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Xi Chao Wei,1 Zhong Hua Lv21Department of Urology, Jining Hospital of Traditional Chinese Medicine, Jining 272000, Shandong, People’s Republic of China; 2Department of Urology, Jining No. 1 People’s Hospital, Jining 272011, Shandong, People’s Republic of ChinaBackground and aim: Increasing evidence shows that microRNAs play an important regulatory role in the development of several types of cancers. However, the role of microRNA-132 (miR-132) in human bladder cancer (BC) metastasis remains unclear. In this research, we aimed to investigate the effect of miR-132 on the cell migration and relate potential mechanism in BC.Methods: miR-132 expression level was assessed by quantitative real-time PCR (qRT-PCR) in 32 BC tissues and BC cell lines (T24). The function of miR-132 was evaluated by Transwell assay. Gene expression was determined by using qRT-PCR or Western blot.Results: The results showed that miR-132 had a lower expression in BC tissues than in adjacent normal tissues. At the same time, compared to human normal urethral epithelium cells, the expression level of miR-132 was downregulated in T24 cell lines. miR-132 overexpression significantly inhibited migration and invasion capacities in T24 cells, while downregulation of miR-132 expression strengthened such capacities. Compared with those transfected with miR-132 mimic, EMT-related markers and TGFβ1/Smad2 expression levels were higher in T24 cells transfected with miR-132 inhibitor. Moreover, EMT-related markers and Smad2 expression levels was obviously increased in BC tissues compared to the adjacent normal tissues. The correlation result indicated that the expression of miR-132 and Smad2 was reversed.Conclusion: In short, our results suggest that miR-132 may play a suppressive role in the metastasis of BC cells via TGFβ1/Smad2 signaling pathway.Keywords: human bladder cancer, microRNA-132, metastasis, epithelial-mesenchymal transition

The formation of a plasma sheath on the surface of spacecraft or satellites during high-speed atmospheric entry is a significant factor that affects communication and radar detection. Experimental research apparatus for electromagnetic science can simulate this plasma sheath and study the interaction mechanisms between electromagnetic waves and plasma sheaths. Electron density is a crucial parameter for this research. Therefore, in this paper, a HCN heterodyne interferometer has been designed to measure the electron densities of the device, which range from 1 × 109 to 3 × 1013 cm-3 and the pressure ranges from 50 to 1500 Pa. The light source is a HCN laser with a wavelength of 337 µm, which exhibits higher spatial resolution compared to microwave interferometers. The interferometer is configured as a Mach-Zehnder interferometer, which generates an intermediate frequency through the Doppler shift achieved by a rotating grating. The spatial and temporal resolution of the HCN interferometry reach ∼14 mm and 100 µs, respectively. Antenna-coupled ALGaN/GaN-HEMT detectors have been utilized, as they possess higher sensitivity-with a typical reduction factor responsivity of around 900 V/W-than VDI planar-diode Integrated Conical Horn Fundamental Mixers in HCN interferometry. Recently, the initial results of the HCN interferometer designed for ERAES have been obtained during an experimental campaign, demonstrating a phase resolution of up to 0.04π., (© 2024 Author(s). Published under an exclusive license by AIP Publishing.)

Objective: To investigate application of the Codamotion 2CX1 three-dimensional dynamic joint motion capture system to analyze the kinematic characteristics of patients with different degrees of meniscus injury., Methods: From December 2020 to June 2022, 135 patients with meniscus injury and recruited normal people were collected, including 82 males and 53 females, aged 14 to 29 years old, with disease duration of 1 to 3 months. Combined with clinical symptoms and MRI examination, the diagnosis of meniscus injury was confirmed, and the patients were divided into stages, including 37 cases of grade 0(normal), 30 cases of gradeⅠ, 33 cases of gradeⅡ, 35 cases of grade Ⅲ according to Stoller grading standard. Subjects in each group were tested walking by using Codamotion 2CX1 three-dimensional dynamic joint motion capture system. Quantitative indexes of walking and kinematics were collected, including knee flexion and extension, internal and external rotation and internal and external turning, and their kinematics were analyzed., Results: In the distribution of knee flexion/extension, there were significant differences in maximum knee flexion, minimum knee extension and knee flexion and extension range among 4 groups( P <0.05). In the distribution of internal/external rotation of knee joint, there were significant differences in the range of internal rotation and rotation of knee joint among 4 groups( P <0.05). In the distribution of internal/external turning of knee joint, there were significant differences in the range of internal and external turning of knee joint among 4 groups( P <0.05). The clinical stage progression was positively correlated with the range of motion of knee extension, external rotation, internal and external turning and turning range( P <0.05). It was negatively correlated with knee flexion, internal rotation, flexion extension and rotation range( P <0.05). The internal and external rotation angles of knee joint could be used as independent factors influencing the clinical stage of meniscus injury ( P =0.006, 0.019<0.05)., Conclusion: The knee movement of patients with meniscus injury has obvious changes, and the changes are different under different clinical stages. Gait analysis provides a reliable basis for the kinematic analysis of meniscus injury, helps to better understand the kinematic indexes of joints, and provides a reliable auxiliary diagnosis and treatment plan, which provides a new direction for the follow-up medical research.

In childhood drug-resistant focal epilepsy, the identification of a magnetic resonance imaging lesion significantly affects the management and prognosis, although it is often challenging. Herein we report the preliminary results of a modified MR sequence, in which both magnetization transfer and chemical shift selective preparation pulses are added to a 3D fast spin echo T1-weighted sequence to recognize focal cortical dysplasia. The scan time is short, and the images have expected uniform suppression of the background normal gray and white matter. We report four children with focal epilepsy, in whom the focal cortical and subcortical lesions are superiorly conspicuous on the aforementioned MR sequence compared to the high-resolution fluid-attenuated inversion recovery images obtained with typical epilepsy MR protocols., (© 2024 The Author(s). Epileptic Disorders published by Wiley Periodicals LLC on behalf of International League Against Epilepsy.)

Background: Current liver magnetic resonance elastography (MRE) scans often require adjustments to driver amplitude to produce acceptable images. This could lead to time wastage and the potential loss of an opportunity to capture a high-quality image., Purpose: To construct a linear regression model of individualized driver amplitude to improve liver MRE image quality., Material and Methods: Data from 95 liver MRE scans of 61 participants, including abdominal missing volume ratio (AMVR), breath-holding status, the distance from the passive driver on the skin surface to the liver edge (D d-l ), body mass index (BMI), and lateral deflection of the passive driver with respect to the human sagittal plane (Angle α), were continuously collected. The Spearman correlation analysis and lasso regression were conducted to screen the independent variables. Multiple linear regression equations were developed to determine the optimal amplitude prediction model., Results: The optimal formula for linear regression models: driver amplitude (%) = -16.80 + 78.59 × AMVR - 11.12 × breath-holding (end of expiration = 1, end of inspiration = 0) + 3.16 × D d-l  + 1.94 × BMI + 0.34 × angle α, with the model passing the F test ( F  = 22.455, P <0.001) and R 2 value of 0.558., Conclusion: The individualized amplitude prediction model based on AMVR, breath-holding status, D d-l , BMI, and angle α is a valuable tool in liver MRE examination., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To compare screw versus Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children., Methods: A systematic search was conducted in PubMed, Embase, the Cochrane library, Web of Science, China National Knowledge Internet(CNKI), Wanfang Datebase from in ception to February 2022. Studies comparing screws and Kirschner wire fixation in the treatment of lateral humeral condyle fractures in children were included. Outcome measures included and excluded by a set of inclusion and exclusion criteria and evaluated for their quality, their excellent and good rate of fracture healing, malunion, delayed union or nonunion, infection, limitation of elbow flexion or extension(>10°) were extracted and analyzed using software Rev Man 5.3., Results: A total of 9 retrospective studies involving 647 patients were included, with 255 patients in the screw fixation group(including screw combined with Kirschner wire) and 392 patients in the Kirschner wire fixation group. Meta analysis showed the following:infection rate in the screw group was significantly lower than that in the Kirschner wire group[ OR =0.22, 95% CI (0.09, 0.56), P =0.001]. There were no significant differences between the 2 groups in excellent and good rate of fracture healing, malunion rate( P >0.05). Subgroup analysis showed that infection rate in the screw-only group was significantly lower than that in the Kirschner wire group[ OR =0.18, 95% CI (0.05, 0.65), P =0.009]., Conclusion: For lateral humeral condyle fractures, Screw fixation alone had a lower infection rate than kirschner wire fixation and screw combined with Kirschner wire fixation. There were no significant differences in the excellent and good rate of fracture healing, malunion. In terms of postoperative efficacy and safety of internal fixation, orthopaedic surgeons are more likely to recommend screws for fixation of lateral humeral condyle fractures in children.

The objective of this study was to evaluate the efficacy of various dosing regimens of omadacycline against main drug-resistant pathogens in the treatment of acute bacterial skin and skin structure infections (ABSSSI) and community-acquired bacterial pneumonia (CABP). Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to calculate cumulative fractions of response (CFRs) in terms of drug area under the concentration curve/minimum inhibition concentration targets.CFR ≥ 90% was considered optimal for a dosage regimen. CFR of any approved oral/intravenous regimen with loading-dose was ≥ 90% against methicillin-resistant Staphylococcus aureus (MRSA) for ABSSSI and penicillin-resistant Streptococcus pneumonia , tetracycline-resistant Streptococcus pneumonia , MRSA and β -lactamase positive Haemophilus influenzae for CABP. In conclusion, approved oral/intravenous loading and maintenance doses of omadacycline showed enough efficacy in the treatment of ABSSI and CABP caused by the main drug-resistant pathogens.

Objective: To explore clinical efficacy of autologous bone grafts and bone substitute for the treatment of tibial plateau fractures by Meta analysis., Methods: Controlled clinical studies on autogenous bone transplantation and bone substitutes in treating tibial plateau fractures published on PubMed,Web of Science,CNKI,Wanfang and other databases from January 2005 to August 2022 were searched by computer. Literature screening and data extraction were performed according to randomized controlled trial(RCT),and the quality of RCT were evaluated by using intervention meta-analysis criteria in Cochrane manual. Meta-analysis of joint depression,secondary collapse rate of articular surface,blood loss,operative time and infection rate between two methods were performed by Rev Man 5.3 software., Results: Seven RCT studies (424 patients) were included,296 patients in bone replacement group and 128 patients in autograft group. Operative time [ MD =-16.79,95% CI (-25.72,-7.85), P =0.000 2] and blood loss[ MD =-70.49,95% CI (-79.34,-61.65), P <0.000 01] between two groups had statistically differences,while joint depression[ MD =-0.17,95% CI (-0.91,0.58), P =0.66],secondary collapse rate of joint surface[ RR =-0.74, 95% CI (0.35,1.57), P =0.43],infection rate [ RR =1.21,95% CI (0.31,4.70), P =0.78] between two groups had no differences., Conclusion: The effects of bone substitute and autograft for the treatment of tibial plateau fracture have similar effects in terms of joint depression,secondary articular surface collapse rate and infection rate. However,compared with autologous bone transplantation,bone replacement could reduce blood loss and shorten operation time.

Objective: To explore the mechanism of cross-linked hyaluronic acid-dexamethasone hydrogel (cHA-Dex) in inhibiting chondrocyte apoptosis and alleviating early post-traumatic osteoarthritis (PTOA). Methods: To generate PTOA model, anterior cruciate ligament transection (ACLT)was performed on SD rats ( n =70), and the sham surgery group ( n =70) was set as control. The changes in inflammatory indicators such as interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), matrix metalloproteinase-3 (MMP-3), and matrix metalloproteinase-13 (MMP-13) in the joint lavage fluid were measured at different time points (1-14 days, 5 rats at each time point) after surgery. The cHA-Dex (0.5 mg/ml) hydrogel (experimental group, n =70) and ordinary low-molecular-weight hyaluronic acid (HA) hydrogel premixed with Dex, that was, HA-Dex (0.5 mg/ml) hydrogel (control group, n =70) were injected into the joint cavity of PTOA rats, and the release amount and cumulative release amount of Dex in the joint fluid of rats at each time point(1-14 days, 5 rats at each time point) were detected to reveal the release mechanism of cHA-Dex hydrogel. The cartilage of knee joint of patients with osteoarthritis (OA) who underwent knee arthroplasty in the Second Hospital of Shanxi Medical University from January 2020 to December 2022 was taken for in vitro tissue block culture (Outbridge score=1 or 2, n =18). After the cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1β, IL-6, TNF-α, MMP-3, and MMP-13 in the articular cartilage tissue block were detected. OA chondrocytes were isolated from cartilage samples using enzymatic hydrolysis and cultured in vitro ( n =18). Chondrocytes were divided into 4 groups: saline, cHA hydrogel, Dex (0.5 mg/ml), and cHA-Dex (0.5 mg/ml) hydrogel group. The effects of different interventions on chondrocyte proliferation and apoptosis were tested. Results: The Osteoarthritis Research Society International (OARSI) score of safranine O-solid green staining in PTOA group was 3.34±0.35, and it was 1.17±0.21 in Sham group( P =0.010). The Meachim score of knee joint osteophytes in PTOA rats was significantly higher than that in the Sham group (2.66±0.41 vs 0.22±0.17, P =0.010), indicating PTOA model in rat was established successfully. The cHA-Dex hydrogel, which corresponded to the peak changes of inflammatory factors in the joints of PTOA rats in the early stage, was also released in the early stage and sustained-released in the late stage. After the OA articular cartilage tissue block was treated with cHA-Dex hydrogel premixed with 0.1, 0.2, and 0.5 mg/ml Dex, the mRNA expression levels of IL-1 β, IL-6, TNF-α, MMP-3, and MMP-13 in the tissue block were reduced significantly (all P <0.05) and in a dose-dependent manner. Compared with Dex (0.5 mg/ml) alone group, the apoptosis rate of cHA-Dex (0.5 mg/ml) hydrogel group was significantly reduced (0.60±0.07 vs 6.63±0.98, P =0.010).Compared with the normal saline or the cHA hydrogel alone group, the cHA-Dex (0.5 mg/ml) hydrogel group had significant cell proliferation, and the difference at each time point were all significant statistically (all P <0.05). Conclusion: For the early inflammation of PTOA, cHA-Dex hydrogel can not only inhibit cartilage inflammation, but also reverse the increased apoptosis and decreased proliferation rate of chondrocytes caused by Dex, and finally alleviate the progress of PTOA by releasing Dex.

This study aimed to identify the potential factors associated with immune thyroid dysfunction caused by programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) inhibitors in cancer patients. We conducted a retrospective study of thyroid immune-related adverse events (irAEs) in cancer patients treated with PD-1/PD-L1 inhibitors at Tianjin First Central Hospital from January 2020 to March 2023. Thyroid irAEs were characterized as hypothyroidism, hyperthyroidism and thyrotoxicosis followed by hypothyroidism. A total of 175 patients were screened in the study, of whom 48 patients (27%) developed thyroid irAEs (including 24 hypothyroidism, 11 hyperthyroidism and 13 thyrotoxicosis followed by hypothyroidism) following PD-1/PD-L1 inhibitors treatment. Multivariate logistic regression analysis showed that combination therapy with PD-1/PD-L1 inhibitors and tyrosine kinase inhibitors (lenvatinib/regorafenib) and high baseline anti-TPO level were associated with the development of thyroid irAEs caused by PD-1/PD-L1 inhibitors. The nomogram models showed good discriminant ability and could bring net benefits for more patients according to the decision curve analysis. However, the model needs to be further validated in other large cohorts.

The objective of this study was to evaluate the efficacy of various micafungin dosing regimens against Candida spp. in pediatric patients undergoing hematopoietic stem cell transplantation (HSCT). Monte Carlo simulations were conducted using pharmacokinetic (PK) parameters and pharmacodynamic (PD) data to determine the probabilities of target attainment and cumulative fractions of response in terms of area under the concentration curve/minimum inhibition concentration targets of micafungin. Current standard clinical micafungin dosing regimens of 1 and 2 mg/kg/day were appropriate for the prevention and treatment of Candida glabrata infection in pediatric patients undergoing HSCT, respectively. Moreover, the high-dose prophylactic dosage (2 mg/kg/day) and therapeutic dosage (4 mg/kg/day) should be the preferred option to optimize efficacy against Candida albicans . However, none of the simulated regimens was effective against Candida parapsilosis in pediatric HSCT patients. These PK/PD-based simulations rationalize and optimize the micafungin dosing regimens against Candida spp. in pediatric patients undergoing HSCT.

Vinca alkaloid (VA)-induced ileus, a rare but severe autonomic neuropathy, can be enhanced by concomitant use of antifungal triazole agents. We herein present a case of VA-induced ileus in a 17-year-old girl who was diagnosed with B-cell acute lymphoblastic leukemia. On day 1, the patient received cyclophosphamide, vincristine, and methylprednisolone. On day 2, she began treatment with posaconazole oral suspension at 200 mg three times daily for prophylaxis against invasive fungal infection. On day 5, she began induction therapy consisting of vindesine, methylprednisolone, daunorubicin, and cyclophosphamide. The patient developed severe abdominal pain with marked constipation on day 11 and was diagnosed with incomplete ileus. After switching the antifungal agent to micafungin, performing gastrointestinal decompression, administering parenteral nutrition, and omitting the fourth dose of vindesine, the ileus symptoms were relieved. This case emphasizes the potential interaction between VAs and posaconazole. We also herein present a review of the literature on ileus caused by the combination of VAs and antifungal triazole agents. In clinical practice, physicians and pharmacists should be aware of the possibility of ileus caused by the use of VAs in combination with posaconazole. It is important to reduce complications during chemotherapy to improve patients' prognosis.

Objective: To compare the long-term follow-up effect and complications of ceramic on ceramic (CoC) interface and ceramic on polyethyleneon ceramic (CoP) interface in primary total hip arthroplasty, and provide clinical evidence., Methods: Search PubMed, EMBase, the CoChrane Library databases, Web of science, Wanfang database, and CNKI from January 2000 to September 2021, screening and inclusion of randomized controlled trials (RCTs) comparing the long-term efficacy and complications of CoC interface and CoP interface in total hip arthroplasty. Literature screening, quality evaluation and data extraction were carried out according to the inclusion and exclusion criteria, using Review Manager 5.3 statistical software. The software was used to perform statistical analysis on joint function, revision, prosthesis fracture, abnormal joint noise, and prosthesis wear rate after CoC or CoP., Results: Seven RCTs studies were included, including 390 cases of hips with CoC artificial joints and 384 cases of hips with CoP artificial joints. The long-term joint function improvement of CoC and CoP artificial joints was similar and there was no significant differences, with an average difference was MD =0.63, 95% CI =(-1.81, 3.07), P =0.61. About the postoperative complications, CoC artificial joints have higher incidence rate of abnormal joint noise, with odds ratio ( OR )=11.05, 95% CI =(2.04, 59.84), P =0.005. CoP artificial joints wear faster, with an average MD =-87.11, 95% CI =(-114.40, -59.82), P <0.000 1. There was no significant difference between the two groups in the replacement-related complications such as joint dislocation, prosthesis loosening, osteolysis, and the rate of prosthesis revision caused by various reasons., Conclusion: The clinical function results and complications of CoC artificial joints are comparable to those of CoP artificial joints. Although CoP artificial joint prosthesis has a faster wear rate, it does not affect joint function and increase complications, and there is no abnormal joint noise. CoC is expensive and the long-term efficacy is equivalent to CoP. Clinicians should consider cost performance when choosing CoC.

A girl in middle childhood was referred to rheumatology with a 1-month history of progressive skull pain, preceded by fleeting musculoskeletal symptoms. Apart from a scaly rash on her scalp, she was well, with moderately elevated inflammatory markers. Skull imaging (radiographs, CT and MRI) revealed osteolytic lesions, soft tissue swelling and pachymeningeal enhancement at frontal and temporal convexities. Langerhans cell histiocytosis, bone infection/inflammation or malignancy was considered. Skin and bone biopsies eventually ruled out mimicking diseases and confirmed the diagnosis of chronic recurrent multifocal osteomyelitis (CRMO). She was treated with intravenous pamidronate (IVPAM) for 9 months, with rapid resolution of pain and gradual resolution of bony abnormalities. She remains in remission at 15-month follow-up. While CRMO can affect any bone, skull involvement is extremely rare, with a broad differential diagnosis. We recommend bone biopsy to confirm skull CRMO. The patient achieved excellent clinical and radiological response to IVPAM., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: To explore clinical effects regrarding functional recovery, pain relief, and range of motion of shoulder of platelet-rich plasma (PRP) injection and corticosteroid(CS) injection in treating rotator cuff tendinopathy., Methods: Randomized controlled trials (RCT) of PRP injection and CS injection in Cochrane Library, EMBASE(Excerpta Medica Database), PebMed, China knowledge Network(CNKI) and Wanfang database were searched from building database to April 20, 2022. According to inclusion and exclusion criteria, literature screening, data extraction and quality evaluation were carried out between two independent researchers, and extracted data were statistically analyzed by Review Manager 5.4.1 software. Short-term (3-6 weeks), medium-term (8-12 weeks) and long-term (≥24 weeks) visual analogue score (VAS), American Shoulder and Elbow Surgeons (ASES) score, Xi'an Western Ontario Rotator Cuff Index (WORC) and shoulder range of motion (ROM) were compared between two groups., Results: Totally 7 RCT were included with 379 patients, 188 patients in PRP group and 191 patients in CS group. Meta analysis results showed there were no significant difference in VAS, ASES and WORC between short-term group and medium-term group( P >0.05). During long-term follow-up, there were significant differences in ASES score[ MD =7.1, 95% CI (2.06, 12.14), P =0.006] and VAS [ MD =-1.55, 95% CI (-2.65, 0.55), P =0.002]. There was no significant difference in shoulder ROM between two groups( P >0.05)., Conclusion: For patients with shoulder cuff tendon disease, there are no significant difference in pain relief and functional recovery during short and medium-term follow-up period. However, RPR injection showed advantages over corticosteroid injection in terms of functional recovery and pain relief during long-term follow-up. There is no significant difference in shoulder range of motion between two groups during the whole follow-up period.

Purpose: To investigate the diagnostic value of synthetic MRI combined MUSE DWI and 3D-pCASL in hippocampal sclerosis (HS)., Method: A total of 30 HS patients participated in the study. At the same time, 51 healthy volunteers were collected as the control group. All patients and healthy volunteers underwent epilepsy MR scanning protocol (including oblique coronal MAGiC, MUSE DWI, and axial 3D-pCASL) at 3.0 T MR scanner.The independent samples T test and Mann-Whitney U test were used to compare the differences of the apparent dispersion coefficient(ADC), cerebral blood flow(CBF) and quantitative parameters, including T1 relaxation time (T1), T2 relaxation time (T2), and proton density (PD) values, in the hippocampus of the affected side of HS and the contralateral and control groups, respectively. The diagnostic performance was evaluated using binary logistic regression analysis and area under the receiver operating characteristic (ROC) curves (AUC)., Results: Significant statistical differences in T1, T2, CBF, and ADC values were observed between the affected hippocampus of HS patients and contralateral and control hippocampus (all P < 0.005). The T2 has higher discrimination abilities compared with other univariable parameters, with the AUC of 0.899. The combined T2, ADC and CBF model had the best diagnostic performance of HS in MTLE patients with AUC, sensitivity and specificity of 0.946, 86.67 %, 93.33 %, respectively., Conclusions: Relaxometry parameters derived from synthetic MRI contributed to diagnosis of HS. The proposed approach combining T2, ADC and CBF showed a strong diagnostic capability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Besides the controversy of the association of high glycemic index and glycemic load with precancerous cervical lesions, only a few studies have examined the impact of fasting blood glucose levels on human papillomavirus (HPV) multiple infections. In the present study, we appraised the relationship between blood glucose levels and multiple HPV infections in a population of HPV-positive women with cervical high-grade squamous intraepithelial lesions (HSIL). The present study was designed as a cross-sectional correlative analysis. A total of 560 participants with a pathologically confirmed HSIL with HPV infection were included from a hospital in China during January 1, 2018, and December 31, 2019. The target variables and the outcome variables were the glucose levels at the baseline and HPV multiplicity, respectively. The odds ratio and 95% confidence intervals were calculated to estimate the risk of multiple infections via logistic regression analysis. The average age of the 560 participants was 44.63 ± 10.61 years; the nonlinear relationship was detected between the glucose levels and multiplicity of HPV, with an inflection point at 5.4. After adjusting for the full range of variables, the effect sizes and confidence intervals for the left and right sides of the inflection points were found to be 0.379 (0.196-0.732) and 5.083 (1.592-16.229), respectively. In this cross-sectional study, both high and low blood glucose levels increased the risk of multiple HPV infections, demonstrating a U-shaped relationship between the blood glucose levels and multiple HPV infections., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The application of antibiotics loaded bone cement (ALBC) in the revision of failed total knee arthroplasty (TKA) has been widely accepted to reduce risk of peri-prosthetic infection. However, the prophylactic use of ALBC in primary TKA remains controversial. This study was aimed to identify the prophylactic effect on peri-prosthetic infection and safety of ALBC in primary TKA., Hypothesis: The application of ALBC could reduce the risk of peri-prosthetic infection in primary TKA., Materials and Methods: Electronic platforms including PubMed, EMBASE, and CENTRAL were retrieved to identify studies comparing outcomes of prophylactic ALBC and plain cement in primary TKA. For outcomes reported as dichotomous variable and continuous variable, risk ratio (RR) and weighted mean difference (WMD) as well as their 95% confidence intervals (95% CI) were selected as the effect sizes for pooling. While for those outcomes reported the adjusted effect sizes such as odds ratio (OR, derived from multivariate logistic regression), and hazard ratio (HR, derived from multivariate COX proportional hazard model), the reported effect sizes were selected for pooling., Results: A total of 17 studies with 2,074,844 patients (1,093,920 in ALBC group and 980,924 in plain cement group) were eligible for final inclusion. No significant difference was found between ALBC and plain cement groups both for the unadjusted (RR=1.02, 95% CI: 0.86∼1.21, p=0.832) and adjusted (OR=0.94, 95% CI: 0.76∼1.17, p=0.596) peri-prosthetic infection rate. ALBC application was related to significantly increased length of hospital stay (WMD=0.13, 95% CI: 0.10∼0.17, p<0.001). There was no significance on the difference of operation related adverse events between two groups (RR=1.31, 95% CI: 0.68∼2.52, p=0.420). Significantly increased risks of acute renal failure and readmission, and temporarily increased ototoxicity in ALBC group were reported in one of the primary study., Discussion: There is no sufficient evidence supporting decreased peri-prosthetic infection rate with ALBC application in primary TKA. What's more, it must be taken into consideration about the safety and added cost of additional impregnated antibiotics., Level of Evidence: III; meta-analysis., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

We investigated the therapeutic effects of superoxide dismutase (SOD) from thermophilic bacterium HB27 on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and its underlying mechanisms. A Sprague-Dawley rat model of CP/CPPS was prepared and then administered saline or Thermus thermophilic (Tt)-SOD intragastrically for 4 weeks. Prostate inflammation and fibrosis were analyzed by hematoxylin and eosin staining, and Masson staining. Alanine transaminase (ALT), aspartate transaminase (AST), serum creatinine (CR), and blood urea nitrogen (BUN) levels were assayed for all animals. Enzyme-linked immunosorbent assays (ELISA) were performed to analyze serum cytokine concentrations and tissue levels of malondialdehyde, nitric oxide, SOD, catalase, and glutathione peroxidase. Reactive oxygen species levels were detected using dichlorofluorescein diacetate. The messenger ribonucleic acid (mRNA) expression of tissue cytokines was analyzed by reverse transcription polymerase chain reaction (RT-PCR), and infiltrating inflammatory cells were examined using immunohistochemistry. Nuclear factor-κB (NF-κB) P65, P38, and inhibitor of nuclear factor-κBα (I-κBα) protein levels were determined using western blot. Tt-SOD significantly improved histopathological changes in CP/CPPS, reduced inflammatory cell infiltration and fibrosis, increased pain threshold, and reduced the prostate index. Tt-SOD treatment showed no significant effect on ALT, AST, CR, or BUN levels. Furthermore, Tt-SOD reduced inflammatory cytokine expression in prostate tissue and increased antioxidant capacity. This anti-inflammatory activity correlated with decreases in the abundance of cluster of differentiation 3 (CD3), cluster of differentiation 45 (CD45), and macrophage inflammatory protein 1α (MIP1α) cells. Tt-SOD alleviated inflammation and oxidative stress by reducing NF-κB P65 and P38 protein levels and increasing I-κBα protein levels. These findings support Tt-SOD as a potential drug for CP/CPPS., Competing Interests: None

Objective: Ciprofol is a newly developed intravenous sedative-hypnotic drug. The objective of the study was to prove whether ciprofol was non-inferior to propofol for the successful induction of general anesthesia. The ideal post-induction sedation level was assessed by comparing patients' clinical symptoms and their hemodynamic effects in responding to noxious stimuli, mostly tracheal intubation and bispectral index (BIS) alterations following ciprofol/propofol administration., Patients and Methods: In this multi-center, randomized, double-blind phase 3 trial, selective surgery patients were randomly assigned in a 1:1 ratio to either ciprofol 0.4 mg/kg (n = 88) or propofol 2.0 mg/kg (n = 88) groups. The primary endpoint was the percentage of patients with successful anesthesia inductions. Secondary endpoints included the times to successful induction of general anesthesia and loss of the eyelash reflex, changes in BIS, as well as safety indicators., Results: The anesthesia induction success rates for both ciprofol 0.4 mg/kg and propofol 2 mg/kg groups were 100.0%, with a 95% CI lower success limit of -4.18% difference between the two groups, indicating that ciprofol was non-inferior to propofol. For secondary outcomes, the average time to successful anesthesia and loss of the eyelash reflex were 0.91 min and 0.80 min for ciprofol and 0.80 min and 0.71 min for propofol, respectively. The pattern of BIS changes with ciprofol was similar to propofol and stable during the anesthesia maintenance period. Safety was comparable with 88.6% TEAEs in the ciprofol group compared to 95.5% in the propofol group. The incidence of injection pain was significantly lower in the ciprofol group compared to the propofol group (6.8% vs. 20.5%, p < 0.05). In addition, the patients treated with ciprofol had a lesser increase in blood pressure and heart rate, and fewer cases with BIS > 60 within 15 min of intravenous administration, which indicated that ciprofol may provide a better ideal sedation level during the post-induction period under an equivalent dosing regimen to propofol., Conclusions: Ciprofol for patients undergoing selective surgery is a new option for the induction of general anesthesia.

Objective: To evaluate the efficacy and safety of HSK3486 for the induction and maintenance of general anesthesia in elective surgical patients, but excluding emergency, cardiothoracic, cerebral and endoscopic sinus cases., Patients and Methods: A total of 40 eligible patients were randomly assigned to HSK3486 (n = 30) or propofol (n = 10) dosage groups in a ratio of 3:1. Drugs were administered as a bolus injection of 0.4 mg/kg (HSK3486) or 2.0 mg/kg (propofol) for induction, followed by maintenance infusion with the same anesthetic. An additional 6 non-randomized patients received propofol (2.0 mg/kg) for induction and were given HSK3486 for maintenance., Results: The primary efficacy endpoint - the success rate of anesthesia maintenance - was 100% in the 3 arms. The secondary efficacy endpoints included times from discontinuation of HSK3486 or propofol maintenance to full alertness, respiratory recovery, extubation and reaching the goal of the Aldrete score. Also, the proportion of patients who constantly maintained BIS40-60 or those with a period of BIS40-60 during maintenance anesthesia showed no significant difference in the HSK3486 and propofol groups (all p > 0.05). Patients who received HSK3486 exhibited a higher satisfaction score from anesthesiologists during the induction period (p = 0.024). The occurrence and types of treatment-emergent adverse events were similar among the 3 arms, both with a severity of grade 1 or 2. Drug-related hypotension occurred in 14 (46.7%) and 7 (70.0%) patients treated with HSK3486 and propofol, respectively., Conclusions: HSK3486 exhibited good efficacy for the induction and maintenance of general anesthesia and was well tolerated by patients who underwent elective surgery.

Background: Liver cancer is the fourth most significant cause of cancer-related death. Lack of early diagnosis strategy and a scarcity of efficient therapy constitute the main reasons for its lethality. Exosomes, which contain various bioactive molecules, are characterized by high biocompatibility, low immunogenicity, and high transport efficiency. As a result, exosomes have become a research hotspot and present significant potential for cancer diagnosis biomarkers, biotherapeutics, therapy targets, drug carriers and therapeutic agents., Aim: To explore the potential of exosomes in the diagnosis and treatment of liver cancer., Methods: We conducted a systematic literature search via PubMed and Web of Science. The following keywords were used: "exosomal biomarkers", "exosomal therapy", "exosomal therapy", and "liver cancer" or "HCC". The duplicate data were deleted by EndNote software. Literature search focused on full-texts and references of each article were carefully checked. One author (Xiao-Cui Wei) screened the literature that met the following inclusion criteria: (1) Detection of exosomes or their contents in clinical samples (body fluid or tissue); or (2) Exosomes served as drug carriers or therapeutic factors. Two authors (Xiao-Cui Wei and Li-Juan Liu) independently reviewed all retained literature and analyzed the information., Results: A total of 1295 studies were identified using the systematic literature search. Of these, 835 duplicate studies were removed. A further 402 irrelevant studies were excluded due to being irrelevant, including other diseases, review articles, the literature containing neither clinical samples nor animal experiments, exosome-independent studies, methods for detecting exosomes, or articles in Chinese. Finally, 58 published papers were retained and analyzed in the study. It showed a list of potential exosomal biomarkers that were upregulated in the blood samples of patients with liver cancer. Those downregulated in exosomes might serve as possible biotherapeutics. Some exosomes derived from cells in vitro were used for cytology or animal experiments to explore the mechanism of these exosome contents in disease. These contents might serve as potential targets for liver cancer. Additionally, we also discussed that exosomes serve as drug carriers or therapeutic factors., Conclusion: Exosomes might serve as potential biomarkers or therapeutic biotargets in liver cancer and have the potential to act as drug carriers and self-treatment factors for liver cancer patients., Competing Interests: Conflict-of-interest statement: All authors do not have any conflicts of interest relevant to this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The association of hepatitis B virus (HBV) infection with HCC is hitherto documented. Exosomal miRNAs contribute to cancer progression and chemoresistance. HBV X protein has been known to modulate miRNAs that facilitate cell proliferation and the process of hepatocarcinogenesis. However, there has been no report on hepatitis B core antigen (HBc) regulating exosomal miRNAs to induce drug resistance of HCC cells., Aim: To elucidate the mechanism by which HBc promotes Doxorubicin hydrochloride (Dox) resistance in HCC., Methods: Exosomes were isolated by ultracentrifugation. The morphology and size of exosomes were evaluated by Dynamic Light Scattering (DLS) and transmission electron microscopy (TEM). The miRNAs differentially expressed in HCC were identified using The Cancer Genome Atlas (TCGA) database. The level of miR-135a-5p in patient tissue samples was detected by quantitative polymerase chain reaction. TargetScan and luciferase assay were used to predict and prove the target gene of miR-135a-5p. Finally, we identified the effects of miR-135a-5p on anti-apoptosis and the proliferation of HCC in the presence or absence of Dox using flow cytometry, Cell counting kit 8 (CCK-8) assay and western blot., Results: We found that HBc increased the expression of exosomal miR-135a-5p. Integrated analysis of bioinformatics and patient samples found that miR-135a-5p was increased in HCC tissues in comparison with paracancerous tissues. Bioinformatic analysis and in vitro validation identified vesicle-associated membrane protein 2 (VAMP2) as a novel target gene of miR-135a-5p. Functional assays showed that exosomal miR-135a-5p induced apoptosis protection, cell proliferation, and chemotherapy resistance in HCC. In addition, the rescue experiment demonstrated that VAMP2 reversed apoptosis protection, cell growth, and drug resistance by miR-135a-5p. Finally, HBc promoted HCC anti-apoptosis, proliferation, and drug resistance and prevented Dox-induced apoptosis via the miR-135a-5p/VAMP2 axis., Conclusion: These data suggested that HBc upregulated the expression of exosomal miR-135a-5p and promoted anti-apoptosis, cell proliferation, and chemical resistance through miR-135a-5p/VAMP2. Thus, our work indicated an essential role of the miR-135a-5p/VAMP2 regulatory axis in chemotherapy resistance of HCC and a potential molecular therapeutic target for HCC., Competing Interests: Conflict-of-interest statement: The authors hereby declare that no conflict of interest exists., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: Schizophrenia afflicts 1% of the world population. Clinical studies suggest that schizophrenia patients may have an imbalance of mitochondrial energy metabolism via inhibition of mitochondrial complex I activity. Moreover, recent studies have shown that ERVWE1 is also a risk factor for schizophrenia. Nevertheless, there is no available literature concerning the relationship between complex I deficits and ERVWE1 in schizophrenia. Identifying risk factors and blood-based biomarkers for schizophrenia may provide new guidelines for early interventions and prevention programs., Aim: To address novel potential risk factors and the underlying mechanisms of mitochondrial complex I deficiency caused by ERVWE1 in schizophrenia., Methods: Quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay were used to detect differentially expressed risk factors in blood samples. Clinical statistical analyses were performed by median analyses and Mann-Whitney U analyses. Spearman's rank correlation was applied to examine the correlation between different risk factors in blood samples. qPCR, western blot analysis, and luciferase assay were performed to confirm the relationship among ERVWE1, cytoplasmic polyadenylation element-binding protein 1 (CPEB1), NADH dehydrogenase ubiquinone flavoprotein 2 (NDUFV2), and NDUFV2 pseudogene (NDUFV2P1). The complex I enzyme activity microplate assay was carried out to evaluate the complex I activity induced by ERVWE1., Results: Herein, we reported decreasing levels of CPEB1 and NDUFV2 in schizophrenia patients. Further studies showed that ERVWE1 was negatively correlated with CPEB1 and NDUFV2 in schizophrenia. Moreover, NDUFV2P1 was increased and demonstrated a significant positive correlation with ERVWE1 and a negative correlation with NDUFV2 in schizophrenia. In vitro experiments disclosed that ERVWE1 suppressed NDUFV2 expression and promoter activity by increasing NDUFV2P1 level. The luciferase assay revealed that ERVWE1 could enhance the promoter activity of NDUFV2P1. Additionally, ERVWE1 downregulated the expression of CPEB1 by suppressing the promoter activity, and the 400 base pair sequence at the 3' terminus of the promoter was the minimum sequence required. Advanced studies showed that CPEB1 participated in regulating the NDUFV2P1/NDUFV2 axis mediated by ERVWE1. Finally, we found that ERVWE1 inhibited complex I activity in SH-SY5Y cells via the CPEB1/NDUFV2P1/NDUFV2 signaling pathway., Conclusion: In conclusion, CPEB1 and NDUFV2 might be novel potential blood-based biomarkers and pathogenic factors in schizophrenia. Our findings also reveal a novel mechanism of ERVWE1 in the etiology of schizophrenia., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Phyllanthus emblica is a fruit widely consumed in subtropical areas, which is rich in polyphenols and other nutrients. There are increasing evidences that as a daily and nutritious fruit, it may have a positive role in controlling diabetic complications. According to the new study, its mechanisms include enhancing the functioning of insulin, reducing insulin resistance, activating the insulin-signaling pathway, protecting β-cells, scavenging free radicals, alleviating inflammatory reactions, and reducing the accumulation of advanced glycation end products. Owing to its few side effects, and low price, it should be easily accepted by patients and has potential for preventing diabetes. Taken together, Phyllanthus emblica may be an ideal fruit for controlling diabetic complications. This review highlights the latest findings of the role of Phyllanthus emblica in anti-diabetes and its complications, especially clarifies the molecular mechanism of the chemical components related to this effect, and prospects some existing problems and future research directions., (© 2021. Springer-Verlag GmbH, DE part of Springer Nature.)

Objective: To evaluate clinical efficacy of arthroscopic with platelet-rich plasma (PRP) in treating meniscus injury., Methods: From January 2015 to December 2019, clinical control study on repair meniscus injury by arthroscopic with PRP between arthroscopic were searched by PubMed, Science Direct, Cochrane library, Chinese Journal Full-text Database, Wanfang and VIP database. Literature screening, data extraction and quality evaluation according to inclusion and exclusion criteria. Visual analogue scale(VAS) of knee joint and Lysholm score at 1, 6 and 12 months after opertaion between two groups were compared, and Western Ontario and McMaster University Osteoarthritis Index (WOMAC) at 3, 6 and 12 months after opertaion between twogroups were also compared., Results: Totally 9 literatures and 329 patients with meniscal injuries were screened, include 146 patients treated by arthroscopic with PRP and 183 patients treated by arthroscopic. There were no statistical differences in VAS between two groups at 1, 6 and 12 months after opertaion. There were differences in Lysholm score at 1 and 6 months after operation between two groups [ MD =3.85, 95% CI (1.25, 6.44), P <0.05], [ MD =2.88, 95% CI (0.13, 5.63), P <0.05];while there was no difference at 12 months[ MD =5.88, 95% CI (-8.72, 20.48), P =0.43]. There were differneces in WOMAC score at 3 and 6 months after operation between two groups[ MD =-8.07, 95% CI (-11.17, -4.89), P <0.000 01], [ MD =-7.96, 95% CI (-11.44, -4.48), P <0.000 01];and no difference at 12 months after operation[ MD =-6.61, 95% CI (-16.64, 3.41), P >0.05]., Conclusion: Arthroscopic with PRP for repair meniscus injury has short term efficacy of knee function and delay arthritis, while has similar effect in long term clinical efficacy and relieve pain.

Protein C is a circulating anticoagulant that inhibits factor Va and VIIIa and promotes fibrinolysis. Compound heterozygous or homozygous variants in the Protein C gene (PROC) lead to severe deficiency of protein C and affected neonates typically present shortly after birth with purpura fulminans. We describe an infant who suffered a diffuse intracranial hemorrhage as a neonate and presented with purpura fulminans as an older infant which led to investigations that were consistent with severe protein C deficiency. We demonstrate subacute findings on neuroimaging and suggest this condition should be considered with neonatal presentations of bilateral intraparenchymal hemorrhage., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

The development of the cerebral cortex requires balanced expansion and differentiation of neural stem/progenitor cells (NPCs), which rely on precise regulation of gene expression. Because NPCs often exhibit transcriptional priming of cell-fate-determination genes, the ultimate output of these genes for fate decisions must be carefully controlled in a timely fashion at the post-transcriptional level, but how that is achieved is poorly understood. Here, we report that de novo missense variants in an RNA-binding protein CELF2 cause human cortical malformations and perturb NPC fate decisions in mice by disrupting CELF2 nucleocytoplasmic transport. In self-renewing NPCs, CELF2 resides in the cytoplasm, where it represses mRNAs encoding cell fate regulators and neurodevelopmental disorder-related factors. The translocation of CELF2 into the nucleus releases mRNA for translation and thereby triggers NPC differentiation. Our results reveal that CELF2 translocation between subcellular compartments orchestrates mRNA at the translational level to instruct cell fates in cortical development., Competing Interests: Declaration of interests M.M. is employed by Blueprint Genetics. L.M. has received personal fees from Mendelian Ltd outside the submitted work. The other authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: The effect of a combination of a goal-directed fluid protocol and preoperative carbohydrate loading on postoperative complications in elderly patients still remains unknown. Therefore, we designed this trial to evaluate the relative impact of preoperative carbohydrate loading and intraoperative goal-directed fluid therapy versus conventional fluid therapy (CFT) on clinical outcomes in elderly patients following gastrointestinal surgery., Methods: This prospective randomized controlled trial with 120 patients over 65 years undergoing gastrointestinal surgery were randomized into a CFT group (n = 60) with traditional methods of fasting and water-deprivation, and a GDFT group (n = 60) with carbohydrate (200 ml) loading 2 h before surgery. The CFT group underwent routine monitoring during surgery, however, the GDFT group was conducted by a Vigileo/FloTrac monitor with cardiac index (CI), stroke volume variation (SVV), and mean arterial pressure (MAP). For all patients, demographic data, intraoperative parameters and postoperative outcomes were recorded., Results: Patients in the GDFT group received significantly less crystalloids fluid (1111 ± 442.9 ml vs 1411 ± 412.6 ml; p < 0.001) and produced significantly less urine output (200 ml [150-300] vs 400 ml [290-500]; p < 0.001) as compared to the CFT group. Moreover, GDFT was associated with a shorter average time to first flatus (56 ± 14.1 h vs 64 ± 22.3 h; p = 0.002) and oral intake (72 ± 16.9 h vs 85 ± 26.8 h; p = 0.011), as well as a reduction in the rate of postoperative complications (15 (25.0%) vs 29 (48.3%) patients; p = 0.013). However, postoperative hospitalization or hospitalization expenses were similar between groups (p > 0.05)., Conclusions: Focused on elderly patients undergoing open gastrointestinal surgery, we found perioperative fluid optimisation may be associated with improvement of bowel function and a lower incidence of postoperative complications., Trial Registration: ChiCTR, ChiCTR1800018227 . Registered 6 September 2018 - Retrospectively registered.

Objective: To perform a bibliometric analysis of research on articular cartilage repair published in Chinese and English over the past decade. Fundamental and clinical research topics of high interest were further comparatively analyzed., Methods: Relevant studies published from 1 January 2009 to 31 December 2018 (10 years) were retrieved from the Wanfang database (Chinese articles) and six databases, including MEDLINE, WOS, INSPEC, SCIELO, KJD, and RSCI on the website "Web of Science" (English articles), using key words: "articular cartilage" AND "injury" AND "repair". The articles were categorized according to research focuses for a comparative analysis between those published in Chinese vs English, and further grouped according to publication date (before and after 2014). A comparative analysis was performed on research focus to characterize the variation in research trends between two 5-year time spans. Moreover, articles were classified as basic and clinical research studies., Results: Overall, 5762 articles were retrieved, including 2748 in domestic Chinese journals and 3014 in international English journals. A total of 4937 articles focused on the top 10 research topics, with the top 3 being stem cells (32.1%), tissue-engineered scaffold (22.8%), and molecular mechanisms (16.4%). Differences between the numbers of Chinese and English papers were observed for 3 topics: chondrocyte implantation (104 vs 316), osteochondral allograft (27 vs 86), and microfracture (127 vs 293). The following topics gained more research interest in the second 5-year time span compared with the first: microfracture, osteochondral allograft, osteochondral autograft, stem cells, and tissue-engineered scaffold. Articles with a focus on three-dimensional-printing technology have shown the fastest increase in publication numbers. Among 5613 research articles, basic research studies accounted for the majority (4429), with clinical studies described in only 1184 articles. The top 7 research topics of clinical studies were: chondrocyte implantation (28.7%), stem cells (21.9%), microfracture (19.2%), tissue scaffold (10.6%), osteochondral autograft (10.5%), osteochondral allograft (6.3%), and periosteal transplantation (2.8%)., Conclusion: Studies focused on stem cells and tissue-engineered scaffolds led the field of damaged articular cartilage repair. International researchers studied allograft-related implantation approaches more often than Chinese researchers. Traditional surgical techniques, such as microfracture and osteochondral transplantation, gained high research interest over the past decade., (© 2021 The Authors. Orthopaedic Surgery published by Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.)

Objective: To compared with the modified Robert Jones bandage of 3M elastic bandage, to evaluate the fitness, convenience, safety and comfort of the modular combination lower limb elastic compression device., Methods: Forty healthy adult college students, including 28 males and 12 females, aged 16 to 25 (20.3±2.2) years old and weighing 40 to 81 (60.4±20.2) kg, were randomly divided into two groups with 40 samples in each group. According to the body surface parameters of Chinese lower limbs and guided by the concept of modularization, a group of modular combined lower limb elastic compression device was designed. Each module was combined to evaluate the fitness of the modular combined compression device in thelength and circumference of the lower limbs. The left and right lower limbs were randomly paired and divided into groups, with 40 samples in each group. The convenience of the operation time, adjustment times and required time were compared between two groups. The safety of the two groups after 24 hours of application of pressure injury was compared. The subjective pain feeling changes within 24 hours were recorded by visual analogue scale (VAS) to evaluate the comfort., Results: The device was composed of several elastic compression outer lining modules with different length and width of 15 cm, an inner lining module for buffering, positioning and attaching the main body, and an elastic ankle compression module. The length of the elastic compression outer lining module covers the circumference of the human lower limbs. The length of a single outer lining module increased from 15 cm to 80 cm every 5 cm interval, and the length of a single inner lining module increased from 62 cm to 83 cm every 3 cm interval. After the modules were selected and combined, the length and circumference of the lower limbs can reach 100% fitness. The operation time of the first placement(118.23±7.33) s and re operation(60.08±5.88) s of experimental group were significantly shorter than those of control group (164.68±8.93) s and re operation (131.23±7.91) s. The adjustment times (3) and operation time (3.50±0.71) s of experimental group were significantly shorter than those of control group(11)and operation time(139.00±5.66) s ( P <0.05), but there was no significant difference between two groups ( P >0.05). The VAS score of experimental group was significantly lower than that of control group at each time point ( P <0.01)., Conclusion: The modular combined elastic compression device has good fitness, better placement and flexible adjustment, convenience and safety, and better comfort than modified Robert Jones bandage of 3M elastic bandage.

Phateacid esters (PAEs), such as dibutyl phthalate (DBP), have been widely used and human exposure results into serious toxic effects; such as the development of fatty liver disease. In the present study, SD rat models for in vivo study (normal and fatty liver model group) and hepatocytes for in vitro study (normal and abnormal lipid metabolism model group) were established to determine the effects of DBP on liver function and discover the possible mechanisms. Meanwhile, the peroxisome proliferator activated receptor (PPARα) blocker, GW6471, with the Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) activator, AICAR, were applied in vitro study to clarify the role of PPARα/SREBP-1c/FAS/GPAT/AMPK signal pathway in the process. Results suggested that DBP could activate PPARα signaling pathway and affected the protein expression of SREBP, FAS and GPAT to cause hyperlipidemia and abnormal liver function. DBP also could inhibit the phosphorylation and activation of AMPK to inhibit the decomposition and metabolism of lipids. Interestingly, the effects of DBP could be alleviated by GW6471 and AICAR. Our experimental results provide reliable evidence that DBP exposure could further induce liver lipid metabolism disorder and other hepatic toxicity through PPARα/SREBP-1c/FAS/GPAT/AMPK signal pathway., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Based on conventional MRI images, it is difficult to differentiatepseudoprogression from true progressionin GBM patients after standard treatment, which isa critical issue associated with survival. The aim of this study was to evaluate the diagnostic performance of machine learning using radiomics modelfrom T 1 -weighted contrast enhanced imaging(T 1 CE) in differentiating pseudoprogression from true progression after standard treatment for GBM., Methods: Seventy-sevenGBM patients, including 51 with true progression and 26 with pseudoprogression,who underwent standard treatment and T 1 CE, were retrospectively enrolled.Clinical information, including sex, age, KPS score, resection extent, neurological deficit and mean radiation dose, were also recorded collected for each patient. The whole tumor enhancementwas manually drawn on the T 1 CE image, and a total of texture 9675 features were extracted and fed to a two-step feature selection scheme. A random forest (RF) classifier was trained to separate the patients by their outcomes.The diagnostic efficacies of the radiomics modeland radiologist assessment were further compared by using theaccuracy (ACC), sensitivity and specificity., Results: No clinical features showed statistically significant differences between true progression and pseudoprogression.The radiomic classifier demonstrated ACC, sensitivity, and specificity of 72.78%(95% confidence interval [CI]: 0.45,0.91), 78.36%(95%CI: 0.56,1.00) and 61.33%(95%CI: 0.20,0.82).The accuracy, sensitivity and specificity of three radiologists' assessment were66.23%(95% CI: 0.55,0.76), 61.50%(95% CI: 0.43,0.78) and 68.62%(95% CI: 0.55,0.80); 55.84%(95% CI: 0.45,0.66),69.25%(95% CI: 0.50,0.84) and 49.13%(95% CI: 0.36,0.62); 55.84%(95% CI: 0.45,0.66), 69.23%(95% CI: 0.50,0.84) and 47.06%(95% CI: 0.34,0.61), respectively., Conclusion: T 1 CE-based radiomics showed better classification performance compared with radiologists' assessment.The radiomics modelwas promising in differentiating pseudoprogression from true progression.

In this research, a very practical QuEChERS-GC-MS/MS analytical approach for 74 pesticide residues in herb based on retention index was established. This novel analytical approach has two important technical advantages. One advantage is to quickly screen pesticide compounds in herbs without having to use a large number of pesticide standard substances at the beginning of the experiment. The other advantage is to assist in identifying the target pesticide compound accurately. A total of 74 kinds of pesticides were quickly prescreened in all chuanxiong rhizoma samples. The results showed that three kinds of pesticides were screened out in all the samples, including chlorpyrifos, fipronil, and procymidone, and the three pesticides were qualitatively and quantitatively determined. The RSD values for interday and intraday variation were acquired to evaluate the precision of the analytical approach, and the overall interday and intraday variations are not more than 1.97% and 3.82%, respectively. The variations of concentrations of the analyzed three pesticide compounds in sample CX16 are 0.74%-4.15%, indicating that the three pesticides in the sample solutions were stable in 48 h. The spiked recoveries of the three pesticides are 95.22%, 93.03%, and 94.31%, and the RSDs are less than ± 6.0%. The methodological verification results indicated the good reliability and accuracy of the new analytical method. This research work is a new application of retention index, and it will be a valuable tool to assist quickly and accurately in the qualitative and quantitative analysis of multipesticide residues in herbs., Competing Interests: The authors declare they have no conflicts of interest., (Copyright © 2021 Peng Tan et al.)

To compare the effect of hot or warm property of Chinese medicine(CM) on the skin toxicity of essential oils(EOs) as penetration enhancer in vitro and in vivo, and explore the mechanism. EOs were extracted from WIM of Bichengqie(Litseae Fructus), Dingxiang(Flos Syzygii Aromatici), Huajiao(Pericarpium Zanthoxyli Bungeani), and Xiaohuixiang(Fructus Foeniculi) with warm property, and Ganjiang(Rhizoma Zingiberis), Gaoliangjiang(Rhizoma Alpiniae Officinari), Hujiao(Fructus Piperis), and Wuzhuyu(Fructus Evodiae Rutaecarpae) with hot property, respectively. Then the in vitro toxicity was evaluated by human keratinocyte cytotoxicity. In vivo skin irritation potency was also evaluated through pathological observation after topical administration. The components, especially those located in stratum corneum, were analyzed by GC-MS. The main components, namely monoterpenes and sesquiterpenes, of EOs extracted from CM with hot property,were detected for the interaction with keratino-lipid ceramide 3 by molecular simulation technology; and the interaction energy value was calculated based on the optimal conformation. It was found that the skin cell toxicity of EOs from CM with hot property was significantly higher than that of EOs from CM with warm property. However, there was no significant difference between them by in vivo skin irritation evaluation. Whether from CM with hot property or warm property, EOs showed a significant reduced toxicity compared with azone. Sesquiterpenes(33.56%±19.38%) were found to be one of the main components in EOs from CM with hot property, while almost no sesquiterpenes was found in EOs from CM with warm property. After topical administration of EOs from CM with hot property, sesquiterpenes were demonstrated to be prone to locate in stratum corneum. The results of molecular simulation also revealed that the interaction between sesquiterpenes and ceramide 3 was significantly stronger than that of monoterpenes(P&lt;0.01). In conclusion, the location of sesquiterpenes in stratum corneum resulted in the significant difference between in vitro skin cell toxicity and in vivo skin irritation potency. The EOs from CM with hot property shall be taken into account for further development of potent penetration enhancer.

Background and Purpose: Neonatal subpial hemorrhage with underlying cerebral infarct is a previously described but poorly understood clinicoradiographic syndrome. We sought to further characterize the cranial ultrasound and MR imaging characteristics and associated outcomes of this condition across the full range of gestational ages, including extreme and very preterm neonates., Materials and Methods: This was a single tertiary pediatric center retrospective case series. Brain MR imaging and cranial ultrasound of neonates with subpial hemorrhage with underlying cerebral infarct were identified from a population-based radiology registry (2006-2020). Original images were reviewed by 2 neuroradiologists blinded to history and outcome. Clinical presentation, course, and outcome at >12 months were abstracted from medical records. The diagnostic utility of cranial ultrasound was compared with that of MR imaging., Results: Sixteen patients were included (median gestational age, 36.5 weeks; range, 27-41 weeks; 31% premature). MR images were obtained acutely at the time of presentation between days 0 and 9 of life. On T2WI and DWI, a consistent presence of a hypointense subpial bleed and an underlying hyperintense cerebral cortex were recognized, which created a distinct MR imaging pattern resembling the yin-yang symbol. Findings of all the MRAs and MRVs were normal. Cranial ultrasound detected 6 of 7 MR imaging lesions with sonographic features correlating well with MR imaging. The 3 extreme or very preterm neonates did not survive. The remainder survived with relatively mild neurologic deficits., Conclusions: Subpial hemorrhage with underlying infarction is a recognizable condition with unique MR imaging and sonographic features. Improved recognition may advance understanding of risk factors and outcomes., (© 2021 by American Journal of Neuroradiology.)

Abstract: The diagnosis and treatment of unexplained recurrent spontaneous abortion (URSA) is an important and hot topic in the field of obstetrics and gynecology. During our clinical investigation (observation), we have found that URSA patients usually experience recurrent vaginitis or vaginal dysbacteriosis during periods of non-pregnancy, pregnancy, and post-abortion. However, there is no research on vaginal dysbacteriosis's influence on URSA. Using women with normal induced abortion as a control group, and using 16S rRNA sequencing, which helps to screen differentially expressed flora, this study discusses the relevance between differential bacteria at the genus level and the incidence of URSA. Another aim of this study is to determine whether certain pathogenic genera can cause an imbalance in immune tolerance of the maternal and fetal interface through regulatory chemokines, which leads to recurrent spontaneous abortion. This article has explored URSA pathogenesis from the perspective of differentially expressed vaginal flora, which has great theoretical significance for the early diagnosis and treatment of URSA., Competing Interests: We declare that we do not have any commercial or associative interest that represents a conflicts of interest in connection with the work submitted., (Copyright © 2020 the Author(s). Published by Wolters Kluwer Health, Inc.)

Heart surgery in patients from high-altitude areas is more challenging than usual. Few studies have been published on this issue, and none of them have discussed the effect of an altitude change (from high to low altitude) on a patient's physiology or its effects on a patient's perioperative management. Here, we present the case of a 46-year-old man who was a long-time resident of Tibetan area in Sichuan (altitude >3000 m) who underwent Stanford type A aortic dissection emergency surgery on the plain. Anesthetic management occurred through monitoring of the bispectral index (BIS) and transesophageal echocardiography (TEE), and we used a relatively loose fluid hydration strategy. The surgery was performed using cardiopulmonary bypass (CPB), deep hypothermia (DH), and selective antegrade cerebral perfusion. The most prominent anesthesia challenges for these patients are physiological changes due to habitation in an high-altitude environment (chronic hypoxemia), which can cause hyperhemoglobinemia, polycythemia, hypercoagulable blood, and even pulmonary hypertension, cor pulmonale, or congestive heart failure. Optimized perioperative management and close cooperation among the entire cardiac medical team were the key factors in the successful management of this rare case.

The objective of this study was to evaluate the efficacy of various posaconazole dosing regimens of the different formulations against Aspergillus spp. in adults. Monte Carlo simulations were conducted using pharmacokinetic (PK) parameters and pharmacodynamic (PD) data to determine the probability of target attainment (PTA) and cumulative fraction of response (CFR) in terms of area under the concentration-time curve/minimum inhibition concentration (AUC/MIC) targets of posaconazole. According to the results of the PTA analysis, currently recommended clinical dosing regimens of the delayed-release tablet and intravenous (i.v.) solution were appropriate in prophylaxis against Aspergillus spp. with MICs ≤ 0.125 µg/mL. However, only high-dose regimens of the delayed-release tablet could achieve the target PTA in the treatment against Aspergillus spp. at an MIC of 0.125 µg/mL. Furthermore, the CFR was calculated for each dosing regimen. For the oral suspension, none of the simulated dosing regimens was effective against Aspergillus spp. For the delayed-release tablet and i.v. solution, the recommended dosing regimens were effective for prophylaxis of invasive fungal infections by four Aspergillus spp. (Aspergillus flavus, Aspergillus fumigatus, Aspergillus nidulans and Aspergillus terreus). However, these recommended dosing regimens were only effective for the treatment of A. terreus infection. Therefore, the high-dose regimen (200 mg oral every 12 h) of the delayed-release tablet should be recommended to achieve optimal therapeutic efficacy against four Aspergillus spp. (A. flavus, A. fumigatus, A. nidulans and A. terreus). These PK/PD-based simulations rationalise and optimise the dosing regimens of the different posaconazole formulations against Aspergillus spp. in adults., (Copyright © 2020 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Mitochondrial diseases, due to nuclear or mitochondrial genome mutations causing mitochondrial dysfunction, have a wide range of clinical features involving neurologic, muscular, cardiac, hepatic, visual, and auditory symptoms. Making a diagnosis of a mitochondrial disease is often challenging since there is no gold standard and traditional testing methods have required tissue biopsy which presents technical challenges and most patients prefer a non-invasive approach. Since a diagnosis invariably involves finding a disease-causing DNA variant, new approaches such as next generation sequencing (NGS) have the potential to make it easier to make a diagnosis. We evaluated the ability of our traditional diagnostic pathway (metabolite analysis, tissue neuropathology and respiratory chain enzyme activity) in 390 patients. The traditional diagnostic pathway provided a diagnosis of mitochondrial disease in 115 patients (29.50%). Analysis of mtDNA, tissue neuropathology, skin electron microscopy, respiratory chain enzyme analysis using inhibitor assays, blue native polyacrylamide gel electrophoresis were all statistically significant in distinguishing patients between a mitochondrial and non-mitochondrial diagnosis. From these 390 patients who underwent traditional analysis, we recruited 116 patients for the NGS part of the study (36 patients who had a mitochondrial diagnosis (MITO) and 80 patients who had no diagnosis (No-Dx)). In the group of 36 MITO patients, nuclear whole exome sequencing (nWES) provided a second diagnosis in 2 cases who already had a pathogenic variant in mtDNA, and a revised diagnosis (GLUL) in one case that had abnormal pathology but no pathogenic mtDNA variant. In the 80 NO-Dx patients, nWES found non-mitochondrial diagnosis in 26 patients and a mitochondrial diagnosis in 1 patient. A genetic diagnosis was obtained in 53/116 (45.70%) cases that were recruited for NGS, but not in 11/116 (9.48%) of cases with abnormal mitochondrial neuropathology. Our results show that a non-invasive, bigenomic sequencing (BGS) approach (using both a nWES and optimized mtDNA analysis to include large deletions) should be the first step in investigating for mitochondrial diseases. There may still be a role for tissue biopsy in unsolved cases or when the diagnosis is still not clear after NGS studies., (Copyright © 2020 Elsevier Inc. All rights reserved.)

We recently observed a type of MR imaging artifact that consistently mimics an abnormal appearance of the cerebral cortex, leading to initial misinterpretation and repeat scans. The artifact is caused by malfunction of part of the multichannel phased array head coil and is manifested by irregularity of cortical surface and gray-white matter junctions. The presence of such an artifact can be confirmed by assessing the background noise of the MR images and checking the coil element status on the MR imaging operator console., (© 2020 by American Journal of Neuroradiology.)