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Abstract Background Gastric cancer poses a significant global health challenge. We aim to use period analysis to assess the changes in gastric cancer treatment at our center over the past 15 years. This study reflects the current state of gastric cancer treatment at our center and provides valuable data to support clinical advancements. Method We used period analysis to evaluate the survival status of 3915 patients with gastric cancer at Nanfang Hospital, Southern Medical University, over a 15-year period spaning from 2008 to 2022. The 5-year relative survival rates were analyzed. Result Our findings indicate that the 5-year relative survival rate at our center from 2018 to 2022 is 71.4%. From 2018 to 2022, the 5-year relative survival rates for patients aged

Abstract Background Pulmonary hypertension (PH) is marked by elevated pulmonary artery pressures due to various causes, impacting right heart function and survival. Disulfidptosis, a newly recognized cell death mechanism, may play a role in PH, but its associated genes (DiGs) are not well understood in this context. This study aims to define the diagnostic relevance of DiGs in PH. Methods Using GSE11726 data, we analyzed DiGs and their immune characteristics to identify core genes influencing PH progression. Various machine learning models, including RF, SVM, GLM, and XGB, were compared to determine the most effective diagnostic model. Validation used datasets GSE57345 and GSE48166. Additionally, a CeRNA network was established, and a hypoxia-induced PH rat model was used for experimental validation with Western blot analysis. Results 12 DiGs significantly associated with PH were identified. The XGB model excelled in diagnostic accuracy (AUC = 0.958), identifying core genes DSTN, NDUFS1, RPN1, TLN1, and MYH10. Validation datasets confirmed the model’s effectiveness. A CeRNA network involving these genes, 40 miRNAs, and 115 lncRNAs was constructed. Drug prediction suggested therapeutic potential for folic acid, supported by strong molecular docking results. Experimental validation in a rat model aligned with these findings. Conclusion We uncovered the distinct expression patterns of DiGs in PH, identified core genes utilizing an XGB machine-learning model, and established a CeRNA network. Drugs targeting the core genes were predicted and subjected to molecular docking. Experimental validation was also conducted for these core genes.

Abstract Background Voiding trials are used to identify women at risk for postoperative urinary retention while performing optimal voiding trial management with minimal burden to the patient and medical service team. We performed a systematic review and meta-analysis of postoperative void trials following urogynecologic surgery to investigate (1) the optimal postoperative void trial methodology and (2) the optimal criteria for assessing void trial. Method We searched PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and relevant reference lists of eligible articles from inception to April 2022. We identified any randomized controlled trials (RCTs) in English that studied void trials in patients undergoing urogynecologic surgery. Study selection (title/abstract and full text), data extraction, and risk of bias assessment were conducted by two independent reviewers. Extracted study outcomes included the following: the correct passing rate, time to discharge, discharge rate without a catheter after the initial void trial, postoperative urinary tract infection, and patient satisfaction. Results Void trial methodology included backfill-assisted and autofill studies (2 RCTs, n = 95). Backfill assistance was more likely to be successful than autofill (RR 2.12, 95% CI 1.29, 3.47, P = 0.00); however, no significant difference was found in the time to discharge (WMDs = − 29.11 min, 95% CI − 57.45, 1.23, P = 0.06). The criteria for passing void trial included subjective assessment of the urinary force of stream and objective assessment of the standard voiding trial (3 RCTs, n = 377). No significant differences were found in the correct passing rate (RR 0.97, 95% CI 0.93, 1.01, P = 0.14) or void trial failure rate (RR 0.78, 95% CI 0.52, 1.18, P = 0.24). Moreover, no significant differences were found in the complication rates or patient satisfaction between the two criteria. Conclusion Bladder backfilling was associated with a lower rate of catheter discharge after urogynecologic surgery. The subjective assessment of FOS is a reliable and safe method for assessing postoperative voiding because it is less invasive. Systematic review registration PROSPERO CRD42022313397

Abstract Background Venous thromboembolism (VTE) including Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE), is a serious cause of patient morbidity and mortality in hospitals. Neurosurgical hospitalized patients have higher rates of immobility and bed rest, thus increasing their risk of developing VTE. This highlights the need for their thromboprophylaxis regimens. Patients’ awareness of VTE is essential for promoting strategies such as early ambulation and encouraging self-assessment and self-reporting of VTE signs and symptoms. This study evaluated neurosurgical hospitalized patients’ awareness of VTE and explored the influencing factors to provide a theoretical basis for nursing intervention. Methods We selected one tertiary level hospital in Hunan Province and randomly sampled eligible patients from each five neurosurgical units. We conducted a cross-sectional survey of the hospitalized patients of neurosurgery using the self-designed and validated VTE knowledge questionnaire, and the influencing factors were analyzed using SPSS 26.0. Results A total of 386 neurosurgical hospitalized patients completed the survey. The score of VTE knowledge in neurosurgical hospitalized patients was 13.22 (SD = 11.52). 36.0% and 21.2% of participants reported they had heard of DVT and PE, respectively. 38.9% of participants were unable to correctly identify any symptoms of VTE. The most frequently identified risk factor was ‘immobility or bed rest for more than three days’ (50.0% of participants), and 38.1% of patients agreed that PE could cause death. 29.5% of participants were unable to identify any prophylactic measures of VTE. The results of Negative Binomial Regression showed that the influencing factors of VTE knowledge in neurosurgical hospitalized patients were education level (P

Abstract Background Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of beta cells in pancreatic islets. Identification of the key genes involved in T1D progression and their mechanisms of action may contribute to a better understanding of T1D. Methods The microarray profile of T1D-related gene expression was searched using the Gene Expression Omnibus (GEO) database. Then, the expression data of two messenger RNAs (mRNAs) were integrated for Weighted Gene Co-Expression Network Analysis (WGCNA) to generate candidate genes related to T1D. In parallel, T1D microRNA (miRNA) data were analyzed to screen for possible regulatory miRNAs and their target genes. An miRNA–mRNA regulatory network was then established to predict the key regulatory genes and their mechanisms. Results A total of 24 modules (i.e., clusters/communities) were selected using WGCNA analysis, in which three modules were significantly associated with T1D. Further correlation analysis of the gene module revealed 926 differentially expressed genes (DEGs), of which 327 genes were correlated with T1D. Analysis of the miRNA microarray showed that 13 miRNAs had significant expression differences in T1D. An miRNA–mRNA network was established based on the prediction of miRNA target genes and the combined analysis of mRNA, in which the target genes of two miRNAs were found in T1D correlated genes. Conclusion An miRNA–mRNA network for T1D was established, based on which 2 miRNAs and 12 mRNAs were screened, suggesting that they may play key regulatory roles in the initiation and development of T1D.

Abstract Background Radiation-induced lung injury (RILI) often occurs during clinical chest radiotherapy and acute irradiation from accidental nuclear leakage. This study explored the role of monophosphoryl lipid A (MPLA) in RILI. Materials and Methods The entire thoracic cavity of C57BL/6N mice was irradiated at 20 Gy with or without pre-intragastric administration of MPLA. HE staining, Masson trichrome staining, and TUNEL assay were used to assess lung tissue injury after treatment. The effect of irradiation on the proliferation of MLE-12 cells was analyzed using the Clonogenic assay. The effect of MPLA on the apoptosis of MLE-12 cells was analyzed using flow cytometry. Expression of γ-H2AX and epithelial-mesenchymal transition (EMT) markers in MLE-12 cells was detected by immunofluorescence and Western blot, respectively. Results MPLA attenuated early pneumonitis and late pulmonary fibrosis after thoracic irradiation and reversed radiation-induced EMT in C57 mice. MPLA further promoted proliferation and inhibited apoptosis of irradiated MLE-12 cells in vitro. Mechanistically, the radioprotective effect of MPLA was mediated by exosomes secreted by stimulated macrophages. Macrophage-derived exosomes modulated DNA damage in MLE-12 cells after irradiation. MPLA promoted the polarization of RAW 264.7 cells to the M1 phenotype. The exosomes secreted by M1 macrophages suppressed EMT in MLE-12 cells after irradiation. Conclusion MPLA is a novel treatment strategy for RILI. Exosomes derived from macrophages are key to the radioprotective role of MPLA in RILI.

Abstract Background In regard to central nervous system tumour resection, preserving vital venous structures to avoid devastating consequences such as brain oedema and haemorrhage is important. However, in clinical practice, it is difficult to obtain clear and vivid intraoperative venous visualization and blood flow analyses. Methods We retrospectively reviewed patients who underwent brain tumour resection with the application of indocyanine green videoangiography (ICG-VA) integrated with FLOW 800 from February 2019 to December 2020 and present our clinical cases to demonstrate the process of venous preservation. Galen, sylvian and superior cerebral veins were included in these cases. Results Clear documentation of the veins from different venous groups was obtained via ICG-VA integrated with FLOW 800, which semiquantitatively analysed the flow dynamics. ICG-VA integrated with FLOW 800 enabled us to achieve brain tumour resection without venous injury or obstruction of venous flux. Conclusions ICG-VA integrated with FLOW 800 is an available method for venous preservation, although further comparisons between ICG-VA integrated with FLOW 800 and other techniques of intraoperative blood flow monitoring is needed.

Abstract Background The purpose of this in vitro study was to evaluate the effect of the percentages of preserved enamel on ceramic laminate veneers’ (CLVs) shear bond strength (SBS). Methods Seventy extracted human maxillary central incisors were scanned and reconstructed into three-dimensional models. The extracted teeth were then embedded and randomly divided into seven groups (n = 10 per group). Based on digital analyses of the three-dimensional models, guided tooth preparation and bonding procedures were performed individually to form seven different percentages (100%, 80%, 60% 50%, 40%, 20% and 0%) of remaining enamel thickness on the bonding surface. Finally, the SBS test was performed, and the data were statistically analysed by one-way ANOVA with LSD post hoc test (α = 0.05). Results The complete enamel surface exhibited the highest SBS (19.93 ± 4.55 MPa), followed by 80% enamel (19.03 ± 3.66 MPa), 60% enamel (18.44 ± 3.65 MPa), 50% enamel (18.18 ± 3.41 MPa), 40% enamel (17.83 ± 3.01 MPa) and 20% enamel (11.32 ± 3.42 MPa) group. The lowest SBS (9.63 ± 3.46 MPa) was detected in 0% enamel group. No significant difference was observed among the 40–100% enamel groups, while the 20% or 0% enamel group demonstrated a significantly lower mean SBS than the 40% enamel group (p

Abstract Background Hemagglutinin (HA), as the surface immunogenic protein, is the most important component of influenza viruses. Previous studies showed that the stability of HA was significant for HA’s immunogenicity, and many efforts have been made to stabilize the expressed HA proteins. Methods In this study, the protein disulfide isomerases (PDIs) were investigated for the ability to improve the stability of HA protein. Two members of the PDIs family, PDI and ERp57, were over-expressed or down-expressed in 293 T cells. The expression of H3 HA and PDIs were investigated by real-time qPCR, western-blot, immunofluorescence assay, and flow cytometry. The stability of HA was investigated by western-blot under non-reducing condition. Moreover, BALB/c mice were immunized subcutaneously twice with the vaccine that contained HA proteins from the ERp57-overexpressed and conventional 293 T cells respectively to investigate the impact of ERp57 on the immunogenicity of H3N2 HA. Results The percentage of the disulfide-bonded HA trimers increased significantly in the PDIs-overexpressed 293 T cells, and ERp57 was more valid to the stability of HA than PDI. The knockdown of ERp57 by small interfering RNA significantly decreased the percentage of the disulfide-bonded HA trimers. HA proteins from ERp57-overexpressed 293 T cells stimulated the mice to generate significantly higher HA-specific IgG against H1N1 and H3N2 viruses than those from the conventional cells. The mice receiving H3 HA from ERp57-overexpressed 293 T cells showed the better resistance against H1N1 viruses and the higher survival rate than the mice receiving H3 HA from the conventional cells. Conclusion ERp57 could improve the stability and immunogenicity of H3N2 HA.

Abstract Background The purpose/aim of this study was to 1) use magnetic resonance diffusion tensor imaging (DTI), fibre bundle/tract-based spatial statistics (TBSS) and machine learning methods to study changes in the white matter (WM) structure and whole brain WM network in different periods of the nasopharyngeal carcinoma (NPC) patients after radiotherapy (RT), 2) identify the most discriminating WM regions and WM connections as biomarkers of radiation brain injury (RBI), and 3) supplement the understanding of the pathogenesis of RBI, which is useful for early diagnosis in the clinic. Methods A DTI scan was performed in 77 patients and 67 normal controls. A fractional anisotropy map was generated by DTIFit. TBSS was used to find the region where the FA differed between the case and control groups. Each resulting FA value image is registered with each other to create an average FA value skeleton. Each resultant FA skeleton image was connected to feature vectors, and features with significant differences were extracted and classified using a support vector machine (SVM). Next, brain segmentation was performed on each subject’s DTI image using automated anatomical labeling (AAL), and deterministic white matter fiber bundle tracking was performed to generate symmetrical brain matrix, select the upper triangular component as a classification feature. Two-sample t-test was used to extract the features with significant differences, then classified by SVM. Finally, we adopted a permutation test and ROC curves to evaluate the reliability of the classifier. Results For FA, the accuracy of classification between the 0–6, 6–12 and > 12 months post-RT groups and the control group was 84.5, 83.9 and 74.5%, respectively. In the case groups, the FA with discriminative ability was reduced, mainly in the bilateral cerebellum and bilateral temporal lobe, with prolonged time, the damage was aggravated. For WM connections, the SVM classifier classification recognition rates of the 0–6, 6–12 and > 12 months post-RT groups reached 82.5, 78.4 and 76.3%, respectively. The WM connections with discriminative ability were reduced. Conclusions RBI is a disease involving whole brain WM network anomalies. These brain discriminating WM regions and WM connection modes can supplement the understanding of RBI and be used as biomarkers for the early clinical diagnosis of RBI.

Abstract Background The mitogen-activated extracellular signal-regulated kinase 1/2 (MEK1/2) inhibitor trametinib has shown promising therapeutic effects on melanoma, but its efficacy on colorectal cancer (CRC) is limited. Synthetic lethality arises with a combination of two or more separate gene mutations that causes cell death, whereas individual mutations keep cells alive. This study aimed to identify the genes responsible for resistance to trametinib in CRC cells, using a synthetic lethal short hairpin RNA (shRNA) screening approach. Methods We infected HT29 cells with a pooled lentiviral shRNA library and applied next-generation sequencing to identify shRNAs with reduced abundance after 8-day treatment of 20 nmol/L trametinib. HCT116 and HT29 cells were used in validation studies. Stable ring finger protein 183 (RNF183)-overexpressing cell lines were generated by pcDNA4-myc/his-RNF183 transfection. Stable RNF183-knockdown cell lines were generated by infection of lentiviruses that express RNF183 shRNA, and small interference RNA (siRNA) was used to knock down RNF183 transiently. Quantitative real-time PCR was used to determine the mRNA expression. Western blotting, immunohistochemical analysis, and enzyme-linked immunosorbent assay (ELISA) were used to evaluate the protein abundance. MTT assay, colony formation assay, and subcutaneous xenograft tumor growth model were used to evaluate cell proliferation. Results In the primary screening, we found that the abundance of RNF183 shRNA was markedly reduced after treatment with trametinib. Trametinib induced the expression of RNF183, which conferred resistance to drug-induced cell growth repression and apoptotic and non-apoptotic cell deaths. Moreover, interleukin-8 (IL-8) was a downstream gene of RNF183 and was required for the function of RNF183 in facilitating cell growth. Additionally, elevated RNF183 expression partly reduced the inhibitory effect of trametinib on IL-8 expression. Finally, xenograft tumor model showed the synergism of RNF183 knockdown and trametinib in repressing the growth of CRC cells in vivo. Conclusion The RNF183-IL-8 axis is responsible for the resistance of CRC cells to the MEK1/2 inhibitor trametinib and may serve as a candidate target for combined therapy for CRC.

Abstract Background To assess the long-term outcomes of patients with glaucoma secondary to iridocorneal endothelial syndrome (GS-ICE) who underwent Ahmed glaucoma valve (AGV) implantation combined with phacoemulsification and intraocular lens (IOL) implantation surgery. Methods In this non-comparative retrospective case series study, twelve patients with uncontrolled GS-ICE and cataract underwent Ahmed aqueous shunt combined with phacoemulsification and IOL implantation surgery at Beijing Tongren Eye Center between June 2014 and June 2022. Main medical records included best-corrected visual acuity (BCVA), intraocular pressure (IOP), number of antiglaucoma medications (AGM), corneal status and further surgical interventions. Surgical success was defined as a postoperative IOP ≥ 6mmHg and ≤ 21mmHg without (complete success) or with/without (qualified success) topical AGM and vision of at least light perception during the follow-up period. Results Twelve eyes of twelve patients were reviewed. Preoperative IOP was decreased from a mean of 38.5 ± 6.7 mmHg on 3.3 ± 0.9 AGM to a mean of 16.3 ± 4.3 mmHg (P

Abstract Background Gallstones are a common digestive disorder that threatens human health. Iron deficiency may be related to the formation of gallstones, but there is limited current epidemiological research. The objective of this study was to investigate the relationship between iron status and gallstones. Methods The datasets from the National Health and Nutrition Examination Survey (NHANES) 2017–2020 were used in a cross-sectional investigation. Gallstones were determined by using the 2007–2010 NHANES questionnaire. Multivariate linear regression models were used to examine the association between serum iron, serum ferritin and iron intake with the risk for gallstones. Subgroup analysis based on gender, age, race, and diabetes were performed. Fitted smoothing curves were used to describe the linear relationship. Results The research involved 7847 participants aged 20 and above, among whom 845 were identified as having gallstones. Participants with higher serum iron levels tended to have a lower gallstones prevalence. A negative relationship between serum iron and gallstones prevalence was observed (OR = 0.979, 95% CI:0.965–0.992). The group with the highest serum iron tertile had a 23.7% lower risk of gallstones compared to the lowest tertile (OR = 0.763, 95% CI:0.628‒0.929). Gallstone prevalence was inversely correlated with iron intake in model 1. The negative association between serum iron and gallstones remained stable in stratifications, including gender, age, race, and diabetes. Conclusions Elevated serum iron was associated with a decreased prevalence of gallstones. However, to confirm the impact of long-term iron metabolism on gallstone formation, additional prospective research is necessary.

Abstract Background Balance and mobility deficits are major concerns in stroke rehabilitation. Virtual reality (VR) training and Swiss-ball training are commonly used approaches to improve balance and mobility. However, no study has compared the efficacy of VR training, Swiss-ball training, and their combination in improving balance and mobility function or investigated cortical activation and connectivity in individuals with stroke. Methods A prospective, single-blinded, parallel-armed, multi-center randomized controlled trial with factorial design will be conducted. Seventy-six participants aged 30–80 years with stroke will be recruited. Participants will be allocated to one of the four groups: (A) the VR training + Swiss-ball training + conventional physical therapy group; (B) the Swiss-ball training + conventional physical therapy group; (C) the VR training + conventional physical therapy group; or (D) the conventional physical therapy group. All participants will receive 50 min of training per day, 5 times per week, for a total of 4 weeks. The primary outcomes will be balance and mobility measures. Secondary outcomes will include the 10-min walk test, dynamic gait index, and cortical activation. Outcomes will be measured on three occasions: at baseline, after the training, and at the 4-week follow-up. Discussion This trial will provide evidence to determine whether there are differences in clinical outcomes and cortical activation following two different types of exercise programs and their combination, and to elucidate the recovery mechanisms of balance and mobility function in individuals with stroke. Trial registration Chinese Clinical Trial Registry reference: www.chictr.org.cn (No. ChiCTR2400082135). Registered on May 24, 2024.

Abstract Background Type 2 diabetes mellitus (T2DM) and metabolic-associated fatty liver disease (MAFLD) are both metabolic disorders that negatively impact the cardiovascular system. This study comprehensively analyzed the additive effect of MAFLD on left ventricular function and global strain in T2DM patients by cardiac magnetic resonance (CMR). Methods Data of 261 T2DM patients, including 109 with and 152 without MAFLD, as well as 73 matched normal controls from our medical center between June 2015 and March 2022 were retrospectively analyzed. CMR-derived parameters, including LV function and global strain parameters, were compared among different groups. Univariate and multivariate linear regression analyses were conducted to investigate the impact of various factors on LV function and global strain. Results Our investigation revealed a progressive deterioration in LV functional parameters across three groups: control subjects, T2DM patients without MAFLD, and T2DM patients with MAFLD. Statistically significant increases in left ventricular end-diastolic volume index (LVEDVI), left ventricular end-systolic volume index (LVESVI), left ventricular mass index (LVMI) were observed, along with decreases in left ventricular ejection fraction (LVEF) and left ventricular global function index (LVGFI). Among these three groups, significant reductions were also noted in the absolute values of LV global radial, circumferential, and longitudinal peak strains (GRPS, GCPS, and GLPS), as well as in peak systolic (PSSR) and peak diastolic strain rates (PDSR). MAFLD was identified as an independent predictor of LVEF, LVMI, LVGFI, GRPS, GCPS, and GLPS in multivariate linear analysis. Besides, the incidence of late gadolinium enhancement was higher in MAFLD patients than in non-MAFLD patients (50/109 [45.9%] vs. 42/152 [27.6%], p = 0.003). Furthermore, escalating MAFLD severity was associated with a numerical deterioration in both LV function parameters and global strain values. Conclusions This study thoroughly compared CMR parameters in T2DM patients with and without MAFLD, uncovering MAFLD’s adverse impact on LV function and deformation in T2DM patients. These findings highlight the critical need for early detection and comprehensive management of cardiac function in T2DM patients with MAFLD.

Abstract The skin epidermis is continually influenced by a myriad of internal and external elements. At its basal layer reside epidermal stem cells, which fuels epidermal renovation and hair regeneration with powerful self-renewal ability, as well as keeping diverse signals that direct their activity under surveillance with quick response. The importance of epidermal stem cells in wound healing and immune-related skin conditions has been increasingly recognized, and their potential for clinical applications is attracting attention. In this review, we delve into recent advancements and the various physiological and psychological factors that govern distinct epidermal stem cell populations, including psychological stress, mechanical forces, chronic aging, and circadian rhythm, as well as providing an overview of current methodological approaches. Furthermore, we discuss the pathogenic role of epidermal stem cells in immune-related skin disorders and their potential clinical applications.

Abstract Background The Latarjet procedure (LP) is performed as a primary stabilization procedure (primary LP) and a salvage procedure when an earlier shoulder stabilization procedure has failed (salvage LP). However, whether primary LP or salvage LP provides better outcomes for anterior shoulder instability remains unknown. Methods Two independent reviewers performed the literature search based on the PRISMA guidelines. A comprehensive search of PubMed, Embase, web of science and Cochrane Library was performed from their inception date to December 4, 2023. Inclusion criteria mainly included the comparison of postoperative outcomes between primary and salvage LP, English language, and full text availability. Two reviewers independently examined the literature, collected data, and evaluated the methodological robustness of the included studies. The Methodological Index for Nonrandomized Studies was used to evaluate the quality of nonrandomized studies. Recurrent instability, complications, reoperations, return to sports, patient-reported outcomes, and range of motion were assessed. Statistical evaluations were conducted using Manager V.5.4.1 (The Cochrane Collaboration, Software Update, Oxford, UK). Results Twelve studies were included in the systematic review, with 940 shoulders undergoing primary LP and 631 shoulders undergoing salvage LP. Statistically significant differences in favor of primary LP were found in 2 of the 11 and 2 of 4 included studies in terms of recurrent instability and returning to the same sports (RTS) at preinjury level, respectively. In terms of the visual analog scale, subjective shoulder value and the Western Ontario Shoulder Instability Index, 2 of the 4, 1 of the 3 and 1 of the 3 included studies reported statistically significant differences in favor of primary LP. Differences were not noticed regarding complications, reoperations, the time to RTS, the Rowe score, the Athletic Shoulder Outcome Scoring System, and forward flexion. Conclusion Current evidence suggests that compared with primary LP, salvage LP may provide inferior postoperative outcomes in terms of recurrent instability and the rate of RTS at preinjury level. Primary and salvage LP may yield comparable efficacy in terms of complications, reoperations, the rate of RTS, the time to RTS, pain, shoulder function, and range of motion. Prospero id CRD42023492027.

Abstract Background Extensive research has been conducted to investigate the short-term and long-term outcomes of arthroscopic Bankart repair, yielding varying results across different populations. However, there remains a dearth of studies specifically focused on evaluating outcomes in recreational athletes. Methods A retrospective case series study was conducted on recreational athletes who underwent isolated arthroscopic Bankart repair between 2013 and 2021. The primary outcome assessed was recurrent instability, defined as dislocation or subluxation. Secondary outcomes included patient satisfaction, rates of returning to the same sports (RTS) and RTS at preinjury level, and patient-reported outcomes. Evaluation of the Rowe score, Constant score, American Shoulder and Elbow Surgeons score, and VAS pain score were performed. Prognostic factors for recurrent instability, including demographic and clinical characteristics, as well as postoperative magnetic resonance imaging (MRI) appearance of the labrum were analyzed. Results A total of 191 patients met the selection criteria, with 150 (78.5%) available for the final follow-up. Recurrent instability occurred in 10.7% of patients, with a mean follow-up duration of 4.1 years. Younger age at surgery and more critical glenoid bone loss were significantly associated with recurrent instability (p = .038 and p = .011, respectively). The satisfaction rate regarding surgery was 90.0%. Rates of return to the same sports (RTS) and RTS at preinjury level were 82.0% and 49.3%, respectively. Clinical outcomes measured at the final follow-up were as follows: Rowe score − 92.8; Constant score − 98.0; ASES score − 98.3; VAS pain score − 0.2. Patients with recurrent instability had significantly inferior outcomes in terms of satisfaction rate, RTS at preinjury level rate, Rowe score, and Constant score (p = .000, p = .039, p = .000, and p = .015, respectively). A total of thirty-seven patients underwent MRI examination six months after surgery in our institution. The T2-weighted anterior labrum morphology was found to be poorer in patients with recurrent instability. No significant difference was observed between patients with or without recurrent instability in terms of anterior Slope, anterior labral glenoid height index (LGHI), inferior Slope, inferior LGHI, and T2-weighted inferior labrum morphology. Conclusion Arthroscopic Bankart repair can yield satisfactory medium-term outcomes for recreational athletes. Younger age at surgery, more critical glenoid bone loss, and poorer T2-weighted anterior labrum morphology assessed six months postoperatively were significantly associated with recurrent instability.

Abstract Background The current literature shows that dyslipidemia can lead to a higher incidence of rotator cuff tears (RCTs) and an increased retear rate after repair. We aimed to evaluate the influence of preoperative dyslipidemia on postoperative pain, patient-reported outcomes (PROs), active range of motion (ROM), and structural integrity. Methods A cohort of 111 patients who underwent arthroscopic RCT repair between January 2021 and July 2022, and whose complete preoperative serum lipid data were available within one week prior to surgery was retrospectively reviewed. Dyslipidemia was defined as the presence of an increase or decrease in at least one blood lipid profile (triglycerides, total cholesterol, low-density lipoprotein, high-density lipoprotein, or non-high-density lipoprotein). There were 43 patients in the dyslipidemia group and 68 in the ortholiposis group. Patient evaluations, including pain score, PROs, and ROMs, were conducted preoperatively; at 3 and 6 months postoperatively; and at the last follow-up. Structural integrity was assessed by magnetic resonance imaging (MRI) 6 months after surgery if possible, and Sugaya type 4 or 5 was considered a retear. Propensity score matching (PSM) was used to reduce bias. Results The RCT size, surgical technique, preoperative pain status, PROs, and active ROM were comparable between patients with dyslipidemia and those with ortholiposis. Three months after surgery, patients in the dyslipidemia group had worse average PROs (Constant score: P = 0.001; ASES score: P = 0.012; UCLA score: P = 0.015), forward flexion (P = 0.012), and internal rotation (P = 0.001) than patients in the ortholiposis group did. The difference between the two groups persisted after PSM but disappeared at the sixth month after surgery. No significant differences in pain score, PROs, or active ROMs were detected between the dyslipidemia and ortholiposis groups after a mean follow-up of 24 months. Of the 72 patients who underwent MRI, 4 retears (5.6%) were found, and all were in the ortholiposis group. There was no difference in the rate of retears between the two groups (P = 0.291) or with (P = 0.495) PSM. Conclusions In conclusion, we found that perioperative dyslipidemia may impact initial recovery within the first 3 months following arthroscopic rotator cuff repair but may have no effect on pain, PROs, or active ROMs at a mean 2-year follow-up or rotator cuff integrity at 6 months postoperatively. Trail registration Retrospectively registered.

Abstract Background The weight-adjusted-waist index (WWI) is a novel obesity index, and gallstones are associated with obesity. This study aimed to investigate the possible relationship between WWI and gallstones. Methods The datasets from the National Health and Nutrition Examination Survey (NHANES) 2017–2020 were used in a cross-sectional investigation. Multivariate linear regression models were used to examine the linear connection between WWI and gallstones incidence. Fitted smoothing curves and threshold effect analysis were used to describe the nonlinear relationship. Results The study comprised 8004 participants over the age of 20, including 833 reported with gallstones. Participants in the higher WWI tertile tended to have a higher gallstones prevalence. In the final adjusted model, a positive association between WWI and gallstones prevalence was observed (OR = 1.34, 95% CI: 1.20‒1.49). Participants in the highest WWI tertile had a significantly 71% higher risk of gallstones than those in the lowest WWI tertile (OR = 1.71, 95% CI: 1.35‒2.17). A nonlinear correlation was found between the WWI and gallstones prevalence, with an inflection point of 12.7. Conclusions Our study found that higher WWI levels connected with increased prevalence of gallstones. However, more prospective studies are needed to validate our findings.

Abstract Background Surgical treatment of finger nerve injury is common for hand trauma. However, there are various surgical options with different functional outcomes. The aims of this study are to compare the outcomes of various finger nerve surgeries and to identify factors associated with the postsurgical outcomes via a systematic review and meta-analysis. Methods The literature related to digital nerve repairs were retrieved comprehensively by searching the online databases of PubMed from January 1, 1965, to August 31, 2021. Data extraction, assessment of bias risk and the quality evaluation were then performed. Meta-analysis was performed using the postoperative static 2-point discrimination (S2PD) value, moving 2-point discrimination (M2PD) value, and Semmes–Weinstein monofilament testing (SWMF) good rate, modified Highet classification of nerve recovery good rate. Statistical analysis was performed using the R (V.3.6.3) software. The random effects model was used for the analysis. A systematic review was also performed on the other influencing factors especially the type of injury and postoperative complications of digital nerve repair. Results Sixty-six studies with 2446 cases were included in this study. The polyglycolic acid conduit group has the best S2PD value (6.71 mm), while the neurorrhaphy group has the best M2PD value (4.91 mm). End-to-side coaptation has the highest modified Highet’s scoring (98%), and autologous nerve graft has the highest SWMF (91%). Age, the size of the gap, and the type of injury were factors that may affect recovery. The type of injury has an impact on the postoperative outcome of neurorrhaphy. Complications reported in the studies were mainly neuroma, cold sensitivity, paresthesia, postoperative infection, and pain. Conclusion Our study demonstrated that the results of surgical treatment of digital nerve injury are generally satisfactory; however, no nerve repair method has absolute advantages. When choosing a surgical approach to repair finger nerve injury, we must comprehensively consider various factors, especially the gap size of the nerve defect, and postoperative complications. Type of study/level of evidence Therapeutic IV.

Abstract Background One-stage treatment involving rotator cuff repair and shoulder capsule release is mainly used to treat patients with rotator cuff tears (RCTs) and concomitant shoulder stiffness. Despite the increasing attention to the efficacy and safety of one-stage treatment, controversy still remains. Therefore, this systematic review aims to summarize the indications, operation procedure and rehabilitation protocol, and compare the range of motions (ROMs), functional outcomes and retear rates of one-stage treatment for RCTs in stiff shoulders and non-stiff shoulders. Methods Multiple databases (PubMed, the Cochrane Library, Embase and MEDLINE) were searched for studies that investigated outcomes after one-stage treatment for RCTs concomitant with shoulder stiffness compared with rotator cuff repair for RCTs alone, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. Descriptive statistics, including range of motion, patient-reported outcome and retear rate, are presented without meta-analysis due to the heterogeneity and low levels of evidence. Results A total of 9 cohort studies were included, with 305 patients treated with one-stage treatment involving rotator cuff repair and simultaneous shoulder capsular release and 1059 patients treated with rotator cuff repair alone. Patients in both groups had significant symptom improvement and functional recovery after the one-stage treatment for the stiffness group and standard repair for the non-stiffness group, and most patients could return to normal life and work within 6 months after the operation. The retear rate in the one-stage treatment group was not higher than that in the rotator cuff repair group. No statistically significant differences between the two groups were observed in terms of range of motion and patient-reported outcomes in the vast majority of studies at the final follow-up, including the visual analog scale for pain, the Constant score, the American Shoulder and Elbow Surgeons score, the University of California Los Angeles Shoulder Score, the Oxford shoulder score and the Simple Shoulder Test. Conclusion One-stage treatment for RCTs in stiff shoulders provides comparable ROM and patient-reported clinical outcomes as rotator cuff repair for non-stiff RCTs. In addition, the rate of postoperative retear in stiff shoulder treated with one-stage treatment was not higher than in non-stiff shoulders.

Abstract Background Knee arthroscopic arthrolysis serves as an effective treatment for knee arthrofibrosis. However, hemarthrosis is the most common complication in arthroscopic surgery, which has potential adverse effects on postoperative rehabilitation. The purpose of this study was to evaluate the effects of topical tranexamic acid (TXA) in knee arthroscopic arthrolysis. Methods A total of 87 patients with knee arthrofibrosis who underwent arthroscopic arthrolysis from September 2019 to June 2021 were eligible for this retrospective review. Patients in the TXA group (n = 47) received topical administration of TXA (50 mL, 10 mg/mL) at the end of the surgery, and patients in the control group (n = 40) received no TXA. The postoperative drainage volumes, hematologic levels, inflammatory marker levels, knee range of motion (ROM), visual analog scale (VAS) pain scores, Lysholm knee scores and complications were compared between the two groups. The curative effect of each group was calculated according to Judet’s criteria. Results The mean drainage volumes on postoperative day (POD) 1 and POD 2, and total drainage volume were significantly lower in the TXA group than in the control group (P

Abstract Purpose To summarize the incidence, risk factors, diagnosis methods, prophylaxis methods, and treatment of venous thromboembolism (VTE) following arthroscopic shoulder surgery. Methods Literature on VTE after arthroscopic shoulder surgeries was summarized, and all primary full-text articles reporting at least 1 case of deep vein thrombosis (DVT) or pulmonary embolism (PE) after arthroscopic shoulder surgeries were included. Articles were critically appraised and systematically analyzed to determine the incidence, risk factors, diagnosis, prophylaxis, and management of VTE following arthroscopic shoulder surgeries. Results This study included 42 articles in which the incidence of VTE ranges from 0 to 5.71% and the overall incidence was 0.26%. Most VTE events took place between the operation day and the 14th day after the operation (35/51). Possible risk factors included advanced age (> 70 years), obesity (BMI ≥ 30 kg/m2), diabetes mellitus, thrombophilia, history of VTE, prolonged operation time, hormone use, and immobilization after surgery. The most common prophylaxis method was mechanical prophylaxis (13/15). No statistical difference was detected when chemoprophylaxis was applied. The management included heparinization followed by oral warfarin, warfarin alone and rivaroxaban, a direct oral anticoagulant. Conclusion Based on the included studies, the incidence rate of VTE after arthroscopic shoulder surgeries is relatively low. The risk factors for VTE are still unclear. CT/CTA and ultrasound were the mainstream diagnosis methods for PE and DVT, respectively. Current evidence shows that chemical prophylaxis did not deliver significant benefits, since none of the existing studies reported statistically different results. High-quality studies focusing on the prophylaxis and management of VTE population undergoing arthroscopic shoulder surgeries should be done in the future.

Abstract Background Chimeric antigen receptor (CAR) T cells and immune checkpoint blockades (ICBs) have made remarkable breakthroughs in cancer treatment, but the efficacy is still limited for solid tumors due to tumor antigen heterogeneity and the tumor immune microenvironment. The restrained treatment efficacy prompted us to seek new potential therapeutic methods. Methods In this study, we conducted a small molecule compound library screen in a human BC cell line to identify whether certain drugs contribute to CAR T cell killing. Signaling pathways of tumor cells and T cells affected by the screened drugs were predicted via RNA sequencing. Among them, the antitumor activities of JK184 in combination with CAR T cells or ICBs were evaluated in vitro and in vivo. Results We selected three small molecule drugs from a compound library, among which JK184 directly induces tumor cell apoptosis by inhibiting the Hedgehog signaling pathway, modulates B7-H3 CAR T cells to an effector memory phenotype, and promotes B7-H3 CAR T cells cytokine secretion in vitro. In addition, our data suggested that JK184 exerts antitumor activities and strongly synergizes with B7-H3 CAR T cells or ICBs in vivo. Mechanistically, JK184 enhances B7-H3 CAR T cells infiltrating in xenograft mouse models. Moreover, JK184 combined with ICB markedly reshaped the tumor immune microenvironment by increasing effector T cells infiltration and inflammation cytokine secretion, inhibiting the recruitment of MDSCs and the transition of M2-type macrophages in an immunocompetent mouse model. Conclusion These data show that JK184 may be a potential adjutant in combination with CAR T cells or ICB therapy.

Abstract Background Shoulder pigmented villonodular synovitis (PVNS) is a severe clinical condition, while few studies have focused on this situation due to its rarity. This study was to investigate the efficacy of arthroscopic treatment of patients diagnosed with shoulder PVNS. Methods From Jan 1st, 2010 to Dec. 31st, 2019, 6 patients (5 females and 1 male) diagnosed with shoulder PVNS underwent arthroscopic synovectomy in our hospital and combined rotator cuff repair was performed in 3 of them. The outcomes of this study include Constant score, Visual Analogue Scale (VAS), University of California, Los Angeles (UCLA) score and American Shoulder and Elbow Surgeons (ASES) score. The data were retrieved from the patients’ medical records. Results With a mean follow-up of 52.0 months (range, 28–92 months), the mean difference of Constant, VAS, UCLA and ASES scores were 27.83 ± 21.60, 2.83 ± 2.56, 11.67 ± 10.93 and 17.83 ± 25.35, respectively. Statistically significant improvements were detected in all the patient-reported outcomes except ASES score. One of the patients suffered from recurrence. Two patients suffered from mild complications after the surgeries while both of them achieved satisfactory recovery finally. Conclusion Arthroscopic synovectomy in the setting of shoulder PVNS can improve patients’ function. A concurrent rotator cuff repair is recommended if it is needed. The conclusion still needs testifying by further high-quality research with larger sample size.

Abstract Background Prostaglandin analogs (PGAs) are the first-line treatment for primary open-angle glaucoma (POAG) and ocular hypertension (OH). This study aimed to confirm the effectiveness and safety of Tapros® (0.0015% tafluprost eye drops) in Chinese patients with POAG and OH. Methods This phase IV, multicenter, non-comparative, prospective study enrolled patients with POAG and OH in China between 12/27/2017 and 04/15/2020. Patients who were treatment-naïve or untreated within one month (group A) or with unreached intraocular pressure (IOP) target after previous monotherapy of other PGAs (group B) or non-PGA IOP-lowering drugs (group C) were treated with 0.0015% tafluprost for three months. The IOP reduction, response rate, and safety were observed. Results There were 165, 89, and 31 patients in groups A, B, and C, with baseline IOPs of 22.4 ± 4.7, 21.0 ± 3.5, and 22.5 ± 3.2 mmHg, respectively. The least-square means and percentages of IOP reduction at 3 months for groups A, B, and C were 4.7 (19.8%), 1.6 (6.1%), and 4.6 mmHg (20.3%), respectively. A significant reduction in IOP was observed at each visit compared with baseline (all P

Abstract Background This study compared the incidence of postoperative venous thromboembolism (VTE) between meniscectomy and anterior cruciate ligament reconstruction (ACLR) under arthroscopy and assessed whether ACLR increases the VTE risk compared with meniscectomy. Methods A retrospective study of prospectively collected clinical data, including data on 436 patients ranging in age from 18 to 60 years who underwent ACLR or meniscectomy surgery, was performed between October 2018 and October 2019 in our hospital. All patients underwent routine VTE screening by venous ultrasonography in postoperative week 2 and then clinical follow-up at 4 and 6 weeks post-surgery. The incidence of VTE was calculated, and clinical factors such as age, sex, body mass index (BMI), smoking, concomitant procedure, Caprini score, and duration of tourniquet use were evaluated in relation to the risk factors for VTE. Results A total of 320 patients who underwent arthroscopic ACLR or meniscectomy were available for analysis. Of these patients, 130 (40.6%) underwent ACLR, and 190 (59.4%) underwent meniscectomy. No cases of pulmonary embolism (PE) or femoral deep vein thrombosis (DVT) were reported in either group. Fourteen patients (10.8%) developed VTE in the ACLR group compared with 10 (5.3%) in the meniscectomy group, with no significant difference (p = 0.066). Among these patients, 4 (3.1%) patients in the ACL reconstruction group and 2 (1.1%) patients in the meniscectomy group had DVT confirmed by Doppler ultrasound (p > 0.05). ACLR, age, and BMI (OR = 3.129; 1.061; 1.435) tended to increase the risk of VTE, but the results were not statistically significant (p = 0.056, 0.059, 0.054). Conclusions The incidence of VTE after ACLR and meniscectomy within 6 weeks post-surgery was 10.8 and 5.3%, respectively. ACLR, age, and BMI had a tendency to increase the risk of VTE.

Abstract Background Glenohumeral dislocation combined with fracture of the proximal humerus is extremely rare in children, and this study aims to investigate its incidence in the pediatric population and review the treatment strategy for this condition. Methods Between Jan 2014 and Jan 2019, 280 patients with unilateral proximal humeral fractures were retrospectively reviewed. Imaging and follow-up notes were reviewed for patients with a predilection for glenohumeral joint dislocation. Six (2.14%) patients between the ages of 5 and 10 years were confirmed as glenohumeral joint dislocation and included in the study. All these patients underwent closed reduction and external fixation under general anesthesia. Results Out of 280 patients with proximal humeral fractures, only 6 patients, including 4 males and 2 females, were confirmed as glenohumeral joint dislocation. ROM was normal compared with the contralateral shoulder in every patient at the last follow-up. There was no case of radiological abnormality, including avascular necrosis or devascularization of the humeral head. Conclusions Glenohumeral dislocation is a rare entity associated with the proximal humerus fracture in children, with an overall incidence in our case series was 2.14%. Reduction and stabilization of such injury using an external fixator is a suitable choice for pediatric patients that failed closed reduction.

Abstract Background Craniopharyngioma (CP) is rare histologically benign but clinically challenging tumor because of its intimate relationship with the critical structure in the central brain. CP can be divided into two major histologic subtypes: adamantinomatous-type CP (ACP) and papillary-type CP (PCP). Although some genetic aberrations for both categories have been revealed in previous studies, the complete spectrum of genetic changes of this tumor remains unknown. Methods In this study, we conducted whole genome sequencing (WGS) on twenty-six CPs including 16 ACPs and 10 PCPs together with their matched blood samples. Somatic variants (SNVs, InDels, SVs and CNVs) were identified and mutational signatures were characterized for each patient. We investigated the impact of a novel CTNNB1 mutant on its protein stability, ubiquitination and Wnt pathway activity. Cell proliferation ability of the CTNNB1 mutant in ACP primary cells was additionally analyzed by CCK8 and colony formation assays. Results We found that CPs had showed less complexity with fewer somatic mutations compared with malignant tumors. Moreover, mutations in CTNNB1 (68.75% of ACP) and BRAF V600E (70.00% of PCP) are mutually exclusive in ACP and PCP, consolidating that the driving roles of these two genes in ACP and PCP, respectively. A novel mutation in the exon 3 of CTNNB1 which compromised both a transversion and in-frame deletion was identified in ACP. This mutation was experimentally validated to confer β-catenin increased stability by inhibiting its ubiquitination, thus activating Wnt-signaling pathway and promoting cell proliferation. Conclusions Whole genome landscape for CP was revealed by WGS analysis, and a novel mutation in the exon 3 of CTNNB1 was identified. This novel mutation activates Wnt-signaling pathway through increasing the stability of β-catenin. Our findings provided us with more comprehensive insight into the spectrum of genetic alterations in CP.

Abstract Background The poor regenerative capability and structural complexity make the reconstruction of meniscus particularly challenging in clinic. 3D printing of polymer scaffolds holds the promise of precisely constructing complex tissue architecture, however the resultant scaffolds usually lack of sufficient bioactivity to effectively generate new tissue. Results Herein, 3D printing-based strategy via the cryo-printing technology was employed to fabricate customized polyurethane (PU) porous scaffolds that mimic native meniscus. In order to enhance scaffold bioactivity for human mesenchymal stem cells (hMSCs) culture, scaffold surface modification through the physical absorption of collagen I and fibronectin (FN) were investigated by cell live/dead staining and cell viability assays. The results indicated that coating with fibronectin outperformed coating with collagen I in promoting multiple-aspect stem cell functions, and fibronectin favors long-term culture required for chondrogenesis on scaffolds. In situ chondrogenic differentiation of hMSCs resulted in a time-dependent upregulation of SOX9 and extracellular matrix (ECM) assessed by qRT-PCR analysis, and enhanced deposition of collagen II and aggrecan confirmed by immunostaining and western blot analysis. Gene expression data also revealed 3D porous scaffolds coupled with surface functionalization greatly facilitated chondrogenesis of hMSCs. In addition, the subcutaneous implantation of 3D porous PU scaffolds on SD rats did not induce local inflammation and integrated well with surrounding tissues, suggesting good in vivo biocompatibility. Conclusions Overall, this study presents an approach to fabricate biocompatible meniscus constructs that not only recapitulate the architecture and mechanical property of native meniscus, but also have desired bioactivity for hMSCs culture and cartilage regeneration. The generated 3D meniscus-mimicking scaffolds incorporated with hMSCs offer great promise in tissue engineering strategies for meniscus regeneration. Graphical Abstract

Abstract Background There is still a lack of clinical data in arthroscopic treatment for treating multiple ligament injuries. This study aims to evaluate the clinical outcomes of patients with multiple ligament injuries undergoing treatment based on the classification stage and type of injury. Methods A prospective, clinical trial on multiple ligament injuries was planned, which included 95 patients (58 men and 37 women; age: 42.8 ± 11.9 [range, 18–63] years) from October 2017 to June 2018. Injuries were classified into three stages (emergency stage 3 weeks) and six types (KD I–VI) based on injuries time and structures, which indicated appropriate treatments. The clinical outcomes were evaluated at 2, 4, 6, 8, and 12 weeks and at 6, 9, 12 months and 24 months after surgery. The final choices in efficacy index included International Knee Documentation Committee (IKDC) score, Lysholm score, visual analog scale (VAS) score, and range of motion. Results During the follow-up, all patients exhibited statistically significant functional improvement in the injured limb compared with their preoperative situation. The mean postoperative scores of acute stage patients at 2-year follow-up were IKDC subjective score, 77.54 ± 11.53; Lysholm score, 85.96 ± 9.39; Tegner score, 4.13 ± 1.08; and VAS score, 1.21 ± 0.76. The mean postoperative scores of chronic stage patents at 2-year follow-up were IKDC subjective score, 74.61 ± 12.38; Lysholm score, 81.71 ± 10.80; Tegner score, 3.96 ± 1.14; and VAS score, 1.71 ± 0.60. The IKDC subjective score, Lysholm score, and Tegner score were significantly improved (P

Abstract Objective This study aimed to explore the epidemiological and microbiological characteristics of fracture-related infection (FRI), analyze the drug resistance characteristics of major pathogens, and provide timely and relatively complete clinical and microbiological data for antimicrobial treatment of FRI. Methods The clinical and microbiological data of patients with FRI from January 1, 2011, to December 31, 2020, were collected from three tertiary hospitals in Northeast China. The automatic microbial analysis system was used for strain identification and drug susceptibility testing, and the drug susceptibility results were determined in accordance with the latest Clinical and Laboratory Standards Institute (CLSI) criteria (as applicable each year). Results A total of 744 patients with FRI were enrolled. The incidence of FRI was about 1.5%, and 81.7% were male patients, with an average age of 48.98 ± 16.01 years. Open fractures accounted for 64.8%. Motor crush (32.8%) and falling (29.8%) were the main causes of injuries. The common sites of infection were the tibia and fibula (47.6%), femur (11.8%), foot (11.8%), and hand (11.6%). A total of 566 pathogenic bacteria were cultured in 378 patients with positive bacterial cultures, of which 53.0% were Gram-positive bacteria and 47.0% were Gram-negative bacteria. The most common pathogen at all sites of infection is Staphylococcus aureus. Staphylococcus aureus had a high resistance rate to penicillin (PEN), erythromycin (ERY), and clindamycin (CLI), exceeding 50%. Methicillin-resistant Staphylococcus aureus (MRSA) was more than 80% resistant to CLI and ERY. Conclusions The incidence of FRI in Northeast China was at a low level among major medical centers nationwide. Staphylococcus aureus was still the main pathogen causing bone infections, and the proportion of MRSA was lower than reported abroad, but we have observed an increase in the proportion of infections. Enterobacteriaceae have a higher resistance rate to third-generation cephalosporins and quinolones. For Enterobacteriaceae, other sensitive treatment drugs should be selected clinically.

Abstract Introduction External fixator (EF) is a popular choice for open tibial fractures, but pin tract infection (PTI) and refracture are common complications. Elastic stable intramedullary nail (ESIN) has been reported in the treatment for open tibial fractures. This study aims to compare the clinical outcomes of EF vs. ESIN in the treatment for open tibial shaft fracture in children retrospectively. Methods Patients aged 5–11 years with Gustilo-Anderson II and IIIA tibial shaft fracture treated at our institute from January 2008 to January 2018 were reviewed retrospectively and categorized into EF and ESIN groups. Patients with pathological fracture, neuromuscular disorder, metabolic disease, previous tibial fracture or instrumentation, and polytrauma were excluded. Patients with follow-up

Abstract Background Tumor mutation burden (TMB) is an emerging prognostic biomarker of immunotherapy for bladder cancer (BLCA). We aim at investigating radiomic features’ value in predicting the TMB status of BLCA patients. Methods Totally, 75 patients with BLCA were enrolled. Radiomic features extracted from the volume of interest of preoperative pelvic contrast-enhanced computed tomography (CECT) were obtained for each case. Unsupervised hierarchical clustering analysis was performed based on radiomic features. Sequential univariate Logistic regression, the least absolute shrinkage and selection operator (LASSO) regression and the backward stepwise regression were used to develop a TMB-predicting model using radiomic features. Results The unsupervised clustering analysis divided the total cohort into two groups, i.e., group A (32.0%) and B (68.0%). Patients in group A had a significantly larger proportion of having high TMB against those in group B (66.7% vs. 41.2%, p = 0.039), indicating the intrinsic ability of radiomic features in TMB-predicting. In univariate analysis, 27 radiomic features could predict TMB. Based on six radiomic features selected by logistic and LASSO regression, a TMB-predicting model was built and visualized by nomogram. The area under the ROC curve of the model reached 0.853. Besides, the calibration curve and the decision curve also revealed the good performance of the model. Conclusions Our work firstly proved the feasibility of using radiomics to predict TMB for patients with BLCA. The predictive model based on radiomic features from pelvic CECT has a promising ability to predict TMB. Future study with a larger cohort is needed to verify our findings.

Abstract Background Congenital pseudoarthrosis of the clavicle (CPC) is an uncommon entity. Owing to its scarce presentation, treatment of this disorder has not been well established. This study aimed (1) to compare surgical treatment methods that included excision of pseudoarthrosis and iliac crest bone graft and fixate with either the elastic stable intramedullary nail (ESIN) or K-wires or plate and screws, and (2) to assess the clinical outcomes of two different surgical methods. Methods A multi-central retrospective study was performed between 2013 and 2017 in four tertiary teaching hospitals. Fifteen clavicles of 11 children were identified as CPC. All patients underwent pseudarthrosis resection and iliac crest bone autograft. They were divided into two groups as per the surgical treatment they underwent—plate stabilization as group A and elastic stable intramedullary nailing (ESIN) or K-wires as group B. Nine clavicles in 6 patients in group A and 6 clavicles in 5 patients in group B, were included. The Quick Disabilities of the Arm and Shoulder (QuickDASH) score was used to assess patients’ satisfaction and function following treatment at each follow-up. Results There were eight boys and three girls, with an average age of 4.7 years. All patients, except one with intellectual impairments, had radiological healing. Implant removal time was significantly shorter in group B compared to group A. No statistically significant differences existed in terms of age at surgery, time of radiological healing, complication, and clinical outcome between different groups. Conclusion Surgical resection of pseudoarthrosis with an iliac crest bone graft was an effective means of surgical treatment in CPC. However, ESIN or K-wires can achieve shorter union time compared to the plate. Hence, surgical treatment is recommended for congenital pseudarthrosis of clavicular in pediatric patients. Level of evidence Retrospective comparative study; Level III

Abstract Background COVID-19 has resulted in high mortality worldwide. Information regarding cardiac markers for precise risk-stratification is limited. We aim to discover sensitive and reliable early-warning biomarkers for optimizing management and improving the prognosis of COVID-19 patients. Methods A total of 2954 consecutive COVID-19 patients who were receiving treatment from the Wuhan Huoshenshan Hospital in China from February 4 to April 10 were included in this retrospective cohort. Serum levels of cardiac markers were collected after admission. Coronary artery disease diagnosis and survival status were recorded. Single-cell RNA-sequencing and bulk RNA-sequencing from different cohorts of non-COVID-19 were performed to analyze SARS-CoV-2 receptor expression. Results Among 2954 COVID-19 patients in the analysis, the median age was 60 years (50–68 years), 1461 (49.5%) were female, and 1515 (51.3%) were severe/critical. Compared to mild/moderate (1439, 48.7%) patients, severe/critical patients showed significantly higher levels of cardiac markers within the first week after admission. In severe/critical COVID-19 patients, those with abnormal serum levels of BNP (42 [24.6%] vs 7 [1.1%]), hs-TNI (38 [48.1%] vs 6 [1.0%]), α- HBDH (55 [10.4%] vs 2 [0.2%]), CK-MB (45 [36.3%] vs 12 [0.9%]), and LDH (56 [12.5%] vs 1 [0.1%]) had a significantly higher mortality rate compared to patients with normal levels. The same trend was observed in the ICU admission rate. Severe/critical COVID-19 patients with pre-existing coronary artery disease (165/1,155 [10.9%]) had more cases of BNP (52 [46.5%] vs 119 [16.5%]), hs-TNI (24 [26.7%] vs 9.6 [%], α- HBDH (86 [55.5%] vs 443 [34.4%]), CK-MB (27 [17.4%] vs 97 [7.5%]), and LDH (65 [41.9%] vs 382 [29.7%]), when compared with those without coronary artery disease. There was enhanced SARS-CoV-2 receptor expression in coronary artery disease compared with healthy controls. From regression analysis, patients with five elevated cardiac markers were at a higher risk of death (hazards ratio 3.4 [95% CI 2.4–4.8]). Conclusions COVID-19 patients with pre-existing coronary artery disease represented a higher abnormal percentage of cardiac markers, accompanied by high mortality and ICU admission rate. BNP together with hs-TNI, α- HBDH, CK-MB and LDH act as a prognostic biomarker in COVID-19 patients with or without pre-existing coronary artery disease.

Abstract Background Cardiac myxomas (CMs) and thrombi are associated with high morbidity and mortality. These two conditions need totally different treatments. However, they are difficult to distinguish using naked eye. In clinical, misdiagnoses occur now and then. This study aimed to compare the characteristics of CMs and cardiac thrombi and investigate the value of a radiomics signature in distinguishing CMs from cardiac thrombi, based on cardiovascular contrast-enhanced computed tomography (CECT) images. Methods A total of 109 patients who had CMs (n = 59) and cardiac thrombi (n = 50) were enrolled in this retrospective study from 2009 to 2019. First, the lesion characteristics of cardiovascular CECT images were documented and compared by two radiologists. Then all patients were randomly allotted to either a primary group or a validation group according to a 7:3 ratio. Univariate analysis and the least absolute shrinkage and selection operator were used to select robust features. The best radiomics signature was constructed and validated using multivariate logistic regression. An independent clinical model was created for comparison. Results The best radiomics signature was developed using eight selected radiomics. The classification accuracies of the radiomics signature were 90.8% and 90.9%, and the area under the receiver operating characteristic curves were 0.969 and 0.926 in the training and testing cohorts, respectively. Cardiovascular CECT images showed that the two diseases had significant differences in location, surface, Hydrothorax, pericardial effusion and heart enlargement. The naked eye findings were used to create the clinical model. All metrics of the radiomics signature were higher than those of clinical model. Conclusions Compared with clinical model, the radiomics signature based on cardiovascular CECT performed better in differentiating CMs and thrombi, suggesting that it could help improving the diagnostic efficiency.

Abstract Background The ipsilateral olecranon with associated radial neck fractures does not include in the Bado classification of Monteggia fractures and equivalent lesions. The primary aims of this retrospective multicenter study were to characterize this type of injury and, noting its unique properties, evaluate the results of the treatment, determine the prognostic factors that influence the radiological and clinical outcome, and also give treatment strategies. Methods Between July 2011 and July 2016, forearm fracture patient charts were retrospectively reviewed from seven pediatric trauma centers. Patients diagnosed with ipsilateral olecranon with associated radial neck fractures and followed up for at least 24 months were included. Fracture characteristics, treatment, outcome, and complications were assessed. The clinical outcome of treatments was evaluated by the Mayo Elbow Performance Score (MEPS) and the Flynn criteria. Fisher’s exact test and ANOVA test were used; significance was defined as P < 0.05. Results One hundred thirty-seven consecutive patients (54 girls and 83 boys) from 8292 forearm fractures patients, the mean age of 7.5 years (1.5 to 14.8), with fractures of the ipsilateral olecranon with associated radial neck fractures were identified. One hundred twenty-five patients had radiologic and clinical follow-up. According to a simplified classification system with “operate” and “don’t operate” groups, including five subtypes proposed in this study, ipsilateral olecranon with associated radial neck fractures subtypes could be classified with significantly different characteristics and outcome in treatment and complications. Conclusions Fractures of the ipsilateral olecranon associated with the radial neck are not so rare as previously reported. Complications and poor outcomes were easy to encounter without knowing this type of fracture. Appropriate treatment strategies could be made according to a simple classification system based on the treatment result of follow-up. Level of evidence Retrospective comparative study; Level III

Abstract Background The optimal dosage and administration approach of tranexamic acid (TXA) in primary total knee arthroplasty (TKA) remains controversial. In light of recently published 14 randomized controlled trials (RCTs), the study aims to incorporate the newly found evidence and compare the efficacy and safety of intra-articular (IA) vs. intravenous (IV) application of TXA in primary TKA. Methods PubMed, Embase, Web of Science, and Cochrane Library were searched for RCTs comparing IA with IV TXA for primary TKA. Primary outcomes included total blood loss (TBL) and drain output. Secondary outcomes included hidden blood loss (HBL), hemoglobin (Hb) fall, blood transfusion rate, perioperative complications, length of hospital stay, and tourniquet time. Result In all, 34 RCTs involving 3867 patients were included in our meta-analysis. Significant advantages of IA were shown on TBL (MD = 33.38, 95% CI = 19.24 to 47.51, P < 0.001), drain output (MD = 28.44, 95% CI = 2.61 to 54.27, P = 0.03), and postoperative day (POD) 3+ Hb fall (MD = 0.24, 95% CI = 0.09 to 0.39, P = 0.001) compared with IV. There existed no significant difference on HBL, POD1 and POD2 Hb fall, blood transfusion rate, perioperative complications, length of hospital stay, and tourniquet time between IA and IV. Conclusion Intra-articular administration of TXA is superior to intravenous in primary TKA patients regarding the performance on TBL, drain output, and POD3+ Hb fall, without increased risk of perioperative complications. Therefore, intra-articular administration is the recommended approach in clinical practice for primary TKA.

Abstract Background The clinical outcome of open reduction and internal fixation (ORIF) for delayed lateral condylar fracture of the humerus (LCFH) varies in different studies, but ORIF for LCFH with an early-delayed presentation usually resulted in significant improvement of elbow function. Early delayed presentation is defined as a period of 3 to 12 weeks from the injury. This study aims to compare the clinical outcomes of biodegradable pin (BP) vs. Kirschner wire (KW) in the treatment of LCFH with an early delayed presentation. Methods LCFH with an early-delayed presentation treated with KW or BP were retrospectively reviewed in our hospital. The patients were divided into two groups KW (n = 17) and BP group (n = 26). Baseline information, including sex, age, operative side, duration from injury to surgery, and implant choice, was reviewed. Radiographs and medical records were collected from the Hospital Database. Results In all, 17 patients (male/female, 9/8) in KW and 26 patients (male/female,13/13) in the BP group were included. The age showed no statistically significant difference between the KW (52.3 ± 10.2, month) and the BP (56.1 ± 10.7, month), (P = 0.258). At the last follow-up, there existed no statistically significant difference between the two groups concerning Baumann’s angle (P = 0.272) and carrying angle (P = 0.911). The MEPS at the last follow-up was better in the KW group (91.1 ± 2.7) than the BP group (89.2 ± 3.0), (P = 0.048). There was no case of nonunion or malunion in both groups. The incidence of fishtail deformity was (8/17, 47.1%) in KW and (13/26, 50%) in the BP group. The incidence of lateral prominence was (5/17, 29.4%) in the KW and (7/26, 26.9%) in the BP group. Furthermore, the incidence of implant prominence was higher in KW (12/17, 70.6%) than BP (0) (P

Abstract Background Hypopharyngeal squamous cell carcinoma (HSCC) is a rare type of head and neck cancer with poor prognosis. However, till now, there is still no model predicting the survival outcomes for HSCC patients. We aim to develop a novel nomogram predicting the long-term cancer-specific survival (CSS) for patients with HSCC and establish a prognostic classification system. Methods Data of 2021 eligible HSCC patients were retrieved from the Surveillance, Epidemiology and End Results database between 2010 and 2015. We randomly split the whole cases (ratio: 7:3) into the training and the validation cohort. Cox regression as well as the Least absolute shrinkage and selection operator (LASSO) COX were used to select significant predictors of CSS. Based on the beta-value of these predictors, a novel nomogram was built. The concordance index (C-index), the calibration curve and the decision curve analysis (DCA) were utilized for the model validation and evaluation using the validation cohort. Results In total, cancer-specific death occurred in 974/2021 (48.2%) patients. LASSO COX indicated that age, race, T stage, N stage, M stage, surgery, radiotherapy and chemotherapy are significant prognosticators of CSS. A prognostic model based on these factors was constructed and visually presented as nomogram. The C-index of the model was 0.764, indicating great predictive accuracy. Additionally, DCA and calibration curves also demonstrated that the nomogram had good clinical effect and satisfactory consistency between the predictive CSS and actual observation. Furthermore, we developed a prognostic classification system that divides HSCC patients into three groups with different prognosis. The median CSS for HSCC patients in the favorable, intermediate and poor prognosis group was not reached, 39.0-Mo and 10.0-Mo, respectively (p

Abstract Background To demonstrate the correlation between guide pin-shaft angle (PSA) at the anteroposterior film and anteversion angle of guide pin at the lateral film and investigate whether excellent tip–apex distance (TAD) can be obtained by changing the entry point via axial rotation of the main intramedullary nail. Methods Fifty patients with intertrochanteric femoral fractures (IFFs) undergoing internal fixation with intramedullary nails under 2D fluoroscopy were retrospectively enrolled. Both of the PSA at the anteroposterior film and anteversion angle at the lateral film before and after adjustment of the guide pin were collected. Pearson correlation analysis was performed to investigate their correlation. Intraoperative and postoperative outcomes were recorded. Furthermore, the software of Mimics 10.0 and Pro/E were used to establish the 3D models of the proximal femur and main intramedullary nail/guide pin, respectively. Surgery was simulated on the Pro/E software platform and solid geometry analysis was conducted to calculate the correlation between the PSA and the anteversion angle. Results Pearson correlation analysis indicated there was a positive correlation between PSA and anteversion angle, with the correlation coefficient of 0.902 (p

Abstract Background Global resource reallocation is an established critical strategy through which organisms deal with environmental stress. The regulation of intracellular lipid storage or utilization is one of the most important strategies for maintaining energy homeostasis and optimizing growth. Oleaginous microorganisms respond to nitrogen deprivation by inducing lipid hyper accumulation; however, the associations between resource allocation and lipid accumulation are poorly understood. Results Here, the time-resolved metabolomics, lipidomics, and proteomics data were generated in response to nutrient availability to examine how metabolic alternations induced by nitrogen deprivation drive the triacylglycerols (TAG) accumulation in M. alpina. The subsequent accumulation of TAG under nitrogen deprivation was a consequence of the reallocation of carbon, nitrogen sources, and lipids, rather than an up-regulation of TAG biosynthesis genes. On one hand, nitrogen deprivation induced the down-regulation of isocitrate dehydrogenase level in TCA cycle and redirected glycolytic flux of carbon from amino acid biosynthesis into fatty acids’ synthesis; on the other hand, nitrogen deprivation induced the up-regulation of cell autophagy and ubiquitin-mediated protein proteolysis which resulted in a recycling of preformed protein nitrogen and carbon. Combining with the up-regulation of glutamate decarboxylase and succinic semialdehyde dehydrogenase in GABA shunt, and the phosphoenolpyruvate carboxykinase in the central hub involving pyruvate/phosphoenolpyruvate/oxaloacetate, the products from nitrogen-containing compounds degradation were recycled to be intermediates of TCA cycle and be shunted toward de novo biosynthesis of fatty acids. We found that nitrogen deprivation increased the protein level of phospholipase C/D that contributes to degradation of phosphatidylcholine and phosphatidylethanolamine, and supplied acyl chains for TAG biosynthesis pathway. In addition, ATP from substrate phosphorylation was presumed to be a critical factor regulation of the global resource allocation and fatty acids’ synthesis rate. Conclusions The present findings offer a panoramic view of resource allocation by M. alpina in response to nutrient stress and revealed a set of intriguing associations between resource reallocation and TAG accumulation. This system-level insight provides a rich resource with which to explore in-depth functional characterization and gain information about the strategic combination of strain development and process integration to achieve optimal lipid productivity under nutrient stress.

Abstract Background Most patients suffering from distal femoral unicameral bone cysts (UBCs) are adolescents that require an early return to normal activities, including school attendance and sports exercises. However, the optimal choice of implants for such patients remains controversial. This study evaluated the application of pediatric physeal slide-traction plate (PPSP) in the treatment of pathological distal femoral fracture caused by UBCs. Methods Between Jan 2014 and Jan 2016, 11 (male = 6, female = 5) patients were reviewed retrospectively. Age, sex, operative time, limb-length discrepancy (LLD), and valgus angulation were all recorded for every patient. Results The average age of 11 patients was 12.2 ± 1.1 years. The operating time was 94.8 ± 7.8 min. The postoperative hospital stay was 5 to 7 days. The epiphyseal morphology in the operative leg was nearly normal. The plate was removed in an average of 19.5 ± 3.1 months. The knee range of motion (ROM) was normal in 9 patients, whereas 2 female patients reported a loss of less than 10 degrees of ROM as compared to the contralateral knee joint. Breakage of plates or refracture did not occur in our cases. All patients had a follow-up of at least 24 months. At the latest follow-up visit, all patients walked without a limp. None of the patients manifested obvious LLD and valgus deformity. Conclusion PPSP combined with curettage and bone grafting allows early mobilization and produces satisfactory outcomes for pathological fracture of distal femur secondary to UBCs in adolescents.

Abstract Background Conservative treatment remains the preferred choice for distal radius fracture in children. However, loss of reduction is problematic, especially in an older child. Crossed Kirschner-wires is widely used to treat distal radius fracture in adolescents. This study aimed to compare the application of crossed Kirschner-wiring (KW) and non-bridging external fixator (EF) for the treatment of delayed distal radial fracture involving metaphyseal diaphyseal junction (MDJ) in adolescents. Methods Between January 2012 to January 2017, 146 (male = 101, female = 45) patients in EF group and 117 (male = 76, female = 41) in KW group, were reviewed retrospectively. Preoperative data were collected from the hospital database, and postoperative clinical outcomes data were collected during the follow-up visits. We used SPSS for data analysis. Results There existed no significant difference between EF and KW regarding sex, body weight, fracture side, duration from injury to surgery. The duration of surgery was significantly shorter in EF (30.5 ± 6.1 min) than the KW group (44.6 ± 9.4 min), P