatal Depression Scale (EPDS) were used to observe changes of mental state scores before and 2 weeks after intervention. Results:The treatment time of the observation group was shorter than that of the control group, the incidence of breast abscess was lower than that of the control group, and the rate of continued breastfeeding was higher than that of the control group. The differences were statistically significant ( P<0.05) . After 2 weeks of intervention, scores of S-AI and T-AI in STAI and EPDS of patients of the two groups were lower than before the intervention, and scores of the observation group were lower than those of the control group ( P<0.05) . Conclusions:Targeting nursing combined with positive psychological intervention under the focused solution mode can effectively shorten the treatment time, improve the treatment effect and relieve anxiety and depression of patients.

Objective:To evaluate the treatment of pseudoarticular scaphoid nonunion with bone graft and percutaneous fixation under wrist arthroscopy.Methods:Six patients with pseudoarticular scaphoid nonunion were treated with arthroscopic debridement, bong grafting and percutaneous fixation between October 2015 and October 2018 at Department of Hand Surgery, Xuzhou Renci Hospital. They were 5 men and one woman with 4 left and 2 right sides affected, aged from 28 to 51 years (mean, 39.5 years). The sclerotic bone was erased under wrist arthroscopy. Percutaneous fixation started after autoallergic cancellous bone chips were implanted and impacted through a sleeve inserted via the medial carpal approach. For the nonunion with a pseudarthrosis connecting the midcarpal and radiocarpal joints, we put an inflated Foley catheter through a 3/4 portal underneath the proximal edge of the pseudarthrosis to block the possible leakage of the small cancellous bone chips. The wrist functions were evaluated at the final follow-up using the modified Mayo elbow performance score (MEPS); the flexion-extension motion and ulnar-radial deviation of the wrist were recorded.Results:The operation time for the 6 patients ranged from 2 to 4 hours (average, 3.2 hours); their follow-up duration ranged from 6 to 15 months (average, 11.3 months). All the patients obtained bony union after 8 to 14 weeks (average, 12.1 weeks). The flexion-extension motion of their affected wrist ranged from 75° to 135° (average, 107.0°), accounting for 85% of that of the healthy side; the ulnar-radial deviation of their affected wrist ranged from 40° to 80° (average, 51.5°), accounting for 88% of that of the healthy side. MEPS at the final follow-up revealed 4 excellent, one good and one fair cases.Conclusion:Arthroscopic bone grafting and percutaneous fixation is a reliable and effective minimally invasive treatment for pseudarthrotic scaphoid nonunions.

Objective: To understand the consistency of ALK Ventana-D5F3 immunohistochemistry (IHC) interpretation in Chinese lung adenocarcinoma among histopathologists from different hospitals, and to recommend solution for the problems found during the interpretation of ALK IHC in real world, with the aim of the precise selection of patients who can benefit from ALK targeted therapy. Methods: This was a multicenter and retrospective study. A total of 109 lung adenocarcinoma cases with ALK Ventana-D5F3 IHC staining were collected from 31 lung cancer centers in RATICAL research group from January to June in 2018. All cases were scanned into digital imaging with Ventana iSCANcoreo Digital Slide Scanning System and scored by 31 histopathologists from different centers according to ALK binary (positive or negative) interpretation based on its manufacturer′s protocol. The cases with high inconsistency rate were further analyzed using FISH/RT-PCR/NGS. Results: There were 49 ALK positive cases and 60 ALK negative cases, confirmed by re-evaluation by the specialist panel. Two cases (No. 2302 and No.2701) scored as positive by local hospitals were rescored as negative, and were confirmed to be negative by RT-PCR/FISH/NGS. The false interpretation rate of these two cases was 58.1% (18/31) and 48.4% (15/31), respectively. Six out of 31 (19.4%) pathologists got 100% accuracy. The minimum consistency between every two pathologists was 75.8%.At least one pathologist gave negative judgement (false negative) or positive judgement (false positive) in the 49 positive or 60 negative cases, accounted for 26.5% (13/49), 41.7% (25/60), respectively, with at least one uncertainty interpretation accounted for 31.2% (34/109). Conclusion There are certain heterogeneities and misclassifications in the real world interpretation of ALK-D5F3 IHC test, which need to be guided by the oncoming expert consensus based on the real world data.