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Background More than 60% of stroke survivors experience residual deficits of the paretic upper limb/hand. Standard rehabilitation generates modest gains. Stimulation delivered to the surviving Primary Motor Cortex in the stroke-affected hemisphere has been considered a promising adjunct. However, recent trials challenge its advantage. We discuss our pilot clinical trial that aims to address factors implicated in divergent success of the approach. We assess safety, feasibility and efficacy of targeting an alternate locus during rehabilitation- the premotor cortex. In anticipating variance across patients, we measure neural markers differentiating response from non-response. Methods/Design In a randomized, sham-controlled, double-blinded pilot clinical study, patients with chronic stroke (n = 20) are assigned to receive transcranial direct current stimulation delivered to the premotor cortex or sham during rehabilitation of the paretic arm/hand. Patients receive the designated intervention for 30 min, twice a day for 3 days a week for 5 weeks. We assess hand function and patients' reports of use of paretic hand. A general linear mixed methods model will analyze changes from pre- to post-intervention. Responders and non-responders will be compared upon baseline level of function, and neural substrates, including function and integrity of output tracts, bi-hemispheric balance, and lesion profile. Incidence of adverse events will be compared using Fisher's Exact test, while rigor of blinding will be assessed with Chi-square analysis to ascertain feasibility. Discussion Variable success of cortical stimulation in rehabilitation can be related to gaps in theoretical basis and clinical investigation. Given that most patients with severe deficits have damage to the primary motor cortex or its output pathways, it would be futile to target stimulation to this site. We suggest targeting premotor cortex because it contributes substantially to descending output, a role that is amplified with greater damage to the motor cortex. With regards to clinical investigation, paired cortical stimulation in rehabilitation has been compared to rehabilitation alone in unblinded trials or to unconvincing sham conditions. Transcranial direct current stimulation, a noninvasive technique of brain stimulation, which offers a more effective placebo and has a favorable safety-feasibility profile, may improve scientific rigor. Neural markers of response would help inform patient selection for future clinical trials so we can address limitations of recent negative studies. [ABSTRACT FROM AUTHOR]

Background: A persistent redox state and excessive reactive species involved in carbohydrate and lipid metabolism lead to oxidative damage in the liver, however, how fasting plasma concentrations of lipids and glucose are associated with fasting blood levels of alanine transaminase (ALT) and aspartate transaminase (AST) remains to be evaluated in large-scale population., Methods: A cross-sectional study with 182,971 residents aged 18 to 92 years; multidimensional stratified analyses including quantile linear regression analysis and sex stratification were adopted to improve the quality of the evidence., Results: The associations between the concentrations of non-HDL-C and triglyceride and ALT levels were positive, stronger in males in each quantile of ALT levels and the coefficients expanded with increasing ALT levels at slopes of 3.610 and 5.678 in males and 2.977 and 5.165 in females, respectively. The associations between the HDL-C concentrations and ALT levels were negative, also stronger in males in each quantile and the coefficients expanded with increasing ALT levels at slopes of -7.839 in females and - 5.797 in males. The associations between glucose concentrations and ALT levels were positive, but stronger in females in each quantile and the coefficients expanded with increasing ALT levels at slopes of 1.736 in males and 2.177 in females, respectively. Similar pattern consist of relatively weaker coefficients and slops were observed between concentrations of non-HDL-C, triglyceride and glucose and AST levels. The associations between albumin concentration and concentrations of blood lipids and glucose were relatively steady across all quantiles., Conclusions: The dose dependent effect between blood concentrations of lipids and glucose and liver function changes suggests that excessive carbohydrate and lipid metabolism may cause subclinical liver damage. Long term sustained primary and secondary inflammatory factors produced in the liver might be transmitted to adjacent organs, such as the heart, kidneys, and lungs, to cause and/or exacerbate pathological changes in these visceral organs., (© 2024. The Author(s).)

Background: Mesenchymal stem cells (MSCs) possess powerful immunomodulatory ability. This study aimed to assess the efficacy and safety of human umbilical cord-derived mesenchymal stem cells (UMSCs) in patients with ulcerative colitis (UC) and to explore the potential mechanisms., Methods: This prospective, self-controlled clinical study was conducted at Henan Provincial People's Hospital. Patients with moderate-to-severe active UC, unresponsive to traditional drugs were continuously enrolled from September 2018 to March 2023. UMSCs were administered intravenously monthly for two months at a cell dosage of 1 × 10 6 per kg. The primary outcome was a clinical response at 2 months. The levels of cytokines and progerin in the plasma of the patients were analyzed using enzyme-linked immunosorbent assay kits, and longitudinal data was analyzed using generalized estimation equation., Results: Forty-one patients were enrolled and received UMSC therapy. At 2 months, 73.2% (30/41) of patients achieved a clinical response, and 41.5% (17/41) achieved a clinical remission. At 6 months, 2 patients were lost to follow-up; the corresponding figures were 70.0% (25/41) and 34.2% (14/41), respectively. After UMSC therapy, the Mayo score, Mayo endoscopy score, mean and maximum values of Ulcerative Colitis Endoscopic Index of Severity and Nancy index were significantly reduced compared with baseline values. Additionally, the levels of progerin and inflammatory markers, such as interleukin (IL)-1β, IL-6, IL-8, IL-12, and IL-17 A decreased, while hemoglobin, albumin, and IL-10/IL-17 A ratio increased, particularly in the response group. Multiple stepwise logistic regression analysis showed age was an independent risk factor affecting efficacy (odds ratio, 0.875 (95% confidence interval (0.787, 0.972)); the area under the receiver operating characteristic curve for age was 0.79. No serious adverse events were observed during or after UMSC therapy., Conclusion: UMSCs are safe and effective for patients with UC, with age being an independent risk factor affecting efficacy. Mechanistically, UMSC treatment may ameliorate cell senescence and suppress the secretion of pro-inflammatory cytokines., Trial Registration: The study was retrospectively registered at www.chictr.org.cn/ (ChiCTR1900026035) on September 18, 2019., (© 2024. The Author(s).)

Objective: Cerebral malperfusion (CM) is a common comorbidity in acute type A aortic dissection (ATAAD), which is associated with high mortality and poor neurological prognosis. This meta-analysis investigated the surgical strategy of ATAAD patients with CM, aiming to compare the difference in therapeutic effectiveness between the central repair-first and the early reperfusion-first according to clinical outcomes., Methods: The meta-analysis and systematic review was conducted based on studies sourced from the PubMed, Embase, and Cochrane literature database, in which cases of ATAAD with CM underwent surgical repair were included. Data for baseline characteristics, mortality, survival were extracted, and risk ratio (RR) values and the pooled mortality were calculated., Results: A total of 17 retrospective studies were analyzed, including 1010 cases of ATAAD with CM underwent surgical repair. The pooled early mortality in early reperfusion group was lower (8.1%; CI, 0.02 to 0.168) than that in the central repair group (16.2%; CI, 0.115 to 0.216). The pooled long-term mortality was 7.9% in the early reperfusion cohort and 17.4% the central repair-first cohort, without a statistically significant heterogeneity (I [2] = 51.271%; p = 0.056). The mean time of symptom-onset-to-the-operation-room in all the reports was 8.87 ± 12.3 h., Conclusion: This meta-analysis suggested that early reperfusion-first may achieved better outcomes compared to central repair-first in ATAAD patients complicated with CM to some extent. Early operation and early restoration of cerebral perfusion may reduce the occurrence of some neurological complications., Trial Registration: The meta-analysis was registered in the International Prospective Register of Systematic Reviews database (No. CRD CRD42023475629) on Nov. 8th, 2023., (© 2024. The Author(s).)

Background: Acute pancreatitis (AP) is a prevalent exocrine inflammatory disorder of the pancreas characterized by pancreatic inflammation and injury to acinar cells. Vitamin B6 (VB6) is a vital nutrient that plays a significant role in preserving human health and has anti-inflammatory and anti-apoptotic effects., Methods: This study aimed to explore the potential pancreatic protective effects of VB6 in mitigating pancreatic inflammation and apoptosis induced by taurocholate sodium (TLCS) in an AP model and to assess the underlying mechanism of action. AP was induced in Sprague‒Dawley (SD) rats through TLCS administration and lipopolysaccharide (LPS)-treated AR42J cells, followed by treatment with VB6., Results: Various parameters associated with AP were assessed in both plasma and pancreatic tissues. VB6 has been shown to ameliorate the severity of AP through various mechanisms. It effectively reduces the levels of serum amylase, lipase, and inflammatory factors, thereby mitigating histological injury to the pancreas. Moreover, VB6 inhibited pancreatic apoptosis by downregulating bax expression and up-regulating Bcl2 expression in TLCS-treated rats. Additionally, VB6 suppressed the expression of caspase3. The anti-inflammatory and anti-apoptotic effects of VB6 observed in LPS-treated AR42J cells are consistent with those observed in a rat model of AP., Conclusions: These results suggest that VB6 exerts anti-inflammatory and anti-apoptotic effects through inhibition of the caspase3 signaling pathway and has a protective effect against AP., (© 2024. The Author(s).)

Background: The severity and frequency of drought are expected to increase substantially in the coming century and dramatically reduce crop yields. Manipulation of rhizosphere microbiomes is an emerging strategy for mitigating drought stress in agroecosystems. However, little is known about the mechanisms underlying how drought-resistant plant recruitment of specific rhizosphere fungi enhances drought adaptation of drought-sensitive wheats. Here, we investigated microbial community assembly features and functional profiles of rhizosphere microbiomes related to drought-resistant and drought-sensitive wheats by amplicon and shotgun metagenome sequencing techniques. We then established evident linkages between root morphology traits and putative keystone taxa based on microbial inoculation experiments. Furthermore, root RNA sequencing and RT-qPCR were employed to explore the mechanisms how rhizosphere microbes modify plant response traits to drought stresses., Results: Our results indicated that host plant signature, plant niche compartment, and planting site jointly contribute to the variation of soil microbiome assembly and functional adaptation, with a relatively greater effect of host plant signature observed for the rhizosphere fungi community. Importantly, drought-resistant wheat (Yunhan 618) possessed more diverse bacterial and fungal taxa than that of the drought-sensitive wheat (Chinese Spring), particularly for specific fungal species. In terms of microbial interkingdom association networks, the drought-resistant variety possessed more complex microbial networks. Metagenomics analyses further suggested that the enriched rhizosphere microbiomes belonging to the drought-resistant cultivar had a higher investment in energy metabolism, particularly in carbon cycling, that shaped their distinctive drought tolerance via the mediation of drought-induced feedback functional pathways. Furthermore, we observed that host plant signature drives the differentiation in the ecological role of the cultivable fungal species Mortierella alpine (M. alpina) and Epicoccum nigrum (E. nigrum). The successful colonization of M. alpina on the root surface enhanced the resistance of wheats in response to drought stresses via activation of drought-responsive genes (e.g., CIPK9 and PP2C30). Notably, we found that lateral roots and root hairs were significantly suppressed by co-colonization of a drought-enriched fungus (M. alpina) and a drought-depleted fungus (E. nigrum)., Conclusions: Collectively, our findings revealed host genotypes profoundly influence rhizosphere microbiome assembly and functional adaptation, as well as it provides evidence that drought-resistant plant recruitment of specific rhizosphere fungi enhances drought tolerance of drought-sensitive wheats. These findings significantly underpin our understanding of the complex feedbacks between plants and microbes during drought, and lay a foundation for steering "beneficial keystone biome" to develop more resilient and productive crops under climate change. Video Abstract., (© 2024. The Author(s).)

Two-dimensional nanomaterials (2D NMs), characterized by a large number of atoms or molecules arranged in one dimension (typically thickness) while having tiny dimensions in the other two dimensions, have emerged as a pivotal class of materials with unique properties. Their flat and sheet-like structure imparts distinctive physical, chemical, and electronic attributes, which offers several advantages in biomedical applications, including enhanced surface area for efficient drug loading, surface-exposed atoms allowing precise chemical modifications, and the ability to form hierarchical multilayer structures for synergistic functionality. Exploring their nano-bio interfacial interactions with biological components holds significant importance in comprehensively and systematically guiding safe applications. However, the current lack of in-depth analysis and comprehensive understanding of interfacial effects on cancer treatment motivates our ongoing efforts in this field. This study provides a comprehensive survey of recent advances in utilizing 2D NMs for cancer treatment. It offers insights into the structural characteristics, synthesis methods, and surface modifications of diverse 2D NMs. The investigation further delves into the formation of nano-bio interfaces during their in vivo utilization. Notably, the study discusses a wide array of biomedical applications in cancer treatment. With their potential to revolutionize therapeutic strategies and outcomes, 2D NMs are poised at the forefront of cancer treatment, holding the promise of transformative advancements., (© 2024. The Author(s).)

Background: Myocardial ischemia-reperfusion injury (MIRI) is widespread in the treatment of ischemic heart disease, and its treatment options are currently limited. Adiponectin (APN) is an adipocytokine with cardioprotective properties; however, the mechanisms of APN in MIRI are unclear. Therefore, based on preclinical (animal model) evidence, the cardioprotective effects of APN and the underlying mechanisms were explored., Methods: The literature was searched for the protective effect of APN on MIRI in six databases until 16 November 2023, and data were extracted according to selection criteria. The outcomes were the size of the myocardial necrosis area and hemodynamics. Markers of oxidation, apoptosis, and inflammation were secondary outcome indicators. The quality evaluation was performed using the animal study evaluation scale recommended by the Systematic Review Center for Laboratory animal Experimentation statement. Stata/MP 14.0 software was used for the summary analysis., Results: In total, 20 papers with 426 animals were included in this study. The pooled analysis revealed that APN significantly reduced myocardial infarct size [weighted mean difference (WMD) = 16.67 (95% confidence interval (CI) = 13.18 to 20.16, P < 0.001)] and improved hemodynamics compared to the MIRI group [Left ventricular end-diastolic pressure: WMD = 5.96 (95% CI = 4.23 to 7.70, P < 0.001); + dP/dtmax: WMD = 1393.59 (95% CI = 972.57 to 1814.60, P < 0.001); -dP/dtmax: WMD = 850.06 (95% CI = 541.22 to 1158.90, P < 0.001); Left ventricular ejection fraction: WMD = 9.96 (95% CI = 7.29 to 12.63, P < 0.001)]. Apoptosis indicators [caspase-3: standardized mean difference (SMD) = 3.86 (95% CI = 2.97 to 4.76, P < 0.001); TUNEL-positive cells: WMD = 13.10 (95% CI = 8.15 to 18.05, P < 0.001)], inflammatory factor levels [TNF-α: SMD = 4.23 (95% CI = 2.48 to 5.98, P < 0.001)], oxidative stress indicators [Superoxide production: SMD = 4.53 (95% CI = 2.39 to 6.67, P < 0.001)], and lactate dehydrogenase levels [SMD = 2.82 (95% CI = 1.60 to 4.04, P < 0.001)] were significantly reduced. However, the superoxide dismutase content was significantly increased [SMD = 1.91 (95% CI = 1.17 to 2.65, P < 0.001)]., Conclusion: APN protects against MIRI via anti-inflammatory, antiapoptotic, and antioxidant effects, and this effect is achieved by activating different signaling pathways., (© 2024. The Author(s).)

Introduction: There is a high morbidity and mortality rate in mechanical trauma (MT)-induced hepatic injury. Currently, the molecular mechanisms underlying liver MT are largely unclear. Exploring the underlying mechanisms and developing safe and effective medicines to alleviate MT-induced hepatic injury is an urgent requirement. The aim of this study was to reveal the role of mitochondria-associated ER membranes (MAMs) in post-traumatic liver injury, and ascertain whether melatonin protects against MT-induced hepatic injury by regulating MAMs., Methods: Hepatic mechanical injury was established in Sprague-Dawley rats and primary hepatocytes. A variety of experimental methods were employed to assess the effects of melatonin on hepatic injury, apoptosis, MAMs formation, mitochondrial function and signaling pathways., Results: Significant increase of IP 3 R1 expression and MAMs formation were observed in MT-induced hepatic injury. Melatonin treatment at the dose of 30 mg/kg inhibited IP 3 R1-mediated MAMs and attenuated MT-induced liver injury in vivo. In vitro, primary hepatocytes cultured in 20% trauma serum (TS) for 12 h showed upregulated IP 3 R1 expression, increased MAMs formation and cell injury, which were suppressed by melatonin (100 μmol/L) treatment. Consequently, melatonin suppressed mitochondrial calcium overload, increased mitochondrial membrane potential and improved mitochondrial function under traumatic condition. Melatonin's inhibitory effects on MAMs formation and mitochondrial calcium overload were blunted when IP 3 R1 was overexpressed. Mechanistically, melatonin bound to its receptor (MR) and increased the expression of phosphorylated ERK1/2, which interacted with FoxO1 and inhibited the activation of FoxO1 that bound to the IP 3 R1 promoter to inhibit MAMs formation., Conclusion: Melatonin prevents the formation of MAMs via the MR-ERK1/2-FoxO1-IP 3 R1 pathway, thereby alleviating the development of MT-induced liver injury. Melatonin-modulated MAMs may be a promising therapeutic therapy for traumatic hepatic injury., (© 2024. The Author(s).)

Wu-tou decoction (WTD), a traditional Chinese medicine prescription, is used to treat rheumatoid arthritis (RA). It works by controlling intestinal flora and its metabolites, which in turn modulates the inflammatory response and intestinal barrier function. Small molecular compounds (SM) and polysaccharides (PS) were the primary constituents of WTD extract. In this work, a model of adjuvant-induced arthritis (AIA) in rats was established and treated with WTD, SM, and PS, respectively. 16S rRNA gene sequencing was used to examine the regulatory impact of the various groups on the disturbance of the gut flora induced by RA. Further, since PS cannot be absorbed into the blood, the influence of PS on the absorption and metabolism of SM was studied by examining their pharmacokinetic (PK) parameters of 23 active components in SM by UPLC-MS/MS. WTD was found to be more effective than PS and SM in alleviating arthritis in AIA rats, which may be related to changes in gut flora. The PK properties of 13 active compounds were altered after PS intervene. Based on the findings, PS may be able to manage the disruption of intestinal microbiota, enhance the intestinal environment of model animals, and hence influence SM absorption and metabolism., (© 2024. The Author(s).)

Aims: In-depth studies on plant ion uptake and plant growth-promoting rhizobacteria (PGPR) at the molecular level will help to further reveal the effects of PGPR on plants and their interaction mechanisms under salt stress., Methods: Cotton was inoculated with a PGPR-Enterobacter cloacae Rs-35, and the ion uptake capacity, membrane transporter protein activity, and expression of key genes were determined under salt stress. Changes in the endogenous hormone content of cotton were also determined. Further, the genome-wide metabolic pathway annotation of E. cloacae Rs-35 and its differential enrichment pathway analysis of multi-omics under salinity environments were performed., Results: In a pot experiment of saline-alkali soil, E. cloacae Rs-35-treated cotton significantly increased its uptake of K + and Ca 2+ and decreased uptake of Na + , elevated the activity of the H + -ATPase, and increased the sensitivity of the Na + /H + reverse transporter protein on the vesicle membrane. Meanwhile, inoculation with E. cloacae Rs-35 could promote cotton to maintain the indole-3-acetic acid (IAA) content under salt stress. Genome-wide annotation showed that E. cloacae Rs-35 was respectively annotated to 31, 38, and 130 related genes in osmotic stress, phytohormone and organic acid metabolism, and ion uptake metabolic pathway. Multi-omics differences analysis showed that E. cloacae Rs-35 were enriched to tryptophan metabolism, multiple amino acid biosynthesis, carbon and glucose synthesis, and oxidative phosphorylation metabolic pathways at the transcriptome, proteome, and metabolome., Conclusion: E. cloacae Rs-35 can promote cotton balance cell ion concentration, stabilize intracellular IAA changes, stimulate induction of systemic tolerance, and promote the growth of cotton plants under salt stress., (© 2023. The Author(s).)

Background: Epithelial ovarian cancer (OC) is the fourth leading cause of cancer-related deaths in women, with a 5-year survival rate of 30%-50%. Platinum resistance is the chief culprit for the high recurrence and mortality rates. Several studies confirm that the metabolic regulation of ubiquitinating enzymes plays a vital role in platinum resistance in OC., Methods: In this study, we selected ubiquitin-conjugating enzyme E2S (UBE2S) as the candidate gene for validation. The levels of UBE2S expression were investigated using TCGA, GTEx, UALCAN, and HPA databases. In addition, the correlation between UBE2S and platinum resistance in OC was analyzed using data from TCGA. Cisplatin-resistant OC cell lines were generated and UBE2S was knocked down; the transfection efficiency was verified. Subsequently, the effects of knockdown of UBE2S on the proliferation and migration of cisplatin-resistant OC cells were examined through the CCK8, Ki-67 immunofluorescence, clone formation, wound healing, and transwell assays. In addition, the UBE2S gene was also validated in vivo by xenograft models in nude mice. Finally, the relationship between the UBE2S gene and autophagy and the possible underlying regulatory mechanism was preliminarily investigated through MDC and GFP-LC3-B autophagy detection and western blotting experiments. Most importantly, experimental validation of mTOR agonist reversion (the rescuse experiments) was also performed., Results: UBE2S was highly expressed in OC at both nucleic acid and protein levels. The results of immunohistochemistry showed that the level of UBE2S expression in platinum-resistant samples was significantly higher relative to the platinum-sensitive samples. By cell transfection experiments, knocking down of the UBE2S gene was found to inhibit the proliferation and migration of cisplatin-resistant OC cells. Moreover, the UBE2S gene could inhibit autophagy by activating the PI3K/AKT/mTOR signaling pathway to induce cisplatin resistance in OC in vivo and in vitro., Conclusion: In conclusion, we discovered a novel oncogene, UBE2S, which was associated with platinum response in OC, and examined its key role through bioinformatics and preliminary experiments. The findings may open up a new avenue for the evaluation and treatment of OC patients at high risk of cisplatin resistance., (© 2023. The Author(s).)

Background: Milk production traits are complex traits with vital economic importance in the camel industry. However, the genetic mechanisms regulating milk production traits in camels remain poorly understood. Therefore, we aimed to identify candidate genes and metabolic pathways that affect milk production traits in Bactrian camels., Methods: We classified camels (fourth parity) as low- or high-yield, examined pregnant camels using B-mode ultrasonography, observed the microscopic changes in the mammary gland using hematoxylin and eosin (HE) staining, and used RNA sequencing to identify differentially expressed genes (DEGs) and pathways., Results: The average standard milk yield over the 300 days during parity was recorded as 470.18 ± 9.75 and 978.34 ± 3.80 kg in low- and high-performance camels, respectively. Nine female Junggar Bactrian camels were subjected to transcriptome sequencing, and 609 and 393 DEGs were identified in the low-yield vs. high-yield (WDL vs. WGH) and pregnancy versus colostrum period (RSQ vs. CRQ) comparison groups, respectively. The DEGs were compared with genes associated with milk production traits in the Animal Quantitative Trait Loci database and in Alashan Bactrian camels, and 65 and 46 overlapping candidate genes were obtained, respectively. Functional enrichment and protein-protein interaction network analyses of the DEGs and candidate genes were conducted. After comparing our results with those of other livestock studies, we identified 16 signaling pathways and 27 core candidate genes associated with maternal parturition, estrogen regulation, initiation of lactation, and milk production traits. The pathways suggest that emerged milk production involves the regulation of multiple complex metabolic and cellular developmental processes in camels. Finally, the RNA sequencing results were validated using quantitative real-time PCR; the 15 selected genes exhibited consistent expression changes., Conclusions: This study identified DEGs and metabolic pathways affecting maternal parturition and milk production traits. The results provides a theoretical foundation for further research on the molecular mechanism of genes related to milk production traits in camels. Furthermore, these findings will help improve breeding strategies to achieve the desired milk yield in camels., (© 2023. The Author(s).)

Background: Laryngopharyngeal cancer (LPC) includes laryngeal and hypopharyngeal cancer, whose early diagnosis can significantly improve the prognosis and quality of life of patients. Pathological biopsy of suspicious cancerous tissue under the guidance of laryngoscopy is the gold standard for diagnosing LPC. However, this subjective examination largely depends on the skills and experience of laryngologists, which increases the possibility of missed diagnoses and repeated unnecessary biopsies. We aimed to develop and validate a deep convolutional neural network-based Laryngopharyngeal Artificial Intelligence Diagnostic System (LPAIDS) for real-time automatically identifying LPC in both laryngoscopy white-light imaging (WLI) and narrow-band imaging (NBI) images to improve the diagnostic accuracy of LPC by reducing diagnostic variation among on-expert laryngologists., Methods: All 31,543 laryngoscopic images from 2382 patients were categorised into training, verification, and test sets to develop, validate, and internal test LPAIDS. Another 25,063 images from five other hospitals were used as external tests. Overall, 551 videos were used to evaluate the real-time performance of the system, and 200 randomly selected videos were used to compare the diagnostic performance of the LPAIDS with that of laryngologists. Two deep-learning models using either WLI (model W) or NBI (model N) images were constructed to compare with LPAIDS., Results: LPAIDS had a higher diagnostic performance than models W and N, with accuracies of 0·956 and 0·949 in the internal image and video tests, respectively. The robustness and stability of LPAIDS were validated in external sets with the area under the receiver operating characteristic curve values of 0·965-0·987. In the laryngologist-machine competition, LPAIDS achieved an accuracy of 0·940, which was comparable to expert laryngologists and outperformed other laryngologists with varying qualifications., Conclusions: LPAIDS provided high accuracy and stability in detecting LPC in real-time, which showed great potential for using LPAIDS to improve the diagnostic accuracy of LPC by reducing diagnostic variation among on-expert laryngologists., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Purpose: Manual clinical target volume (CTV) and gross tumor volume (GTV) delineation for rectal cancer neoadjuvant radiotherapy is pivotal but labor-intensive. This study aims to propose a deep learning (DL)-based workflow towards fully automated clinical target volume (CTV) and gross tumor volume (GTV) delineation for rectal cancer neoadjuvant radiotherapy., Materials & Methods: We retrospectively included 141 patients with Stage II-III mid-low rectal cancer and randomly grouped them into training (n = 121) and testing (n = 20) cohorts. We adopted a divide-and-conquer strategy to address CTV and GTV segmentation using two separate DL models with DpuUnet as backend-one model for CTV segmentation in the CT domain, and the other for GTV in the MRI domain. The workflow was validated using a three-level multicenter-involved blind and randomized evaluation scheme. Dice similarity coefficient (DSC) and 95th percentile Hausdorff distance (95HD) metrics were calculated in Level 1, four-grade expert scoring was performed in Level 2, and head-to-head Turing test in Level 3., Results: For the DL-based CTV contours over the testing cohort, the DSC and 95HD (mean ± SD) were 0.85 ± 0.06 and 7.75 ± 6.42 mm respectively, and 96.4% cases achieved clinical viable scores (≥ 2). The positive rate in the Turing test was 52.3%. For GTV, the DSC and 95HD were 0.87 ± 0.07 and 4.07 ± 1.67 mm respectively, and 100% of the DL-based contours achieved clinical viable scores (≥ 2). The positive rate in the Turing test was 52.0%., Conclusion: The proposed DL-based workflow exhibited promising accuracy and excellent clinical viability towards automated CTV and GTV delineation for rectal cancer neoadjuvant radiotherapy., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Knee osteoarthritis (KOA) is a common public health problem and a leading cause of long-term pain, decreased muscle strength, and even disability. Tai Chi has been proved effective and highly recommended for KOA management worldwide. However, little is known about its benefits on quadriceps strength which is closely associated with relieving knee pain. This trial is designed to evaluate the efficacy and safety of Tai Chi on knee pain and muscle strength in middle-aged and older adults with KOA., Methods: A total of 100 participants will be randomly divided into a Tai Chi group (TC group) (1x/week for 12 weeks) and a control group with a health education and stretching program (1x/week for 12 weeks) with a follow-up period of 6 weeks. The primary outcome is the change of Western Ontario and McMaster Universities (WOMAC) pain subscale at week 12 compared with baseline. Secondary outcomes include WOMAC stiffness and function subscales, data from isokinetic dynamometry, gait analysis with electromyography (EMG), and a 36-item short form health survey (SF-36). The daily dose of pain-relieving medication will also be recorded. All adverse effects will be assessed by the Treatment Emergent Symptom Scale (TESS)., Discussion: We expect this randomized trial to evaluate the effectiveness of Tai Chi on relieving pain and increasing quadriceps strength in KOA patients. This protocol, if proven effective, will contribute to providing a promising alternative intervention for middle-aged and older adults with KOA., Trials Registration Number: This trial has been registered in the China Clinical Trials Registry (registration number: ChiCTR2300069339)., (© 2023. The Author(s).)

Background: For recurrent laryngeal cancer, the feasibility of salvage transoral laser microsurgery (TLM) remains controversial. This study compared the efficacy of TLM and open partial laryngectomy (OPL) for treatment of early local recurrence of glottic squamous cell cancer (GSCC) and confirm the effectiveness of salvage TLM as a treatment option., Methods: This retrospective study involved 55 patients with early local recurrent GSCC treated with TLM, and the oncologic outcomes, functional outcomes, hospitalization time and complications were compared with a group of 40 recurrent GSCC patients matched for clinical variables of TLM group, treated by OPL by the same team of surgeons., Results: The 5-year overall survival and disease-specific survival rates were 65.8% and 91.5%, respectively, for 55 patients with rT is -rT 2 stage treated by TLM and 77.1% and 94.7%, respectively, for 40 patients with rT is -rT 2 stage treated by OPL (OPL group). In the TLM and OPL groups, the local control rates after 5 years were 77.5% and 79.3%, respectively, and the laryngeal preservation rates were 94.4% and 83.6%, respectively (p > 0.05). Compared with the OPL group, the complication rate (1.82%) and hospitalization duration (5.42 ± 2.26 days) were significantly lower in the TLM group (p < 0.05). Compared with the OPL group, postsurgical health-related quality of life and quality of voice were significantly better in the TLM group (p < 0.001)., Conclusion: Salvage TLM can be used as an effective treatment option for suitable patients after a full, comprehensive, and careful assessment of the characteristics of early locally recurrent glottic carcinoma., (© 2023. The Author(s).)

Background: The rhizosphere microbiome, which is shaped by host genotypes, root exudates, and plant domestication, is crucial for sustaining agricultural plant growth. Despite its importance, how plant domestication builds up specific rhizosphere microbiomes and metabolic functions, as well as the importance of these affected rhizobiomes and relevant root exudates in maintaining plant growth, is not well understood. Here, we firstly investigated the rhizosphere bacterial and fungal communities of domestication and wild accessions of tetraploid wheat using amplicon sequencing (16S and ITS) after 9 years of domestication process at the main production sites in China. We then explored the ecological roles of root exudation in shaping rhizosphere microbiome functions by integrating metagenomics and metabolic genomics approaches. Furthermore, we established evident linkages between root morphology traits and keystone taxa based on microbial culture and plant inoculation experiments., Results: Our results suggested that plant rhizosphere microbiomes were co-shaped by both host genotypes and domestication status. The wheat genomes contributed more variation in the microbial diversity and composition of rhizosphere bacterial communities than fungal communities, whereas plant domestication status exerted much stronger influences on the fungal communities. In terms of microbial interkingdom association networks, domestication destabilized microbial network and depleted the abundance of keystone fungal taxa. Moreover, we found that domestication shifted the rhizosphere microbiome from slow growing and fungi dominated to fast growing and bacteria dominated, thereby resulting in a shift from fungi-dominated membership with enrichment of carbon fixation genes to bacteria-dominated membership with enrichment of carbon degradation genes. Metagenomics analyses further indicated that wild cultivars of wheat possess higher microbial function diversity than domesticated cultivars. Notably, we found that wild cultivar is able to harness rhizosphere microorganism carrying N transformation (i.e., nitrification, denitrification) and P mineralization pathway, whereas rhizobiomes carrying inorganic N fixation, organic N ammonification, and inorganic P solubilization genes are recruited by the releasing of root exudates from domesticated wheat. More importantly, our metabolite-wide association study indicated that the contrasting functional roles of root exudates and the harnessed keystone microbial taxa with different nutrient acquisition strategies jointly determined the aboveground plant phenotypes. Furthermore, we observed that although domesticated and wild wheats recruited distinct microbial taxa and relevant functions, domestication-induced recruitment of keystone taxa led to a consistent growth regulation of root regardless of wheat domestication status., Conclusions: Our results indicate that plant domestication profoundly influences rhizosphere microbiome assembly and metabolic functions and provide evidence that host plants are able to harness a differentiated ecological role of root-associated keystone microbiomes through the release of root exudates to sustain belowground multi-nutrient cycles and plant growth. These findings provide valuable insights into the mechanisms underlying plant-microbiome interactions and how to harness the rhizosphere microbiome for crop improvement in sustainable agriculture. Video Abstract., (© 2023. The Author(s).)

Background: Hair follicle stem cells (HFSCs) are considered as a promising cell type in the stem cell transplantation treatment of neurological diseases because of their rich sources, easy access, and the same ectoderm source as the nervous system. Hepatocyte growth factor (HGF) is a pleiotropic cytokine that shows neuroprotective function in ischemic stroke. Here we assessed the therapeutic effects of HFSCs on ischemic stroke injury and the synthetic effect of HGF along with HFSCs., Methods: Rat HFSCs were intravenously transplanted into a middle cerebral artery ischemia/reperfusion (I/R) rat model. Neurological scoring and TTC staining were performed to assess the benefits of HFSC transplantation. Inflammatory cytokines, blood-brain barrier integrity and angiogenesis within penumbra were estimated by Western blot and immunohistochemistry. The differentiation of HFSCs was detected by immunofluorescence method 2 weeks after transplantation., Results: HFSC transplantation could significantly inhibit the activation of microglia, improve the integrity of blood-brain barrier and reduce brain edema. Moreover, the number of surviving neurons and microvessels density in the penumbra were upregulated by HFSC transplantation, leading to better neurological score. The combination of HFSCs and HGF could significantly improve the therapeutic benefit., Conclusion: Our results indicate for the first time that HGF modified HFSCs can reduce I/R injury and promote the neurological recovery by inhibiting inflammatory response, protecting blood-brain barrier and promoting angiogenesis., (© 2023. The Author(s).)

Background: The overall survival rate of patients with advanced ovarian cancer (OC) has remained static for several decades. Advanced ovarian cancer is known for its poor prognosis due to extensive metastasis. Epigenetic alterations contribute to tumour progression and therefore are of interest for potential therapeutic strategies., Methods: Following our previous study, we identified that CHD4, a chromatin remodelling factor, plays a strong role in ovarian cancer cell metastasis. We investigated the clinical significance of CHD4 through TCGA and GEO database analyses and explored the effect of CHD4 expression modulation and romidepsin treatment on the biological behaviour of ovarian cancer through CCK-8 and transwell assays. Bioluminescence imaging of tumours in xenografted mice was applied to determine the therapeutic effect of romidepsin. GSEA and western blotting were used to screen the regulatory mechanism of CHD4., Results: In ovarian cancer patient specimens, high CHD4 expression was associated with a poor prognosis. Loss of function of CHD4 in ovarian cancer cells induced suppression of migration and invasion. Mechanistically, CHD4 knockdown suppressed the expression of EZH2 and the nuclear accumulation of β-catenin. CHD4 also suppressed the metastasis of ovarian cancer cells and prevented disease progression in a mouse model. To inhibit the functions of CHD4 that are mediated by histone deacetylase, we evaluated the effect of the HDAC1/2 selective inhibitor romidepsin. Our findings indicated that treatment with romidepsin suppressed the progression of metastases in vitro and in vivo., Conclusions: Collectively, our results uncovered an oncogenic function of CHD4 in ovarian cancer and provide a rationale for clinical trials of romidepsin in ovarian cancer patients., (© 2023. The Author(s).)

Background: Brugada syndrome (Brs) and long QT syndrome (LQTs) are the most observed "inherited primary arrhythmia syndromes" and "channelopathies", which lead to sudden cardiac death., Methods: Detailed clinical information of Brs and LQTs patients was collected. Genomic DNA samples of peripheral blood were conducted for whole-exome sequencing on the Illumina HiSeq 2000 platform. Then, we performed bioinformatics analysis for 200 genes susceptible to arrhythmias and cardiomyopathies. Protein interaction and transcriptomic co-expression were analyzed using the online website and GTEx database., Results: All sixteen cases of Brs and six cases of LQTs were enrolled in the current study. Four Brs carried known pathogenic or likely pathogenic of single-point mutations, including SCN5A p.R661W, SCN5A p.R965C, and KCNH2 p.R692Q. One Brs carried the heterozygous compound mutations of DSG2 p.F531C and SCN5A p.A1374S. Two Brs carried the novel heterozygous truncated mutations (MAF &lt; 0.001) of NEBL (p.R882X) and NPPA (p.R107X), respectively. Except for the indirect interaction between NEBL and SCN5A, NPPA directly interacts with SCN5A. These gene expressions had a specific and significant positive correlation in myocardial tissue, with high degrees of co-expression and synergy. Two Brs carried MYH7 p.E1902Q and MYH6 p.R1820Q, which were predicted as "damaging/possibly damaging" and "damaging/damaging" by Polyphen and SIFT algorithm. Two LQTs elicited the pathogenic single splicing mutation of KCNQ1 (c.922-1G &gt; C). Three LQTs carried a single pathogenic mutation of SCN5A p.R1880H, KCNH2 p.D161N, and KCNQ1 p.R243S, respectively. One patient of LQTs carried a frameshift mutation of KCNH2 p. A188Gfs*143., Conclusions: The truncated mutations of NEBL (p.R882X) and NPPA (p.R107X) may induce Brugada syndrome by abnormally affecting cardiac sodium channel. SCN5A (p.R661W, p.R965C and p.A1374S) and KCNH2 (p.R692Q) may cause Brugada syndrome, while SCN5A (p.R1880H), KCNQ1 (c.922-1G &gt; C and p.R243S) and KCNH2 (p.D161N and p.A188Gfs*143) may lead to long QT syndrome., (© 2022. The Author(s).)

Background: The global burden of hepatocellular carcinoma (HCC) is increasing, negatively impacting social health and economies. The discovery of novel and valuable biomarkers for the early diagnosis and therapeutic guidance of HCC is urgently needed., Methods: Extracellular matrix (ECM)-related gene sets, transcriptome data and mutation profiles were downloaded from the Matrisome Project and The Cancer Genome Atlas (TCGA)-LIHC datasets. Coexpression analysis was initially performed with the aim of identifying ECM-related lncRNAs (r > 0.4, p < 0.001). The screened lncRNAs were subjected to univariate analysis to obtain a series of prognosis-related lncRNA sets, which were incorporated into least absolute selection and shrinkage operator (LASSO) regression for signature establishment. Following the grouping of LIHC samples according to risk score, the correlations between the signature and clinicopathological, tumour immune infiltration, and mutational characteristics as well as therapeutic response were also analysed. lncRNA expression levels used for modelling were finally examined at the cellular and tissue levels by real-time PCR. All analyses were based on R software., Results: AL031985.3 and MKLN1-AS were ultimately identified as signature-related lncRNAs, and both were significantly upregulated in HCC tissue samples and cell lines. The prognostic value of the signature reflected by the AUC value was superior to that of age, sex, grade and stage. Correlation analysis results demonstrated that high-risk groups exhibited significant enrichment of immune cells (DCs, macrophages and Tregs) and increased expression levels of all immune checkpoint genes. Prominent differences in clinicopathological profiles, immune functions, tumour mutation burden (TMB) and drug sensitivity were noted between the two risk groups., Conclusions: Our signature represents a valuable predictive tool in the prognostic management of HCC patients. Further validation of the mechanisms involved is needed., (© 2022. The Author(s).)

Background: In camels, nasopharyngeal myiasis is caused by the larvae of Cephalopina titillator, which parasitize the tissues of nasal and paranasal sinuses, pharynx, and larynx. C. titillator infestation adversely affects the health of camels and decreases milk and meat production and even death. However, the C. titillator infestation in Bactrian camels has not been widely studied., Methods: The present study was conducted to determine the prevalence and risk factors of C. titillator in Bactrian camels of northwestern Xinjiang. Suspected larvae recovered from infested camels were evaluated for C. titillator by microscopy and polymerase chain reaction. Nucleotide sequences of the partial mitochondrial cytochrome c oxidase subunit I (COX1) and cytochrome b (CYTB) genes from the C. titillator of camels were aligned from the NCBI database. Furthermore, the gross and histopathological alterations associated with C. titillator infestation were evaluated via pathological examination., Results: Of 1263 camels examined 685 (54.2%) camels were infested with suspected C. titillator larvae. Different larval stages were topically detected in the nasal passages and pharynx of the camel heads. Microscopy analysis of the pharyngeal mucosa tissue revealed necrotic tissue debris and some inflammatory cells. Molecular detection of the larval COX1 and CYTB genes indicated that pathogen collected in Bactrian camels was C. titillator. The epidemiological study demonstrated that the prevalence rate of C.titillator infestation was significantly higher in camels of Bestierek Town Pasture (67.2%) and Karamagai Town Pasture (63.6%) compared to Kitagel Town Pasture (38.7%) and Qibal Town Pasture (35.8%) (P < 0.05). No significant difference was observed between the prevalence rates in male (52.6%) and female (54.6%) camels (P > 0.05). The prevalence was higher in warm (64.2%) than that in cold (48.4%) seasons (P < 0.001). The prevalence in camels with non-nomadic method (67.2%) was significantly higher than in animals with nomadic method (47.5%) (P < 0.001). The prevalence of C.titillator infestation was significantly higher in animals of aged 5-10 (60.1%) and aged > 10 (61.1%) years old compared to those of aged < 5 (31.7%) years old camels (P < 0.001)., Conclusion: Our results confirm that there is a high prevalence of C. titillator in Bactrian camels from Xinjiang, closely related to age, season, pasture environment, and husbandry methods. Developing prevention, diagnosis, and control programs to prevent transmission is necessary., (© 2022. The Author(s).)

Background: To explore the prevalence, outcome and perinatal risks of neonatal hypoxemic respiratory failure (NRF) in a survey of all livebirths from a regional network of perinatal-neonatal care during the transition period after 5-year universal health insurance implemented in China., Methods: Clinical data of all neonatal respiratory morbidities in Huai'an were retrospectively collected in the regional perinatal network database of all livebirths as vital statistics in 2015. NRF was defined as hypoxemia requiring continuous positive airway pressure (CPAP) and/or mechanical ventilation (MV) for at least 24 h. Mortality risks of antenatal and perinatal morbidities, major respiratory therapies and complications were analyzed by multivariable logistic regression model., Results: There were 788 NRF cases identified in 9.9% (7960) hospitalized, or 13.3‰ (59056) livebirths, in which 6.7% received intensive care and 93.0% critical care. The major underlying morbidities were respiratory distress syndrome (RDS, 36.4%) and pneumonia/sepsis (35.3%), treated mainly by CPAP, MV and surfactant. Significantly improved outcomes by surfactant in RDS were in patients with birthweight (BW) < 1500 g or gestational age (GA) < 32 weeks. The overall mortality rate in NRF was 18.4% whereas for those of BW < 1000 g and GA < 28 weeks, 70% and 54%, respectively. The multivariable regression analysis showed the highest odds for NRF death among meconium aspiration syndrome, congenital anomalies, BW < 1500 g and necrotizing enterocolitis, whereas born in level III hospitals, cesarean delivery, CPAP and MV were associated with markedly reduced death odds., Conclusions: The salient findings with associated risk estimates reflected efficiency of respiratory support as critical care in a prefectural regional network infrastructure for annual livebirths in 5.6 million inhabitants. It implicated the representativeness of contemporaneous perinatal-neonatal care standard at medium to medium-high level, in one/fourth of the population of China, aiming at saving more life of very critical and preterm infants for better survival., (© 2022. The Author(s).)

Purpose: To propose a specific surface guided stereotactic radiotherapy (SRT) treatment procedure with open-face mask immobilization and evaluate the initial clinical experience in improving setup accuracy., Methods and Materials: The treatment records of 48 SRT patients with head lesions were retrospectively analyzed. For each patient, head immobilization was achieved with a double-shell open-face mask. The anterior shell was left open to expose the forehead, nose, eyes and cheekbones. The exposed facial area was used as region-of-interest for surface tracking by AlignRT (VisionRT Inc, UK). The posterior shell provided a sturdy and personalized headrest. Patient initial setup was guided by 6DoF real-time deltas (RTD) using the reference surface obtained from the skin contour delineated on the planning CT images. The endpoint of initial setup was 1 mm in translational RTD and 1 degree in rotational RTD. CBCT guidance was performed to derive the initial setup errors, and couch shifts for setup correction were applied prior to treatment delivery. CBCT couch shifts, AlignRT RTD values, repositioning rate and setup time were analyzed., Results: The absolute values of median (maximal) CBCT couch shifts were 0.4 (1.3) mm in VRT, 0.1 (2.5) mm in LNG, 0.2 (1.6) mm in LAT, 0.1(1.2) degree in YAW, 0.2 (1.4) degree in PITCH and 0.1(1.3) degree in ROLL. The couch shifts and AlignRT RTD values exhibited highly agreement except in VRT and PITCH (p value < 0.01), of which the differences were as small as negligible. We did not find any case of patient repositioning that was due to out-of-tolerance setup errors, i.e., 3 mm and 2 degree. The surface guided setup time ranged from 52 to 174 s, and the mean and median time was 97.72 s and 94 s respectively., Conclusions: The proposed surface guided SRT procedure with open-face mask immobilization is a step forward in improving patient comfort and positioning accuracy in the same process. Minimized initial setup errors and repositioning rate had been achieved with reasonably efficiency for routine clinical practice., (© 2022. The Author(s).)

Background: Gastric cancer (GC) is a highly heterogeneous disease with many different histological and molecular subtypes. Due to their reduced systemic adverse effects, nanoformulation agents have attracted increasing attention for use in the treatment of GC patients in the clinic. To improve therapeutic outcomes, it is vitally necessary to provide individual medication references and guidance for use of these nanoformulations, and patient-derived organoids (PDOs) are promising models through which to achieve this goal., Results: Using an improved enzymatic digestion process, we succeeded in constructing GC PDOs from surgically resected tumor tissues and endoscopic biopsies from GC patients; these PDOs closely recapitulated the histopathological and genomic features of the corresponding primary tumors. Next, we chose two representative paclitaxel (PTX) nanoformulations for comparative study and found that liposomal PTX outperformed albumin-bound PTX in killing GC PDOs at both the transcriptome and cellular levels. Our results further showed that the different distributions of liposomal PTX and albumin-bound PTX in PDOs played an essential role in the distinct mechanisms through which they kill PDOs. Finally, we constructed patient-derived xenografts model in which we verified the above distinct therapeutic outcomes via an intratumoral administration route., Conclusions: This study demonstrates that GC PDOs are reliable tools for predicting nanoformulation efficacy., (© 2022. The Author(s).)

Background: Gastroscopy procedures are frequently performed under general sedation to minimize discomfort. Patients who refuse a sedative injection may experience more discomfort and adverse reactions such as pain and nausea. These instances reduce patient compliance and willingness to participate in future procedures. Acupuncture has been shown to have an anti-nausea and analgesic effect; however, there is limited data available that demonstrates the efficacy of acupuncture when applied before gastroscopy., Methods: A total of 60 participants will be randomly assigned to the electroacupuncture (EA) group and the sham electroacupuncture (SEA) group at a ratio of 1:1. Acupuncture treatment will be performed before gastroscopy for a duration of 30 min. All patients will complete detailed questionnaires at 30 min and 7 days post-procedure to record the severity of their symptoms. The primary outcome will be the average of 4 standard visual analogue scale (VAS) scores in the categories of nausea, vomiting, throat discomfort, and agitation as reported by the patient. The secondary outcomes will be patient's anxiety level as recorded by the 6-item short form of the State-Trait Anxiety Inventory (STAI-S6) and Amsterdam Pre-Operative Anxiety and Information Scale (APAIS), preference in a future endoscopy, pulse oxygen saturation (SpO2), heart rate (HR), and blood pressure (BP). Anxiety scales will be assessed before and after acupuncture; others will be completed at 30 min and 7 days post-procedure. The duration of the gastroscopy and the number of biopsies will be recorded after operation., Discussion: This randomized controlled trial will explore the feasibility of the further clinical application of electroacupuncture for the improvement of patient discomfort during gastroscopy without systemic sedation., Trial Registration: ChiCTR2000040726 . This trial has been approved by the Ethics Committee of Shanghai Municipal Hospital of Traditional Chinese Medicine (2020SHL-KY-11). Registration date 12 August 2020., (© 2022. The Author(s).)

Background: Current vital statistics of birth population and neonatal outcome in China lacked information and definition of deaths at delivery and during hospitalization, especially for extreme preterm (EPT) birth. This study aims to delineate the prevalence of neonatal hospitalization, neonatal and infant mortality rates (NMR, IMR) and associated perinatal risks based on all livebirths in Huai'an, an evolving sub-provincial region in eastern China., Methods: This retrospective cohort study established a comprehensive database linking information of whole regional livebirths and neonatal hospitalization in 2015, including deaths at delivery and EPT livebirths. The primary outcomes were NMR and IMR stratified by gestational age (GA) and birthweight (BW) with 95% confidence intervals. Causes of the neonatal and infant deaths were categorized according to the International Statistical Classification of Diseases 10th version, and population attributable fractions of GA and BW strata were analyzed. Perinatal risks of infant mortalities in continuum periods were estimated by Cox regression models., Results: Among the whole livebirth population (59056), 7960 were hospitalized (prevalence 13.5%), with 168 (2.8‰) in-hospital deaths. The NMR was 3.6 (3.2, 4.1)‰ and IMR 4.9 (1.4, 4.5)‰, with additionally 35 (0.6‰) deaths at delivery. The major causes of infant deaths were perinatal conditions (2.6‰, mainly preterm-related), congenital anomalies (1.5‰), sudden unexpected death in infancy (0.6‰) and other causes (0.2‰). The deaths caused by preterm and low BW (LBW) accounted for 50% and 40% of NMR and IMR, with 20-30% contributed by EPT or extremely LBW, respectively. Multivariable Cox regression analysis revealed that peripartum factors and LBW strata had strong association with early- and late-neonatal deaths, whereas those of GA < 28 weeks were highly associated with postneonatal deaths. Congenital anomalies and neonatal hospitalization remained high death risks over the entire infancy, whereas maternal co-morbidities/complications were modestly associated with neonatal but not postneonatal infant mortality., Conclusions: The NMR, IMR, major causes of deaths and associated perinatal risks in continuum periods of infancy, denote the status and quality improvement of the regional perinatal-neonatal care associated with socioeconomic development. The study concept, applicability and representativeness may be validated in other evolving regions or countries for genuine comparison and better maternal-infant healthcare., (© 2022. The Author(s).)

Background: Psychological distress (depression, anxiety and stress) is more common among medical students than in the general population, and is an important cause of insomnia, internet addiction, substance abuse, decreased academic performance and increased suicidality in medical students., Methods: To examine the mechanism by which regulatory emotional self-efficacy affects medical students' psychological distress, a questionnaire of 539 medical students using an interpersonal adaptability scale, regulatory emotional self-efficacy scale, self-acceptance scale and depression-anxiety-stress scale was conducted., Results: ① Regulatory emotional self-efficacy, interpersonal adaptability and self-acceptance are positively correlated, but they are negatively correlated with psychological distress. ② The mediation model shows that interpersonal adaptation and self-acceptance are the mediation variables of the effect of regulatory emotional self-efficacy on psychological distress, and the total mediation effect value is -0.37, accounting for 86.05% of the total effect (-0.43). Specifically, the effect involves three paths: first, regulatory emotional self-efficacy indirectly affects psychological distress through interpersonal adaptation (effect value-0.24); second, regulatory emotional self-efficacy indirectly affects psychological distress through interpersonal adaptation and self-acceptance (effect value-0.08); and third, regulatory emotional self-efficacy indirectly affects psychological distress through self-acceptance (effect value -0.05)., Conclusions: Interpersonal adaptation and self-acceptance have a significant mediating effect between regulatory emotional self-efficacy and psychological distress, and the chain mediating effect of interpersonal adaptation and self-acceptance is also significant., (© 2022. The Author(s).)

Background: IgG4-related ophthalmic disease (IgG4ROD) is a phenotype of IgG4-related disease (IgG4RD) with ophthalmic involvement. The pathological IgG4+ plasmacyte count has only been used for diagnosis. We aimed to explore its possible clinical value in the management of IgG4ROD., Methods: Fifty-five pathologically diagnosed IgG4ROD patients were included, and their clinical, pathological, serological, and radiological findings and treatment outcomes were reviewed and analyzed. The pathological IgG4+ plasmacyte counts in lesions from different anatomic sites were compared, and their association with serum IgG4 concentrations, systemic involvement, and relapse risk was analyzed., Results: The patients were divided into groups according to the anatomic site of their biopsied lesions, namely, the lacrimal gland, extraocular muscle, and orbital soft tissue. No significant difference was found in the pathological IgG4+ plasma cell counts among these groups (p = 0.975). The pathological IgG4+ plasmacyte count positively correlated with the IgG4 concentration in peripheral blood (R 2 = 0.5469, p < 0.001). The serum IgG4 concentration and the pathological infiltrating IgG4+ plasmacyte count were significantly higher in patients with extraophthalmic involvement (p < 0.001 and p = 0.005, respectively). The areas under the receiver operating characteristic (ROC) curve (AUCs) of the serum IgG4 level and pathological IgG4+ plasmacyte count for identifying systemic involvement were 0.897 (p < 0.001) and 0.759 (p = 0.015), respectively. The patients with relapse had higher levels of serum IgG4, more germinal centers (GCs), and infiltrating IgG4+ plasmacytes in lesions. Multivariate Cox regression analysis revealed that a pathological IgG4+ plasmacyte count of > 150/high-power field (HPF) and an elevated serum IgG4 level of > 500 mg/dL were risk factors for relapse after steroid treatment., Conclusions: Lesions from different ophthalmic sites in IgG4ROD patients have similar counts of IgG4+ and IgG+ plasmacytes. The quantity of pathological IgG4+ plasmacytes corresponded to the serum IgG4 concentration in patients with IgG4ROD and could be meaningful in identifying systemic involvement and predicting subsequent relapse., (© 2022. The Author(s).)

Background: Deep neck space abscess (DNSA) is a serious infection in the head and neck. Antibiotic therapy is an important treatment in patients with DNSA. However, the results of bacterial culture need at least 48 h, and the positive rate is only 30-50%, indicating that the use of empiric antibiotic treatment for most patients with DNSA should at least 48 h or even throughout the whole course of treatment. Thus, how to use empiric antibiotics has always been a problem for clinicians. This study analyzed the distribution of bacteria based on disease severity and clinical characteristics of DNSA patients, and provides bacteriological guidance for the empiric use of antibiotics., Methods: We analyzed 433 patients with DNSA who were diagnosed and treated at nine medical centers in Guangdong Province between January 1, 2015, and December 31, 2020. A nomogram for disease severity (mild/severe) was constructed using least absolute shrinkage and selection operator-logistic regression analysis. Clinical characteristics for the Gram reaction of the strain were identified using multivariate analyses., Results: 92 (21.2%) patients developed life-threatening complications. The nomogram for disease severity comprised of seven predictors. The area under the receiver operating characteristic curves of the nomogram in the training and validation cohorts were 0.951 and 0.931, respectively. In the mild cases, 43.2% (101/234) had positive culture results (49% for Gram-positive and 51% for Gram-negative strains). The positive rate of cultures in the patients with severe disease was 63% (58/92, 37.9% for Gram-positive, and 62.1% for Gram-negative strains). Diabetes mellitus was an independent predictor of Gram-negative strains in the mild disease group, whereas gas formation and trismus were independent predictors of Gram-positive strains in the severe disease group. The positivity rate of multidrug-resistant strains was higher in the severe disease group (12.1%) than in the mild disease group (1.0%) (P < 0.001). Metagenomic sequencing was helpful for the bacteriological diagnosis of DNSA by identifying anaerobic strains (83.3%)., Conclusion: We established a DNSA clinical severity prediction model and found some predictors for the type of Gram-staining strains in different disease severity cases. These results can help clinicians in effectively choosing an empiric antibiotic treatment., (© 2022. The Author(s).)

Background: Advances in DNA sequencing technologies have transformed our capacity to perform life science research, decipher the dynamics of complex soil microbial communities and exploit them for plant disease management. However, soil is a complex conglomerate, which makes functional metagenomics studies very challenging., Results: Metagenomes were assembled by long-read (PacBio, PB), short-read (Illumina, IL), and mixture of PB and IL (PI) sequencing of soil DNA samples were compared. Ortholog analyses and functional annotation revealed that the PI approach significantly increased the contig length of the metagenomic sequences compared to IL and enlarged the gene pool compared to PB. The PI approach also offered comparable or higher species abundance than either PB or IL alone, and showed significant advantages for studying natural product biosynthetic genes in the soil microbiomes., Conclusion: Our results provide an effective strategy for combining long and short-read DNA sequencing data to explore and distill the maximum information out of soil metagenomics., (© 2022. The Author(s).)

Background: Lymphovascular space invasion (LVSI) is the first step of hematogenous metastasis. Exploration of the differential miRNA expression profiles between LVSI-positive and LVSI-negative ovarian cancer tissues may help to identify key miRNAs involved in the hematogenous metastasis of ovarian cancer. This study is aimed to identify microRNAs (miRNAs) that are differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tissues, followed by exploring their association with bevacizumab response in ovarian cancer patients., Methods: The Cancer Genome Altas (TGGA) dataset was used to identify the differentially expressed miRNAs between LVSI-positive and LVSI-negative ovarian cancer tissues. The prognostic value of the differentially expressed miRNAs was determined using GSE140082 dataset., Results: We showed that miR-25 and miR-142 were differentially expressed between LVSI-positive and LVSI-negative ovarian cancer tumors. Kaplan-Meier analysis indicated that high miR-25 expression was associated with increased progression free survival (PFS) and extended overall survival (OS). Moreover, patients with low miR-25 expression benefited significantly from bevacizumab treatment in terms of PFS. A similar trend was observed in terms of OS though without reaching statistical significance. In contrast, no significant survival benefits from bevacizumab were observed in patients with high miR-25 expression in terms of PFS and OS. There was no significant correlation between miR-142 expression and PFS. In contrast, high miR-142 expression was associated with reduced OS. Moreover, patients with high miR-142 expression benefited significantly from bevacizumab treatment in terms of PFS and OS. However, bevacizumab treatment conferred no significant improvements in both PFS and OS in patients with low miR-142 expression. The nomogram for PFS indicated that miR-25 expression had a larger contribution to PFS than debulking status and bevacizumab treatment. And the nomogram for OS illustrated both miR-25 expression and miR-142 expression as sharing a larger contribution to OS than bevacizumab treatment and debulking status., Conclusion: In conclusion, miR-25 expression correlates with a better PFS and OS in ovarian cancer. Patients with low miR-25 expression and high miR-142 expression could benefit from bevacizumab treatment significantly., (© 2021. The Author(s).)

Background: Persistent pain following back surgery called failed back surgery syndrome remains a major treatment challenge. The aim of this study is to evaluate the efficacy and safety of electroacupuncture on relieving back pain in FBSS patients., Methods/design: This is a randomized, single-blind, single-site, placebo-controlled trial. A total of 144 eligible FBSS patients will be randomly assigned to the electroacupuncture, manual acupuncture, or sham acupuncture group in a 1:1:1 ratio. Each group will receive 2 treatment sessions per week for 12 weeks. The primary outcome will be low back pain intensity based on the 11-point numerical rating scale (NRS). The secondary outcomes include Oswestry Disability Index (ODI) questionnaire, Beck Depression Inventory-II (BDI-II), Pittsburgh Sleep Quality Index (PSQI), and analgesic consumption. All clinical outcomes will be collected at baseline, during the treatment phase (at 8 and 12 weeks), and at the 16-, 24- and 36-week follow-ups. All data will be analyzed based on the intention-to-treat principle and adverse events will be assessed during the trial., Discussion: This pilot randomized controlled trial will evaluate the efficacy of electroacupuncture for treating failed back surgery syndrome. The outcomes will determine whether electroacupuncture is efficacious in relieving low back pain as well as improving the quality of life in failed back surgery syndrome patients., Trial Registration: Chinese Clinical Trial Registry ChiCTR2000040144 . Registered on 22 November 2020., (© 2021. The Author(s).)

Background: Lignin is a complex aromatic heteropolymer comprising 15-30% dry weight of the lignocellulose. The complex structural characteristic of lignin renders it difficult for value-added utilization. Exploring efficient lignin-degrading microorganisms and investigating their lignin-degradation mechanisms would be beneficial for promoting lignin valorization. In this study, a newly isolated white-rot basidiomycete, Trametes hirsuta X-13, with capacity to utilize alkaline lignin as the sole substrate was investigated., Results: The analysis of the fermentation properties of T. hirsuta X-13 using alkaline lignin as the sole substrate, including the mycelial growth, activities of ligninolytic enzymes and the rates of lignin degradation and decolorization confirmed its great ligninolysis capacity. The maximum lignin degradation rate reached 39.8% after 11 days of T. hirsuta X-13 treatment, which was higher than that of reported fungi under the same condition. Fourier transform infrared spectrometry (FTIR), gas chromatography-mass spectrometry (GC-MS) scanning electron micrographs (SEM), two-dimensional heteronuclear single quantum coherence NMR analysis (2D-HSQC NMR) collaborated with pyrolysis gas chromatography-mass spectrometry (py-GC/MS) analyses proved that lignin structure was severely deconstructed along with amounts of monomer aromatics generated. Furthermore, according to those chemical analysis, in addition to canonical C α -C β breakage, the cleavage of lignin interunit linkages of β-β might also occur by T. hirsuta X-13., Conclusions: This study characterized a newly isolated white-rot basidiomycete T. hirsuta X-13 with impressive alkaline lignin degradation ability and provided mechanistic insight into its ligninolysis mechanism, which will be valuable for the development of lignin valorization strategies., (© 2021. The Author(s).)

Background: Pretreatment is a critical step required for efficient conversion of woody biomass into biofuels and platform chemicals. Fungal pretreatment is regarded as one of the most promising technology for woody biomass conversion but remains challenging for industrial application. The exploration of potential fungus strain with high efficient delignification and less processing time for woody biomass pretreatment will be valuable for development of biorefinery industry. Here, a newly isolated white-rot basidiomycete Peniophora incarnate T-7 was employed for poplar wood pretreatment., Results: The chemical component analysis showed that cellulose, hemicellulose and lignin from poplar wood declined by 16%, 48% and 70%, respectively, after 7 days submerged fermentation by P. incarnate T-7. Enzymatic saccharification analysis revealed that the maximum yields of glucose and xylose from 7 days of P. incarnate T-7 treated poplar wood reached 33.4% and 27.6%, respectively, both of which were enhanced by sevenfold relative to the untreated group. Fourier transform infrared spectroscopy (FTIR), scanning electron microscope (SEM), X-ray diffraction (XRD) and pyrolysis gas chromatography-mass spectrometry (Py-GC/MS) characterization confirmed that lignocellulosic structure of poplar wood was largely broken by P. incarnate T-7, including delignification and de-crystalline of cellulose. Meanwhile, lignin component of poplar wood was selectively degraded by P. incarnate T-7, and G-type unit of lignin was preferentially attacked by the strain. Furthermore, quantitative proteomic analysis revealed that a considerable amount of lignocellulolytic enzymes were detected in the secretory proteins of P. incarnate T-7, especially with high abundance of lignin-degrading enzymes and hemicellulases. Combination of quantitative proteomic with transcriptomic analysis results showed that most of those lignocellulolytic enzymes were highly upregulated on poplar wood substrate compared to glucose substrate., Conclusions: This study showed that P. incarnate T-7 could selectively delignify poplar wood by submerged fermentation with short time of 7 days, which greatly improved its enzymatic saccharification efficiency. Our results suggested that P. incarnate T-7 might be a promising candidate for industrial woody biomass pretreatment.

Background: The complications caused by diabetes mellitus (DM) are the focus of clinical treatment. However, little is known about diabetic enteropathy (DE) and its potential underlying mechanism., Methods: Intestinal epithelial cells (IECs) and intestinal epithelial stem cells (IESCs) were harvested from BKS.Cg-Dock7 m +/+Lepr db /JNju (DM) mice, and the expression of R-Spondin 3 (Rspo3) was detected by RT-qPCR, Western blotting, immunohistochemistry, and immunofluorescence. The role of Rspo3 in the abnormal differentiation of IECs during DM was confirmed by knockdown experiments. Through miRNA expression profiling, bioinformatics analysis, and RT-qPCR, we further analyzed the differentiation-related miRNAs in the IECs from mice with DM., Results: Abnormal differentiation of IECs was observed in the mice with DM. The expression of Rspo3 was upregulated in the IECs from the mice with DM. This phenomenon was associated with Rspo3 overexpression. Additionally, Rspo3 is a major determinant of Lgr5+ stem cell identity in the diabetic state. Microarray analysis, bioinformatics analysis, and luciferase reporter assays revealed that microRNA (miR)-380-5p directly targeted Rspo3. Moreover, miR-380-5p upregulation was observed to attenuate the abnormal differentiation of IECs by regulating Rspo3 expression., Conclusions: Together, our results provide definitive evidence of the essential role of Rspo3 in the differentiation of IECs in DM.

Background: Airway management, including noninvasive endotracheal intubation or invasive tracheostomy, is an essential treatment strategy for patients with deep neck space abscess (DNSA) to reverse acute hypoxia, which aids in avoiding acute cerebral hypoxia and cardiac arrest. This study aimed to develop and validate a novel risk score to predict the need for airway management in patients with DNSA., Methods: Patients with DNSA admitted to 9 hospitals in Guangdong Province between January 1, 2015, and December 31, 2020, were included. The cohort was divided into the training and validation cohorts. The risk score was developed using the least absolute shrinkage and selection operator (LASSO) and logistic regression models in the training cohort. The external validity and diagnostic ability were assessed in the validation cohort., Results: A total of 440 DNSA patients were included, of which 363 (60 required airway management) entered into the training cohort and 77 (13 required airway management) entered into the validation cohort. The risk score included 7 independent predictors (p < 0.05): multispace involvement (odd ratio [OR] 6.42, 95% confidence interval [CI] 1.79-23.07, p < 0.001), gas formation (OR 4.95, 95% CI 2.04-12.00, p < 0.001), dyspnea (OR 10.35, 95% CI 3.47-30.89, p < 0.001), primary region of infection, neutrophil percentage (OR 1.10, 95% CI 1.02-1.18, p = 0.015), platelet count to lymphocyte count ratio (OR 1.01, 95% CI 1.00-1.01, p = 0.010), and albumin level (OR 0.86, 95% CI 0.80-0.92, p < 0.001). Internal validation showed good discrimination, with an area under the curve (AUC) of 0.951 (95% CI 0.924-0.971), and good calibration (Hosmer-Lemeshow [HL] test, p = 0.821). Application of the clinical risk score in the validation cohort also revealed good discrimination (AUC 0.947, 95% CI 0.871-0.985) and calibration (HL test, p = 0.618). Decision curve analyses in both cohorts demonstrated that patients could benefit from this risk score. The score has been transformed into an online calculator that is freely available to the public., Conclusions: The risk score may help predict a patient's risk of requiring airway management, thus advancing patient safety and supporting appropriate treatment.

Background: Pulmonary mucormycosis caused by Mucorales is a highly lethal invasive fungal infection usually found in immunocompromised patients. Isolated pulmonary mucormycosis in immunocompetent patients is very rare. Here, we present a case of a 32-year-old male who developed pulmonary mucormycosis without any known immunodeficiency., Case Presentation: The patient presented to our hospital because of cough and chest pain along with blood in the sputum. He was first treated for community-acquired pneumonia until bronchoalveolar lavage fluid culture confirmed the growth of Absidia. His symptoms were relieved with the use of amphotericin B, and he eventually recovered. We also provide a systematic review of relevant literature to summarize the characteristics of pulmonary mucormycosis in immunocompetent patients., Conclusions: Pulmonary mucormycosis has variable clinical presentations and is difficult to identify. Due to its high fatality rate, clinicians should make judgements regarding suspected cases correctly and in a timely manner to avoid misdiagnosis and delayed treatment.

Background: Despite 15-17 millions of annual births in China, there is a paucity of information on prevalence and outcome of preterm birth. We characterized the outcome of preterm births and hospitalized preterm infants by gestational age (GA) in Huai'an in 2015, an emerging prefectural region of China., Methods: Of 59,245 regional total births, clinical data on 2651 preterm births and 1941 hospitalized preterm neonates were extracted from Huai'an Women and Children's Hospital (HWCH) and non-HWCH hospitals in 2018-2020. Preterm prevalence, morbidity and mortality rates were characterized and compared by hospital categories and GA spectra. Death risks of preterm births and hospitalized preterm infants in the whole region were analyzed with multivariable Poisson regression., Results: The prevalence of extreme, very, moderate, late and total preterm of the regional total births were 0.14, 0.53, 0.72, 3.08 and 4.47%, with GA-specific neonatal mortality rates being 44.4, 15.8, 3.7, 1.5 and 4.3%, respectively. There were 1025 (52.8% of whole region) preterm admissions in HWCH, with significantly lower in-hospital death rate of inborn (33 of 802, 4.1%) than out-born (23 of 223, 10.3%) infants. Compared to non-HWCH, three-fold more neonates in HWCH were under critical care with higher death rate, including most extremely preterm infants. Significantly all-death risks were found for the total preterm births in birth weight <  1000 g, GA < 32 weeks, amniotic fluid contamination, Apgar-5 min < 7, and birth defects. For the hospitalized preterm infants, significantly in-hospital death risks were found in out-born of HWCH, GA < 32 weeks, birth weight <  1000 g, Apgar-5 min < 7, birth defects, respiratory distress syndrome, necrotizing enterocolitis and ventilation, whereas born in HWCH, antenatal glucocorticoids, cesarean delivery and surfactant use decreased the death risks., Conclusions: The integrated data revealed the prevalence, GA-specific morbidity and mortality rate of total preterm births and their hospitalization, demonstrating the efficiency of leading referral center and whole regional perinatal-neonatal network in China. The concept and protocol should be validated in further studies for prevention of preterm birth.

Background: Prosthetic valve detachment is not rare after aortic valve replacement in Behcet's disease. However, destruction of the intervalvular fibrous body (IFB) due to Behcet's disease was rarely reported., Case Presentation: We report a case of 30 year-old woman, with valve detachment and IFB separation. The patient received aortic valve replacement three months ago. Her medical history included recurrent oral ulcers and cutaneous lesions. Finally, reoperation was performed and peri-operative steroid therapy was carried out., Conclusions: The case presented a rare complication of valve detachment in Behcet's disease.

Background: The role of nicotinamide N-methyltransferase (NNMT) in ovarian cancer is still elusive. Our aim is to explore the expression of NNMT in ovarian cancer and to assess its association with patient prognosis and treatment response., Methods: We first analyzed the differential expression of NNMT among fallopian tube epithelium, primary ovarian cancers, metastatic ovarian cancers, and recurrent ovarian cancers using Gene Expression Ominus (GEO) database (GSE10971, GSE30587, GSE44104 and TCGA datasets). Then, we assessed the association of NNMT expression with clinical and molecular parameters using CSIOVDB database and GSE28739 dataset. Next, we evaluate the association of NNMT expression with the prognosis of ovarian cancer patients in both GSE9891 dataset and TCGA dataset. Finally, GSE140082 dataset was used to explore the association of NNMT expression with bevacizumab response., Results: NNMT expression was significantly elevated in lymphovascular space invasion (LVSI)-positive ovarian cancers compared with that in LVSI-negative ovarian cancers (TCGA dataset, P < 0.05), Moreover, increased expression of NNMT was associated with increased tumor stage, grade, and mesenchymal molecular subtype (CSIOVDB database). Survival analysis indicated that increased expression of NNMT was associated with a reduced OS in both GSE9891 dataset (HR: 2.28, 95%CI: 1.51-3.43, Log-rank P < 0.001) and TCGA dataset (HR: 1.55, 95%CI: 1.02-2.36, Log-rank P = 0.039). Multivariate analysis further confirmed the negative impact of NNMT expression on OS in ovarian cancer patients in those two datasets. Furthermore, the NNMT-related nomogram showed that NNMT shared a larger contribution to OS, compared with debulking status. More interestingly, bevacizumab conferred significant improvements in OS for patients with low NNMT expression (HR: 0.56, 95%CI: 0.31-0.99, Log-rank P = 0.049). In contrast, patients with high NNMT expression didn't benefit from bevacizumab treatment significantly (HR: 0.85, 95%CI: 0.48-1.49, Log-rank P = 0.561). NNMT expression was positively correlated with the expression of genes, LDHA and PGAM1, involved in Warburg effect., Conclusions: In conclusion, NNMT expression is associated with the aggressive behavior of ovarian cancer, correlates with a poor prognosis, and is predictive of sensitivity to bevacizumab treatment.

Background: Dorr type C femoral bone exhibits a wide, stovepipe-shaped femoral canal, and thin cortices in the proximal femur. Dorr C bone combined with severe osteoporosis is an important challenge in primary hip arthroplasty. In this study, we assessed the effects of short metaphyseal fitting cementless stems on preformatted primary total hip arthroplasties in young adult osteoporotic patients with this femoral presentation., Methods: A total of 42 hip arthroplasties were performed in 35 young patients (range 20 to 36 years) using a short Tri-lock bone preservation metaphyseal-fitting cementless femoral component between 2012 and 2017. The mean age at surgery of the 27 male (33 hips) and 8 female (9 hips) patients was 27.5 years (range 20.3 to 35.8 years). The mean body mass index (BMI) was 20.2 kg/m 2 (range, 16.8-23.2 kg/m 2 ). According to Dorr's criteria, all 42 femora were classified as type C bone and all femurs suffered from severe osteoporosis (Singh index ≤ 3)., Results: The mean follow-up period was 5.5 years (range 3.0 to 8.0 years). The clinical and functional results improved for the Harris hip score, WOMAC, and UCLA activity scores. The Harris Hip score improved from 48.0 ± 8.0 (range 38.0 to 61.0) preoperatively to 87.0 ± 9.0 (range 77.0 to 92.0) at 12 months after surgery and 91.0 ± 8.0 (range 85.0 to 98.0) at final follow-up. The preoperative UCLA activity score was 3.0 ± 0.5 points (range, 1.0-4.0 points), which significantly improved to 7.5 ± 0.7 points (range 6.0 to 8.0 points) at the final follow-up. No patient exhibited thigh pain at the final follow-up. The mean stem-to-canal fill percentages were 97% ± 2.1% (anteroposterior view at midstem). For stem alignment, 40 hips (95.2%) of the femoral stem were positioned neutrally to 3° of varus with reference to the femoral shaft axis. The remaining two were positioned at 4° varus to 4° valgus. Radiographic evaluation showed good osteointegration of the implants in follow-up., Conclusions: Based on the tapered-wedge design and proximal porous coating, the shortened tapered conventional stem can achieve reliable stability through neck filling and metaphyseal fixation, which does not depend on the isthmus hoop stress. This stem was suitable in severe osteoporotic patients with type C bones in young adults who presented with a correspondingly straightened femoral canal with a wide isthmus and thin cortex.

Background: Ischaemic stroke has become the main cause of death and severe neurological disorders, for which effective restorative treatments are currently limited. While stem cell transplantation offers therapeutic potential through neural regeneration, this approach is associated with the challenges of limited applicable sources. Hair follicle stem cells (HFSCs) are multipotential cells that can differentiate into ectodermal and mesodermal lineages and proliferate for long periods. The therapeutic potentials of HFSCs have not been investigated in ischaemic stroke models, and therefore, in this study, we aimed to determine whether they could survive and migrate to ischaemic areas after a stroke attack., Methods: A rat model of middle cerebral artery ischaemia/reperfusion was established and intravenously administered HFSCs. The potential of HFSCs to migrate and differentiate into neuron-like cells as well as their ability to reduce the infarct size was evaluated. Rat brain tissue samples were collected 2 weeks after cell transplantation and analysed via TTC staining, immunofluorescence and immunohistochemistry methods. The data were statistically analysed and presented as the means ± standard deviations., Results: Intravenously administrated rat HFSCs were able to migrate to the penumbra where they expressed neuron-specific markers, reduced the infarct volume and promoted neurological recovery., Conclusion: HFSC transplantation has therapeutic potential for ischaemic stroke and is, therefore, worthy of further investigation toward possible clinical development for treating stroke patients.

Background: Cancer-related insomnia (CRI) is one of the most prevalent complaints among cancer survivors and severely impairs patients' quality of life. As a popular non-pharmacological alternative treatment, acupuncture provides a good clinical curative effect on insomnia. The aim of this trial is to evaluate efficacy and safety of electro-acupuncture on insomnia in patients with lung cancer., Method: This is a protocol for a multicenter randomized single-blinded sham-controlled trial. We will randomly assign 252 eligible patients with lung cancer-related insomnia into two groups at a ratio of 1:1, the treatment group (EA) and the control group (sham EA). All treatment will be given 3 times per week for 8 weeks, and a 12-week follow-up will be conducted. The primary outcome will be measured by the Pittsburgh Sleep Quality Index (PSQI). The secondary outcomes will include sleep parameters recorded from the actigraphy, scores from Quality of Life Questionnaire Core-30 (QLQ-C30), and Patient Health Questionnaire-9 (PHQ-9). All adverse effects during the trial will be assessed by the Treatment Emergent Symptom Scale (TESS). All analyses will be based on ITT principle and performed with the statistical software SPSS (version 24.0) by t test, rank-sum test, chi-square, and so on. A two-sided significance level will be set at 5%., Discussion: This large-sample trial protocol will evaluate the efficacy of electro-acupuncture on insomnia in patients with lung cancer. This protocol, if proven to be effective, will contribute to filling the gap in treatment options in the CRI field and provide a promising intervention for insomnia in lung cancer survivors., Trial Registration: ChiCTR ChiCTR1900026395. Registered on 8 October 2019, http://www.chictr.org.cn/showproj.aspx?proj=44068.

Background: Deregulation of integrins signaling had been documented to participate in multiple fundamental biological processes, and the aberrant expression of integrin family members were linked to the prognosis of various cancers. However, the role of integrins in predicting progression and prognosis of ovarian cancer patients are still largely elusive. This study is aimed to explore the prognostic values of ITGA and ITGB superfamily members in high grade serous ovarian cancers (HGSOC)., Methods: GSE26712 dataset was used to determine the differential expression of ITGA and ITGB superfamily member between HGSOC and normal counterparts. The Cancer Genome Altas (TGGA) and GSE9891 datasets were used to determine the prognostic values of ITGA and ITGB superfamily members in HGSOC, followed by the development of nomograms predictive of recurrence free survival (RFS) and overall survival (OS)., Results: ITGA6 and ITGB5 expression were significantly downregulated in HGSOC compared with that in normal counterparts. In contrast, ITGA2, ITGA5, ITGA7, ITGA8, ITGA9, ITGA10, ITGB3, ITGB4, ITGB6, and ITGB8 were all significantly upregulated in HGSOC compared with that in normal counterparts. Both univariable and multivariable analysis indicated that ITGB1 was associated with extended RFS. The ITGB1-related nomogram indicated that ITGB1 had the largest contribution to RFS, followed by FIGO stage and debulking status. The C-index for predicting RFS was 0.55 (95% CI 0.50-0.59) in TCGA dataset (training dataset) and 0.65 (95% CI 0.59-0.72) in GSE9891 dataset (validation dataset), respectively. Regarding OS, ITGB8 was associated with reduced survival suggested by both univariable and multivariable analysis. ITGA7 appeared to be associated with improved survival though without reaching statistical significance. The ITGA7/ITGB8-based nomogram showed that age at initial diagnosis had the largest contribution to OS, followed by ITGB8 and ITGA7 expression. The C-index for predicting OS was 0.65 (95% CI 0.60-0.69) in TCGA dataset (training dataset) and 0.59 (95% CI 0.51-0.66) in GSE9891 dataset (validation dataset), respectively., Conclusion: In conclusion, ITGB1, ITGA7 and ITGB8 added prognostic value to the traditional clinical risk factors used to assess the clinical outcomes of HGSOC., Competing Interests: Competing interestsThe authors declare that there are no conflicts of interest., (© The Author(s) 2020.)

Background: In the past 30 years, incidences of non-alcoholic fatty liver disease (NAFLD) has risen by 30%. However, there is still no clear mechanism or accurate method of anticipating liver failure. Here we reveal the phase transitions of liquid crystalline qualities in hepatic lipid droplets (HLDs) as a novel method of anticipating prognosis., Methods: NAFLD was induced by feeding C57BL/6J mice on a high-fat (HiF) diet. These NAFLD livers were then evaluated under polarized microscopy, X-ray diffraction and small-angle scattering, lipid component chromatography analysis and protein expression analysis. Optically active HLDs from mouse model and patient samples were both then confirmed to have liquid crystal characteristics. Liver MAP1LC3A expression was then evaluated to determine the role of autophagy in liquid crystal HLD (LC-HLD) formation., Results: Unlike the normal diet cohort, HiF diet mice developed NAFLD livers containing HLDs exhibiting Maltese cross birefringence, phase transition, and fluidity signature to liquid crystals. These LC-HLDs transitioned to anisotropic crystal at 0 °C and remain crystalline. Temperature increase to 42 °C causes both liquid crystal and crystal HLDs to convert to isotropic droplet form. These isotropic HLDs successfully transition to anisotropic LC with fast temperature decrease and anisotropic crystal with slow temperature decrease. These findings were duplicated in patient liver. Patient LC-HLDs with no inner optical activity were discovered, hinting at lipid saturation as the mechanism through which HLD acquire LC characteristics. Downregulation of MAP1LC3A in conjunction with increased LC-HLD also implicated autophagy in NAFLD LC-HLD formation., Conclusions: Increasing concentrations of amphiphilic lipids in HLDs favors organization into alternating hydrophilic and hydrophobic layers, which present as LC-HLDs. Thus, evaluating the extent of liquid crystallization with phase transition in HLDs of NAFLD patients may reveal disease severity and predict impending liver damage., Competing Interests: Competing interestsThe submitted work were currently applying for patents relating to the content of the manuscript. The authors declare no other competing interests., (© The Author(s) 2020.)