[Application of intra-articular graft length measurement in total anterior cruciate ligament reconstruction].

OBJECTIVE: To investigate the clinical efficacy of arthroscopic measurement of intra-articular graft length in the application of total internal reconstruction of the anterior cruciate ligament(ACL). METHODS: The 60 patients with ACL injury treated between January 2020 and January 2022 were retrospectively analyzed. There were 37 males and 23 females, aged from 22 to 44 years. According to the different surgical methods, they were divided into two groups:conventional surgery group (conventional group) and pull-line measurement group (measurement group), with 30 cases in each group. In the conventional group, there were 20 males and 10 females, with an average age of (30.00±3.95) years old;the body mass index (BMI) was (22.58±1.41) kg·m-2;there were 9 cases on the left side and 21 cases on the right side;the time from injury to operation was (3. 00±1.35) days. In the measurement group, there were 17 males and 13 females, with an average of(32.00±4.29) years;BMI was (23.29±1.39) kg·m-2;there were 12 cases on the left side and 18 cases on the right side;the time from injury to operation was (3.00±1.27) days. The clinical data of the patients before surgery, 6 months after surgery and 12 months after surgery were collected and recorded. The clinical efficacy of the two methods was compared in terms of postoperative VAS, KOOS, Lysholm score, IKDC score, knee stability (Lachman test, anterior drawer test and axial shift test), the degree of widening of bone tunnel diameter measured by CT at different stages of the postoperative period and MRI scoring system. RESULTS: At 12 months after surgery, the VAS of the measurement group was lower than that of the conventional group(P<0.001). At 12 months after surgery, KOOS scores in the measurement group were higher than those in the conventional group, and there were statistically significant differences in all scores except symptom scores (P<0.05). Six months after operation, Lysholm total score and IKDC total score in the measurement group were higher than those in the conventional group, and the difference was statistically significant (P<0.05). At 12 months after surgery, knee stability tests were performed, and the differences between the Lachman test, anterior drawer test and axial shift test measurement group and the conventional group were not statistically significant (P>0.05). However, overall knee instability analysis showed that the knee stability of the measurement group was better than that of the control group, and the difference between the groups was statistically significant (P=0.038). The imaging assessment of patients in both groups at 6 months after surgery showed that the widening of tendon tunnel diameter in both femur and tibia was reduced in the measurement group compared with the conventional group after surgery, and the difference was statistically significant(P<0.05);MRI scores were higher in all patients in the measurement group those in the conventional group, at 6 months and 12 months agter surgery(P<0.05). CONCLUSION: Arthroscopic measurement of intra-articular cavity graft length in total internal technique for ACL reconstruction, high tendon utilization, good stability, the knee joint function has recovered satisfactorily within one year, and the therapeutic effect is affirmed.

Peroxynitrite-Triggered Carbon Monoxide Donor Improves Ischemic Stroke Outcome by Inhibiting Neuronal Apoptosis and Ferroptosis.

Cerebral ischemia-reperfusion injury produces excessive reactive oxygen and nitrogen species, including superoxide, nitric oxide, and peroxynitrite (ONOO-). We recently developed a new ONOO--triggered metal-free carbon monoxide donor (PCOD585), exhibiting a notable neuroprotective outcome on the rat middle cerebral artery occlusion model and rendering an exciting intervention opportunity toward ischemia-induced brain injuries. However, its therapeutic mechanism still needs to be addressed. In the pharmacological study, we found PCOD585 inhibited neuronal Bcl2/Bax/caspase-3 apoptosis pathway in the peri-infarcted area of stroke by scavenging ONOO-. ONOO- scavenging further led to decreased Acyl-CoA synthetase long-chain family member 4 and increased glutathione peroxidase 4, to minimize lipoperoxidation. Additionally, the carbon monoxide release upon the ONOO- reaction with PCOD585 further inhibited the neuronal Iron-dependent ferroptosis associated with ischemia-reperfusion. Such a synergistic neuroprotective mechanism of PCOD585 yields as potent a neuroprotective effect as Edaravone. Additionally, PCOD585 penetrates the blood-brain barrier and reduces the degradation of zonula occludens-1 by inhibiting matrix metalloproteinase-9, thereby protecting the integrity of the blood-brain barrier. Our study provides a new perspective for developing multi-functional compounds to treat ischemic stroke.

Application of enhanced recovery after surgery in perioperative nursing care of elderly patients with hip and knee arthroplasty: A systematic review and meta-analysis.

BACKGROUND: To collect data from randomized controlled trials (RCTs) to evaluate the effects of enhanced recovery after surgery on postoperative recovery of elderly patients who underwent hip or knee arthroplasty. METHODS: The search was limited to studies published prior to January 1, 2023, in the electronic databases of Cochrane, Embase, Ovid Medline, Proquest, PubMed, Scopus, Web of Science, and Chinese databases, including China National Knowledge Internet (CNKI) and SinoMed. All relevant data were collected from the studies that met the inclusion criteria. The outcome variables were recovery of joint function and incidence of complications. STATA software (version 14.0) was used for the meta-analysis. RESULTS: A total of 44 published studies met the inclusion criteria. The cumulative data included 2203 cases receiving enhanced recovery after surgery (ERAS), and 2173 cases receiving traditional recovery after surgery (non-ERAS). The meta-analysis showed that the VAS score was significantly lower in the ERAS group than in the non-ERAS group (P < .01), and there were fewer incidences of complications in the ERAS group than in the control group (P < .01). CONCLUSIONS: ERAS significantly reduced pain and the incidence of complications in elderly patients who had undergone joint replacement surgery.

Effect of mesenchymal stromal cells transplantation on the outcomes of patients with knee osteoarthritis: A systematic review and meta-analysis.

Cell therapy has been explored as a new regenerative treatment for osteoarthritis in the field of regenerative medicine. However, the efficacy of stem cell transplantation from different sources for the treatment of knee osteoarthritis (KOA) remains controversial. This study integrates and evaluates the previously published data of stem cell transplantation for KOA to explore the curative effect of different stem cells. We conducted a meta-analysis of randomized controlled trials on stem cell therapy for KOA. Measures of efficacy included Visual Analog Scale (VAS), Lequesne index, Lysholm Knee Scoring Scale (LKSS), and Western Ontario and McMaster University Osteoarthritis Index (WOMAC). Joint injury was evaluated through the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system. We analyzed 16 studies involving 875 KOA patients. The stem cell treatment showed significant VAS reduction from the third month onwards. Subgroup analysis suggested the most significant pain relief at different postoperative months came from adipose-derived and umbilical cord-derived stem cells. Autologous adipose tissue resulted in better pain alleviation compared with allogenic. However, autologous bone marrow stem cells did not show increased pain relief over allogeneic ones. Combination therapy (HA and/or PRP) showed no effect. Autologous adipose-derived stem cells demonstrate the most effective recovery of knee joint function. In WORMS assessment, there was no significant difference between the stem cell group and control. Stem cell transplantation proved safe and effective for KOA treatment. Different sources stem cells have a good effect on alleviating knee joint pain, restoring knee joint function, and minimizing patient trauma.

Tuft cells utilize taste signaling molecules to respond to the pathobiont microbe Ruminococcus gnavus in the proximal colon.

Tuft cells are a type of rare epithelial cells that have been recently found to utilize taste signal transduction pathways to detect and respond to various noxious stimuli and pathogens, including allergens, bacteria, protists and parasitic helminths. It is, however, not fully understood how many different types of pathogens they can sense or what exact molecular mechanisms they employ to initiate targeted responses. In this study, we found that an anaerobic pathobiont microbe, Ruminococcus gnavus (R. gnavus), can induce tuft cell proliferation in the proximal colon whereas the microbe's lysate can stimulate these proximal colonic tuft cells to release interleukin-25 (IL-25). Nullification of the Gng13 and Trpm5 genes that encode the G protein subunit Gγ13 and transient receptor potential ion channel Trpm5, respectively, or application of the Tas2r inhibitor allyl isothiocyanate (AITC), G protein Gßγ subunit inhibitor Gallein or the phospholipase Cß2 (PLCß2) inhibitor U73122 reduces R. gnavus-elicited tuft cell proliferation or IL-25 release or both. Furthermore, Gng13 conditional knockout or Trpm5 knockout diminishes the expression of gasdermins C2, C3 and C4, and concomitantly increases the activated forms of caspases 3, 8 and 9 as well as the number of TUNEL-positive apoptotic cells in the proximal colon. Together, our data suggest that taste signal transduction pathways are not only involved in the detection of R. gnavus infection, but also contribute to helping maintain gasdermin expression and prevent apoptotic cell death in the proximal colon, and these findings provide another strategy to combat R. gnavus infection and sheds light on new roles of taste signaling proteins along with gasdermins in protecting the integrity of the proximal colonic epithelium.

Recent progress in 2D bipolar magnetic semiconductors.

Bipolar magnetic semiconductor (BMS) is a class of magnetic semiconductors, whose valence band maximum and conduction band minimum are fully spin-polarized with opposite spin directions. Due to the special energy band, half-metallicity can be easily obtained in BMS by gate voltage, and the spin polarization can be reversed between spin-up and down when the gate voltage switches from positive to negative. BMSs have great potential applications in spintronic devices, such as the field-effect spin valves, spin filters and spin transistors,etc. With the rapid progress of the two-dimensional (2D) magnetic materials, researchers have identified a series of potential intrinsic 2D BMS materials using high-throughput computational methods. Additionally, methods such as doping, application of external stress, introduction of external fields, stacking of interlayer antiferromagnetic semiconductors, and construction of Janus structures have endowed existing materials with BMS properties. This paper reviews the research progress of 2D BMS. These advancements provide crucial guidance for the design and synthesis of BMS materials and offer innovative pathways for the future development of spintronics.

Ferromagnetism emerged from non-ferromagnetic atomic crystals.

The recently emerged ferromagnetic two-dimensional (2D) materials provide unique platforms for compact spintronic devices down to the atomic-thin regime; however, the prospect is hindered by the limited number  of ferromagnetic 2D materials discovered with limited choices of magnetic properties. If 2D antiferromagnetism could be converted to 2D ferromagnetism, the range of 2D magnets and their potential applications would be significantly broadened. Here, we discovered emergent ferromagnetism by interfacing non-magnetic WS2 layers with the antiferromagnetic FePS3. The WS2 exhibits an order of magnitude enhanced Zeeman effect with a saturated interfacial exchange field ~38 Tesla. Given the pristine FePS3 is an intralayer antiferromagnet, the prominent interfacial exchange field suggests the formation of ferromagnetic FePS3 at interface. Furthermore, the enhanced Zeeman effect in WS2 is found to exhibit a strong WS2-thickness dependence, highlighting the layer-tailorable interfacial exchange coupling in WS2-FePS3 heterostructures, which is potentially attributed to the thickness-dependent interfacial hybridization.

Anti-Oxidative and Anti-Aging Effects of Probiotic Fermented Ginseng by Modulating Gut Microbiota and Metabolites in Caenorhabditis elegans.

Antioxidative and antiaging abilities of probiotic fermented ginseng (PG) were evaluated in Caenorhabditis elegans (C. elegans). Lifespan and effect on heat stress and acute oxidative stress in C. elegans were significantly enhanced by PG. Antioxidative enzymes such as T-SOD, GSH-PX, CAT were significantly up-regulated, and MDA, ROS and apoptosis levels were significantly down-regulated. At the same time, PG exerted antioxidant and anti-aging activities by reducing the expression of DAF-2 mRNA and increasing the expression of SKN-1 and SOD-3 mRNA in C. elegans. In addition, the mechanism of antioxidative and antiaging activities of PG was explored through gut microbiota sequencing and untargeted metabolomics. The results of gut microbiota indicated that PG could significantly improve the composition and structure of microbes in the gut of C. elegans, and the relative abundance of beneficial bacteria was up-regulated. Untargeted metabolomic results elucidated that PG modulated antioxidant and antiaging activities through neuroactive ligand-receptor interaction, Citrate cycle (TCA cycle), pyruvate metabolism, ascorbate and aldarate metabolism and D-Arginine and D-ornithine metabolism of C. elegans. These results indicated that PG had excellent antioxidant and anti-aging activities, providing research value for the development of functional foods and improvement of aging-related diseases.

NDGA enhances the physicochemical and anti-biodegradation performance of dentin collagen.

OBJECTIVES: Collagen fibrils from carious dentin matrix are prone to enzymatic degradation. This study investigates the feasibility and mechanism of nordihydroguaiaretic acid (NDGA), as a collagen crosslinker, to bio-modify the demineralized dentin matrix. METHODS: The physicochemical properties of the crosslinked dentin matrix were characterized by swelling ratio, ninhydrin assay, Fourier Transform Infrared spectroscopy, and atomic force microscopy. The collagenase degradation resistance was evaluated by measuring loss of dry mass, hydroproline release, loss of elasticity, and micro-nano structure integrity. The cytotoxicity of NDGA-crosslinked dentin collagen was evaluated by flow cytometry. RESULTS: NDGA crosslinked dentin matrix without destroying the integrity of collagen. Mechanistically, NDGA formed bisquinone bond between two adjacent o-quinone groups, resulting in NDGA polymeric matrix in which collagen fibrils were embedded. NDGA modification could significantly enhance the stiffness of dentin matrix at macro-nano scale. The NDGA-crosslinked dentin matrix exhibited remarkably low collagen degradation and sustained bulk elasticity after collagenase challenge, which were attributed to decreased water content, physical masking of collagenase bind sites on collagen, and improved stiffness of collagen fibrils. Notably, NDGA-crosslinked dentin matrix exhibited excellent biocompatibility. CONCLUSION: NDGA, as a biocompatible collagen crosslinker, improves the mechanical properties and biodegradation resistance of demineralized dentin matrix.

Availability and Affordability of Therapeutic Monoclonal Antibodies After the New Medical Reform in Hubei Province, China.

OBJECTIVE: In 2017, China launched a new round of medical reform (NMR) to address the inaccessibility of high-priced drugs for patients with serious diseases. This study explored the impact of the NMR on the accessibility and affordability of high-priced monoclonal antibodies (mAbs), and the effective promotion policies after the NMR. METHODS: We used a standard method developed by the World Health Organization to conduct two surveys on the availability of mAbs and their prices before and after the NMR in the public hospitals in Hubei province, China. By interviewing hospital pharmacy experts, we identified the potential value of the current NMR in improving the access to therapeutic mAbs. RESULTS: The average availability of 13 mAbs increased by 8.1% in the surveyed hospitals of Hubei province after the NMR. The median unit price of 10 mAbs dropped by 34.3%. The average affordability of a treatment cycle of 10 mAbs dropped from 680 days to 298 days of the disposable daily income for a middle-income resident (56.2% reduction). The drug price negotiation of medical insurance inclusion and the promotion of consistent evaluation of generic and original drugs could effectively promote the accessibility of mAbs. However, the zero markup of drug pricing and the limit on the proportion of drug revenues in public hospitals showed certain negative effects on the availability of mAbs. CONCLUSION: Not all current NMR policies play a positive role in promoting the accessibility of mAbs. To further improve the accessibility of mAbs in the future in China, it is therefore critical to increase the investment in independent research and development of high-quality mAbs, establish localized guidelines for the rational use of mAbs in clinical practice, and have a cost-sharing mechanism for high-priced drugs with multiple stakeholders.

Ferroelectric control of band alignments and magnetic properties in the two-dimensional multiferroic VSe2/In2Se3.

Our first-principles evidence shows that the two-dimensional (2D) multiferroic VSe2/In2Se3experiences continuous change of electronic structures, i.e. with the change of the ferroelectric (FE) polarization of In2Se3, the heterostructure can possess type-I, -II, and -III band alignments. When the FE polarization points from In2Se3to VSe2, the heterostructure has a type-III band alignment, and the charge transfer from In2Se3into VSe2induces half-metallicity. With reversal of the FE polarization, the heterostructure enters the type-I band alignment, and the spin-polarized current is turned off. When the In2Se3is depolarized, the heterostructure has a type-II band alignment. In addition, influence of the FE polarization on magnetism and magnetic anisotropy energy of VSe2was also analyzed, through which we reveal the interfacial magnetoelectric coupling effects. Our investigation about VSe2/In2Se3predicts its wide applications in the fields of both 2D spintronics and multiferroics.

Association of Circulating Apolipoprotein AI Levels in Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis.

With the development of medicine, our research on Alzheimer's disease (AD) has been further deepened, but the mechanism of its occurrence and development has not been fully revealed, and there is currently no effective treatment method. Several studies have shown that apolipoprotein AI (ApoA-I) can affect the occurrence and development of Alzheimer's disease by binding to amyloid ß (Aß). However, the association between circulating levels of ApoA-I and AD remains controversial. We conducted a meta-analysis of 18 studies published between 1992 and 2017 to determine whether the ApoA-I levels in the blood and cerebrospinal fluid (CSF) are abnormal in AD. Literatures were searched in PubMed, EMBASE and Web of Science databases without language limitations. A pooled subject sample including 1,077 AD patients and 1,271 healthy controls (HCs) was available to assess circulating ApoA-I levels; 747 AD patients and 680 HCs were included for ApoA-I levels in serum; 246 AD patients and 456 HCs were included for ApoA-I levels in plasma; 201 AD patients and 447 HCs were included for ApoA-I levels in CSF. It was found that serum and plasma levels of ApoA-I were significantly reduced in AD patients compared with HCs {[standardized mean difference (SMD) = -1.16; 95% confidence interval (CI) (-1.72, -0.59); P = 0.000] and [SMD = -1.13; 95% CI (-2.05, -0.21); P = 0.016]}. Patients with AD showed a tendency toward higher CSF ApoA-I levels compared with HCs, although this difference was non-significant [SMD = 0.20; 95% CI (-0.16, 0.56); P = 0.273]. In addition, when we analyzed the ApoA-I levels of serum and plasma together, the circulating ApoA-I levels in AD patients was significantly lower [SMD = -1.15; 95% CI (-1.63, -0.66); P = 0.000]. These results indicate that ApoA-I deficiency may be a risk factor of AD, and ApoA-I has the potential to serve as a biomarker for AD and provide experimental evidence for diagnosis of AD. Systematic Review Registration: PROSPERO, identifier: 325961.

Direct Synthesis of Bienzyme-like Carbide-derived Carbons via Mild Electrochemical Oxidation of Ti 3AlC 2 MAX.

Objective: To develop effective alternatives to natural enzymes, it is crucial to develop nanozymes that are economical, resource efficient, and environmentally conscious. Carbon nanomaterials that have enzyme-like activities have been extensively developed as substitutes for traditional enzymes. Methods: Carbide-derived carbons (CDCs) were directly synthesized via a one-step electrochemical method from a MAX precursor using an ammonium bifluoride electrolyte at ambient conditions. The CDCs were characterized by systematic techniques. Results: CDCs showed bienzyme-like activities similar to that of peroxidase and superoxide dismutase. We systematically studied the dependence of CDC enzyme-like activity on different electrolytes and electrolysis times to confirm activity dependence on CDC content. Additionally, the synthesis mechanism and CDC applicability were elaborated and demonstrated, respectively. Conclusion: The demonstrated synthesis strategy eliminates tedious intercalation and delamination centrifugation steps and avoids using high concentrations of HF, high temperatures, and halogen gases. This study paves the way for designing two-dimensional material-based nanocatalysts for nanoenzyme and other applications.

Effect and Mechanism of LRP6 on Cardiac Myocyte Ferroptosis in Myocardial Infarction.

BACKGROUND: This study was aimed at exploring the biological function and molecular mechanism of ferroptosis of LRP6 modulation in cardiomyocytes of myocardial infarction (MI). METHOD: We established the ferroptosis model of MI in vivo and in vitro and constructed the modulation network of circRNA-miRNA-LRP6 by bioinformatics analysis; then, we focused on exploring the regulatory relationship of LRP6 and its upstream genes circRNA1615 and miR-152-3p in the RIP experiments and the double luciferase reporter gene assay. Also, we tested the LRP6-mediated autophagy-related ferroptosis in MI. RESULTS: Ferroptosis was found in cardiomyocytes of MI, and ferroptosis inhibitor Ferrostatin-1 (Fer-1) could improve the pathological process of MI. LRP6 was involved in the process of ferroptosis in cardiomyocytes, and LRP6 deletion regulated ferroptosis in cardiomyocytes through autophagy. Screening and identification of the upstream gene circRNA1615 would target LRP6. circRNA1615 inhibited ferroptosis in cardiomyocytes, and circRNA1615 could regulate the expression of LRP6 through sponge adsorption of miR-152-3p, prevent LRP6-mediated autophagy-related ferroptosis in cardiomyocytes, and finally control the pathological process of MI. CONCLUSIONS: circRNA1615 inhibits ferroptosis via modulation of autophagy by the miRNA152-3p/LRP6 molecular axis in cardiomyocytes of myocardial infarction.

Perceptions of Generic Drugs in the Pharmacists of Public Hospitals: A Cross-sectional Survey in Hubei Province of China.

OBJECTIVE: Generic drugs provide an opportunity for savings in drug expenditure since they are available at a lower cost and do not affect patients' health. A better understanding of pharmacists' knowledge, attitudes, and perception can promote the quality use of generic drugs. The objective of this study was to investigate the knowledge, attitudes, and perception of pharmacists from tertiary hospitals in China regarding generic drugs. METHODS: A cross-sectional survey using a postal questionnaire was conducted, which was sent to 200 hospital pharmacists randomly selected from tertiary hospitals in Hubei Province. A total of 125 questionnaires out of 200 were received. Of the respondents, 80 were female and 45 were male. RESULTS: The majority of respondents (87.2%) could clearly distinguish between original and generic drugs. Pharmacists agreed that generic drugs were less effective (52.8%) and produced more side effects (52%). Fortynine respondents thought that generic drug products were not adequately tested. Approximately 78% and 60% of the pharmacists indicated that generic substitution was not feasible for drugs with narrow therapeutic windows and drugs for critical diseases, respectively. Most of them supported the recommendation of generic drugs based on professional judgment. CONCLUSION: Our study showed that a considerable portion of Chinese hospital pharmacists hold negative perceptions of generic drugs. Interventions to improve pharmacists' knowledge of generic drugs are needed.

Structures of (NaSCN)2(H2O)n -/0 (n = 0-7) and solvation induced ion pair separation: Gas phase anion photoelectron spectroscopy and theoretical calculations.

We studied (NaSCN)2(H2O)n - clusters in the gas phase using size-selected anion photoelectron spectroscopy. The photoelectron spectra and vertical detachment energies of (NaSCN)2(H2O)n - (n = 0-5) were obtained in the experiment. The structures of (NaSCN)2(H2O)n -/0 up to n = 7 were investigated with density functional theory calculations. Two series of peaks are observed in the spectra, indicating that two types of structures coexist, the high electron binding energy peaks correspond to the chain style structures, and the low electron binding energy peaks correspond to the Na-N-Na-N rhombic structures or their derivatives. For the (NaSCN)2(H2O)n - clusters at n = 3-5, the Na-N-Na-N rhombic structures are the dominant structures, the rhombic four-membered rings start to open at n = 4, and the solvent separated ion pair (SSIP) type of structures start to appear at n = 6. For the neutral (NaSCN)2(H2O)n clusters, the Na-N-Na-N rhombic isomers become the dominant starting at n = 3, and the SSIP type of structures start to appear at n = 5 and become dominant at n = 6. The structural evolution of (NaSCN)2(H2O)n -/0 (n = 0-7) confirms the possible existence of ionic clusters such as Na(SCN)2 - and Na2(SCN)+ in NaSCN aqueous solutions.

PCAT6 may be a new prognostic biomarker in various cancers: a meta-analysis and bioinformatics analysis.

BACKGROUND: LncRNA prostate cancer-associated transcript 6 (PCAT6) has been reported to be dysregulated in several cancers and is associated with tumor progression. Here, we have performed a meta-analysis to assess the general prognostic role of PCAT6 in malignancies. METHODS: Four public databases (Embase, Pubmed, Web of Science, Cochrane Library) were used to identify eligible studies, then data was extracted and associations between prognostic indicators and clinical characteristics were combined to estimate hazard ratio (HR) or odds ratio (OR) with a 95% confidence interval (CI). Publication bias was measured using the Begg's test, and the stability of the combined results was measured using sensitivity analysis. Subsequently, results were validated using Gene Expression Profiling Interactive Analysis (GEPIA) and the National Genomics Data Center (NGDC). RESULTS: Ten studies were considered eligible for inclusion. In total, 937 patients and eight types of cancer were included. Our results revealed that overexpression of PCAT6 was significantly associated with a shorter OS (HR = 1.82; 95% CI, [1.40, 2.38]; P < 0.0001) and progression-free survival (PFS) (HR = 1.66; 95% CI, [1.22, 2.25]; P < 0.0001) in cancer patients, and that PCAT6 overexpression was significantly associated with individual tumor clinicopathological parameters, including TNM stage (OR = 0.29; 95% CI, [0.09, 0.94]; P = 0.04), gender (OR = 1.84; 95% CI, [1.31, 2.59]; P = 0.0005), and whether the tumor was metastatic (OR = 5.02; 95% CI, [1.36, 18.57]; P = 0.02). However, PCAT6 overexpression was not correlated with patient age and tumor differentiation. PCAT6 expression was significantly up-regulated in four types of cancer, which was validated using the GEPIA cohort. Combining OS and disease-free survival (DFS) of these four types of cancer revealed a shorter OS and DFS in patients with PCAT6 overexpression. PCAT6 expression in various types of cancer was also validated in NGDC. A total of eight cancers were analyzed and PCAT6 was highly expressed in all eight cancers. Further functional predictions suggest that PCAT6 is correlated with tumor prognosis, and that PCAT6 may be useful as a new tumor-specific marker. CONCLUSIONS: LncRNA PCAT6 is highly expressed in multiple cancer types and its upregulation was significantly associated with patient prognosis and poorer clinical features, thereby suggesting that PCAT6 may be a novel prognostic factor in multiple cancer types.

miR­29b suppresses proliferation and induces apoptosis of hepatocellular carcinoma ascites H22 cells via regulating TGF­ß1 and p53 signaling pathway.

MicroRNA (miR)­29b is a key tumor regulator. It can inhibit tumor cell proliferation, induce apoptosis, suppress tumor invasion and migration, thus delaying tumor progression. Our previous studies revealed an increased level of miR­29b in hepatoma 22 (H22) cells in ascites tumor­bearing mice. The present study investigated the effect of miR­29b on proliferation and apoptosis of hepatocellular carcinoma ascites H22 cells and its association with the transforming growth factor­ß1 (TGF­ß1) signaling pathway and p53­mediated apoptotic pathway. Briefly, H22 cells were transfected with miR­29b­3p (hereinafter referred to as miR­29b) mimic or miR­29b inhibitor. MTS cell proliferation assay and flow cytometry were used to analyze cell viability and apoptosis. The expression change of the TGF­ß1 signaling pathway and p53­mediated apoptotic pathway were detected by reverse transcription­quantitative PCR, western blotting and immunofluorescence. Furthermore, cells were treated with exogenous TGF­ß1 and TGF­ß1 small interfering RNA to evaluate the crosstalk between TGF­ß1 and p53 under miR­29b regulation. The overexpression of miR­29b decreased cell viability, increased cell apoptosis, activated the TGF­ß1 signaling pathway and p53­mediated apoptotic pathway. Conversely, these effects were reversed by the miR­29b inhibitor. Moreover, the effect of miR­29b mimic was further increased after treating cells with exogenous TGF­ß1. The activation of the TGF­ß1 signaling pathway and p53­mediated apoptotic pathway induced by miR­29b overexpression were reversed by TGF­ß1 inhibition. In summary, these data indicated that miR­29b has an important role in proliferation and apoptosis of H22 cells by regulating the TGF­ß1 signaling pathway, the p53­dependent apoptotic pathway, and the crosstalk between TGF­ß1 and p53.

Deep learning for predicting COVID-19 malignant progression.

As COVID-19 is highly infectious, many patients can simultaneously flood into hospitals for diagnosis and treatment, which has greatly challenged public medical systems. Treatment priority is often determined by the symptom severity based on first assessment. However, clinical observation suggests that some patients with mild symptoms may quickly deteriorate. Hence, it is crucial to identify patient early deterioration to optimize treatment strategy. To this end, we develop an early-warning system with deep learning techniques to predict COVID-19 malignant progression. Our method leverages CT scans and the clinical data of outpatients and achieves an AUC of 0.920 in the single-center study. We also propose a domain adaptation approach to improve the generalization of our model and achieve an average AUC of 0.874 in the multicenter study. Moreover, our model automatically identifies crucial indicators that contribute to the malignant progression, including Troponin, Brain natriuretic peptide, White cell count, Aspartate aminotransferase, Creatinine, and Hypersensitive C-reactive protein.

Comparison of the Microsolvation of CaX2 (X = F, Cl, Br, I) in Water: Size-Selected Anion Photoelectron Spectroscopy and Theoretical Calculations.

To understand the microsolvation of alkaline-earth dihalides in water and provide information about the dependence of solvation processes on different halides, we investigated CaBr2(H2O)n-, CaI2(H2O)n-, and CaF2(H2O)n- (n = 0-6) clusters using size-selected anion photoelectron spectroscopy and conducted theoretical calculations on these clusters and their neutrals. The results are compared with those of CaCl2(H2O)n-/0 clusters reported previously. It is found that the vertical detachment energies (VDEs) of CaCl2(H2O)n-, CaBr2(H2O)n-, and CaI2(H2O)n- show a similar trend with increasing cluster size, while the VDEs of CaF2(H2O)n- show a different trend. The VDEs of CaF2(H2O)n- are much lower than those of CaCl2(H2O)n-, CaBr2(H2O)n-, and CaI2(H2O)n-. A detailed probing of the structures shows that a significant increase of the Ca-X distance (separation of Ca2+-X- ion pair) in CaCl2(H2O)n-/0, CaBr2(H2O)n-/0, and CaI2(H2O)n-/0 clusters occurred at about n = 5. However, for CaF2(H2O)n-/0, no abrupt change of the Ca-F distance with the increasing cluster size has been observed. In CaCl2(H2O)6-/0, CaBr2(H2O)6-/0, and CaI2(H2O)6-/0, the Ca atom coordinates directly with 5 H2O molecules. However, in CaF2(H2O)n-/0, the Ca atom coordinates directly with only 2 or 3 H2O molecules. The similarity or differences in the structures and coordination numbers are consistent with the fact that CaCl2, CaBr2, and CaI2 have similar solubility, while CaF2 has much lower solubility.