Facile and rapid fabrication of a novel 3D-printable, visible light-crosslinkable and bioactive polythiourethane for large-to-massive rotator cuff tendon repair.

Facile and rapid 3D fabrication of strong, bioactive materials can address challenges that impede repair of large-to-massive rotator cuff tears including personalized grafts, limited mechanical support, and inadequate tissue regeneration. Herein, we developed a facile and rapid methodology that generates visible light-crosslinkable polythiourethane (PHT) pre-polymer resin (∼30 min at room temperature), yielding 3D-printable scaffolds with tendon-like mechanical attributes capable of delivering tenogenic bioactive factors. Ex vivo characterization confirmed successful fabrication, robust human supraspinatus tendon (SST)-like tensile properties (strength: 23 MPa, modulus: 459 MPa, at least 10,000 physiological loading cycles without failure), excellent suture retention (8.62-fold lower than acellular dermal matrix (ADM)-based clinical graft), slow degradation, and controlled release of fibroblast growth factor-2 (FGF-2) and transforming growth factor-ß3 (TGF-ß3). In vitro studies showed cytocompatibility and growth factor-mediated tenogenic-like differentiation of mesenchymal stem cells. In vivo studies demonstrated biocompatibility (3-week mouse subcutaneous implantation) and ability of growth factor-containing scaffolds to notably regenerate at least 1-cm of tendon with native-like biomechanical attributes as uninjured shoulder (8-week, large-to-massive 1-cm gap rabbit rotator cuff injury). This study demonstrates use of a 3D-printable, strong, and bioactive material to provide mechanical support and pro-regenerative cues for challenging injuries such as large-to-massive rotator cuff tears.

Research of wet string grid dust removal vehicle and creation of dust control area on tunnel working face.

The spread of blast dust throughout the tunnel becomes a common problem in drill and blast tunneling,the key to breaking through the problem is the creation of a dust control area on the working face.In view of this key problem, a wet string grid dust removal crawler vehicle was developed, the power of the vehicle came from the diesel generator, and further, the air cooler of the diesel generator was used to generate airflow, and the suction process formed by the on-board axial flow fan was coupled to create a dust control area of the working face after blasting.The results show that when the frequency of the axial flow fan is adjusted to 30 Hz, the airflow speed of the wet chord grid section reaches 3.34 m/s, and the dust removal efficiency is the highest, with a value of 94.3%.Compared with the non-use of the dust removal vehicle, when the air outlet of the air cooler is front, horizontal front, horizontal rear, the dust concentration is reduced by 74.37, 92.39 and 50.53%.Finally, the optimized wet grid dust removal crawler was installed in the Dading tunnel, and the actual dust reduction efficiency was about 78.49%. The results obtained provide an important technical way to improve the working environment of the drilling and blasting construction tunnel.

Engineering an extracellular matrix-functionalized, load-bearing tendon substitute for effective repair of large-to-massive tendon defects.

A significant clinical challenge in large-to-massive rotator cuff tendon injuries is the need for sustaining high mechanical demands despite limited tissue regeneration, which often results in clinical repair failure with high retear rates and long-term functional deficiencies. To address this, an innovative tendon substitute named "BioTenoForce" is engineered, which uses (i) tendon extracellular matrix (tECM)'s rich biocomplexity for tendon-specific regeneration and (ii) a mechanically robust, slow degradation polyurethane elastomer to mimic native tendon's physical attributes for sustaining long-term shoulder movement. Comprehensive assessments revealed outstanding performance of BioTenoForce, characterized by robust core-shell interfacial bonding, human rotator cuff tendon-like mechanical properties, excellent suture retention, biocompatibility, and tendon differentiation of human adipose-derived stem cells. Importantly, BioTenoForce, when used as an interpositional tendon substitute, demonstrated successful integration with regenerative tissue, exhibiting remarkable efficacy in repairing large-to-massive tendon injuries in two animal models. Noteworthy outcomes include durable repair and sustained functionality with no observed breakage/rupture, accelerated recovery of rat gait performance, and >1 cm rabbit tendon regeneration with native tendon-like biomechanical attributes. The regenerated tissues showed tendon-like, wavy, aligned matrix structure, which starkly contrasts with the typical disorganized scar tissue observed after tendon injury, and was strongly correlated with tissue stiffness. Our simple yet versatile approach offers a dual-pronged, broadly applicable strategy that overcomes the limitations of poor regeneration and stringent biomechanical requirements, particularly essential for substantial defects in tendon and other load-bearing tissues.

Non-collagenous proteins, rather than the collagens, are key biochemical factors that mediate tenogenic bioactivity of tendon extracellular matrix.

Despite the growing clinical use of extracellular matrix (ECM)-based biomaterials for tendon repair, undesired healing outcomes or complications have frequently been reported. A major scientific challenge has been the limited understanding of their functional compositions and mechanisms of action due to the complex nature of tendon ECM. Previously, we have reported a soluble ECM fraction from bovine tendons (tECM) by urea extraction, which exhibited strong, pro-tenogenic bioactivity on human adipose-derived stem cells (hASCs). In this study, to advance our previous findings and gain insights into the biochemical nature of its pro-tenogenesis activity, tECM was fractionated using (i) an enzymatic digestion approach (pepsin, hyaluronidase, and chondroitinase) to yield various enzyme-digested tECM fractions; and (ii) a gelation-based approach to yield collagen matrix-enriched (CM) and non-collagenous matrix-enriched (NCM) fractions. Their tenogenic bioactivity on hASCs was assessed. Our results collectively indicated that non-collagenous tECM proteins, rather than collagens, are likely the important biochemical factors responsible for tECM pro-tenogenesis bioactivity. Mechanistically, RNA-seq analysis revealed that tECM and its non-collagenous portion induced similar transcriptional profiles of hASCs, particularly genes associated with cell proliferation, collagen synthesis, and tenogenic differentiation, which were distinct from transcriptome induced by its collagenous portion. From an application perspective, the enhanced solubility of the non-collagenous tECM, compared to tECM, should facilitate its combination with various water-soluble biomaterials for tissue engineering protocols. Our work provides insight into the molecular characterization of native tendon ECM, which will help to effectively translate their functional components into the design of well-defined, ECM biomaterials for tendon regeneration. STATEMENT OF SIGNIFICANCE: Significant progress has been made in extracellular matrix (ECM)-based biomaterials for tendon repair. However, their effectiveness remains debated, with conflicting research and clinical findings. Understanding the functional composition and mechanisms of action of ECM is crucial for developing safe and effective bioengineered scaffolds. Expanding on our previous work with bovine tendon ECM extracts (tECM) exhibiting strong pro-tenogenesis activity, we fractionated tECM to evaluate its bioactive moieties. Our findings indicate that the non-collagenous matrix within tECM, rather than the collagenous portions, plays a major role in the pro-tenogenesis bioactivity on human adipose-derived stem cells. These insights will drive further optimization of ECM-based biomaterials, including our advanced method for preparing highly soluble, non-collagenous matrix-enriched tendon ECM for effective tendon repair.

Effect of Aging on Tendon Biology, Biomechanics and Implications for Treatment Approaches.

Tendon aging is associated with an increasing prevalence of tendon injuries and/or chronic tendon diseases, such as tendinopathy, which affects approximately 25% of the adult population. Aged tendons are often characterized by a reduction in the number and functionality of tendon stem/progenitor cells (TSPCs), fragmented or disorganized collagen bundles, and an increased deposition of glycosaminoglycans (GAGs), leading to pain, inflammation, and impaired mobility. Although the exact pathology is unknown, overuse and microtrauma from aging are thought to be major causative factors. Due to the hypovascular and hypocellular nature of the tendon microenvironment, healing of aged tendons and related injuries is difficult using current pain/inflammation and surgical management techniques. Therefore, there is a need for novel therapies, specifically cellular therapy such as cell rejuvenation, due to the decreased regenerative capacity during aging. To augment the therapeutic strategies for treating tendon-aging-associated diseases and injuries, a comprehensive understanding of tendon aging pathology is needed. This review summarizes age-related tendon changes, including cell behaviors, extracellular matrix (ECM) composition, biomechanical properties and healing capacity. Additionally, the impact of conventional treatments (diet, exercise, and surgery) is discussed, and recent advanced strategies (cell rejuvenation) are highlighted to address aged tendon healing. This review underscores the molecular and cellular linkages between aged tendon biomechanical properties and the healing response, and provides an overview of current and novel strategies for treating aged tendons. Understanding the underlying rationale for future basic and translational studies of tendon aging is crucial to the development of advanced therapeutics for tendon regeneration.

Research on the development methodology for clinical practice guidelines for organic integration of traditional Chinese and Western medicine.

Integrated traditional Chinese medicine (TCM) and Western medicine (WM) is a new medical science grounded in the knowledge bases of both TCM and WM, which then forms a unique modern medical system in China. Integrated TCM and WM has a long history in China, and has made important achievements in the process of clinical diagnosis and treatment. However, the methodological defects in currently published clinical practice guidelines limit its development. The organic integration of TCM and WM is a deeper integration of TCM and WM. To realize the progression of "integration" to "organic integration", a targeted and standardized guideline development methodology is needed. Therefore, the purpose of this study is to establish a standardized development procedure for clinical practice guidelines for the organic integration of TCM and WM to promote the systematic integration of TCM and WM research results into clinical practice guidelines in order to achieve optimal results as the whole is greater than the sum of the parts.

Mechanisms of plant saline-alkaline tolerance.

Saline-alkaline soil affects crop growth and development, thereby suppressing the yields. Human activities and climate changes are putting arable land under the threat of saline-alkalization. To feed a growing global population in limited arable land, it is of great urgence to breed saline-alkaline tolerant crops to cope with food security. Plant salt-tolerance mechanisms have already been explored for decades. However, to date, the molecular mechanisms underlying plants responses to saline-alkaline stress have remained largely elusive. Here, we summarize recent advances in plant response to saline-alkaline stress and propose some points deserving of further exploration.

Identification and validation of reference genes for qRT-PCR analyses under different experimental conditions in Allium wallichii.

Himalayan onion (Allium wallichii) is a perennial bulbous herb with high ornamental value and has long been used as traditional medicines in Nepal and China because of the anti-cancer and anti-microbial activities. Wild Allium wallichii features different flower colors, including purple, pink, deep purple and white. However, little is known about the molecular mechanisms of color formation during A. wallichii flower development stages due to the lack of optimal reference genes. Quantitative real-time polymerase chain reaction (qRT-PCR) is a powerful tool for quantifying expression levels of target genes. The accuracy of qRT-PCR analyses is largely dependent on the identification of stable reference genes for data normalization. The stability of reference gene expression may vary with plant species and environmental conditions. The aim of this study was to select stable reference genes for qRT-PCR analyses of target genes at flower development stages, in different flower colors and organs for Allium wallichii. The CDSs of eight potential reference genes (TUB2, ACT1, GAPC, EF1α, UBQ, UBC, SAND and CYP1) were cloned and their stability was evaluated by four programs (Delta Ct, geNorm, NormFinder and BestKeeper), and the results were further integrated into a comprehensive rank by RefFinder. The results showed that TUB2 and GAPC were the most stable two reference genes at different developmental stages of purple- and white-flower genotypes and across all samples. UBC and TUB2 expression was stable at different developmental stages of purple flowers. CYP1 and TUB2 were stably expressed at different developmental stages of white flowers. GAPC and SAND showed the highest rankings in different flower colors. TUB2 and EF1α performed the best in different tissues. ACT1 was the least stable gene in all tested samples. Moreover, DIHYDROFLAVONOL-4-REDUCTASE (DFR) gene that involved in anthocyanin synthesis was used to evaluate the effectiveness of the selected candidates. This study identified the first set of suitable reference genes for qRT-PCR analyses, which will lay the foundation for gene function study in A. wallichii.

Pharmacology of orange-spotted grouper (Epinephelus coioides) melanocortin-5 receptor and its modulation by Mrap2.

The mammalian melanocortin-5 receptors (MC5Rs) are involved in various functions, including exocrine gland secretion, glucose uptake, adipocyte lipolysis, and immunity. However, the physiological role of fish Mc5r is rarely studied. Melanocortin-2 receptor accessory protein 2 (MRAP2) modulates pharmacological properties of melanocortin receptors. Herein, to lay the foundation for future physiological studies, we cloned the orange-spotted grouper (Epinephelus coioides) mc5r, with a 1008 bp open reading frame and a predicted protein of 334 amino acids. Grouper mc5r had abundant expression in the brain, skin, and kidney. Four ligands could bind to grouper Mc5r and dose-dependently increase intracellular cAMP levels. Grouper Mrap2 did not affect binding affinity or potency of Mc5r; however, grouper Mrap2 decreased cell surface expression and maximal binding of Mc5r. Mrap2 also significantly decreased the maximal response to a superpotent agonist but not the endogenous agonist. This study provided new data on fish Mc5r pharmacology and its regulation by Mrap2.

Application of sevoflurane combined with remifentanil anesthesia in laparoscopic radical hysterectomy for cervical cancer.

OBJECTIVE: To explore the effects of sevoflurane combined with remifentanil anesthesia on the physical stress and immunologic function of patients undergoing laparoscopic radical hysterectomy for cervical cancer. METHODS: The clinical data of 74 patients undergoing laparoscopic radical hysterectomy for cervical cancer were retrospectively analyzed. Patients were divided into two groups according to the different anesthesia methods, among which 37 cases received propofol and remifentanil anesthesia were set as a control group (CG), and 37 cases received sevoflurane and remifentanil anesthesia were set as an observation group (OG). RESULTS: The OG showed a lower heart rate, Ramsay score and bispectral index than the CG 30 min after the start of the surgery and at the end of the surgery. The levels of glucagon, angiotensin II and cortisol in the OG were lower than those in the CG upon skin incision, at the end of surgery, and at 1 h after surgery (P < 0.05). The levels of CD3+ and CD4+ of the OG were higher than those of the CG at 1 d and 3 d after surgery. In terms of Montreal Cognitive Assessment and Mini-Mental State Examination scores 1 d after surgery, the OG was higher than the CG. CONCLUSION: Sevoflurane combined with remifentanil anesthesia for patients undergoing laparoscopic radical hysterectomy for cervical cancer is superior to propofol and remifentanil, and can ensure stable hemodynamics and mitigate physical stress, so it is worthy of clinical application.

Growth and differentiation factor-7 immobilized, mechanically strong quadrol-hexamethylene diisocyanate-methacrylic anhydride polyurethane polymer for tendon repair and regeneration.

Biological and mechanical cues are both vital for biomaterial aided tendon repair and regeneration. Here, we fabricated mechanically tendon-like (0 s UV) QHM polyurethane scaffolds (Q: Quadrol, H: Hexamethylene diisocyanate; M: Methacrylic anhydride) and immobilized them with Growth and differentiation factor-7 (GDF-7) to produce mechanically strong and tenogenic scaffolds. In this study, we assessed QHM polymer cytocompatibility, amenability to fibrin-coating, immobilization and persistence of GDF-7, and capability to support GDF-7-mediated tendon differentiation in vitro as well as in vivo in mouse subcutaneous and acute rat rotator cuff tendon resection models. Cytocompatibility studies showed that QHM facilitated cell attachment, proliferation, and viability. Fibrin-coating and GDF-7 retention studies showed that mechanically tendon-like 0 s UV QHM polymer could be immobilized with GDF-7 and retained the growth factor (GF) for at least 1-week ex vivo. In vitro differentiation studies showed that GDF-7 mediated bone marrow-derived human mesenchymal stem cell (hMSC) tendon-like differentiation on 0 s UV QHM. Subcutaneous implantation of GDF-7-immobilized, fibrin-coated, QHM polymer in mice for 2 weeks demonstrated de novo formation of tendon-like tissue while implantation of GDF-7-immobilized, fibrin-coated, QHM polymer in a rat acute rotator cuff resection injury model indicated tendon-like tissue formation in situ and the absence of heterotopic ossification. Together, our work demonstrates a promising synthetic scaffold with human tendon-like biomechanical attributes as well as immobilized tenogenic GDF-7 for tendon repair and regeneration. STATEMENT OF SIGNIFICANCE: Biological activity and mechanical robustness are key features required for tendon-promoting biomaterials. While synthetic biomaterials can be mechanically robust, they often lack bioactivity. To biologically augment synthetic biomaterials, numerous drug and GF delivery strategies exist but the large tissue space within the shoulder is constantly flushed with saline during arthroscopic surgery, hindering efficacious controlled release of therapeutic molecules. Here, we coated QHM polymer (which exhibits human tendon-to-bone-like biomechanical attributes) with fibrin for GF binding. Unlike conventional drug delivery strategies, our approach utilizes immobilized GFs as opposed to released GFs for sustained, localized tissue regeneration. Our data demonstrated that GF immobilization can be broadly applied to synthetic biomaterials for enhancing bioactivity, and GDF-7-immobilized QHM exhibit high clinical translational potential for tendon repair.

Association of Ethnicity, Sex, and Age With Cancer Diagnoses and Health Care Utilization Among Children in Inner Mongolia, China.

Importance: China is experiencing a sustained increase in childhood cancer. However, whether differences exist in disease burden by ethnicity remains unclear. Objective: To compare differences in cancer diagnoses and health care utilization in Inner Mongolia among children subgrouped by ethnicity (Han vs Mongolian), sex, and age. Design, Setting, and Participants: This retrospective cohort study in Inner Mongolia, China, used data on children aged 0 to 14 years with cancer from the Inner Mongolia Regional Health Information Platform, which comprises the National Basic Medical Insurance database and the Inner Mongolia cause-of-death reporting system, from January 1, 2013, to December 31, 2019. Ethnicities analyzed included Han and Mongolian; patients of other ethnicities were not included in the analysis because of the small sample size. Cancer was broadly defined as a primary malignant tumor or hematologic cancer; benign central nervous system tumors were also included. A 2-year washout period was used to exclude prevalent cases. After diagnosis, the patients were followed up until the date of death or the end of the insured status, whichever came first. Exposures: Ethnicity (Han vs Mongolian), sex (male vs female), and age (0-4, 5-9, and 10-14 years). Main Outcomes and Measures: Crude incidence, 5-year prevalence, and survival rates at 1 year and 3 years after diagnosis; health care utilization, represented by medical costs during the first year and first 3 years after diagnosis; and hospital attendance with level (tertiary vs secondary and lower-level hospitals) and location of each unique visit. Results: From 2013 to 2019, 1 106 684 (2013), 1 330 242 (2014), 1 763 746 (2015), 2 400 343 (2016), 2 245 963 (2017), 2 901 088 (2018), and 2 996 580 (2019) children aged 0 to 14 years were registered in the NBMI database. Among the 2 996 580 children enrolled in 2019, the mean (SD) age was 6.8 (4.3) years, of whom 1 572 096 (52.5%) were male, 2 572 091 (85.8%) were Han, and 369 400 (12.3%) were Mongolian. A total of 1910 patients with cancer were identified (1048 were male [54.9%]; 1559 were Han [81.6%], and 300 were Mongolian [15.7%]). There were 764 hematologic cancers (40.0%) and 1146 solid tumors (60.0%). The overall crude incidence of cancer from 2015 to 2019 was 129.85 per million children (95% CI, 123.63-136.06), with a higher incidence among Mongolian than among Han children (155.12 [95% CI, 136.81-173.43] vs 134.39 [95% CI, 127.46-141.32]). The 5-year prevalence was 428.97 per million (95% CI, 405.52-452.42) in 2020, with a higher prevalence among Mongolian than among Han children (568.49 [95% CI, 91.62-645.36] vs 404.34 [95% CI, 379.77-428.91]). The combined 1-year (2015-2019) and 3-year (2015-2017) survival rates were 72.5% (95% CI, 67.5%-77.5%) and 66.8% (95% CI, 61.6%-71.9%), respectively. The 1-year (median [IQR], $1991 [$912-$10 181] vs $3991 [$1171-$15 425]) and 3-year (median [IQR], $2704 [$954-$13 909] vs $5375 [$1283-$22 466]) postdiagnosis costs were lower among Mongolian than among Han children. A higher proportion of Mongolian patients attended low-level hospitals (45.9% vs 17.4%). Conclusions and Relevance: In this cohort study, Mongolian children had a higher incidence and prevalence of cancer but a lower demand for medical care, suggesting that further investigations are needed to identify mechanisms underlying ethnic disparities and ensure that care is equitable.

Engineering microparticles based on solidified stem cell secretome with an augmented pro-angiogenic factor portfolio for therapeutic angiogenesis.

Tissue (re)vascularization strategies face various challenges, as therapeutic cells do not survive long enough in situ, while the administration of pro-angiogenic factors is hampered by fast clearance and insufficient ability to emulate complex spatiotemporal signaling. Here, we propose to address these limitations by engineering a functional biomaterial capable of capturing and concentrating the pro-angiogenic activities of mesenchymal stem cells (MSCs). In particular, dextran sulfate, a high molecular weight sulfated glucose polymer, supplemented to MSC cultures, interacts with MSC-derived extracellular matrix (ECM) components and facilitates their co-assembly and accumulation in the pericellular space. Upon decellularization, the resulting dextran sulfate-ECM hybrid material can be processed into MIcroparticles of SOlidified Secretome (MIPSOS). The insoluble format of MIPSOS protects protein components from degradation, while facilitating their sustained release. Proteomic analysis demonstrates that MIPSOS are highly enriched in pro-angiogenic factors, resulting in an enhanced pro-angiogenic bioactivity when compared to naïve MSC-derived ECM (cECM). Consequently, intravital microscopy of full-thickness skin wounds treated with MIPSOS demonstrates accelerated revascularization and healing, far superior to the therapeutic potential of cECM. Hence, the microparticle-based solidified stem cell secretome provides a promising platform to address major limitations of current therapeutic angiogenesis approaches.

Tenogenic induction of human adipose-derived stem cells by soluble tendon extracellular matrix: composition and transcriptomic analyses.

BACKGROUND: Tendon healing is clinically challenging largely due to its inferior regenerative capacity. We have previously prepared a soluble, DNA-free, urea-extracted bovine tendon-derived extracellular matrix (tECM) that exhibits strong pro-tenogenic bioactivity on human adipose-derived stem cells (hASCs). In this study, we aimed to elucidate the mechanism of tECM bioactivity via characterization of tECM protein composition and comparison of transcriptomic profiles of hASC cultures treated with tECM versus collagen type I (Col1) as a control ECM component. METHODS: The protein composition of tECM was characterized by SDS-PAGE, hydroxyproline assay, and proteomics analysis. To investigate tECM pro-tenogenic bioactivity and mechanism of action, differentiation of tECM-treated hASC cultures was compared to serum control medium or Col1-treated groups, as assessed via immunofluorescence for tenogenic markers and RNA Sequencing (RNA-Seq). RESULTS: Urea-extracted tECM yielded consistent protein composition, including collagens (20% w/w) and at least 17 non-collagenous proteins (< 100 kDa) based on MS analysis. Compared to current literature, tECM included key tendon ECM components that are functionally involved in tendon regeneration, as well as those that are involved in similar principal Gene Ontology (GO) functions (ECM-receptor interaction and collagen formation) and signaling pathways (ECM-receptor interaction and focal adhesion). When used as a cell culture supplement, tECM enhanced hASC proliferation and tenogenic differentiation compared to the Col1 and FBS treatment groups based on immunostaining of tenogenesis-associated markers. Furthermore, RNA-Seq analysis revealed a total of 584 genes differentially expressed among the three culture groups. Specifically, Col1-treated hASCs predominantly exhibited expression of genes and pathways related to ECM-associated processes, while tECM-treated hASCs expressed a mixture of ECM- and cell activity-associated processes, which may explain in part the enhanced proliferation and tenogenic differentiation of tECM-treated hASCs. CONCLUSIONS: Our findings showed that urea-extracted tECM contained 20% w/w collagens and is significantly enriched with other non-collagenous tendon ECM components. Compared to Col1 treatment, tECM supplementation enhanced hASC proliferation and tenogenic differentiation as well as induced distinct gene expression profiles. These findings provide insights into the potential mechanism of the pro-tenogenic bioactivity of tECM and support the development of future tECM-based approaches for tendon repair.

A rare case of isolated accessory mitral tissue in an asymptomatic adult female.

Accessory mitral valve tissue (AMVT) is a rare congenital cardiac anomaly, which is associated with other congenital heart diseases. It is diagnosed in neonates or childhood and rarely in adulthood. Nevertheless, AMVT is an incidental finding or described as isolated. Echocardiography, especially three-dimensional echocardiography is considered as an optimal imaging technique for AMVT diagnosis. We herein presented an asymptomatic adult AMVT cases with significant left ventricular outflow tract obstruction and surgical excision was recommended.

Adjunctive vagus nerve stimulation for treatment-resistant depression: a preliminary study.

BACKGROUND: This study is the first to assess the safety and therapeutic efficacy of vagus nerve stimulation (VNS) as an adjunctive treatment for Chinese patients suffering from treatment-resistant depression (TRD). METHODS: A total of seven patients with TRD underwent surgical implantation of a VNS device were followed over a 9-month period. The 24-item Hamilton Rating Scale for Depression (HAMD-24) and the 14-item Hamilton Anxiety Scale (HAMA) were used to assess depressive and anxiety symptoms, respectively. Neurocognitive function was measured with the Wechsler Adult Intelligence Scale (WAIS) and the Wechsler Memory Scale (WMS). RESULTS: After 3 months of treatment with VNS, the antidepressant response and remission rates were 42.9% and 28.6%, respectively. After 9 months of treatment with VNS, the response and remission rates increased to 85.7% and 57.1%, respectively. Significant time main effects were identified for HAMD-24 scores, HAMA scores, the WMS memory quotient, and the full intelligence quotients measured with the WAIS (all ps < 0.05). The most frequent adverse effects of VNS treatment were voice alteration (100%) and cough frequency increase (71.4%). CONCLUSION: This preliminary study indicated that adjunctive VNS was effective and safe in treating Chinese patients who were suffering from TRD, and its efficacy increased with time.Key pointsThere is positive evidence to support the role of VNS as an adjunctive treatment in Chinese patients with TRD.The antidepressant efficacy of adjunctive VNS for Chinese patients with TRD increased with time.The most frequent adverse effects of VNS treatment were voice alteration and cough frequency increase.

Antinuclear Antibodies and Thyroid Autoantibodies in the Serum of Chinese Patients with Acute Psychiatric Disorders: A Retrospective Study.

Background: It has been shown that autoimmune diseases are associated with psychiatric disorders in epidemiological studies. The acute psychiatric disorder patients have higher frequency of autoantibodies in the blood, including antinuclear antibodies, anti-thyroid peroxidase, and thyroglobulin [thyroid antibody carriers]. However, large clinical studies with more relevant control groups in China are few. Methods: This was a retrospective study. A total of 1669 sera were tested for autoantibodies in the clinical laboratory of the Fourth Affiliated Hospital, Zhejiang University School of Medicine from October 2016 to March 2021. All data available during this time period were analyzed. Only the first entry for each patient from inpatient care units was used for analysis. The clinical information and laboratory data of patients were retrospectively collected and analyzed. Results: A significantly lower prevalence of antinuclear antibodies was observed in the healthy control group than in the patient group (21.7% vs 28.8%, P < .05). There was a significant difference in the prevalence of antinuclear antibodies between thyroglobulin-antibody carriers and thyroid peroxidase-antibody- and thyroglobulin-antibody-seronegative individuals in the unipolar depressive disorder group (P < .05). A positive anti-thyroid peroxidase test was significantly associated with patients having nonaffective psychoses (P < .05). Conclusion: The results showed that psychiatric disorders were associated with antinuclear antibodies and thyroid autoantibodies in our large sample of patients admitted to acute psychiatric hospitalization, and autoimmune autoantibodies were potential biomarkers of psychotic disorders. The results might lead to new research directions for the study of psychiatric disorders in the future.

Psychological Status of Clinical Laboratory Staff During the COVID-19 Outbreak.

Background: In early December 2019, during the outbreak of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which was first detected in Wuhan, COVID-19 was suspected, detected, and confirmed in an increasing number of patients every day. The clinical laboratory staff have always played an important role in the laboratory diagnosis of patients. Currently, there are many research studies on the mental health of the first-line doctors or nurses managing the COVID-19 outbreak, both domestically and overseas, but data of the mental health and associated factors among the clinical laboratory staff who handle the blood or biological samples of confirmed cases and are consequently exposed to COVID-19 are limited. Methods: This cross-sectional survey-based study was performed via an online survey in a single designated hospital from April 20 to April 23, 2020 in Yiwu,China. The online survey included questions on sociodemographic and clinical variables. Totally, 45 clinical laboratory staff and 20 nonmedical health workers participated. Mental health variables were assessed via 4 Chinese versions of validated measurement tools : Zung's Self-rating Depression Scale (SDS), Zung's Self-rating Anxiety Scale (SAS), the Pittsburgh Sleep Quality Index (PSQI), and the Eysenck Personality Questionnaire (EPQ). Results: Significant differences were observed in the SDS and SAS scores, between the clinical laboratory staff and the nonmedical health workers (P < .001, P < .003, respectively). The scores for exposure risk and neuroticism of participants were the main factors influencing both the SDS scores of the clinical laboratory staff (P = .002, P = .005, respectively), and also their SAS scores (P = .003 P = .006, respectively). Conclusions: The results showed that a significant proportion of clinical laboratory staff experienced anxiety and depression symptoms. Their scores for mental health problems, exposure risk, and neuroticism were associated with severe symptoms of depression and anxiety. Therefore, the high-risk group of the clinical laboratory staff and those individuals with higher neuroticism scores may need special attention.

Ziyuglycoside II alleviates cyclophosphamide-induced leukopenia in mice via regulation of HSPC proliferation and differentiation.

Ziyuglycoside II (ZGS II) is a major bioactive ingredient of Sanguisorbae officinalis L., which has been widely used for managing myelosuppression or leukopenia induced by chemotherapy or radiotherapy. In the current study, we investigated the pro-hematopoietic effects and underlying mechanisms of ZGS II in cyclophosphamide-induced leukopenia in mice. The results showed that ZGS II significantly increased the number of total white blood cells and neutrophils in the peripheral blood. Flow cytometry analysis also showed a significant increase in the number of nucleated cells and hematopoietic stem and progenitor cells (HSPCs) including ST-HSCs, MPPs, and GMPs, and enhanced HSPC proliferation in ZGS II treated mice. The RNA-sequencing analysis demonstrated that ZGS II effectively regulated cell differentiation, immune system processes, and hematopoietic system-related pathways related to extracellular matrix (ECM)-receptor interaction, focal adhesion, hematopoietic cell lineage, cytokine-cytokine receptor interaction, the NOD-like receptor signaling pathway, and the osteoclast differentiation pathway. Moreover, ZGS II treatment altered the differentially expressed genes (DEGs) with known functions in HSPC differentiation and mobilization (Cxcl12, Col1a2, and Sparc) and the surface markers of neutrophilic precursors or neutrophils (Ngp and CD177). Collectively, these data suggest that ZGS II protected against chemotherapy-induced leukopenia by regulating HSPC proliferation and differentiation.

Adjunctive Vagus Nerve Stimulation for Treatment-Resistant Depression: a Quantitative Analysis.

Vagus nerve stimulation (VNS) has been increasingly studied in treating treatment-resistant depression (TRD), but the findings have been mixed. This updated meta-analysis was conducted to examine the efficacy and safety of adjunctive VNS for TRD. Controlled studies reporting on the efficacy and safety of adjunctive VNS for TRD were screened, identified and analyzed. Standardized mean difference (SMD), risk ratio (RR) and their 95% confidence intervals (CIs) were analyzed using RevMan version 5.3. Three controlled studies with a total of 1048 patients with TRD compared VNS (n = 622) with control (n = 426) groups. Only one study was rated as 'high quality' using the Jadad scale. Adjunctive VNS was significantly superior to the control group regarding study-defined response [SMD:1.96 (95%CI:1.60, 2.40), P < 0.00001, I2 = 0%]. Patient-reported voice alteration occurred more frequently with adjunctive VNS for patients with TRD. No significant group differences were found regarding discontinuation due to any reason [RR:0.50 (95%CI:0.12, 2.09), P = 0.34, I2 = 85%]. Adjunctive VNS appeared to be effective and relatively safe treatment for TRD. Further randomized controlled trials are needed to confirm the efficacy and safety of VNS for TRD.