Microenvironment-responsive smart hydrogels with antibacterial activity and immune regulation for accelerating chronic wound healing.

Current therapeutic strategies for chronic refractory wounds remain challenge owing to their unfavorable wound microenvironment and poor skin regeneration ability. Thus far, a regimen for effective chronic refractory wounds management involves bacterial elimination, alleviation of oxidative stress, inhibition of inflammatory response, and promotion of angiogenesis. In this work, an injectable glycopeptide hydrogel based on phenylboronic acid-grafted ϵ-polylysine (EPBA) and poly (vinyl alcohol) (PVA) with pH/reactive oxygen species (ROS) dual-responsive properties was prepared, which exerted intrinsic antibacterial and antioxidant properties. ROS-responsive micelles (MIC) loaded with herb-derived Astragaloside IV (AST) are introduced into the hydrogel before gelation. Attributed to the acidic condition and oxidative stress microenvironment of wound bed, the hydrogel gradually disintegrates, and the released EPBA could help to eliminate bacterial. Meanwhile, the subsequential release of AST could help to achieve anti-oxidation, anti-inflammatory, proangiogenic effects, and regulation of macrophage polarization to accelerate chronic wound healing. In addition, the wound repair mechanism of composite hydrogel accelerating skin regeneration was assessed by RNA-sequencing, exploring a range of potential targets and pathway for further study. Collectively, this multifunctional hydrogel dressing, matching different healing stages of tissue remodeling, holds a great potential for the treatment of chronic refractory wounds.

Multifunctional Hydrogel Enhances Inflammatory Control, Antimicrobial Activity, and Oxygenation to Promote Healing in Infectious Wounds.

Chronic infected wounds often fail to heal through normal repair mechanisms, and the persistent response of reactive oxygen species (ROS) and inflammation is a major contributing factor to the difficulty in their healing. In this context, we developed an ROS-responsive injectable hydrogel. This hydrogel is composed of ε-polylysine grafted (EPL) with caffeic acid (CA) and hyaluronic acid (HA) grafted with phenylboronic acid (PBA). Before the gelation process, a mixture CaO2@Cur-PDA (CCP) consisting of calcium peroxide (CaO2) coated with polydopamine (PDA) and curcumin (Cur) is embedded into the hydrogel. Under the conditions of chronic refractory wound environments, the hydrogel gradually dissociates. HA mimics the function of the extracellular matrix, while the released caffeic acid-grafted ε-polylysine (CE) effectively eliminates bacteria in the wound vicinity. Additionally, released CA also clears ROS and influences macrophage polarization. Subsequently, CCP further decomposes, releasing Cur, which promotes angiogenesis. This multifunctional hydrogel accelerates the repair of diabetic skin wounds infected with Staphylococcus aureus in vivo and holds promise as a candidate dressing for the healing of chronic refractory wounds.

Highly Bioadaptable Hybrid Conduits with Spatially Bidirectional Structure for Precision Nerve Fiber Regeneration via Gene Therapy.

Peripheral nerve deficits give rise to motor and sensory impairments within the limb. The clinical restoration of extensive segmental nerve defects through autologous nerve transplantation often encounters challenges such as axonal mismatch and suboptimal functional recovery. These issues may stem from the limited regenerative capacity of proximal axons and the subsequent Wallerian degeneration of distal axons. To achieve the integration of sensory and motor functions, a spatially differential plasmid DNA (pDNA) dual-delivery nanohydrogel conduit scaffold is devised. This innovative scaffold facilitates the localized administration of the transforming growth factor ß (TGF-ß) gene in the proximal region to accelerate nerve regeneration, while simultaneously delivering nicotinamide mononucleotide adenylyltransferase 2 (NMNAT2) to the distal region to mitigate Wallerian degeneration. By promoting autonomous and selective alignment of nerve fiber gap sutures via structure design, the approach aims to achieve a harmonious unification of nerve regeneration, neuromotor function, and sensory recovery. It is anticipated that this groundbreaking technology will establish a robust platform for gene delivery in tissue engineering.

Molecular evidence for potential transovarial transmission of Dabieshan tick virus in Haemaphysalis longicornis from Shandong Province, China.

Dabieshan tick virus (DBTV) is a newly identified arbovirus, first detected in Haemaphysalis longicornis collected from Hubei Province in 2015. It has been confirmed that DBTV is widely distributed in Shandong Province, China. However, its entomological and epidemiological features remain to be further explored, particularly the feasibility of transovarial transmission. Our research tries to explain the possibility of transovarial transmission of DBTV from engorged female ticks to their offspring. All engorged female adult ticks were sampled from domestic sheep and allowed to lay eggs and hatch in appropriate laboratory conditions. All engorged ticks, larvae and unhatched eggs were classified into pools for nucleic acid extraction and DBTV RNA detection. According to the results of qRT-PCR, the positive rate of DBTV was 6.25% (8/128) in engorged female ticks, 3.57% (1/28) in eggs and 5% (3/60) in larvae pools, respectively. Phylogenetic analysis indicated that DBTV isolates from larvae were similar to those from maternal ticks with more than 99.5% homology, and DBTV was relatively conservative in evolution. Our findings are the first to provide molecular evidence of potential transovarial transmission of DBTV among H. longicornis. Nonetheless, the transovarial transmission of DBTV in frequency and proportion occurring in nature deserves further investigation.

Highly Biocompatible Polyester-Based Piezoelectric Elastomer with Antitumor and Antibacterial Activity for Ultrasound-Enhanced Piezoelectric Therapy.

Currently, the use of piezoelectric materials to provide sustainable and noninvasive bioelectric stimulation to eradicate tumor cells and accelerate wound healing has raised wide attention. The development of a multifunctional piezoelectric elastomer with the ability to perform in situ tumor therapy as well as wound repair is of paramount importance. However, current piezoelectric materials have a large elastic modulus and limited stretchability, making it difficult to match with the dynamic curvature changes of the wound. Therefore, by copolymerizing lactic acid, butanediol, sebacic acid, and itaconic acid to develop a piezoelectric elastomer (PLBSIE), we construct a new ultrasound-activated PLBSIE-based tumor/wound unified therapeutic platform. Excitedly, it showed outstanding piezoelectric performance and high stretchability, and the separated carrier could react with water to generate highly cytotoxic reactive oxygen species (ROS), contributing to effectively killing tumor cells and eliminating bacteria through piezoelectric therapy. In addition, ultrasound-triggered piezoelectric effects could promote the migration and differentiation of wound-healing-related cells, thus accelerating wound healing. Herein, such a piezoelectric elastomer exerted a critical role in postoperative tumor-induced wound therapy and healing with the merits of possessing multifunctional abilities. Taken together, the developed ultrasound-activated PLBSIE will offer a comprehensive treatment for postoperative osteosarcoma therapy.

Inhibition of IKKß via a DNA-Based In Situ Delivery System Improves Achilles Tendinopathy Healing in a Rat Model.

BACKGROUND: The inhibition of IKKß by the inhibitor 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-(4-piperidinyl)-3-pyridine carbonitrile (ACHP) is a promising strategy for the treatment of Achilles tendinopathy. However, the poor water solubility of ACHP severely hinders its in vivo application. Moreover, the effective local delivery of ACHP to the tendon and its therapeutic effects have not been reported. PURPOSE: To investigate the therapeutic effects of IKKß inhibition via injection of ACHP incorporated into a DNA supramolecular hydrogel in a collagenase-induced tendinopathy rat model. STUDY DESIGN: Controlled laboratory study. METHODS: Dendritic DNA, a Y-shaped monomer, and a crosslinking monomer were mixed with ACHP and self-assembled into an ACHP-DNA supramolecular hydrogel (ACHP-Gel). The effects of ACHP-Gel in tendon stem/progenitor cells were investigated via RNA sequencing and validated using quantitative reverse transcription polymerase chain reaction (qRT-PCR). A total of 120 collagenase-induced rats were randomly assigned to 5 groups: blank, phosphate-buffered saline (PBS), DNA-Gel, ACHP, and ACHP-Gel. Healing outcomes were evaluated using biomechanic and histologic evaluations at 4 and 8 weeks. RESULTS: ACHP-Gel enhanced the solubility of ACHP and sustained its release for ≥21 days in vivo, which significantly increased the retention time of ACHP and markedly reduced the frequency of administration. RNA sequencing and qRT-PCR showed that ACHP effectively downregulated genes related to inflammation and extracellular matrix remodeling and upregulated genes related to tenogenic differentiation. The cross-sectional area (P = .024), load to failure (P = .002), stiffness (P = .039), and elastic modulus (P = .048) significantly differed between the ACHP-Gel and PBS groups at 8 weeks. The ACHP-Gel group had better histologic scores than the ACHP group at 4 (P = .042) and 8 weeks (P = .009). Type I collagen expression (COL-I; P = .034) and the COL-I/collagen type III ratio (P = .015) increased while interleukin 6 expression decreased (P < .001) in the ACHP-Gel group compared with the ACHP group at 8 weeks. CONCLUSION: DNA supramolecular hydrogel significantly enhanced the aqueous solubility of ACHP and increased its release-retention time. Injection frequency was markedly reduced. ACHP-Gel suppressed inflammation in Achilles tendinopathy and promoted tendon healing in a rat model. CLINICAL RELEVANCE: ACHP-Gel injection is a promising strategy for the treatment of Achilles tendinopathy in clinical practice.

The PFNA in treatment of intertrochanteric fractures with or without lateral wall fracture in elderly patients: a retrospective cohort study.

BACKGROUND: There is no consensus about intertrochanteric fractures with lateral wall treated with intramedullary nail-proximal femoral nail antirotation (PFNA). The aim of the present study was to compare function outcomes between lateral wall and no lateral wall fractures after surgery by PFNA. METHODS: This retrospective study evaluated patients with or without lateral wall fractures who underwent PFNA between January 2015 and June 2018. The operative time, intraoperative blood loss, time to fracture healing, complications and functional outcomes qualified by Harris hip score and Parker - Palmer mobility score (PPMS) were compared between the two groups. RESULTS: Two groups were comparable with regard to patient age, sexual distribution, mechanism of injury, fracture type, body mass index (BMI), Time to surgery, American Society of Anesthesiologists (ASA) score and quality of reduction. The incomplete group had a longer operation time (54.1 ± 8.74 min vs. 51.0 ± 9.86 min) and more intraoperative blood loss (228.4 ± 48.8 ml vs. 151.3 ± 43.5 ml) in comparison with the control group (P < 0.01). Regarding functional outcome, the HHSs of the two groups were 76.2 ± 11.6 vs 75.6 ± 12.5 at the 3 months (P = 0.603), 81.9 ± 9.4 vs 82.6 ± 8.7 at the six months (P = 0.224), 83.8 ± 6.6 vs 84.5 ± 6.0 at the twelve months 85.2 ± 5.5 vs 86.0 ± 5.8 at the twenty-four months (P > 0.05), respectively. Similar results were obtained about PPMS. We found no difference in Weight bearing time, Time of fracture healing, and Complications between incomplete group and intact group. CONCLUSIONS: There is no substantial difference in functional results or complication rates for intertrochanteric fractures with lateral wall fractures, except from increased blood loss and operation time. We believe that an intramedullary nail will be sufficient to repair an intertrochanteric fracture with or without a lateral wall fracture.

Oleanolic acid inhibits mercury chloride induced-liver ferroptosis by regulating ROS/iron overload.

Mercury chloride can cause severe liver injury, which involves multiple mechanisms. Ferroptosis plays an important role in regulating the development and progression of liver pathology. Oleanolic acid (OA), a triterpenoid compound widely exists in fruits, has liver protective properties. In this study, we investigated the role of ferroptosis in mercury chloride-induced liver injury and the intervention effect of OA, and clarified the potential mechanism. We found that mercury chloride-induced oxidative stress in liver tissues and cells, leading to lipid peroxidation and iron overload, thereby reducing the expression levels of GPX4 and SLC7A11, and increasing the expression level of TRF1, OA pretreatment improved the changes of GPX4, SLC7A11 and TRF1 induced by mercury chloride, which were related to its inhibition of oxidative stress. Furthermore, We pretreated cells with OA, VC, and Fer-1, respectively and found that VC pretreatment reduced oxidative stress and significantly reversed the gene and protein expressions of GPX4, SLC7A11, and TRF1 in mercury chloride-exposed cells (P < 0.05, vs. HgCl2 group), however, the protein expression level of GPX4 in OA pre-treatment group was lower than that in VC pre-treatment group (P < 0.05). Fer-1 pretreatment decreased the level of iron ions in cells, increased the gene and protein expression levels of GPX4 and SLC7A11, and decreased the gene and protein expression levels of TRF1 (P < 0.05, vs. HgCl2 group), however, the protein expression levels of GPX4 and SLC7A11 in OA pre-treatment group were lower than those in Fer-1 pre-treatment group (P < 0.05). Moreover, vivo experiments also demonstrated that pre-treatment with OA, VC, and Fer-1 reversed the changes in gene expression levels of Nrf2 and SOD1, and protein expression of GPX4 induced by mercury chloride (P < 0.05, vs. HgCl2 group), meanwhile, the difference was not statistically significant among OA, VC, and Fer-1 pretreatment. The improvement effect of OA pretreatment on the change in TFR1 protein expression caused by mercury chloride was similar to that of Fer-1 and VC, however, the intervention effect of OA on SLC7A11 protein expression was not as good as Fer-1 and VC pre-treatment. To sum up, all these results suggest that ferroptosis is involved in mercury chloride-induced liver injury, OA pretreatment alleviated mercury chloride-induced ferroptosis by inhibiting ROS production and iron ion overload, and then alleviate the liver injury.

Programmable DNA Hydrogel Provides Suitable Microenvironment for Enhancing TSPCS Therapy in Healing of Tendinopathy.

Tendon stem/progenitor cells (TSPCs) therapy is a promising strategy for enhancing cell matrix and collagen synthesis, and regulating the metabolism of the tendon microenvironment during tendon injury repair. Nevertheless, the barren microenvironment and gliding shear of tendon cause insufficient nutrition supply, damage, and aggregation of injected TSPCs around tendon tissues, which severely hinders their clinical application in tendinopathy. In this study, a TSPCs delivery system is developed by encapsulating TSPCs within a DNA hydrogel (TSPCs-Gel) as the DNA hydrogel offers an excellent artificial extracellular matrix (ECM) microenvironment by providing nutrition for proliferation and protection against shear forces. This delivery method restricts TSPCs to the tendons, significantly extending their retention time. It is also found that TSPCs-Gel injections can promote the healing of rat tendinopathy in vivo, where cross-sectional area and load to failure of injured tendons in rats are significantly improved compared to the free TSPCs treatment group at 8 weeks. Furthermore, the potential healing mechanism of TSPCs-Gel is investigated by RNA-sequencing to identify a series of potential gene and signaling pathway targets for further clinical treatment strategies. These findings suggest the potential pathways of using DNA hydrogels as artificial ECMs to promote cell proliferation and protect TSPCs in TSPC therapy.

Comparison of femoral neck system vs. dynamic hip system blade for the treatment of femoral neck fracture in young patients: A retrospective study.

Background: Femoral neck fracture is a common fracture in orthopedic practice. This study aimed to compare the clinical outcomes between the femoral neck system and dynamic hip system blade for the treatment of femoral neck fracture in young patients. Methods: This retrospective study included 43 and 52 patients who underwent treatment for femoral neck fracture with the femoral neck system and dynamic hip system blade, respectively, between August 2019 and August 2020. Operative indexes, including operation duration, blood loss, incision length, postoperative complications (femoral neck shortening, non-union, screw pull-out, femoral head necrosis), and Harris scale scores were recorded and analyzed. Results: Compared to that with the dynamic hip system blade, the femoral neck system showed significantly less operation duration (femoral neck system vs. dynamic hip system blade: 47.09 ± 9.19 vs. 52.90 ± 9.64, P = 0.004), less blood loss (48.53 ± 10.69 vs. 65.31 ± 17.91, P < 0.001), and shorter incision length (4.04 ± 0.43 vs. 4.93 ± 0.53, P < 0.001). Femoral neck shortening was significantly lower with the femoral neck system than with the dynamic hip system blade (3.93 ± 2.40, n = 39 vs. 5.22 ± 2.89, n = 44, P = 0.031). No statistical differences were observed between the two groups in nonunion, screw pull-out, and femoral head necrosis. In addition, the latest follow-up Harris scale score was significantly higher with the femoral neck system than with the dynamic hip system blade (92.3 ± 4.5 vs. 89. 9 ± 4.9, P = 0.015). Conclusion: The femoral neck system results in less trauma, less femoral neck shortening, and better hip joint function than the dynamic hip system blade for the treatment of femoral neck fracture in young patients.

UHPLC-ESI-QE-Orbitrap-MS based metabolomics reveals the antioxidant mechanism of icaritin on mice with cerebral ischemic reperfusion.

Background: Icaritin (ICT) has been previously demonstrated to display protective effects against cerebral ischemic reperfusion (I/R) by inhibiting oxidative stress, but the mechanism remains unclear. This study aimed to explore the mechanism from the perspective of metabolomics. Methods: A mice cerebral artery occlusion/reperfusion (MCAO/R) model was explored to mimic cerebral ischemic reperfusion and protective effect of ICT was assessed by neurologic deficit scoring, infarct volume and brain water content. Ultra-high-performance liquid chromatography electrospray ionization orbitrap tandem mass spectrometry (UHPLC-ESI-QE-Orbitrap-MS) based metabolomic was performed to explore potential biomarkers. Brain tissue metabolic profiles were analyzed and metabolic biomarkers were identified through multivariate data analysis. The protein levels of Nrf2, HO-1 and HQO1 were assayed by western blot. The release of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were detected using corresponding assay kits. Results: The results showed that after ICT treatment, the neurological deficit, cerebral infarction area, brain edema and the level of MDA in brain tissue of MCAO/R mice were significantly reduced. Meanwhile, ICT enhanced the activity of SOD, CAT and GSH-Px. Western blot results confirmed that ICT up-regulated the protein levels of antioxidant-related protein including Nrf2, HO-1 and NQO1. According to the metabolomic profiling of brain tissues, clear separations were observed among the Sham, Model and ICT groups. A total of 44 biomarkers were identified, and the identified biomarkers were mainly related to linoleic acid metabolism, arachidonic acid metabolism, alanine, aspartate and glutamate metabolism, arginine biosynthesis, arginine and proline metabolism, D-glutamine and D-glutamate metabolism, taurine and hypotaurine metabolism and purine metabolism, respectively. At the same time, the inhibitory effect of ICT on arachidonic acid and linoleic acid in brain tissue, as well as the promoting effect on taurine, GABA, NAAG, may be the key factors for the anti-neurooxidative function of mice after MCAO/R injury. Conclusion: Our results demonstrate that ICT has benefits for MCAO/R injury, which are partially related to the suppression of oxidative stress via stimulating the Nrf2 signaling and regulating the production of arachidonic acid, linoleic acid, taurine, GABA, NAAG in brain tissue.

A minimally invasive periacetabular osteotomy improves the radiographic parameters and functional outcomes in the treatment of developmental dysplasia of the hip in adolescents and adults: surgical technique and early results.

PURPOSE: To introduce West China Hospital periacetabular osteotomy (WCH PAO) for acetabular dysplasia in adolescent and young adult patients and evaluate the early clinical results of WCH PAO. METHODS: A retrospective analysis of 34 patients with developmental dysplasia of the hip was performed from October 2019 to April 2021. Baseline data with surgical time and perioperative blood-loss volume were retrieved from medical record systems. The lateral center-to-edge angle (LCEA), acetabular inclination (AI), hip disability and osteoarthritis outcome score (HOOS), University of California Los Angeles (UCLA), and modified Harris hip score (mHHS) were compared preoperatively and postoperatively. RESULTS: All patients had significant postoperative radiology improvements, including LCEA and AI. The LCEA was improved from 12.9 to 33.2°, and the AI was decreased from 27.2 to 8.5°. In addition, hip functional outcomes, including HOOS, UCLA and mHHS, were improved. The UCLA was improved from 3.9 to 6.3, and the HOOS was decreased from 71.0 to 10.5. The Harris hip score improved from 50.8 before surgery to 87.4 after surgery. The mean operative time was 155 min (range 120 to 190 min), and the mean intra-operative blood loss was 580.2 ± 285.5 ml. Furthermore, no major complications, including nerve injury or bone nonunion, occurred in the cohort study. CONCLUSION: WCH PAO is a minimally invasive surgical method for acetabular dysplasia in adolescent and young adult patients who that simplifies the surgical procedure and decreases the incidence of complications related to osteotomy.

Effect of Tranexamic Acid on Blood Management during a High Tibial Osteotomy: A Systematic Review and Meta-analysis.

This study aimed to evaluate the efficiency and safety of tranexamic acid for blood management during high tibial osteotomy (HTO). A systematic search was conducted in Medline, Embase, and the Cochrane library database. Six studies and 208 patients were included in this meta-analysis using Review Manager V.5.3 and Stata 15.1 software. For primary outcomes, tranexamic acid lowered the total blood loss (WMD = -219.47, 95% CI [-355.61, -83.33], P = 0.002). For secondary outcomes, a significant reduction was found for decreased hemoglobin (POD1: WMD = -9.86, 95% CI [-13.45, -6.28], P < 0.05; POD2: WMD = -8.41, 95% CI [-11.50, -5.32], P < 0.05; POD5: WMD = -11.48, 95% CI [-14.56, -8.39], P < 0.05) and drainage (total: WMD = -105.93, 95% CI [-187.08, -24.78], P < 0.05; POD1: WMD = -122.195, 95% CI [-168.902, -75.488], P < 0.05). The sex difference (male/female ratio) was determined (total blood loss: P = 0.025; total drainage amount: p = 0.018) using meta-regression analysis. Females benefited more from tranexamic acid in terms of total blood loss (M/F > 40%: WMD = -53.11, 95% CI [-100.16, -6.05], P = 0.03; 40% ≥ M/F ≥ 20%: WMD = -362.20, 95% CI [-423.96, -300.45], P < 0.05; M/F < 20%: WMD = -263.00, 95% CI [-277.17, -248.83], P < 0.05) and total drainage (M/F > 40%: WMD = -7.11, 95% CI [-10.75, -3.47], P < 0.05; 40% ≥ M/F ≥ 20%: WMD = -104.72, 95% CI [-155.36, -54.08], P < 0.05; M/F < 20%: WMD = -222.00, 95% CI [-297.42, -146.58], P < 0.05). No significant differences were found for drainage on POD2 and POD3, wound complications, orthromboembolic events. In conclusion, tranexamic acid is effective and safe for blood management during HTO. Females appeared to benefit more from it, and an additional postoperative dose is suggested fora better effect.

Favorable immune checkpoint inhibitor outcome of patients with melanoma and NSCLC harboring FAT1 mutations.

Immune checkpoint inhibitors (ICIs) are most commonly used for melanoma and non-small cell lung cancer (NSCLC) patients. FAT atypical cadherin 1 (FAT1), which frequently mutates in melanoma and NSCLC. In this study, we aim to investigate the association of FAT1 mutations with ICI response and outcome. We collected somatic mutation profiles and clinical information from ICI-treated 631 melanoma and 109 NSCLC samples, respectively. For validation, a pan-cancer cohort with 1661 patients in an immunotherapy setting was also used. Melanoma and NSCLC samples from the Cancer Genome Atlas were used to evaluate the potential immunologic mechanisms of FAT1 mutations. In melanoma, patients with FAT1 mutations had a significantly improved survival outcome than those wild-type patients (HR: 0.67, 95% CI: 0.46-0.97, P = 0.033). An elevated ICI response rate also appeared in FAT1-mutated patients (43.2% vs. 29.2%, P = 0.032). Associations of FAT1 mutations with improved prognosis and ICI response were confirmed in NSCLC patients. In the pan-cancer cohort, the association between FAT1 mutations and favorable ICI outcome was further validated (HR: 0.74, 95% CI: 0.58-0.96, P = 0.022). Genomic and immunologic analysis showed that a high mutational burden, increased infiltration of immune-response cells, decreased infiltration of immune-suppressive cells, interferon and cell cycle-related pathways were enriched in patients with FAT1 mutations. Our study revealed that FAT1 mutations were associated with better immunogenicity and ICI efficacy, which may be considered as a biomarker for selecting patients to receive immunotherapy.

The prevalence and incidence of major depressive disorder in 8079 Chinese university freshmen before and during COVID-19.

BACKGROUND: COVID-19 pandemic may impact the prevalence and incidence of depression in college students. However, there is no longitudinal study focusing on major depressive disorder (MDD) before and during COVID-19 pandemic. METHODS: A cohort study was carried out among 8079 Chinese college freshmen. The baseline survey was conducted in 2018 (T0) and annual follow-ups were in 2019 (T1, before COVID-19) and in 2020 (T2, during COVID-19). CIDI-3.0 was used to diagnose MDD. Random effects logistic models of panel data analysis were used for the risk of MDD incidence. STATA 15.1 was used for all analysis. RESULTS: The weighted 12-month prevalence of MDD at T2 (2.10%) was significantly lower than that at T1 (2.67%) (p < 0.001). However, among students who reported exposure to the COVID-19 events, the annual prevalence of MDD at T2 was higher than that at T1 (4.21% vs. 2.79%, p < 0.001). The incidence from T0 to T1, incidence from T1 to T2, and the 2-year incidence was 2.23%, 1.34% and 3.75%, respectively. Only 8.93% of MDD students had chosen to seek professional help during the COVID-19 pandemic period. LIMITATIONS: The computer assisted CIDI may not be as sensitive and specific as the diagnosis made by a psychiatrist and may have caused report bias. CONCLUSIONS: Although the MDD incidence of college students was decreasing over time, the impact of the pandemic on student mental health may depend on exposure to COVID-19 events. Not seeking professional help in the Chinese college students is still an important issue.

Gene-gene interaction and new onset of major depressive disorder: Findings from a Chinese freshmen nested case-control study.

BACKGROUND: The gene-gene interaction is known to be the genetic cause of major depressive disorder (MDD). Several genes have been found to be related to MDD. The objectives of this study were to verify the susceptibility genes of MDD in a sample of university students in China, and to investigate possible gene-gene interactions in relation to the risk of MDD. METHODS: 7,627 Chinese Han freshmen were enrolled at baseline survey in 2018. After a 2-year follow-up, 170 new onset MDD cases and 680 controls with DNA samples reserved were sequenced and genotyped for 4 selected Single Nucleotide Polymorphisms (SNPs) in a nested case-control study (ratio of 1:4). Chi-square test was used to identify the relationships between SNPs and risk of MDD. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the gene-gene interactions. RESULTS: The 2-year incidence of MDD in Chinese college students was 3.75% (95% CI: 3.24%, 4.34%). There was no statistical difference in MDD incidences between males (3.74%, 95% CI: 3.12%, 4.49%) and females (3.77%, 95% CI: 2.97%, 4.78%) (p>0.05). TMEM161B (rs768705) was positively associated with new onset MDD (χ2 = 0.75, p = 0.023). The AG genotype of rs768705 was significant (OR=1.640, 95%CI:1.414-2.358). The gene-gene interaction between TMEM161B (rs768705) and LHPP (rs35936514) was statistically significant in this nested case-control study (p = 0.011). The CV consistency was 9/10 and the testing accuracy was 0.5274. LIMITATIONS: The results could not be inferred to other ethnics. CONCLUSIONS: This study provided evidence that combined rs768705 (TMEM161B) and rs35936514 (LHPP) may modulate the risk of MDD.

Salidroside prevents PM2.5-induced BEAS-2B cell apoptosis via SIRT1-dependent regulation of ROS and mitochondrial function.

PM2.5 is a harmful air pollutant currently threatening public health. It has been closely linked to increased morbidity of bronchial asthma and lung cancer worldwide. Salidroside (Sal), an active component extracted from Rhodiola rosea, has been reported to ameliorate the progression of asthma. However, there are few studies on the protective effect of salidroside on PM2.5-induced bronchial epithelial cell injury, and the related molecular mechanism is not clear. Here, we aimed to explore the protective effect and related mechanism of Sal on PM2.5 bronchial injury. We chose 50 µg/mL PM2.5 for 24 h as a PM2.5-induced cell damage model. After that BEAS-2B cells were pretreated with 40, 80, 160 µM Sal for 24 h and then exposed to 50 µg/mL PM2.5 for 24 h. We found that Sal pretreatment significantly inhibited the decrease of cell viability induced by PM2.5. Sal was effective in preventing PM2.5-induced apoptotic features, including Ca2+ overload, the cleavages of caspase 3, and the increases in levels of caspase 9 and Bcl-2-associated X protein (Bax), ultimately, Sal significantly inhibited PM2.5-induced apoptosis. Sal improved mitochondrial membrane potential, inhibited the release of cytochrome c from the mitochondria to cytoplasm. Sal alleviated ROS production, decreased the level of MDA, prevented the reduction of CAT, SOD and GSH-Px and increased the expression of NF-E2-related factor 2 (Nrf2), HO-1 and superoxide dismutase 1 (SOD1) in cells exposed to PM2.5. Furthermore, Sal improved the decrease of SIRT1 and PGC-1 α expression levels caused by PM2.5. In addition, inhibition of SIRT1 by EX527 (SIRT1 inhibitor) reversed the protective effects of Sal, including the decrease of ROS level, the increase of membrane potential level and the decrease of apoptosis level. Thus, Sal may be regarded as a potential drug to prevent PM2.5-induced apoptosis of bronchial epithelial cells and other diseases with similar pathological mechanisms.

Impact of tourniquet on short-term outcomes in opening wedge high tibial osteotomy with modern tranexamic acid protocols: a retrospective cohort study.

BACKGROUND: The use of a tourniquet during high tibial osteotomy (HTO) is a routine procedure, but there is currently no research on the benefits and potential risks of tourniquet use during HTO. The aim of this study was to investigate the impact of tourniquet on perioperative blood loss, early functional recovery and complications in opening wedge HTO with modern tranexamic acid protocols. METHODS: This was a retrospective cohort study of patients who underwent unilateral opening wedge HTO between January 2019 and September 2020. All patients were divided into two groups according to whether a tourniquet was applied during HTO. Patients in both groups received the same surgical procedures, tranexamic acid protocols and other perioperative treatments. Preoperative baseline data, intraoperative data, early postoperative recovery and all complications during the 3-month follow-up were collected and compared between the two groups. RESULTS: A total of 62 patients were enrolled in this study, including 32 in the tourniquet group and 30 in the non-tourniquet group. There was no significant difference in preoperative baseline data between the two groups (P > 0.05 in all). Intraoperative blood loss in the tourniquet group was significantly lower than that in the non-tourniquet group (80.22 ml versus 94.00 ml, P < 0.001), but there was no difference in total blood loss (187.39 ml versus 193.31 ml, P = 0.714). And no patient in either group required blood transfusion. In terms of early postoperative recovery, tourniquet use significantly increased pain scores and reduced knee range of motion on the first and second postoperative days, but there was no significant difference between the two groups at postoperative third day and third month. Furthermore, there was no significant difference between the two groups in terms of lower limb force line correction, length of stay, Knee Society Score or the incidence of complications during the 3-month follow-up (P > 0.05 in all). CONCLUSIONS: In opening wedge HTO with modern tranexamic acid protocols, not using a tourniquet does not increase perioperative total blood loss or the risk of complications, but facilitates early postoperative recovery by reducing pain and increasing range of motion.