Biogeography and impact of nitrous oxide reducers in rivers across a broad environmental gradient on emission rates.

Microbial communities that reduce nitrous oxide (N2O) are divided into two clades, nosZI and nosZII. These clades significantly differ in their ecological niches and their implications for N2O emissions in terrestrial environments. However, our understanding of N2O reducers in aquatic systems is currently limited. This study investigated the relative abundance and diversity of nosZI- and nosZII-type N2O reducers in rivers and their impact on N2O emissions. Our findings revealed that stream sediments possess a high capacity for N2O reduction, surpassing N2O production under high N2O/NO3- ratio conditions. This study, along with others in freshwater systems, demonstrated that nosZI marginally dominates more often in rivers. While microbes containing either nosZI and nosZII were crucial in reducing N2O emissions, the net contribution of nosZII-containing microbes was more significant. This can be attributed to the nir gene co-occurring more frequently with the nosZI gene than with the nosZII gene. The diversity within each clade also played a role, with nosZII species being more likely to function as N2O sinks in streams with higher N2O concentrations. Overall, our findings provide a foundation for a better understanding of the biogeography of stream N2O reducers and their effects on N2O emissions.

PDK4 facilitates fibroblast functions and diabetic wound healing through regulation of HIF-1α protein stability and gene expression.

Fibroblast activation disorder is one of the main pathogenic characteristics of diabetic wounds. Orchestrated fibroblast functions and myofibroblast differentiation are crucial for wound contracture and extracellular matrix (ECM) formation. Pyruvate dehydrogenase kinase 4 (PDK4), a key enzyme regulating energy metabolism, has been implicated in modulating fibroblast function, but its specific role in diabetic wounds remains poorly understood. In this study, we investigated the impact of PDK4 on diabetic wounds and its underlying mechanisms. To assess the effect of PDK4 on human dermal fibroblasts (HDFs), we conducted CCK-8, EdU proliferation assay, wound healing assay, transwell assay, flow cytometry, and western blot analyses. Metabolic shifts were analyzed using the Seahorse XF analyzer, while changes in metabolite expression were measured through LC-MS. Local recombinant PDK4 administration was implemented to evaluate its influence on wound healing in diabetic mice. Finally, we found that sufficient PDK4 expression is essential for a normal wound-healing process, while PDK4 is low expressed in diabetic wound tissues and fibroblasts. PDK4 promotes proliferation, migration, and myofibroblast differentiation of HDFs and accelerates wound healing in diabetic mice. Mechanistically, PDK4-induced metabolic reprogramming increases the level of succinate that inhibits PHD2 enzyme activity, thus leading to the stability of the HIF-1α protein, during which process the elevated HIF-1α mRNA by PDK4 is also indispensable. In conclusion, PDK4 promotes fibroblast functions through regulation of HIF-1α protein stability and gene expression. Local recombinant PDK4 administration accelerates wound healing in diabetic mice.

Resveratrol activates autophagy and protects from UVA-induced photoaging in human skin fibroblasts and the skin of male mice by regulating the AMPK pathway.

Skin photoaging is mostly caused by ultraviolet A (UVA), although active medications to effectively counteract UVA-induced photoaging have not yet been created. Resveratrol, a naturally occurring polyphenol found in the skin of grapes, has been shown to have various biological functions such as anti-inflammatory and antioxidant characteristics. However, the role of resveratrol in UVA-induced photoaging has not been clarified. We investigated the mechanism of action of resveratrol by UVA irradiation of human skin fibroblasts (HSF) and innovatively modified a mouse model of photoaging. The results demonstrated that resveratrol promoted AMP-activated protein kinase (AMPK) phosphorylation to activate autophagy, reduce reactive oxygen species (ROS) production, inhibit apoptosis, and restore normal cell cycle to alleviate UVA-induced photoaging. In addition, subcutaneous injection of resveratrol not only improved the symptoms of roughness, erythema, and increased wrinkles in the skin of UVA photodamaged mice, but also alleviated epidermal hyperkeratosis and hyperpigmentation, reduced inflammatory responses, and inhibited collagen fiber degradation. In conclusion, our studies proved that resveratrol can treat UVA-induced photoaging and elucidated the possible molecular mechanisms involved, providing a new therapeutic strategy for future anti-aging.

Effects of aeration control strategies on nitrous oxide emissions in alternating anoxic-oxic sequencing batch reactor systems.

Reducing N2O emissions is key to controlling greenhouse gases (GHG) in wastewater treatment plants (WWTPs). Although studies have examined the effects of dissolved oxygen (DO) on N2O emissions during nitrogen removal, the precise effects of aeration rate remain unclear. This study aimed to fill this research gap by investigating the influence of dynamic aeration rates on N2O emissions in an alternating anoxic-oxic sequencing batch reactor system. The emergence of DO breakthrough points indicated that the conversion of ammonia nitrogen to nitrite and the release of N2O were nearly complete. Approximately 91.73 ± 3.35% of N2O was released between the start of aeration and the DO breakthrough point. Compared to a fixed aeration rate, dynamically adjusting the aeration rates could reduce N2O production by up to 48.6%. Structural equation modeling revealed that aeration rate and total nitrogen directly or indirectly had significant effects on the N2O production. A novel regression model was developed to estimate N2O production based on energy consumption (aeration flux), water quality (total nitrogen), and GHG emissions (N2O). This study emphasizes the potential of optimizing aeration strategies in WWTPs to significantly reduce GHG and improve environmental sustainability.

Enzymatic properties of ornithine decarboxylase from Clostridium aceticum DSM1496.

Clostridium aceticum DSM1496 is an acid-resistant strain in which ornithine decarboxylase (ODC) plays a crucial role in acid resistance. In this study, we expressed ODC derived from C. aceticum DSM1496 in Escherichia coli BL21 (DE3) and thoroughly examined its enzymatic properties. The enzyme has a molecular weight of 55.27 kDa and uses pyridoxal-5'-phosphate (PLP) as a coenzyme with a Km = 0.31 mM. ODC exhibits optimal activity at pH 7.5, and it maintains high stability even at pH 4.5. The peak reaction temperature for ODC is 30°C. Besides, it can be influenced by certain metal ions such as Mn2+. Although l-ornithine serves as the preferred substrate for ODC, the enzyme also decarboxylates l-arginine and l-lysine simultaneously. The results indicate that ODC derived from C. aceticum DSM1496 exhibits the ability to produce putrescine, cadaverine, and agmatine through decarboxylation. These polyamines have the potential to neutralize acid in an acidic environment, facilitating the growth of microorganisms. These significant findings provide a strong basis for further investigation into the acid-resistant mechanisms contributed by ODC.

Application and effect of tension-reducing suture in surgical treatment of hypertrophic scar.

PURPOSE: To investigate the application and effectiveness of tension-reducing suture in the repair of hypertrophic scars. METHODS: A retrospective analysis of clinical data was conducted on 82 patients with hypertrophic scars treated at the Department of Burns and Plastic Surgery of Nanjing Drum Tower Hospital from September 2021 to December 2022. Patients were operated with combination of heart-shaped tension-reducing suturing technique and looped, broad, and deep buried (LBD) suturing technique or conventional suture method. Outcomes of surgical treatment were assessed before and 6 months after surgery using the Patient and Observer Scar Assessment Scale (POSAS) and the Vancouver Scar Scale (VSS). RESULTS: Improvements were achieved on scar quality compared to that preoperatively, with a reduction in scar width (1.7 ± 0.6 cm vs. 0.7 ± 0.2 cm, P < 0.001). Assessment using the POSAS and VSS scales showed significant improvements in each single parameter and total score compared to preoperative values (P < 0.05). The Combination method group achieved better score in total score of VSS scale, in color, stiffness, thickness and overall opinion of PSAS scale, and in vascularity, thickness, pliability and overall opinion of OSAS scale. CONCLUSION: The amalgamation of the heart-shaped tension-reducing suturing technique and the LBD suturing technique has shown promising outcomes, garnering notably high levels of patient satisfaction in the context of hypertrophic scar repair. Patients have exhibited favorable postoperative recoveries, underscoring the clinical merit and the prospective broader applicability of this approach in the realm of hypertrophic scar management.

Flooding regimes alleviate lead toxicity and enhance phytostabilization of salix: Evidence from physiological responses and iron-plaque formation.

Aggravated metal pollution in wetland and riparian zones has become a global environmental issue, necessitating the identification of sustainable remediation approaches. Salix exhibits great potential as a viable candidate for metal(loid) remediation. However, the underlying mechanisms for its effectiveness in different flooding regimes with Pb pollution have not been extensively studied. In this study, fast-growing Salix×jiangsuensis 'J172' was selected and planted in different Pb polluted soils (control, 400 and 800 mg ∙ kg-1) under non-flooded and flooded (CF: continuous flooding and IF: intermittent flooding) conditions for 60 days. This study aimed to explore the effects of flooding on Salix growth performance, physiological traits, and the relationship between Pb uptake/translocation and root Fe plaques. Salix×jiangsuensis 'J172' exhibited excellent tolerance and adaptation to Pb pollution with a tolerance index (TI) exceeding 0.6, even at the highest Pb levels. Moreover, the TIs under flooded conditions were higher than that under non-flooded conditions, suggesting that flooding could alleviate Pb toxicity under co-exposure to Pb and flooding. Leaf malondialdehyde (MDA) exhibited a dose-dependent response to Pb exposure; however, CF or IF mitigated the oxidative damage induced by Pb toxicity with decreased MDA content (2.2-11.9%). The superoxide dismutase and peroxidase activities were generally enhanced by flooding, but combined stress (flooding and Pb) significantly decreased catalase activity. Pb was predominantly accumulated in Salix roots, and flooding markedly increased root Pb accumulation by 19.2-173.0% compared to non-flooded condition. Additionally, a significant positive correlation was observed between the iron (Fe) content of the root plaque and root Pb accumulation, indicating that the formation of Fe plaque on the root surface could enhance the phytostabilization of Pb in Salix. The current findings highlight that fast-growing woody plants are suitable for phyto-management of metal-polluted wetlands and can potentially minimize the risk of metal mobility in soils.

Land-use simulation for synergistic pollution and carbon reduction: Scenario analysis and policy implications.

Simulations of sustainable land use and management are required to achieve targets to reduce pollution and carbon emissions. Limited research has been conducted on synergistic pollution and carbon reduction (SPCR) in land-use simulations. This study proposed a framework for land-use simulation focused on SPCR. The non-dominated sorting genetic algorithm (NSGA-Ⅱ) and the entropy weight-based technique for order of preference by similarity to an ideal solution (TOPSIS) were used to optimize the land-use structure according to minimum net carbon, nitrogen, and phosphorus emissions. The cellular automata (CA) Markov model was then utilized to simulate the land-use spatial pattern according to the optimal conditions. The proposed framework was applied to the Dongjiang River Basin, South China, and three other scenarios (natural development (ND), carbon minimization (CM), and pollution minimization (PM)) were designed to validate the effectiveness of pollution and carbon emissions reduction under the SPCR scenario. The land-use structure and the pollution and carbon emissions in the scenarios were compared. The results showed the following. (1) The proportions of cultivated land, woodland, grassland, water, and construction land In the SPCR scenario accounted for 14%, 72%, 4%, 3%, and 7% of the total area, respectively. The carbon, nitrogen, and phosphorus emissions were 42.4%, 6.6%, and 7.8% lower, respectively, in the SPCR scenario than in the ND scenario, demonstrating the advantages of simultaneous pollution and carbon reduction. (2) The kappa coefficient of the CA-Markov model was 0.8729, indicating high simulation accuracy. (3) The simulated land-use spatial patterns exhibited low spatial heterogeneity under the CM, PM, and SPCR scenarios. However, there were significant disparities between the ND and SPCR scenarios. The cultivated and construction land areas were significantly smaller in the SPCR scenario than in the ND scenario. In contrast, the woodland and grassland areas were larger, with most differences in the central and southwestern regions of the Dongjiang River Basin. The results of the current study can be used to formulate effective land use policies and strategies in the Dongjiang Basin and similar areas to achieve the Coupling coordination between pollution reduction and carbon reduction. Policy recommendations include increasing the proportion of woodland and grassland, implementing reasonable constraints on expanding cultivated and construction lands, and establishing farmland red lines to promote synergistic pollution and carbon reduction.

Effects of carbon to nitrogen ratio on nitrogen removal in a single-stage microaerobic system: A model-based evaluation.

Single-stage microaerobic systems have been proven to be effective for concurrent removal of ammonium and organic carbon from sewage. While mechanistic models derived from activated sludge models (ASMs) have simulated nutrients removal under microaerobic conditions, classic ASMs exhibit limitations in capturing the intricate effects of carbon to nitrogen (C/N) ratio on nitrogen removal performance. To address this issue, a mechanistic model modified from the classic ASMs was proposed to capture the combined inhibitory effects of carbon and ammonium on microaerobic systems. This modified model was established based on experimental data from a single-stage microaerobic reactor encompassing simultaneous nitrification-denitrification and anammox processes. The inhibition coefficient of C/N ratio was integrated into the process rate equations, and its effectiveness was validated through model performance evaluation. Compared to the classic models, the modified one achieved superior predictions for nitrite and nitrate nitrogen concentrations. Simulations revealed that under optimized conditions with a C/N of 4.57 and a dissolved oxygen (DO) of 0.41 mg/L, the system could achieve up to 95.5% of total nitrogen (TN) removal efficiency. Based on the simulation of substrate uptake/production rate, increasing the nitrogen loading rate (NLR) rather than organic loading rate (OLR) was crucial for efficient nitrogen removal. The proposed modified model served as a valuable tool for designing and optimizing similar biological wastewater treatment systems.

Eutrophication-driven infochemical dimethylsulfide accelerates carbon transfer in freshwater food chain.

Dimethylsulfide (DMS) is a major organic sulfide in aquatic ecosystems and an infochemical that is considered as a key predictor of changes in energy and material fluxes and stocks. It is largely unknown how DMS changes and affects the food webs and material cycles in eutrophicated freshwater. In this study, field monitoring and literature surveys were conducted to analyze the effects of eutrophication on DMS concentrations. Daphnia-zebrafish microcosms were then used to investigate the effects of DMS concentrations on carbon transfer. The results demonstrated that the concentration of DMS was increased by eutrophication related indicators (chlorophyll and phosphorus). Eutrophication driven DMS altered carbon transfer in the freshwater food chain. Low concentrations (0.1-1 nM) of DMS promoted the predation of daphnia by zebrafish compared to the 0.01 nM DMS, which further stimulated the total carbon transfer from daphnia to zebrafish and altered the dissolved organic carbon (DOC) distribution in water. High concentrations (10-100 nM) of DMS did not alter zebrafish predation on daphnia and carbon transfer. DOC excreted by zebrafish altered carbon emission potential, and DMS in water showed a unimodal relationship with the carbon emission potential, peaking at 0.40 nM DMS. Keeping the DMS in water at 1.82 nM may maintain a lower carbon emission potential. These results improved the understanding of the effects of eutrophication on DMS, demonstrated the ecological role of DMS on freshwater fish and the carbon cycle, estimated the effects of DMS on the carbon emission potential of fish, and offered new insights into the management of eutrophication.

Identification and characterization of inhibitors covalently modifying catalytic cysteine of UBE2T and blocking ubiquitin transfer.

UBE2T is an E2 ubiquitin ligase critical for ubiquitination of substrate and plays important roles in many diseases. Despite the important function, UBE2T is considered as an undruggable target due to lack of a pocket for binding to small molecules with satisfied properties for clinical applications. To develop potent and specific UBE2T inhibitors, we adopted a high-throughput screening assay and two compounds-ETC-6152 and ETC-9004 containing a sulfone tetrazole scaffold were identified. Solution NMR study demonstrated the direct interactions between UBE2T and compounds in solution. Further co-crystal structures reveal the binding modes of these compounds. Both compound hydrolysation and formation of a hydrogen bond with the thiol group of the catalytic cysteine were observed. The formation of covalent complex was confirmed with mass spectrometry. As these two compounds inhibit ubiquitin transfer, our study provides a strategy to develop potent inhibitors of UBE2T.

Safety and efficacy of Pucotenlimab (HX008) - a humanized immunoglobulin G4 monoclonal antibody in patients with locally advanced or metastatic melanoma: a single-arm, multicenter, phase II study.

BACKGROUND: Pucotenlimab is a novel recombinant humanized anti-PD-1 (Programmed death-1) monoclonal antibody, which belongs to the human IgG4/kappa subtype, and can selectively block the binding of PD-1 with its ligands PD-L1 and PD-L2. METHODS: In this phase 2 trial, patients with locally advanced or metastatic melanoma who had failed conventional treatment (chemotherapy, targeted therapy, interferon, IL-2, et al.) were recruited. The patients were administrated with Pucotenlimab of 3 mg/kg every 3 weeks until disease progression, intolerable toxicity, or treatment discontinuation for any other reasons. The primary endpoint was the overall response rate (ORR). The secondary endpoints were disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and toxicity. RESULTS: One-hundred and nineteen patients were enrolled and followed up for 19.32 (ranging from 15.901 to 24.608) months by the cutoff date of July 30th, 2021. The ORR was 20.17% (24/119, 95% CI, 13.370%-28.506%) based on both independent review committee (IRC) and the investigator's assessment per RECIST v1.1. The median PFS were 2.89 (95% CI, 2.037-4.074) months and 2.46 (95% CI, 2.004-4.008) months based on IRC and investigator's assessment, respectively, per RECIST v1.1. The median OS was 16.59 (95% CI, 13.963-26.973) months. Treatment-related adverse events (TRAEs) occurred in 77.3% (92/119) of the patients. The incidence of Grade ≥ 3 TRAEs was 15.1% (18/119). In addition, none of the patients died because of TRAEs. As for biomarker analysis, Eotaxin (CCL11) and MCP-1 (CCL2) were related to treatment response, while TNF-α and VEGF were related to treatment failure. CONCLUSIONS: Pucotenlimab as a ≥ 2nd line therapy showed promising efficacy and tolerable toxicity for patients with locally advanced or metastatic melanoma. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT04749485 (registered retrospectively on 11/02/2021).

Controlled dual release of dihydrotestosterone and flutamide from polycaprolactone electrospun scaffolds accelerate burn wound healing.

Wound healing is a complex process involving multiple independent and overlapping sequential physiological mechanisms. In addition to cutaneous injury, a severe burn stimulates physiological derangements that induce a systemic hypermetabolic response resulting in impaired wound healing. Topical application of the anti-androgen drug, flutamide accelerates cutaneous wound healing, whereas paradoxically systemic dihydrotestosterone (DHT) improves burn wound healing. We developed and characterized a PCL scaffold that is capable of controlled release of androgen (DHT) and anti-androgen (F) individually or together. This study aims to investigate whether local modification of androgen actions has an impact on burn injury wound healing. In a full-thickness burn wound healing, mouse model, DHT/F-scaffold showed a significantly faster wound healing compared with F-scaffold or DHT-scaffold. Histology analysis confirmed that DHT/F-scaffold exhibited higher re-epithelization, cell proliferation, angiogenesis, and collagen deposition. Dual release of DHT and F from PCL scaffolds promoted cell proliferation of human keratinocytes and alters the keratinocyte cell cycle. Lastly, no adverse effects on androgen-dependent organs, spleen and liver were observed. In conclusion, we demonstrated DHT plus F load PCL scaffolds accelerated burn wound healing when loading alone did not. These findings point to a complex role of androgens in burn wound healing and open novel therapeutic avenues for treating severe burn patients.

TIGAR Protects Against Adenine-Induced Ferroptosis in Human Proximal Tubular Epithelial Cells by Activating the mTOR/S6KP70 Axis.

TP53-induced glycolysis and apoptosis regulator (TIGAR) acts as a switch for nephropathy, but its underlying mechanism is still unclear. The purpose of this study was to explore the potential biological significance and underlying mechanism of TIGAR in modulating adenine-induced ferroptosis in human proximal tubular epithelial (HK-2) cells. HK-2 cells under- or overexpressing TIGAR were challenged with adenine to induce ferroptosis. The levels of reactive oxygen species (ROS), iron, malondialdehyde (MDA), and glutathione (GSH) were assayed. Expression of ferroptosis-associated solute carrier family seven-member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) at the level of mRNA and protein were measured by quantitative real-time-PCR and western blotting. The phosphorylation levels of proteins in the mTOR/S6KP70 pathway were determined by western blotting. Adenine overload triggered ferroptosis in HK-2 cells, as evidenced by reduced levels of GSH, SLC7A11, and GPX4, and increased levels of iron, MDA, and ROS. TIGAR overexpression repressed adenine-induced ferroptosis and induced mTOR/S6KP70 signaling. Inhibitors of mTOR and S6KP70 weakened the ability of TIGAR to inhibit adenine-induced ferroptosis. TIGAR inhibits adenine-induced ferroptosis in human proximal tubular epithelial cells by activating the mTOR/S6KP70 signaling pathway. Therefore, activating the TIGAR/mTOR/S6KP70 axis may be a treatment for crystal nephropathies.

Cytotoxic C-20 non-oxygenated ent-kaurane diterpenoids from Isodon wardii.

Twenty new ent-kaurane diterpenoids, wardiisins A-T (1-20), along with two previously undescribed artefactual compounds (21 and 22) and twelve known analogues (23-34), were isolated from the aerial part of Isodon wardii. Their structures were elucidated by comprehensive analysis of spectroscopic data and single-crystal X-ray diffraction, and most of them were found to bear unusual C-12 oxygenation. Compounds 4, 7, 8, 19, 20, 21 exhibited remarkable cytotoxicity against the cancer cell lines HL-60, SMMC-7721, A-549, MDA-MB-231, and SW480, with IC50 values ranging from 0.3 to 5.2 µM. Moreover, 7 was found to induce G2/M cell cycle arrest and promote apoptosis in SW480 cell lines.

Risk factors of surgical failure in combined phacoemulsification and excisional goniotomy for angle-closure glaucoma.

PURPOSE: To evaluate the therapeutic success, and risk factors for combined phacoemulsification and Kahook Dual Blade excisional goniotomy (Phaco/KDB) in primary angle-closure glaucoma (PACG). METHODS: A retrospective review was conducted on glaucoma patients who underwent Phaco/KDB between September 2019 and August 2021 at 2 ophthalmology centers. Complete success was defined as unmedicated intraocular pressure (IOP) ≤ 18 mmHg with no further glaucoma surgery, while the medicated IOP ≤ 18 mmHg was defined as qualified success with lesser medications than at baseline. RESULTS: Seventy-two eyes (64 patients) with a mean age of 67.1 ± 8.1 years were included in this study, and 70.2% were female. The mean medicated baseline IOP decreased from 23.4 ± 8.1 to 16.6 ± 3.9 mmHg at an average of 11.6 ± 3.7 months of follow-up (- 29.1%; P < 0.00). Medications decreased from 2.6 ± 1.3 to 0.4 ± 0.9 (- 82.6%; P < 0.001). Complete success and qualified success were achieved in 65.3% and 79.2% of eyes, respectively. Male gender [hazard ratio (HR): 6.00 (1.57-22.9); P = 0.009] was observed a risk factor for surgical failure, whereas higher axial length (HR:0.37 (0.16-0.86); P = 0.021), and a combined circumferential goniosynechialysis procedure (HR: 0.13 (0.02-0.74); P = 0.022) lowered the risk of surgical failure. Hyphema, postoperative shallowing anterior chamber, and IOP spike were the most common complications. The cumulative survival proportion for qualified success at 12 months was 82.5% ± 0.05 (95% CI, 0.70-0.90). CONCLUSION: Phaco/KDB provided acceptable therapeutic success rate and may, therefore, be recommended in patients with coexisting cataract and PACG. Identifying patients with risk factors preoperatively may help clinicians predict surgical success.

What makes a multidisciplinary medication review and deprescribing intervention for older people work well in primary care? A realist review and synthesis.

BACKGROUND: A third of older people take five or more regular medications (polypharmacy). Conducting medication reviews in primary care is key to identify and reduce/ stop inappropriate medications (deprescribing). Recent recommendations for effective deprescribing include shared-decision making and a multidisciplinary approach. Our aim was to understand when, why, and how interventions for medication review and deprescribing in primary care involving multidisciplinary teams (MDTs) work (or do not work) for older people. METHODS: A realist synthesis following the Realist And Meta-narrative Evidence Syntheses: Evolving Standards guidelines was completed. A scoping literature review informed the generation of an initial programme theory. Systematic searches of different databases were conducted, and documents screened for eligibility, with data extracted based on a Context, Mechanisms, Outcome (CMO) configuration to develop further our programme theory. Documents were appraised based on assessments of relevance and rigour. A Stakeholder consultation with 26 primary care health care professionals (HCPs), 10 patients and three informal carers was conducted to test and refine the programme theory. Data synthesis was underpinned by Normalisation Process Theory to identify key mechanisms to enhance the implementation of MDT medication review and deprescribing in primary care. FINDINGS: A total of 2821 abstracts and 175 full-text documents were assessed for eligibility, with 28 included. Analysis of documents alongside stakeholder consultation outlined 33 CMO configurations categorised under four themes: 1) HCPs roles, responsibilities and relationships; 2) HCPs training and education; 3) the format and process of the medication review 4) involvement and education of patients and informal carers. A number of key mechanisms were identified including clearly defined roles and good communication between MDT members, integration of pharmacists in the team, simulation-based training or team building training, targeting high-risk patients, using deprescribing tools and drawing on expertise of other HCPs (e.g., nurses and frailty practitioners), involving patents and carers in the process, starting with 'quick wins', offering deprescribing as 'drug holidays', and ensuring appropriate and tailored follow-up plans that allow continuity of care and management. CONCLUSION: We identified key mechanisms that could inform the design of future interventions and services that successfully embed deprescribing in primary care.

Research on anterior minimally invasive approach in the treatment of children with developmental dysplasia of the hip.

OBJECTIVES: To investigate the clinical efficacy and safety of open reduction through anterior minimally invasive approach in the treatment of children with developmental dysplasia of the hip. METHOD: A total of 23 patients (25 hips) less than 2 years with developmental dysplasia of the hip treated by open reduction through anterior minimally invasive approach were treated in our hospital from August 2016 to March 2019. Through the anterior minimally invasive approach, we enter from the gap between sartorius muscle and tensor fasciae lata without cutting off rectus femoris muscle, which can effectively expose the joint capsule and reduce the damage to medial blood vessels and nerves. The operation time, incision length, intraoperative bleeding, hospital stay and surgical complications were observed. The progression of developmental dysplasia of the hip and avascular necrosis of the femoral head were evaluated by imaging examination. RESULT: All patients were performed with follow-up visit for an average of 22 months. The average incision length was 2.5 cm, the average operation time was 26 min, the average intraoperative bleeding was 12ml, and the average hospital stay was 4.9 days. All patients received concentric reduction immediately after operation, and no re-dislocation occurred. At the last follow-up visit, the acetabular index was (25.8 ± 6.4°). During the follow-up visit, X-ray showed avascular necrosis of the femoral head in 4 hips (16%). CONCLUSION: open reduction through anterior minimally invasive approach can achieve good clinical effect in the treatment of infantile developmental dysplasia of the hip.

The effectiveness of physeal bar resection with or without Hemi-Epiphysiodesis to treat partial growth arrest.

PURPOSE: To evaluate the outcomes of distal femoral, proximal tibial, and distal tibial physeal bar resection combined with or without the Hemi-Epiphysiodesis procedure and provide a better understanding of the application of physeal bar resection combined with Hemi-Epiphysiodesis procedure in the treatment of physeal bar growth arrest. METHODS: We retrospectively reviewed the patients who suffered physeal bar and underwent physeal bar resection with or without the Hemi-Epiphysiodesis technique during 2010-2020. All were followed up for at least 2 years or to maturity. A modified mapping method was used to determine the area of a physeal bar by CT data. The aLDFA, aMPTA, aLDTA, MAD, and LLD were measured to assess the deformity of the lower limb. RESULTS: In total, 19 patients were included in this study. The average age was 8.9 years (range 4.4 to 13.3 years old). During the follow-up, 4 (21.1%) patients had an angular change < 5°; 12 (63.2%) patients had angular deformity improvement > 5° averaging 10.0° (range 5.3° to 23.2°), and 3 (15.8%) patients had improvement of the angular deformity averaging 16.8° (range 7.4° to 27.1°). Eleven patients (57.9%) had significant MAD improvement. After surgery, we found that 7 (36.8%) patients had an LLD change of < 5 mm and were considered unchanged. Only 2 (15%) patients had an LLD improvement > 5 mm averaging 1.0 cm (range 0.7 to 1.3 cm), and 7 (36.8%) patients had increasing of LLD > 5 mm averaging 1.3 cm (range 0.5 to 2.5 cm). There were no postoperative fractures, infections, or intraoperative complications such as neurovascular injury. CONCLUSION: Physeal bar resection combined with Hemi-epiphysiodesis is helpful for partial epiphysis growth arrest. Without statistically verifying, we still believe that patients with limited growth ability could benefit more from physeal bar resection combined with Hemi-epiphysiodesis.

Deceleration of China's human water use and its key drivers.

Increased human water use combined with climate change have aggravated water scarcity from the regional to global scales. However, the lack of spatially detailed datasets limits our understanding of the historical water use trend and its key drivers. Here, we present a survey-based reconstruction of China's sectoral water use in 341 prefectures during 1965 to 2013. The data indicate that water use has doubled during the entire study period, yet with a widespread slowdown of the growth rates from 10.66 km3⋅y-2 before 1975 to 6.23 km3⋅y-2 in 1975 to 1992, and further down to 3.59 km3⋅y-2 afterward. These decelerations were attributed to reduced water use intensities of irrigation and industry, which partly offset the increase driven by pronounced socioeconomic development (i.e., economic growth, population growth, and structural transitions) by 55% in 1975 to 1992 and 83% after 1992. Adoptions for highly efficient irrigation and industrial water recycling technologies explained most of the observed reduction of water use intensities across China. These findings challenge conventional views about an acceleration in water use in China and highlight the opposing roles of different drivers for water use projections.