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BackgroundClozapine is widely regarded as a highly efficacious psychotropic drug that is largely underused worldwide. Recent disproportionality analyses and nationwide case-control studies suggested a potential association between clozapine use and hematological malignancy (HM). Nevertheless, the absolute rate difference is not well-established due to the absence of analytic cohort studies. The clinical significance of such a potential risk remains unclear.Methods and findingsWe extracted data from a territory-wide public healthcare database from January 2001 to August 2022 in Hong Kong to conduct a retrospective cohort study of anonymized patients aged 18+ years with a diagnosis of schizophrenia who used clozapine or olanzapine (drug comparator with highly similar chemical structure and pharmacological mechanisms) for 90+ days, with at least 2 prior other antipsychotic use records within both groups. Weighted by inverse probability of treatment (IPTW) based on propensity scores, Poisson regression was used to estimate the incidence rate ratio (IRR) of HM between clozapine and olanzapine users. The absolute rate difference was also estimated. In total, 9,965 patients with a median follow-up period of 6.99 years (25th to 75th percentile: 4.45 to 10.32 years) were included, among which 834 were clozapine users. After IPTW, the demographic and clinical characteristics of clozapine users were comparable to those of olanzapine users. Clozapine users had a significant weighted IRR of 2.22 (95% confidence interval (CI) [1.52, 3.34]; p < 0.001) for HM compared to olanzapine users. The absolute rate difference was estimated at 57.40 (95% CI [33.24, 81.55]) per 100,000 person-years. Findings were consistent across subgroups by age and sex. Sensitivity analyses all supported the robustness of the results and showed good specificity to HM but no other cancers. The main limitation of this observational study is the potential residual confounding effects that could have arisen from the lack of randomization in clozapine or olanzapine use.ConclusionsAbsolute rate difference in HM incidence associated with clozapine is small despite a 2-fold elevated rate. Given the rarity of HM and existing blood monitoring requirements, more restrictive indication for clozapine or special warnings may not be necessary.

Abstract Purpose The relationship between delayed ambulation (DA) and postoperative adverse events (AEs) following transforaminal lumbar interbody fusion (TLIF) in elderly patients remains elusive. The aim of our study was to evaluate the effects of DA on the postoperative AEs including complications, readmission and prolonged length of hospital stay (LOS). Methods This was a retrospective analysis of a prospectively established database of elderly patients (aged 65 years and older) who underwent TLIF surgery. The early ambulation (EA) group was defined as patients ambulated within 48 h after surgery, whereas the delayed ambulation (DA) group was patients ambulated at a minimum of 48 h postoperatively. The DA patients were 1:1 propensity-score matched to the EA patients based on age, gender and the number of fused segments. Univariate analysis was used to compare postoperative outcomes between the two groups, and multivariate logistic regression analysis was used to identify risk factors for adverse events and DA. Results After excluding 125 patients for various reasons, 1025 patients (≤ 48 h: N = 659 and > 48 h: N = 366) were included in the final analysis. After propensity score matching, there were 326 matched patients in each group. There were no significant differences in the baseline data and the surgery-related variables between the two groups (p > 0.05). The patients in the DA group had a significant higher incidence of postoperative AEs (46.0% vs. 34.0%, p = 0.002) and longer LOS (p = 0.001). Multivariate logistic regression identified that age, operative time, diabetes, and DA were independently associated with postoperative AEs, whereas greater age, higher international normalized ratio, and intraoperative estimated blood loss were identified as independent risk factors for DA. Conclusions Delayed ambulation was an independent risk factor for postoperative AEs after TLIF in elderly patients. Older age, increased intraoperative blood loss and worse coagulation function were associated with delayed ambulation.

Abstract Wounding initiates intricate responses crucial for tissue repair and regeneration. Yet, the gene regulatory networks governing wound healing remain poorly understood. Here, employing single-worm RNA sequencing (swRNA-seq) across 12 time-points, we delineated a three-stage wound repair process in C. elegans: response, repair, and remodeling. Integrating diverse datasets, we constructed a dynamic regulatory network comprising 241 transcription regulators and their inferred targets. We identified potentially seven autoregulatory TFs and five cross-autoregulatory loops involving pqm-1 and jun-1. We revealed that TFs might interact with chromatin factors and form TF-TF combinatory modules via intrinsically disordered regions to enhance response robustness. We experimentally validated six regulators functioning in transcriptional and translocation-dependent manners. Notably, nhr-76, daf-16, nhr-84, and oef-1 are potentially required for efficient repair, while elt-2 may act as an inhibitor. These findings elucidate transcriptional responses and hierarchical regulatory networks during C. elegans wound repair, shedding light on mechanisms underlying tissue repair and regeneration.

Abstract Background Most studies on the impact of the COVID-19 pandemic on depression burden focused on the earlier pandemic phase specific to lockdowns, but the longer-term impact of the pandemic is less well-studied. In this population-based cohort study, we examined the short-term and long-term impacts of COVID-19 on depression incidence and healthcare service use among patients with depression. Methods Using the territory-wide electronic medical records in Hong Kong, we identified all patients aged ≥ 10 years with new diagnoses of depression from 2014 to 2022. We performed an interrupted time-series (ITS) analysis to examine changes in incidence of medically attended depression before and during the pandemic. We then divided all patients into nine cohorts based on year of depression incidence and studied their initial and ongoing service use patterns until the end of 2022. We applied generalized linear modeling to compare the rates of healthcare service use in the year of diagnosis between patients newly diagnosed before and during the pandemic. A separate ITS analysis explored the pandemic impact on the ongoing service use among prevalent patients with depression. Results We found an immediate increase in depression incidence (RR = 1.21, 95% CI: 1.10–1.33, p

Magnesium chelatase (MgCh) plays a pivotal role in photosynthesis, catalyzing the insertion of magnesium into protoporphyrin IX (Proto IX), a key intermediate in chlorophyll (Chl) biosynthesis. MgCh is a heteromeric complex composed of the MgCh D subunit (CHLD), the MgCh H subunit (CHLH), and the MgCh I subunit (CHLI). The bright yellow leaves (byl) mutant was obtained through ethyl methanesulfonate (EMS) mutagenesis of the ‘FT’ Chinese cabbage (Brassica rapa L. ssp. pekinensis) doubled haploid line, whose Chl content, net photosynthetic rate (Pn), and non-photochemical quenching coefficient (NPQ) were decreased, and whose chloroplast development was incomplete. byl recovered to a light green phenotype under weak light conditions. Genetic analysis revealed that the bright yellow leaves phenotype of byl was caused by a single recessive nuclear gene. Using Mutmap sequencing and Kompetitive allele-specific PCR (KASP) identification, BraA01g010040.3.5C, encoding the CHLI subunit of MgCh, was identified as the candidate gene and named Brchli1. A nonsynonymous G-to-A mutation in the Brchli1 exon resulted in the substitution of aspartic acid with asparagine. Brchli1-silenced Chinese cabbage displayed bright yellow leaves with decreased Brchli1 expression. Transiently overexpressed Brchli1 in the byl mutant restored the green leaf phenotype and significantly increased relative Brchli1 expression levels. Both BrCHLI1 and its mutated variant were localized in chloroplasts. Yeast two-hybrid and luciferase complementation imaging assays demonstrated that BrCHLI1 interacted with both BrCHLD and itself. BrCHLI1 mutations did not affect its interaction with BrCHLD. Together, Brchli1 mutations impaired the function of MgCh, providing insights into the molecular mechanism of leaf coloration.

The poor lighting environment in the underground coal mine is easy to cause the miners to have psychological irritability, which leads to the occurrence of accidents. In order to reduce the incidence of accidents and ensure the personal safety of miners. In this paper, different illumination levels are used as control variables. With the help of cognitive ability tests commonly used in psychology, accuracy(AC), reaction time(RT)and performance indicators(PI) are selected to describe how different illumination levels affect the psychological state of miners. The results show that: (1) In the two selected cognitive ability test tasks, when the illumination level is very low, the AC is not high and the RT is longer. As the illumination increases, the AC in the cognitive test task becomes higher and the RT becomes faster. The optimal value is reached at 200lux–300lux.At this time, the illumination level increases again, the AC value decreases, and the RT value increases. When the illuminance is lower than 200Lux, the results of the two tasks are not the same, but when 200Lux∼300Lux, the PI values are larger, and then increase the illuminance, the PI value decreases. (2)The regression analysis of three indicators and illuminance level was carried out, and the binary linear regression equation of different illuminance levels and PI/RT was established to monitor the influence of illuminance on the psychological state of miners. (3) Reasonable control of lighting environment can effectively promote the cognitive ability of miners in the work, and minimize the risk of coal mine accidents.

Observations at (sub-)millimeter wavelengths offer a complementary perspective on our Sun and other stars, offering significant insights into both the thermal and magnetic composition of their chromospheres. Despite the fundamental progress in (sub-)millimeter observations of the Sun, some important aspects require diagnostic capabilities that are not offered by existing observatories. In particular, simultaneously observations of the radiation continuum across an extended frequency range would facilitate the mapping of different layers and thus ultimately the 3D structure of the solar atmosphere. Mapping large regions on the Sun or even the whole solar disk at a very high temporal cadence would be crucial for systematically detecting and following the temporal evolution of flares, while synoptic observations, i.e., daily maps, over periods of years would provide an unprecedented view of the solar activity cycle in this wavelength regime. As our Sun is a fundamental reference for studying the atmospheres of active main sequence stars, observing the Sun and other stars with the same instrument would unlock the enormous diagnostic potential for understanding stellar activity and its impact on exoplanets. The Atacama Large Aperture Submillimeter Telescope (AtLAST), a single-dish telescope with 50m aperture proposed to be built in the Atacama desert in Chile, would be able to provide these observational capabilities. Equipped with a large number of detector elements for probing the radiation continuum across a wide frequency range, AtLAST would address a wide range of scientific topics including the thermal structure and heating of the solar chromosphere, flares and prominences, and the solar activity cycle. In this white paper, the key science cases and their technical requirements for AtLAST are discussed.

In order to establish the internal relationship between the composition and crystallization characteristics of fat and the product quality and whipping properties, the fat composition and crystallization characteristics, emulsion quality, whipped product quality and whipping properties of dairy, non-dairy and mixed creams were analyzed in this study. The results showed that the crystal network formed by mixed animal and vegetable fats had a dense structure and high susceptibility to shear-induced partial aggregation, the resulting emulsion had high viscosity and low overrun, while the whipped product had high hardness and moderate conformal capacity. However, the crystallization properties of vegetable fat were opposite to those of mixed animal and vegetable fats, and the susceptibility to shear-induced partial aggregation was low. The vegetable cream emulsion had low viscosity and high overrun, whereas the whipped product has low hardness and the best conformal capacity. Animal fat had the lowest solid fat content, resulting in the weakest crystal network structure; the rate of partial aggregation, viscosity and overrun of the resulting emulsion were the lowest, and the whipped product had the lowest hardness and conformal capacity. Therefore, the product quality and whipping performance can be controlled by regulating the fat composition and crystallization characteristics. This study can provide theoretical guidance for the development of high-quality whipped cream.

As an essential application of unmanned aerial vehicle (UAV) systems, payload transportation has garnered significant attention in recent years. Collaborative payload transportation utilizing multiple UAVs can effectively increase the payload capacity of the transportation system. Nevertheless, the incorporation of multiple UAVs makes the dynamic model of the transportation system more complex due to the coupled UAV and payload states. In the immediate disaster relief response, the collaborative system is often required to promptly deliver supplies to the target site while avoiding obstacles to ensure the system’s safety. Consequently, devising fast delivery trajectories that avoid collisions for such complicated systems poses a considerable challenge. To this end, a novel trajectory planning method is presented for collaborative transportation systems. Specifically, the dynamic model of the collaborative transportation system is derived by utilizing the Euler–Lagrange method. Then, the trajectory planning problem is formulated as an optimization problem with considerations of dynamics, actuation, safety, and formation constraints. To expedite the optimization process, the collision avoidance safety constraint is constructed using dual variables. The efficacy of this trajectory planning approach is confirmed through multiple real-world flight experiments involving collaborative aerial transportation systems of two and three UAVs.

Phosphorus (P) plays a vital role in fish life and its application in aquatic feed deserves thoroughly study. To evaluate the effects of dietary P on growth performance, serum biochemical parameters and intestinal microbiota of the juvenile hybrid of A. baerii♀ × A. schrenckii♂, five diets containing 3.7, 6.5, 9.6, 12.2 and 14.8 g/kg of available phosphorus (AP) were assigned to feed fish at initial weight of 10.06 ± 0.39 g for 8 weeks. The results showed that weight gain (WG) of juvenile hybrid sturgeon was improved significantly with dietary AP level up to 9.6 g/kg. Feed efficiency (FE) and P digestibility of fish were significantly enhanced by P supplementation, but were dropped when dietary AP level further increased to 12.2 and 14.8 g/kg. Alkaline phosphatase (ALP) activity increased firstly and then slightly decreased at a stable level in the high dietary AP groups (12.2 and 14.8 g/kg). With dietary AP level increasing, significantly decrease of the content of triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) in serum were observed. Serum antioxidant indicators including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px) and total antioxidant capacity (T-AOC) exhibited the improved activity by addition P in diet. Intestinal microbiota analysis indicated that the supplementation of P in diet increased the richness and diversity of bacteria communities. Cyanobacteria was the dominant phyla in the intestine of hybrid sturgeon, and was significantly increased in P addition group. Compared with the basal diet group, abundant genera in dietary P supplementation group exhibited a higher diversity and were composed of Clostridium, Cetobacterium, Bacteroides, Empedobacter, Ruminococcus, Faecalibacterium, Rhodococcus and Candidatus Arthromitus. In conclusion, appropriate dietary P supplementation could positively affect the growth, biological processes and intestinal microbial communities of fish, and a level of 8.5 g/kg of AP in diet is suggested for juvenile hybrid sturgeon.

Enhancing regional ecosystem stability and managing land resources effectively requires identifying ecological function zones and understanding the factors that influence them. However, most current studies have primarily focused on ecosystem service bundles, paying less attention to the trade-offs, synergies, and ecological sensitivity, leading to a more uniform approach to functional zoning. This study aimed to analyze and describe the spatial and temporal patterns of four essential ecosystem services, including water yield (WY), net primary productivity (NPP), soil conservation (SC), and habitat quality (HQ), in the Sichuan-Yunnan ecological buffer area over the period from 2005 to 2019. Spatial overlay analysis was used to assess ecological sensitivity, trade-offs, synergies, and ecosystem service bundles to define ecological functional zones. Geographic detectors were then applied to identify the primary drivers of spatial variation in these zones. The findings showed a progressive improvement in ecosystem service functions within the Sichuan-Yunnan ecological buffer zone. Between 2005 and 2019, NPP, soil conservation, and water yield all demonstrated positive trends, while HQ displayed a declining trend. There was significant spatial heterogeneity and distinct regional patterns in ecosystem service functions, with a general decrease from southwest to northeast, particularly in NPP and HQ. Trade-offs were evident in most ecosystem services, with the most significant between WY and HQ and most in the northeast and east regions. Ecological sensitivity decreased from southwest to northeast. Regions with a higher ecological sensitivity were primarily situated in the southwestern region, and their spatial distribution pattern was comparable to that of high habitat quality. The spatial overlay analysis categorized areas into various types, including human production and settlement zones, ecologically vulnerable zones, ecological transition zones, and ecological conservation zones, accounting for 17.28%, 22.30%, 7.41%, and 53.01% of the total area, respectively. The primary environmental factor affecting ecological function zoning was identified as precipitation, while the main social variables were human activity and population density. This study enhances the understanding of ecological functions and supports sustainable development in the Sichuan-Yunnan ecological buffer area, offering important guidance for ecological zoning.

Abstract Background Preclinical evidence suggests that certain antipsychotic medications may inhibit the development of lung cancer. This study aims to investigate the association between incident lung cancer and different cumulative exposure periods of flupentixol or any antipsychotics. Methods Using electronic health records from the Hospital Authority in Hong Kong, this nested case-control study included case participants aged 18 years or older with newly diagnosed lung cancer after initiating antipsychotics between January 1, 2003, and August 31, 2022. Each case was matched to up to ten controls of the same sex and age, who were also antipsychotic users. Multivariable conditional logistic regression models were conducted to quantify the association between lung cancer and different cumulative exposure times of flupentixol (0–365 days [ref]; 366–1825 days; 1826+ days) and any antipsychotics (1–365 days [ref]; 366–1825 days; 1826+ days), separately. Results Here we show that among 6435 cases and 64,348 matched controls, 64.06% are males, and 52.98% are aged 65–84 years. Compared to patients with less than 365 days of exposure, those with 366–1825 days of exposure to flupentixol (OR = 0.65 [95% CI, 0.47–0.91]) and any antipsychotics (0.42 [0.38–0.45]) have a lower risk of lung cancer. A decreased risk is observed in patients who have 1826+ days of cumulative use of any antipsychotics (0.54 [0.47–0.60]). Conclusions A reduced risk of lung cancer is observed in patients with more than one year of exposure to flupentixol or any antipsychotics. Further research on the association between lung cancer and other antipsychotic agents is warranted.

Microbial natural products have been one of the most important sources for drug development. In the current postgenomic era, sequence-driven approaches for natural product discovery are becoming increasingly popular. Here, we develop an effective genome mining strategy for the targeted discovery of microbial metabolites with antitumor activities. Our method employs uvrA-like genes as genetic markers, which have been identified in the biosynthetic gene clusters (BGCs) of several chemotherapeutic drugs of microbial origin and confer self-resistance to the corresponding producers. Through systematic genomic analysis of gifted actinobacteria genera, identification of uvrA-like gene-containing BGCs, and targeted isolation of products from a BGC prioritized for metabolic analysis, we identified a new tetracycline-type DNA intercalator timmycins. Our results thus provide a new genome mining strategy for the efficient discovery of antitumor agents acting through DNA intercalation.

Abstract Aims Population-wide restrictions during the COVID-19 pandemic may create barriers to mental health diagnosis. This study aims to examine changes in the number of incident cases and the incidence rates of mental health diagnoses during the COVID-19 pandemic. Methods By using electronic health records from France, Germany, Italy, South Korea and the UK and claims data from the US, this study conducted interrupted time-series analyses to compare the monthly incident cases and the incidence of depressive disorders, anxiety disorders, alcohol misuse or dependence, substance misuse or dependence, bipolar disorders, personality disorders and psychoses diagnoses before (January 2017 to February 2020) and after (April 2020 to the latest available date of each database [up to November 2021]) the introduction of COVID-related restrictions. Results A total of 629,712,954 individuals were enrolled across nine databases. Following the introduction of restrictions, an immediate decline was observed in the number of incident cases of all mental health diagnoses in the US (rate ratios (RRs) ranged from 0.005 to 0.677) and in the incidence of all conditions in France, Germany, Italy and the US (RRs ranged from 0.002 to 0.422). In the UK, significant reductions were only observed in common mental illnesses. The number of incident cases and the incidence began to return to or exceed pre-pandemic levels in most countries from mid-2020 through 2021. Conclusions Healthcare providers should be prepared to deliver service adaptations to mitigate burdens directly or indirectly caused by delays in the diagnosis and treatment of mental health conditions.

We investigated the effects of dietary tannic acid (TA) supplementation of a high-carbohydrate diet on growth, feed utilization, whole-body proximate composition, serum biochemical indicators, antioxidant capacity, digestive enzyme activity, and liver and intestinal health of juvenile largemouth bass, Micropterus salmoides (initial mean weight: 8.08 ± 0.08 g). Five diets were prepared, including a positive control (dietary carbohydrate level, 16%, LC0), a negative control (dietary carbohydrate level, 21%, HC0), and three TA-supplementation diets based on the negative control diet with TA addition at 200, 400, and 800 mg/kg, respectively. After 8 weeks of feeding, the results showed that compared with the LC0 diet, 400–800 mg/kg dietary TA significantly improved the survival rate of largemouth bass (P

The Tibetan Plateau is a region where the Indian and Asian-European plates collide. A high-precision Moho topography model is important for the study of plate motion and internal tectonics of the Tibetan Plateau. However, previous gravity-based models failed in representing adequately the Moho topography because crustal effects and biases in the inversion parameters were not fully considered. To address these issues, we extracted the gravity effect caused by the crust using wavelet multi-scale analysis, and used an adaptive linear inversion method with available gravity and seismic data to estimate more accurate inversion parameters. With these two improvements, we inverted for a high-precision Moho topography model of the Tibetan Plateau. The results show that the majority of the Tibetan Plateau has a Moho depth of 60–70 km. The Moho depth in the center of the Qaidam Basin is about 50 km, and the Moho topography between the east and west of the basin has obvious undulations. The Moho depth of the Tarim Basin ranges from 38–50 km. While the undulation of Moho is limited in the center of the basin, obvious uplifts are shown in northern and southern basin. The plate driving force between the Tibetan Plateau and the Tarim Basin may be the primary cause of this phenomenon. By comparing the difference with the seismic data, we found that the RMS of our model is 2.8 km smaller than that of the CRUST 1.0 model, which shows that our model is more accurate.

Plant defensins are widely distributed in the leaves, fruits, roots, stems, seeds, and tubers. Research shows that defensin in plants play a significant role in physiological metabolism, growth and development. Plant defensins can kill and suppress a variety of pathogenic bacteria. In this study, we understand the phylogenetic relationships, protein characterization, chromosomal localization, promoter and gene structural features of the TaPDFs family through sequence alignment and conserved protein structural domain analysis. A total of 73 PDF gene members in wheat, 15 PDF genes in maize, and 11 PDF genes in rice were identified. A total of 35, 65, and 34 PDF gene members were identified in the genomes of Ae. tauschii, T. urartu, and T. dicoccoides, respectively. TaPDF4.9 and TaPDF2.15 were constructed into pART27 vector with YFP by homologous recombination for subcellular localization analysis. Subcellular localization results showed that TaPDF4.9 and TaPDF2.15 were basically located in the cell membrane and cytoplasm, and TaPDF4.9 was also located in the nucleus. TaPDF4.9 and TaPDF2.15 could inhibit the infection of Phytophthora infestans strain ‘88069’. The results suggest that TaPDFs may be able to improve disease resistance. The study of wheat defensins will be beneficial for improving wheat yield and provides a theoretical basis for research on resistance to wheat diseases.

Abstract Purpose The prevalence of degenerative spinal deformity (DSD) and the increased cost of correction surgery impose substantial burdens on the health care and insurance system. The aim of our study was to investigate the effects of the implementation of Enhanced Recovery After Surgery (ERAS) protocol on postoperative outcomes after complex spinal surgery. Methods A retrospective analysis of prospectively established database of DSD was performed. The consecutive patients who underwent open correction surgery for degenerative spinal deformity between August 2016 and February 2022 were reviewed. We extracted demographic data, preoperative radiographic parameters, and surgery-related variables. The ERAS patients were 1:1 propensity-score matched to a historical cohort by the same surgical team based on age, gender, BMI, and number of levels fused. We then compared the length of hospital stay (LOS), physiological functional recovery, and the rates of complications and readmissions within 90 days after surgery between the groups. Results There were 108 patients included, 54 patients in the ERAS cohort, and 54 patients matched control patients in the historical cohort. The historical and ERAS cohorts were not significantly different regarding demographic characteristics, comorbidities, preoperative parameters, operative time, and reoperation rate (P > 0.05). Patients in the ERAS group had significantly shorter postoperative LOS (12.0 days vs. 15.1 days, P = 0.001), average days of drain and urinary catheters placement (3.5 days vs. 4.4 days and 1.9 days vs 4.8 days, respectively), and lower 90-day readmission rate (1.8% vs. 12.9%, P = 0.027). The first day of assisted-walking and bowel movement occurred on average 1.9 days (2.5 days vs. 4.4 days, P = 0.001) and 1.7 days (1.9 days vs. 3.6 days, P = 0.001) earlier respectively in the ERAS group. Moreover, the rate of postoperative urinary retention (3.7% vs. 16.7%, P = 0.026) and surgical site infection (0% vs. 7.4%, P = 0.046) were significantly lower with ERAS protocol applied. Conclusions Our study confirmed that the ERAS protocol was safe and essential for patients undergoing thoracolumbar deformity surgery for DSD. The ERAS protocol was associated with a shorter postoperative LOS, a lower rate of 90-day readmission, less rehabilitation discharge, and less postoperative complications.

Rare and undiagnosed diseases substantially decrease patient quality of life and have increasingly become a heavy burden on healthcare systems. Because of the challenges in disease-causing gene identification and mechanism elucidation, patients are often confronted with difficulty obtaining a precise diagnosis and treatment. Due to advances in sequencing and multiomics analysis approaches combined with patient-derived iPSC models and gene-editing platforms, substantial progress has been made in the diagnosis and treatment of rare and undiagnosed diseases. The aforementioned techniques also provide an operational basis for future precision medicine studies. In this review, we summarize recent progress in identifying disease-causing genes based on GWAS/WES/WGS-guided multiomics analysis approaches. In addition, we discuss recent advances in the elucidation of pathogenic mechanisms and treatment of diseases with state-of-the-art iPSC and organoid models, which are improved by cell maturation level and gene editing technology. The comprehensive strategies described above will generate a new paradigm of disease classification that will significantly promote the precision and efficiency of diagnosis and treatment for rare and undiagnosed diseases.

This study was conducted to recover edible bird’s nest (EBN) hydrolysates from different grades of EBN, including the industrial by-products, using enzymatic treatment. The nutrient, physicochemical properties and antioxidant activities of the recovered hydrolysates at different hydrolysis times were evaluated. Results showed that the recovery yield of enzymatic hydrolysis was above 89 % for all grades of EBN and the degree of hydrolysis increased over time. Nitrite content (0.321–0.433 mg/L) was below the permissible tolerance level for all samples. Interestingly, the antioxidant activities (DPPH and ABTS scavenging activities and ferric reducing antioxidant powder (FRAP) activity) were significantly higher (P ≤ 0.05) in hydrolysates recovered from EBN by-products (EBNhC and EBNhD) as compared to the high grade EBN hydrolysates (EBNhA and EBNhB). The in-vitro probiotic activity of EBN and its hydrolysates were examined using the probiotic bacterium Lactobacillus plantarum. Evidently, EBN by-products hydrolysate (EBNhD) recorded the highest number of L. plantarum (1.1 × 1011 CFU/mL), indicating that low grade EBN has the potential as prebiotic material that promotes probiotic activity. This study demonstrated the concept of using EBN by-products hydrolysates for various applications, such as functional ingredients with enhanced bioactivities, to improve its economic value.

Background: SHR8554 is a novel μ-opioid receptor-biased agonist. It has analgesic effects by selectively activating the G protein-coupled pathway. Additionally, it can weakly activate the ß-arrestin-2 pathway, resulting in a limited number of side effects, such as gastrointestinal inhibition. Previous studies have shown that SHR8554 has good analgesic effects, safety and tolerability, but the pharmacokinetic characteristics of SHR8554 in humans have not been reported. This study was designed to investigate the pharmacokinetics and safety of SHR8554 in healthy Chinese male subjects.Methods: A single 1 mg/41.3 μCi intravenous dose of [14C]SHR8554 was administered to six healthy male subjects. Blood, urine and faecal samples were collected at continuous time points to analyse SHR8554 parent drug levels and their metabolites. The total radioactivity in blood, plasma, urine and faeces was detected by using a liquid scintillation counter. The dynamic changes of SHR8554 and its metabolite concentration were by liquid chromatography-tandem mass spectrometry (LC/MS), and then pharmacokinetic analysis. The safety of the drug on the subjects was also observed after a single intravenous injection.Results: The total recovery of radioactivity in urine and faeces was 99.68% ± 0.79% in 216 h, including 76.22% ± 1.12% in urine and 23.46% ± 1.36% in faeces. Seventeen major metabolites in blood, urine and faeces were analysed and identified. The main metabolic pathways of SHR8554 in the human body involve 1) N-dealkylation; 2) O-deethylation; 3) mono-oxidation; 4) glucuronidation, etc. The primary mechanism of SHR8554 clearance in the human body is through urinary excretion, primarily in its parent drug and metabolite forms. The drug has good safety, and no serious adverse effects were observed.Conclusion: SHR8554 showed favourable pharmacokinetic characteristics and safety profiles in this study. SHR8554 is extensively metabolized in human body. The main metabolic pathways include N-dealkylation and O-deethylation, as well as mono-oxidation and glucuronidation. The main excretion route of SHR8554 and its metabolites is through urine.Clinical Trial Registration:http://www.chinadrugtrials.org.cn/, identifier CTR20220450

Introduction In ageing societies, the number of older adults with complex chronic conditions (CCCs) is rapidly increasing. Care for older persons with CCCs is challenging, due to interactions between multiple conditions and their treatments. In home care and nursing homes, where most older persons with CCCs receive care, professionals often lack appropriate decision support suitable and sufficient to address the medical and functional complexity of persons with CCCs. This EU-funded project aims to develop decision support systems using high-quality, internationally standardised, routine care data to support better prognostication of health trajectories and treatment impact among older persons with CCCs.Methods and analysis Real-world data from older persons aged ≥60 years in home care and nursing homes, based on routinely performed comprehensive geriatric assessments using interRAI systems collected in the past 20 years, will be linked with administrative repositories on mortality and care use. These include potentially up to 51 million care recipients from eight countries: Italy, the Netherlands, Finland, Belgium, Canada, USA, Hong Kong and New Zealand. Prognostic algorithms will be developed and validated to better predict various health outcomes. In addition, the modifying impact of pharmacological and non-pharmacological interventions will be examined. A variety of analytical methods will be used, including techniques from the field of artificial intelligence such as machine learning. Based on the results, decision support tools will be developed and pilot tested among health professionals working in home care and nursing homes.Ethics and dissemination The study was approved by authorised medical ethical committees in each of the participating countries, and will comply with both local and EU legislation. Study findings will be shared with relevant stakeholders, including publications in peer-reviewed journals and presentations at national and international meetings.

Brassinazole-resistant (BZR) transcription factors (TFs) are key players in brassinolides (BRs) signaling pathway, which is widely involved in regulating plant growth and development, as well as in plant responding to a variety stresses. Despite their critical roles, little is known about BZR TFs in wheat. In this study, we performed genome-wide analysis of BZR gene family from wheat genome, and 20 TaBZRs were identified. Based on the phylogenetic relationships of TaBZR and BZRs from rice and Arabidopsis, all BZR genes were clustered into four groups. The intron-exon structural patterns and conserved protein motifs of TaBZRs showed high group specificity. TaBZR5, 7, and 9 were significantly induced after salt, drought treatment, and stripe rust infection. However, TaBZR16, which was significantly upregulated under NaCl application, was not expressed during wheat-stripe rust fungus interaction. These results indicated that BZR genes in wheat play different roles in response to various stresses. The results of this study will lay a foundation for further in-depth functional studies of TaBZRs and will provide information for the breeding and genetic improvement of wheat against drought and salt stresses.

Abstract Background During open-door laminoplasty, the position of the bone gutter is not fixed, and when the gutter migrates inward, the outer end of the titanium plate must be fixed on the lamina edge. It is unclear whether this will affect the clinical efficacy. This study aimed to observe the influence of the titanium plate fixation position on the effectiveness of open-door laminoplasty for cervical spondylotic myelopathy (CSM). Methods A total of 98 patients with CSM who underwent open-door laminoplasty from August 2016 to October 2019 were included in this retrospective study. Fifty-five patients had the titanium plate fixed on the lateral mass (lateral mass group), and 43 patients had the titanium plate fixed on the lamina edge (lamina group). The opening angle, opening width, occurrence of hinge fracture, spinal cord drift distance, cervical curvature index (CCI), neurological function recovery (JOA score), neck function (NDI), C5 palsy and severity of axial symptoms were observed and compared between the two groups. Results The opening angle in the lamina group was significantly larger than that in the lateral mass group, while the opening width and the spinal cord drift distance were significantly smaller than those in the lateral mass group (P 0.05), and there was no significant difference between the groups (P > 0.05). After surgery, the JOA score significantly increased in both groups (P

Nerve guidance conduits with hollow lumen fail to regenerate critical-sized peripheral nerve defects (15 mm in rats and 25 mm in humans), which can be improved by a beneficial intraluminal microenvironment. However, individual cues provided by intraluminal filling materials are inadequate to eliminate the functional gap between regenerated nerves and normal nerves. Herein, an aligned fibrin/functionalized self-assembling peptide (AFG/fSAP) interpenetrating nanofiber hydrogel that exerting synergistic topographical and biochemical cues for peripheral nerve regeneration is constructed via electrospinning and molecular self-assembly. The hydrogel possesses an aligned structure, high water content, appropriate mechanical properties and suitable biodegradation capabilities for nerve repair, which enhances the alignment and neurotrophin secretion of primary Schwann cells (SCs) in vitro, and successfully bridges a 15-mm sciatic nerve gap in rats in vivo. The rats transplanted with the AFG/fSAP hydrogel exhibit satisfactory morphological and functional recovery in myelinated nerve fibers and innervated muscles. The motor function recovery facilitated by the AFG/fSAP hydrogel is comparable with that of autografts. Moreover, the AFG/fSAP hydrogel upregulates the regeneration-associated gene expression and activates the PI3K/Akt and MAPK signaling pathways in the regenerated nerve. Altogether, the AFG/fSAP hydrogel represents a promising approach for peripheral nerve repair through an integration of structural guidance and biochemical stimulation.

Variational mode decomposition (VMD) has been widely applied in sensors. However, the mode number and balance parameter seriously limit VMD application. To solve this problem, this study proposes a novel method, which combines an improved energy fluctuation index (IEFI) and modified VMD (MVMD). In the proposed method, IEFI provided better performance to resist interference from random impulses by considering the periodicity of fault feature components. Consequently, it is applied to determine the initial center frequency for MVMD, which fixed the problem of the mode number. Moreover, a novel balance parameter search strategy, which can adaptively determine the optimal balance parameter, is combined with MVMD whose stop condition is replaced by kurtosis to extract the fault feature. Simulation results indicated that the proposed method does well in detecting the feature of a periodic impulse signal from the signal polluted by some interference impulses. Moreover, the bearing fault diagnosis results demonstrate that the proposed method can accurately detect bearing fault features. Furthermore, the method was validated with bearing fault data. The results showed that the method can accurately extract the fault characteristics of the impulse signal and achieve fault diagnosis.

Wound repair remains a huge clinical challenge, which can cause bleeding, infection, and patient death. In our current research, a bioactive, injectable, multifunctional composite hydrogel doped with nanospheres was prepared with antibacterial and angiogenesis-promoting functions for the treatment of wounds. Amino groups in ε-polylysine (ε-EPL) undergo dynamic Schiff base reaction cross-linking with oxidized hyaluronic acid (OHA), and F127 exhibits unique temperature sensitivity to form an injectable thermosensitive hydrogel (FHE10), which can form a hydrogel to cover the wound at body temperature. Nanospheres (PNs) prepared using poly (glyceryl-sebacate-acrylate) (PGSA) were loaded into hydrogels (FHE10) for promoting wound repair. The prepared FHE10 exhibited rapid gelation, good injectable abilities, and showed resistance to the flourish of Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vitro investigations showed that FHE10 had good hemocompatibility and cytocompatibility. FHE10@PNs exhibited good proliferation, migration, and tube formation of human umbilical vein endothelial cells (HUVECs) and human foreskin fibroblasts (HFF-1). Furthermore, FHE10@PNs significantly promoted reepithelialization and collagen deposition as well as micro-vascularization compared with the use of FHE10 or PNs alone, thereby accelerating the repair of wounds. In general, this study demonstrated that the multifunctional injectable composite hydrogel showed great potential in wound treatment.

Microplastic pollution has attracted a lot of attention in recent years. Not only can it be ingested by animals, but it can easily become a carrier of other pollutants, forming a composite pollutant with potentially toxic effects on organisms. We investigated the effect of Cu on the accumulation of polystyrene microplastics (PS) in the gills of Procambarus clarkii and whether PS exacerbated the immune toxicity of Cu to P. clarkii were exposed to Cu, PS and PS+Cu for 48 h, the accumulation of PS in gill and hepatopancreas immune and antioxidant indices were analyzed. The objective was to investigate the toxic effects of Ps and Cu compound pollutants on P. clarkii and whether the accumulated pollutants would cause food safety problems. The results showed that microplastic particles adhered to each other and aggregated in the PS+Cu group, and the number of microplastic particles in gill in the PS+Cu group was significantly lower than that in the PS group. Compared with the other two treatment groups, SOD, CAT, GPx activities and MDA content increased significantly in the PS+Cu group and were relatively delayed. At 12 h, 24 h, 36 h and 48 h, the SOD mRNA expression levels in the PS+Cu group were all significantly lower than those in the Cu group (P

Summary: Background: Studies on the association between antidepressants and self-harm in adults were mostly conducted over a decade ago and have inconsistent findings. We aimed to compare self-harm risks by antidepressant classes among people aged 40 years or older with depression. Methods: Individuals aged ≥40 years with depression who initiated antidepressant treatment between 2001 and 2015 were retrieved from the Hong Kong Clinical Data Analysis & Reporting system, and were followed up until December 31, 2016. We conducted self-controlled case series (SCCS) analyses to estimate the incidence rate ratio (IRR) of self-harm comparing the pre-exposure (90 days before the first antidepressant use), index exposure (the first antidepressant use), and subsequent exposure (subsequent antidepressant use) periods to nonexposed periods. We applied Cox proportional hazard regressions to estimate the hazard ratio (HR) of self-harm comparing five antidepressant classes (tricyclic and related antidepressant drugs [TCAs], selective serotonin reuptake inhibitors [SSRIs], noradrenergic and specific serotonergic antidepressants [NaSSAs], serotonin–norepinephrine reuptake inhibitors [SNRIs], and others). Findings: A total of 48,724 individuals were identified. SCCS analyses (N = 3,846) found that the increased self-harm risk occurred during the pre-exposure (IRR: 22.24; 95% CI, 20.25-24.42), index exposure (7.03; 6.34-7.80), and subsequent exposure periods (2.47; 2.18-2.79) compared to the unexposed period. Cohort analyses (N = 48,724) found an association of higher self-harm risks in short-term (one year) for NaSSAs vs. TCAs (HR, 2.13; 95% CI, 1.53-2.96), SNRIs vs. TCAs (1.64; 1.01-2.68), and NaSSAs vs. SSRIs (1.75; 1.29-2.36) in the 40-64 years group. The higher risk remained significant in long-term (> one year) for NaSSAs vs. TCAs (1.55; 1.26-1.91) and NaSSAs vs. SSRIs (1.53; 1.26-1.87). In the 65+ group, only short-term differences were observed (SSRIs vs. TCAs [1.31; 1.03-1.66], SNRIs vs. SSRIs [0.44; 0.22-0.87], and SNRIs vs. NaSSAs [0.43; 0.21-0.87]). Interpretation: Within-person comparisons did not suggest that antidepressant exposure is causally associated with an increased risk of self-harm in people with depression. Between-person comparisons revealed differences in self-harm risks between certain pairs of antidepressant classes. These findings may inform clinicians’ benefit-risk assessments when prescribing antidepressants. Funding: Nil.

Abstract Therapeutic regimens for previously treated multiple myeloma (MM) may not provide prolonged disease control and are often complicated by significant adverse events, including peripheral neuropathy. In patients with previously treated MM in the Phase 3 BOSTON study, once weekly selinexor, once weekly bortezomib, and 40 mg dexamethasone (XVd) demonstrated a significantly longer median progression-free survival (PFS), higher response rates, deeper responses, a trend to improved survival, and reduced incidence and severity of bortezomib-induced peripheral neuropathy when compared with standard twice weekly bortezomib and 80 mg dexamethasone (Vd). The pre-specified analyses described here evaluated the influence of the number of prior lines of therapy, prior treatment with lenalidomide, prior proteasome inhibitor (PI) therapy, prior immunomodulatory drug therapy, and prior autologous stem cell transplant (ASCT) on the efficacy and safety of XVd compared with Vd. In this 1:1 randomized study, enrolled patients were assigned to receive once weekly oral selinexor (100 mg) with once weekly subcutaneous bortezomib (1.3 mg/m2) and 40 mg per week dexamethasone (XVd) versus standard twice weekly bortezomib and 80 mg per week dexamethasone (Vd). XVd significantly improved PFS, overall response rate, time-to-next-treatment, and showed reduced all grade and grade ≥ 2 peripheral neuropathy compared with Vd regardless of prior treatments, but the benefits of XVd over Vd were more pronounced in patients treated earlier in their disease course who had either received only one prior therapy, had never been treated with a PI, or had prior ASCT. Treatment with XVd improved outcomes as compared to Vd regardless of prior therapies as well as manageable and generally reversible adverse events. XVd was associated with clinical benefit and reduced peripheral neuropathy compared to standard Vd in previously treated MM. These results suggest that the once weekly XVd regimen may be optimally administered to patients earlier in their course of disease, as their first bortezomib-containing regimen, and in those relapsing after ASCT. Trial registration: ClinicalTrials.gov (NCT03110562). Registered 12 April 2017. https://clinicaltrials.gov/ct2/show/NCT03110562 .

The South China Sea (SCS) is the result of several major tectonic plates’ interaction, and a more detailed density structure is essential to study the tectonic evolution of the marginal seas. In the past decades, density studies in the SCS have focused more on profiles, and the lateral density structure has been less mentioned by scholars. Previously, gravity data have been used many times to study the SCS; this can satisfy the demands of large-scale lateral studies, but a point that cannot be ignored is that the gravity method has certain deficiencies in vertical resolution. Therefore, this paper applies a gravity multiscale analysis method to isolate the Bouguer gravity anomaly signal in the SCS, and then uses the power spectrum method to estimate the mean field source depth, which corresponds to the decomposed gravity anomaly signal. On this basis, we modeled stratified crustal and upper mantle structures in the SCS to determine the lateral density distribution at different depths. The results show the following: (1) There are two large high-density materials in the SCS. The first one is located near the Yinggehai Basin, where the depth ranges from 42.4 km to 71.2 km, with a diameter of nearly 220 km; the second one is located near the northwest sub-basin, where the depth ranges from 106.8 km to 128.8 km, which is probably part of the Paleo-Pacific remnant in the SCS. (2) The proto South China Sea subduction zone is located in the northwestern part of the Sulu Sea and has a northeast–southwest trend.

There are many participating companies involved in the supply chain system. In order to achieve multi-enterprise, multi-resource-oriented service product information sharing, it is necessary to have the ability to match transactions in a highly credible environment. In the current supply chain system, the core enterprise generally builds a centralized supply chain resource-sharing platform to realize knowledge sharing, and the security of the system completely depends on the core enterprise. In addition, the cost of trust establishment is very high. It is urgent to establish a reasonable trust mechanism. On this basis, the factors affecting knowledge sharing and the problems to solve are analyzed, and the plan and factors of using blockchain technology to build a knowledge-sharing platform are proposed. Finally, the conceptual model of the blockchain-based knowledge-sharing platform is designed, and its business process and economic model are emphasized to provide ideas for breaking through the bottleneck of the supply chain system.

Due to the powerful capability of feature extraction, convolutional neural network (CNN) is increasingly applied to the fault diagnosis of key components of rotating machineries. Due to the shortcomings of traditional CNN-based fault diagnosis methods, the continuous convolution and pooling operations result in the constant decrease of feature resolution, which may cause the loss of some subtle fault information in the samples. This paper proposes a CNN-based model with improved structure multi-scale dense fusion network (MSDFN) to realize the fault diagnosis of wind turbines planetary gearboxes under complicated working conditions. First, the continuous wavelet transform is applied to preprocess the vibration signals, and the two-dimensional wavelet time-frequency diagrams are used as the network input. Then, the multi-scale feature fusion (MSFF) module and a feature of maximum (FoM) module are used in the extraction and classification stages of fault features, respectively. Next, the multi-scale features of each network layer are fused to enhance the fault features. Finally, the high fault diagnosis accuracy is achieved by extracting the separable fusion result of fault features. The proposed method achieves more than 99% fault diagnosis average accuracy on a planetary gearbox dataset. The comparative experimental results verify the effectiveness of the proposed method and its superiority to some mainstream approaches. The ablation study further confirms that MSFF module and FoM module play the positive role in fault diagnosis.

Bad weather conditions (such as fog, haze) seriously affect the visual quality of images. According to the scene depth information, physical model-based methods are used to improve image visibility for further image restoration. However, the unstable acquisition of the scene depth information seriously affects the defogging performance of physical model-based methods. Additionally, most of image enhancement-based methods focus on the global adjustment of image contrast and saturation, and lack the local details for image restoration. So, this paper proposes a single image defogging method based on image patch decomposition and multi-exposure fusion. First, a single foggy image is processed by gamma correction to obtain a set of underexposed images. Then the saturation of the obtained underexposed and original images is enhanced. Next, each image in the multi-exposure image set (including the set of underexposed images and the original image) is decomposed into the base and detail layers by a guided filter. The base layers are first decomposed into image patches, and then the fusion weight maps of the image patches are constructed. For detail layers, the exposure features are first extracted from the luminance components of images, and then the extracted exposure features are evaluated by constructing gaussian functions. Finally, both base and detail layers are combined to obtain the defogged image. The proposed method is compared with the state-of-the-art methods. The comparative experimental results confirm the effectiveness of the proposed method and its superiority over the state-of-the-art methods.

The market has seen an emergence of special viewing angle needs with the development of display devices. For instance, some consumers require displays with adjustable viewing angles to accommodate different scenarios. This paper proposes an optical micro‐nano film with an adjustable viewing angle effect. The rotation angle of liquid crystal molecules is controlled through the reasonable design of the liquid crystal layer's thickness and the voltage magnitude to achieve the control of the viewing angle. The display is best viewed at the center of the display when no voltage is applied. However, the quality of the wide viewing angle display is significantly better after voltage is applied. The simulation results indicate that the brightness in the viewing angle range of ‐27°to ‐23°and 37°to 41°is significantly improved after applying a voltage of 15V, suggesting a broad application prospect for this technology. In addition, the use of this technology reduces the difficulty of process preparation and makes it more universally applicable. [ABSTRACT FROM AUTHOR]

Purpose: This study was conducted to determine the influence of ego-identity, parenting efficacy, and stress coping style on depression in mothers of toddlers. Methods: This was a cross-sectional, descriptive study. Data were collected from 164 mothers of toddlers, and analyzed using descriptive statistics, the t-test, analysis of variance, Pearson correlation coefficients, and multiple regression analysis using SPSS for Windows version 24.0. Results: The factors influencing depression in mothers of toddlers included ego-identity, economic status, and perceived health status. These variables explained 60.0% of depression in mothers of toddlers. Conclusion: Lower ego-identity was associated with more intense depression. Therefore, healthcare providers should develop intervention programs that can improve ego-identity to decrease depression among mothers of toddlers.

The dynamics and synchronization of fractional-order (FO) chaotic systems have received much attention in recent years. However, the research are focused mostly on FO commensurate systems. This paper addresses the synchronization of incommensurate FO (IFO) chaotic systems. By employing the comparison principle for FO systems with multi-order and the linear feedback control method, a sufficient condition for ensuring the synchronization of IFO chaotic systems is developed in terms of linear matrix inequalities (LMIs). Such synchronization condition relies just on the system parameters, and is easily verify and implemented. Two typical FO chaotic systems, named the IFO Genesio-Tesi system and Hopfied neural networks are selected to demonstrate the effectiveness and feasibility of the proposed method.

Dendritic cells (DCs) and cytokine-induced killer (CIK) cells play an important role in the anti-tumor immune response. In this study, we evaluated the clinical effectiveness of DC/CIK-CD24 immunotherapies to primary hepatocellular carcinoma patients who received radical resection. 36 resected primary hepatocellular carcinoma (HCC) patients were enrolled from August 2014 to December 2015. All patients received two or four times of DC/CIK immunotherapy after radical resection. 1–4 years patients’ survival rates were evaluated during the follow-up. The 4-year survival rate of patients who received two times of immunotherapy was 47.1%, and the rate of those who received four times of immunotherapies was 52.6%. Compared to baseline, after receiving the DC/CIK-CD24 autotransfusion, the serum Treg concentration of the patients decreased, while CD3+, CD4+, CD56+ increased slightly. The adverse effect of immunotherapy was I–II° transient fever and could be tolerable. DC/CIK-CD24 immunotherapy can delay the relapse time.

Background: A history of self-harm is strongly associated with future self-harm attempts. Large-scale Asian cohort studies examining risk factors for repeated self-harm are lacking. This paper reports on annual prevalence, cumulative risk, annual risk of non-fatal self-harm repetition, and risk factors among Hong Kong patients with a history of self-harm. Methods: The Hong Kong Clinical Data Analysis and Reporting System (CDARS) provided all accident & emergency department and inpatient self-harm records between Jan 1, 2002 and Dec 31, 2016. Demographic and clinical characteristics were extracted. Annual prevalence, over-time cumulative and annual risks of non-fatal self-harm repetition were estimated, and the adjusted hazard ratios (HR; plus 95% CIs) of putative risk factors associated with repetition were estimated using Wei-Lin-Weissfeld (WLW) generalization of the Cox model for recurrent event analysis. Findings: There were 127,801 self-harm episodes by 99,116 individuals. Annual prevalence of repeated self-harm, of all self-harms, ranged from 7•36% to 28•71% during the study period. Risk of self-harm repetition within one year of the index event was 14•25% (95% CI, 14•04%-14•46%). People with four or more previous self-harm episodes carried the highest risk of self-harm repetition (adjusted HR 4•81 [95% CI 4•46–5•18]). Significant risk factors for non-fatal self-harm repetition included male gender (1•08 [1•05–1•11]), older age (65+ years) (1•07 [1•01–1•13]), social welfare for payment (1•30 [1•27–1•34]), psychiatric admission (1•60 [1•50–1•72]), self-injury only (1•19 [1•15–1•23]), self-injury combined with self-poisoning (1•38 [1•24–1•53]), depression and bipolar disorders (1•09 [1•04–1•14]), personality disorders (1•18 [1•06–1•32]), substance misuse (1•31 [1•27–1•36]), and asthma (1•18 [1•02–1•36]). Interpretation: Hong Kong self-harm patients with non-fatal self-harm events should be supported by effective, timely and ongoing aftercare plans based on their risk profiles, to reduce risk of self-harm reoccurrence. Funding: Research Grants Council, General Research Funding: 17611619.