Spatiotemporal drivers of urban water pollution: Assessment of 102 cities across the Yangtze River Basin.

Effective management of large basins necessitates pinpointing the spatial and temporal drivers of primary index exceedances and urban risk factors, offering crucial insights for basin administrators. Yet, comprehensive examinations of multiple pollutants within the Yangtze River Basin remain scarce. Here we introduce a pollution inventory for urban clusters surrounding the Yangtze River Basin, analyzing water quality data from 102 cities during 2018-2019. We assessed the exceedance rates for six pivotal indicators: dissolved oxygen (DO), ammonia nitrogen (NH3-N), chemical oxygen demand (COD), biochemical oxygen demand (BOD), total phosphorus (TP), and the permanganate index (CODMn) for each city. Employing random forest regression and SHapley Additive exPlanations (SHAP) analyses, we identified the spatiotemporal factors influencing these key indicators. Our results highlight agricultural activities as the primary contributors to the exceedance of all six indicators, thus pinpointing them as the leading pollution source in the basin. Additionally, forest coverage, livestock farming, chemical and pharmaceutical sectors, along with meteorological elements like precipitation and temperature, significantly impacted various indicators' exceedances. Furthermore, we delineate five core urban risk components through principal component analysis, which are (1) anthropogenic and industrial activities, (2) agricultural practices and forest extent, (3) climatic variables, (4) livestock rearing, and (5) principal polluting sectors. The cities were subsequently evaluated and categorized based on these risk components, incorporating policy interventions and administrative performance within each region. The comprehensive analysis advocates for a customized strategy in addressing the discerned risk factors, especially for cities presenting elevated risk levels.

[Treatment of open fracture bone defect of distal femur with antibiotic cement column and bone graft].

OBJECTIVE: To investigate the efficacy of antibiotic cement column combined with iliac bone graft in the treatment of open fracture with bone defect of distal femur. METHODS: From October 2014 to March 2021, 16 patients of open fracture bone defect of distal femur were treated with antibiotic bone cement column and iliac bone graft, including 12 males and 4 females. The age ranged from 28 to 68 years old. There were 11 cases of traffic accident injury, 5 cases of falling injury, 3 cases as Gustilo type Ⅰ, 5 cases as type Ⅱ and 8 cases as type ⅢA. AO classification was used:9 cases of C2 type and 7 cases of C3 type. The time from injury to final bone grafting ranged from 4 to 119 days. The length of bone defect ranged from 2 to10 cm. Fractures healing time, complications and knee function Merchan score were recorded. RESULTS: All the 16 patients were followed up from 9 to 29 months. The incisions of 16 patients healed in one stage without postoperative infection, plate fracture, limb shortening and valgus and varus deformity. The healing time randed from 4 to 10 months . Knee joint function according to the Merchant scoring standard, showed that 8 cases were excellent, 4 cases were good, 3 cases were fair, and 1 case was poor. CONCLUSION: The use of antibiotic bone cement column combined with iliac bone graft in the treatment of open and complex bone defects of distal femur is an effective surgical method to prevent infection, assist fracture reduction, increase fixation strength and significantly reduce the amount of bone grafting.

The Role of MicroRNA-206 in the Regulation of Diabetic Wound Healing via Hypoxia-Inducible Factor 1-Alpha.

Successful wound healing in diabetic patients is hindered by dysregulated miRNA expression. This study aimed to investigate the abnormal expression of miRNAs in diabetic wound healing and the potential therapeutic role of modulating the miR-206/HIF-1α pathway. MicroRNA assays were used to identify differentially expressed miRNAs in diabetic wound sites and adjacent areas. In vitro models and a rat diabetic model were established to evaluate the effects of miR-206 on HIF-1α regulation and wound healing. The study revealed differential expression of miR-206 in diabetic wound tissues, its interaction with HIF-1α, and the inhibitory effect of miR-206 on cell growth under high glucose conditions. Modulating the miR-206/HIF-1α pathway using miR-206 antagomir promoted HIF-1α, CD34, and VEGF expression, ultimately enhancing diabetic wound healing.

Comparison of Locking Plate Alone and Locking Plate Combined with 3D Printed Polymethylmethacrylate Augmentation in Treating Proximal Humerus Fractures in the Elderly.

BACKGROUND: Locking plates are widely used in open reduction internal fixation (ORIF) for proximal humeral fracture (PHF). However, the optimal surgical treatment of unstable, displaced PHF in elderly patients remains controversial. This study aimed to compare the radiological and clinical outcomes of surgical treatment of PHF in the elderly with locking plate (LP) alone and locking plate combined with 3D printed polymethylmethacrylate (PMMA) prosthesis augmentation (LP-PA). METHODS: From May 2015 to April 2021, a total of 97 patients aged ≥ 60 years with acute unstable PHF who underwent osteosynthesis with either LP (46 patients) or LP-PA (51 patients) were retrospectively analyzed. For the LP-PA group, a customized proximal humeral prosthesis made of PMMA cement was intra-operatively fabricated by a three-dimensional (3D) printed prototype mold for the humeral medial support. Radiological outcomes were analyzed by measuring the value of neck-shaft angle (NSA) and humeral head height (HHH). The clinical outcomes were evaluated using Constant-Murley Score (CMS), Disabilities of the Arm Shoulder and Hand (DASH) score, American Shoulder and Elbow Surgeons (ASES) score, and the shoulder range of motion (ROM). Pain was measured using a visual analogue scale (VAS). RESULTS: At the one-year follow-up, all fractures healed radiologically and clinically. The mean changes of NSA and HHH over the follow-up period were markedly smaller in the LP-PA group (3.8 ± 0.9° and 1.7 ± 0.3 mm) than those in the LP group (9.7 ± 2.1° and 3.2 ± 0.6 mm, both P < 0.0001). The LP-PA group also presented lower DASH score (17.1 ± 3.6), higher ASES score (89.5 ± 11.2) and better ROM in forward elevation (142 ± 26°) and external rotation (59 ± 11°) compared to the LP group (28.9 ± 4.8 for DASH score, P < 0.0001; 82.3 ± 9.0 for ASES score, P < 0.001; 129 ± 21° for forward elevation, P = 0.008; and 52 ± 9° for external rotation, P = 0.001). There was no significant difference in overall complication rate between the two groups, although the complication rate of screw perforation was higher in the LP-PA group (P = 0.172). CONCLUSIONS: For PHF in elderly patients, the combination of LP fixation and PMMA prosthesis augmentation effectively improved humeral head support and reduction maintenance, providing satisfactory outcomes both radiologically and clinically. This technique also reduced the incidence of screw perforation associated with plate fixation alone, making it a reasonable option to ensure satisfactory clinical outcomes.

Efficient nitrogen removal by multi-stage A/O mud membrane composite process with segmented influent: Performance and microbial community structure.

In this paper, a multi-stage A/O mud membrane composite process with segmented influent was constructed for the first time and compared with the traditional activated sludge process and the multi-stage A/O pure membrane process with segmented influent. The nitrogen removal efficiency of the process under different influencing factors was studied. Under the optimum conditions, the highest removal rate of ammonia nitrogen can reach 99%, and the average removal rate of total nitrogen was 80%. The removal rate of COD in effluent reached 93%. The relative abundance of Proteobacteria was the highest in the multi-stage A/O mud membrane composite reactor with segmented influent. The community diversity and richness of activated sludge and biofilm in aerobic pool were the highest. Dechloromonas, Flavobacterium and Rhodobacter were dominant bacteria, and they were aerobic denitrifying bacteria that significantly contributed to the removal rate of ammonia nitrogen.

Open Distal Femur Fractures Treated with Bone Cement Intramedullary Support Combined with Locked Plate Fixation.

Objective: The objective of this study was to assess the short-term clinical efficacy of the short-term clinical efficacy of bone cement intramedullary support combined with locked plate fixation in the treatment of such fractures. Methods: A retrospective study including 21 patients was reviewed at an urban level one trauma center. There were 17 males and 4 females, with a mean age of 33.9 years. Gustilo grade was II (12 cases), III-A (6 cases), III-B (2 cases), and III-C (1 case). Two fractures were AO-OTA type 33A3, 9 cases were type 33C2, and 10 cases were type 33C3. After the first stage debridement and temporary external fixation, all patients received bone cement intramedullary support combined with locked plate fixation through an anterolateral incision at the second stage.. The perioperative complications, need for bone graft, alignment, and radiographic union were recorded. At 1-year follow-up, the range of knee motion was recorded, and functional results were evaluated by the Hospital for Special Surgery (HSS) knee score. Results: All 21 patients were followed up for 12-36 months, with an average of 18.7 months. 1 case had superficial wound infection, and 2 cases had partial skin edge necrosis of the original open wound. After symptomatic dressing changes, they all healed well. 4 cases had autogenous bone grafting. 18 patients (85.7%) achieved radiographic union, with a mean union time of 6.2 months. Two patients underwent secondary operation 9 months after surgery due to nonunion and finally united after autologous bone grafting. One patient developed a deep infection 8 months after surgery and was successfully treated with Masquelet technique. Finally, bone union was achieved 7 months after surgery. The alignment was good in 17 patients (81.0%). No deep infection or hardware failure occurred during 1-year follow-up. The average range of knee extension and flexion was 5.2 ° and 106.8 °, respectively. The HSS score averaged 83.6. Conclusions: Bone cement intramedullary support combined with locked plate fixation was an effective treatment modality of open distal femur fractures with high union rate, low complication, adequate alignment and satisfactory functional outcomes.

Assessment of mathematical model for elliptical excision: solving the doubt about vertex angle and predicting postoperative wound length.

BACKGROUND: Elliptical excision is the most commonly used method for small benign tumour excision and primary closure. However, elliptical excision remains the topic of debate. The aim of this study was to explore the relationship among postoperative incision, vertex angle, and the length and width of fusiform excision through a mathematical model. METHODS: We collected data from fusiform circle excisions performed at the author's hospital (101 cases). The measured values were applied to the mathematical model formula for statistical analysis. RESULTS: The functional relationships among the length, width, arc, and angle of the fusiform circle were obtained. The mean apical tangent angle was 100.731°±15.782°, and the mean apical inner angle was 50.366°±7.891°. There was no significant difference between the preoperatively designed arc length preoperative and the postoperative incision length (P < 0.001). The apical vertex push-out distance equals half of the value of the fusiform length subtracted from arc. CONCLUSIONS: The mathematical model can be used to design the incision for ellipse fusiform excision to predict the final wound length.

Management of segmental defects post open distal femur fracture using a titanium cage combined with the Masquelet technique A single-centre report of 23 cases.

INTRODUCTION: The segmental bone defects post open distal femur fracture presents a reconstructive challenge, which often requires extreme solutions. The present study reviewed a new treatment strategy which used a cylindrical titanium mesh cage as an adjunct to the Masquelet technique. METHODS: We retrospectively reviewed a consecutive series of 23 patients treated for segmental bone defects post open distal femur fracture using a titanium mesh cage combined with the Masquelet technique under a 2-staged protocol in our institution from 2017 to 2021. The study group consisted of 13 men and 10 women with an average age of 44.1 years. The surgical debridement was performed with antibiotic polymethylmethacrylate (PMMA) cement spacer implanted into the bone defect combined with cement-wrapped plate stabilization, or antibiotic beads with vacuum sealing drainage (VSD) to cover the wound. The second stage of the Masquelet technique for bone defect repair began at least 4-6 weeks after the first stage, once all signs of possible infection were eliminated. After the cement spacer was removed, the definitive reconstruction was completed with exchange to a cylindrical titanium mesh cage filled with cancellous autograft within the induced membrane. The bone defect with cage was stabilized with a distal femoral Less Invasive Stabilization System (LISS). The radiological and clinical records of the enrolled patients were retrospectively analyzed. RESULTS: The mean follow-up was 38.6 months. The average number of operations before the second stage was 1.3. The mean interval between the two stages was 12.7 weeks. The average length of the defect measured 8.3 cm (ranging from 6.1 to 12.4 cm). All the defects filled with autograft within the cage achieved bony union, with a mean healing time of 8.4 months. At the latest follow-up, the mean knee extension measured 6.2° (ranging from 0° to 20°), and the mean flexion measured 101.8° (ranging from 60° to 120°). Complications included two instances of superficial stitch abscess, which eventually healed. CONCLUSIONS: The use of a titanium cage implanted into an induced membrane in a 2-staged Masquelet protocol could achieve satisfactory clinical outcomes in cases of segmental defects following open distal femur fractures.

Application of CRISPR-Cas system in the diagnosis and therapy of ESKAPE infections.

Antimicrobial-resistant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens represent a global threat to human health. ESKAPE pathogens are the most common opportunistic pathogens in nosocomial infections, and a considerable number of their clinical isolates are not susceptible to conventional antimicrobial therapy. Therefore, innovative therapeutic strategies that can effectively deal with ESKAPE pathogens will bring huge social and economic benefits and ease the suffering of tens of thousands of patients. Among these strategies, CRISPR (clustered regularly interspaced short palindromic repeats) system has received extra attention due to its high specificity. Regrettably, there is currently no direct CRISPR-system-based anti-infective treatment. This paper reviews the applications of CRISPR-Cas system in the study of ESKAPE pathogens, aiming to provide directions for the research of ideal new drugs and provide a reference for solving a series of problems caused by multidrug-resistant bacteria (MDR) in the post-antibiotic era. However, most research is still far from clinical application.

[The analysis of the therapeutic effect for 10 cases of type C extreme distal radial fracture in micro needle plate internal fixation].

OBJECTIVE: To analyze the clinical outcomes of mini-plate combined with wireforms in the treatment of Type C distal radial fractures with marginal articular fragments. METHODS: This retrospective study included a total of 10 cases, including 5 males and 5 females, with 6 cases involving the left side and 4 cases involving the right side, of Type C distal radial fractures with marginal articular fragments. The age of the patients ranged from 35 to 67 years old. All patients underwent surgical treatment utilizing mini-plate combined with wireforms for internal fixation. RESULTS: The follow-up period ranged from 6 to 18 months. Complete fracture healing was observed in all cases, with healing times ranging from 10 to 16 weeks. During the entire follow-up period, patients reported high levels of satisfaction with the treatment outcomes, and there were no incidences of incision infection, chronic wrist pain, or wrist traumatic arthritis. At the final follow-up assessment, the Mayo score for the wrist joint ranged from 85 to 95, with 7 cases rated as excellent and 3 cases as good. CONCLUSION: Mini-plate combined with wireforms proves to be an effective fixation method for Type C distal radial fractures with marginal articular fragments. The early initiation of wrist joint exercises, strong fixation, maintenance of proper reduction, minimal complications, and high rates of excellent and good outcomes demonstrate the reliability and efficacy of this treatment approach.

IgG1-Dominant Antibody Response Induced by Recombinant Trimeric SARS-CoV-2 Spike Protein with PIKA Adjuvant.

Recombinant trimeric SARS-CoV-2 Spike protein with PIKA (polyI:C) adjuvant induces potent and durable neutralizing antibodies that protect against multiple SARS-CoV-2 variants. The immunoglobulin subclasses of viral-specific antibodies remain unknown, as do their glycosylation status on Fc regions. In this study, we analyzed immunoglobulins adsorbed by plate-bound recombinant trimeric SARS-CoV-2 Spike protein from serum of Cynomolgus monkey immunized by recombinant trimeric SARS-CoV-2 Spike protein with PIKA (polyI:C) adjuvant. The results showed that IgG1 was the dominant IgG subclass as revealed by ion mobility mass spectrometry. The average percentage of Spike protein-specific IgG1 increased to 88.3% as compared to pre-immunization. Core fucosylation for Fc glycopeptide of Spike protein-specific IgG1 was found to be higher than 98%. These results indicate that a unique Th1-biased, IgG1-dominant antibody response was responsible for the effectiveness of PIKA (polyI:C) adjuvant. Vaccine-induced core-fucosylation of IgG1 Fc region may reduce incidence of severe COVID-19 disease associated with overstimulation of FCGR3A by afucosylated IgG1.

Treating Inferior Pole Fracture of Patella with Hand Plating System: First Clinical Results.

OBJECTIVE: Inferior pole fractures of patella are notorious fractures where it is difficult to obtain rigid internal fixation by conventional methods. The objective of the study was to introduce the Hand Plating System (HPS), which was a novel surgical technique for inferior pole fractures of patella, and to report the radiological and clinical outcomes following the application of the surgical technique. METHODS: The study was designed as a retrospective cohort study. Between July 2017 and December 2018, 30 patients who were diagnosed with inferior pole fracture of the patella without additional orthopaedic injuries were enrolled in this case series. After X-ray and 3D-CT examinations, all patients underwent open reduction and internal fixation by HPS with or without supplementary cannulated screw and lag screw stabilization. The bony union time, final range of motion (ROM), Bostman score, visual analog scale (VAS), and complications were measured as the clinical outcomes under a minimum of 12 months of follow-up. RESULTS: All of the operations went well with the mean operative time of 76.2 ± 15.3 min. Bony union achieved in all the cases at an average of 9.5 ± 1.4 weeks after surgery. There was no loss of reduction, fixative failure, or surgical implant removal during follow-up. The average range of motion 1 year postoperatively was 0°-123.3°. The mean Bostman Score at the last follow-up was 26.8 ± 2.1 with the satisfactory rate of 100%. The pain feeling during walking as measured by VAS averaged at 0.9 ± 1.3. No complications developed except for one case of poor incision healing, which healed eventually after surgical debridement. CONCLUSIONS: HPS was demonstrated as a secure fixation and as a kind of tension band for inferior pole fractures of the patella. Satisfactory recovery of knee function and low complication rate, including no need for hardware removal, could be expected.

CRISPRi-Mediated Gene Suppression Reveals Putative Reverse Transcriptase Gene PA0715 to Be a Global Regulator of Pseudomonas aeruginosa.

Purpose: Pseudomonas aeruginosa is a common pathogen of infection in burn and trauma patients, and multi-drug resistant P. aeruginosa has become an increasingly important pathogen. Essential genes are key to the development of novel antibiotics. The PA0715 gene is a novel unidentified essential gene that has attracted our interest as a potential antibiotic target. Our study aims to determine the exact role of PA0715 in cell physiology and bacterial pathogenicity, providing important clues for antibiotic development. Patients and Methods: The shuttle vector pHERD20T containing an arabinose inducible promoter was used to construct the CRISPRi system. Alterations in cellular physiology and bacterial pathogenicity of P. aeruginosa PAO1 after PA0715 inhibition were characterized. High-throughput RNA-seq was performed to gain more insight into the mechanisms by which PA0715 regulates the vital activity of P. aeruginosa. Results: We found that down-regulation of PA0715 significantly reduced PAO1 growth rate, motility and chemotaxis, antibiotic resistance, pyocyanin and biofilm production. In addition, PA0715 inhibition reduced the pathogenicity of PAO1 to the greater galleria mellonella larvae. Transcriptional profiling identified 1757 genes including those related to amino acid, carbohydrate, ketone body and organic salt metabolism, whose expression was directly or indirectly controlled by PA0715. Unexpectedly, genes involved in oxidative phosphorylation also varied with PA0715 levels, and these findings support a hitherto unrecognized critical role for PA0715 in oxidative respiration in P. aeruginosa. Conclusion: We identified PA0715 as a global regulator of the metabolic network that is indispensable for the survival and reproduction of P. aeruginosa. Our results provide a basis for future studies of potential antibiotic targets for P. aeruginosa and offer new ideas for P. aeruginosa infection control.

[A multicenter retrospective study assessing pelvic unlocking closed reduction device for reducing unstable pelvic posterior ring disruption].

Objective: To explore the application value and effectiveness of pelvic unlocking closed reduction device for the treatment of unstable pelvic posterior ring disruption. Methods: A retrospective analysis of clinical data of 243 cases of unstable pelvic posterior ring disruption treated with pelvic unlocking closed reduction device in 13 orthopaedic trauma centers across the country between December 2018 and June 2020 was performed. There were 139 males and 104 females; the age ranged from 18 to 92 years, with an average age of 48.5 years. The cause of injury included 132 cases of traffic accident injuries, 102 cases of falling from height, and 9 cases of crushing injuries. According to AO/Orthopaedic Trauma Association (AO/OTA) classification, there were 5 cases of type 61-B1, 13 cases of type 61-B2, 32 cases of type 61-C1.1, 47 cases of type 61-C1.2, 89 cases of type 61-C1.3, 35 cases of type 61-C2, and 22 cases of type 61-C3. The time from injury to operation was 2-121 days, with a median of 10 days. Preoperative preparation time, installation time of unlocking closed reduction device, fracture reduction time, intraoperative fluoroscopy times, intraoperative blood loss, and surgical complications were recorded, and Matta scoring standard was used to evaluate the quality of fracture reduction. According to Matta evaluation results, the patients were divided into two subgroups: excellent-good group and fair-poor group. The differences in gender, age, time from injury to operation, AO/OTA classification, and perioperative clinical indicators were compared between the two groups, and the effects of baseline data and perioperative indicators on the quality of fracture reduction were studied. Results: Pelvic unlocking closed reduction device did not interfere with the display of the pelvic structure and fracture displacement direction during the intraoperative fluoroscopy, effectively correcting the displacement of the pelvic ring. The preoperative preparation time was 17-60 minutes, with an average of 30 minutes; installation time of unlocking closed reduction device was 10-32 minutes, with an average of 21 minutes; intraoperative fracture reduction time was 15-205 minutes, with an average of 49.2 minutes; intraoperative fluoroscopy times were 41-420 times, with an average of 132 times; intraoperative blood loss was 40-1 500 mL, with an average of 71.5 mL. The reduction quality of pelvic fracture was evaluated according to Matta score immediately after operation. The results were excellent in 153 cases, good in 61 cases, fair in 24 cases, and poor in 5 cases. The excellent and good rate was 88.1%. Further subgroup analysis showed that there was no significant difference in other indexes ( P>0.05) between the excellent-good group and the fair-poor group except for the time from injury to operation and AO/OTA classification ( P<0.05). Among them, the excellent-good reduction rate was 92.2% (119/129) in patients with injury-to-operation time less than 10 days, and the fair-poor reduction rate was 25.7% (9/35) and 40.9% (9/22) in patients with AO/OTA 61-C2 and 61-C3 types, respectively. There was no surgery-related complication due to the application of the pelvic unlocked reduction device, no secondary iliac fractures, vascular, or nerve injuries, and postoperative CT showed that all channel screws were located in the osseous channel. Conclusion: The pelvic unlocking reduction device can effectively help to reduce the unstable pelvic posterior ring and maintain reduction, meet the needs of different projection angles of pelvic fracture with intraoperative C-arm fluoroscopy. The system facilitate the operation of pelvic reduction and precise fixation.

Calycosin represses AIM2 inflammasome-mediated inflammation and pyroptosis to attenuate monosodium urate-induced gouty arthritis through NF-κB and p62-Keap1 pathways.

Gouty arthritis is an inflammatory disease induced by monosodium urate (MSU), and is closely related to the activation of inflammasomes. Calycosin plays an anti-inflammatory role in arthritis. This study explored the mechanism of Calycosin in MSU-induced gouty arthritis. MSU-induced gouty arthritis mouse models with or without treatment of Calycosin were established, and physiological and pathological indicators were determined. Similarly, peripheral blood mononuclear cells (PBMCs) and THP-1 macrophages were used in vitro. Lactate dehydrogenase (LDH) was tested. The degree of centrifugal infiltration was detected by immunofluorescence. ELISA and quantitative reverse-transcription polymerase chain reaction were conducted to determine the levels of inflammatory factors. Immunohistochemistry, immunofluorescence, and flow cytometry were utilized to detect the content of caspase-1. Protein expressions of NF-κB-, p62-Keap1 pathway-, and pyroptosis-related factors were examined by western blot. In MSU-induced mouse models, calycosin increased mechanical hyperalgesia but decreased the swelling index of the mouse knee joint in a time-dependent manner. MSU treatment increased inflammatory cells and LysM-eGFP+ neutrophils recruitment in vivo, and promoted the LDH content in vitro, and meanwhile, calycosin reversed the aforementioned effects of MSU. In addition, calycosin repressed the release of inflammatory factors, promoted p62 level and diminished the levels of AIM2, caspase-1, ASC, IL-1ß, Keap1, Cleaved GSDMD, and Cleaved caspase-1 and phosphorylation of p65 and IκBα in MSU-induced mouse or cell models. Furthermore, AIM2 silencing also inhibited MSU-induced inflammation and pyroptosis. Collectively, calycosin may inhibit AIM2 inflammasomes-mediated inflammation and pyroptosis through NF-κB and p62-Keap1 pathways, ultimately playing a protective role in gouty arthritis.

Efficacy of TACE+Radiofrequency Ablation+Sorafenib in the Treatment of Patients with Recurrent Liver Cancer and Construction of Prediction Model.

Objective: This study is aimed at exploring the efficacy of transarterial chemotherapy embolization (TACE)+radiofrequency ablation+sorafenib in the treatment of patients with recurrent liver cancer and at constructing its prediction model. Methods: A total of 60 patients with recurrent liver cancer treated in our hospital from March 2020 to March 2022 were enrolled and divided into two groups according to treatment methods, with 30 patients in each group. Group A adopted TACE+radiofrequency ablation+sorafenib therapy while group B adopted TACE+radiofrequency ablation therapy. Clinical efficacy, complications, and adverse reactions of the two groups were observed. A total of 30 patients with nonrecurrent liver cancer in the same period were enrolled. 60 patients with recurrent liver cancer and 30 patients with nonrecurrent liver cancer were taken as the recurrence group and the nonrecurrence group, respectively. The baseline data and clinical data of the patients were queried by the Hospital Information System. The data included age, gender, Child-Pugh grade, HBV/HCV infection, portal vein tumor thrombus, degree of differentiation, vascular invasion, serum alpha fetal protein (AFP) level, number of tumors, maximum diameter of tumors, and number of nodules. The logistic regression analysis was used to analyze the independent risk factors for liver cancer recurrence. The Hosmer-Lemeshow test was used to analyze the degree of fitting between the prediction model and the standard curve. The ROC curve was used to analyze the predictive value of the model for liver cancer recurrence. Results: The objective effective rate and disease control rate in group A (33.33% and 70.00%) were higher than those in group B (10.00% and 43.33%), and the differences were statistically significant (both P < 0.05). There were no significant differences in the incidence of complications such as embolism syndrome, hand and foot skin reaction, gastrointestinal reaction, hypertension, diaphragmatic injury and bleeding, and biliary leakage and fever between the two groups (all P > 0.05). The proportions of patients in the recurrence group with portal vein tumor thrombus (PVTT), medium and high degree of differentiation, combined with vascular invasion, serum AFP level ≥ 400 ng/dL, multiple tumors, maximum tumor diameter ≥ 5 cm, combined with cirrhosis, and polynodules were all higher than those in the nonrecurrence group; the differences were statistically significant (all P < 0.05). Complication of PVTT, the degree of medium and high differentiation, and the maximum tumor diameter ≥ 5 cm were independent risk factors for recurrence of liver cancer (all P < 0.05). The prediction model of liver cancer recurrence was obtained by multiple regression analysis, P = 1/[1 + e -(-5.441 + 6.154∗PVTT + 3.475∗differentiateddegree + 3.001∗maximumdiameteroftumor)]. The Hosmer-Lemeshow test showed that χ 2 = 1.558 (P = 0.992). According to the ROC curve analysis, the AUC, SE, and 95% CI value of the prediction model for liver cancer recurrence were 0.977, 0.012, and 0.953-1.000, respectively. Conclusion: TACE+radiofrequency ablation+sorafenib is effective in the treatment of recurrent liver cancer, and the prediction model established based on the risk factor has high predictive value for patients with recurrent liver cancer.

Silk Fibroin/Hydroxyapatite Coating Improved Osseointegration of Porous Titanium Implants under Diabetic Conditions via Activation of the PI3K/Akt Signaling Pathway.

The application of three-dimensional printed porous titanium implants (TIs) is compromised in patients suffering from diabetes mellitus (DM), which disturbs the normal process of implant osseointegration, resulting in fixation failure. It was possibly because of reactive oxygen species (ROS) overproduction at the bone-implant interface. A silk fibroin-based hydroxyapatite (SF/HA) hybrid material emerged as a novel biological material for accelerating new bone formation. We proposed that the SF/HA hybrid coated titanium implant (SHT) could mitigate DM-mediated impaired osseointegration, which had never been reported previously. To test this assumption and further elucidate the mechanisms, primary rabbit osteoblasts were seeded on TIs or SHTs and cultured with normal serum, diabetic serum (DS), DS + N-acetyl-L-cysteine (NAC) (a potent ROS inhibitor), and DS + LY294002 (a specific PI3K/Akt inhibitor) for osteoblast behavior examinations. An animal study was performed on diabetic rabbits implanted with the two kinds of implants for osseointegration tests. DM-mediated ROS overproduction caused osteoblastic biological dysfunctions and apoptotic injury, associated with suppression of PI3K/Akt signaling in osteoblasts cultured on a TI substrate. Of note, the SHT substrate significantly suppressed ROS overproduction under diabetic conditions, improved osteoblast functional recovery including ameliorative osteoblast adhesion and morphology, improved cellular proliferation and differentiation, and abrogated apoptosis, which exhibited the same effect as NAC administration on the TI. The in vitro results were further corroborated in vivo by enhanced osteogenesis and osseointegration of SHTs in diabetic rabbits. Moreover, the aforesaid promotive effects afforded by the SF/HA coating were totally abolished with administration of LY294002 for blocking PI3K/Akt signaling. The above results collectively demonstrated that the SF/HA hybrid coating significantly ameliorated DM-mediated impaired osseointegration of the TI via reactivation of the ROS-mediated PI3K/Akt signaling pathway. The hybrid coating elicited a novel surface biofunctionalization strategy to attain favorable clinical performance of TI in diabetics.

Perioperative Protocol of Ankle Fracture and Distal Radius Fracture Based on Enhanced Recovery after Surgery Program: A Multicenter Prospective Clinical Controlled study.

Background: The enhanced recovery after surgery (ERAS) program is aimed to shorten patients' recovery process and improve clinical outcomes. This study aimed to compare the outcomes between the ERAS program and the traditional pathway among patients with ankle fracture and distal radius fracture. Methods: This is a multicenter prospective clinical controlled study consisting of 323 consecutive adults with ankle fracture from 12 centers and 323 consecutive adults with distal radial fracture from 13 centers scheduled for open reduction and internal fixation between January 2017 and December 2018. According to the perioperative protocol, patients were divided into two groups: the ERAS group and the traditional group. The primary outcome was the patients' satisfaction of the whole treatment on discharge and at 6 months postoperatively. The secondary outcomes include delapsed time between admission and surgery, length of hospital stay, postoperative complications, functional score, and the MOS item short form health survey-36. Results: Data describing 772 patients with ankle fracture and 658 patients with distal radius fracture were collected, of which 323 patients with ankle fracture and 323 patients with distal radial fracture were included for analysis. The patients in the ERAS group showed higher satisfaction levels on discharge and at 6 months postoperatively than in the traditional group (P < 0.001). In the subgroup analysis, patients with distal radial fracture in the ERAS group were more satisfied with the treatment (P=0.001). Furthermore, patients with ankle fracture had less time in bed (P < 0.001) and shorter hospital stay (P < 0.001) and patients with distal radial fracture received surgery quickly after being admitted into the ward in the ERAS group than in the traditional group (P=0.001). Conclusions: Perioperative protocol based on the ERAS program was associated with high satisfaction levels, less time in bed, and short hospital stay without increased complication rate and decreased functional outcomes.

Comprehensive Analysis of Subtypes and Identification of Key lncRNAs Based on Glutamine Metabolism-Related Long Noncoding RNAs.

Background: Long noncoding RNAs (lncRNAs) are becoming a critical class of metabolic regulate molecule in cancer. Glutamine is a regulator that contributes to each of the core metabolic tasks in proliferating tumor cells. Thus, we aimed to evaluate the association of lncRNAs with glutamine metabolism in lung adenocarcinoma (LUAD). Methods: Using single-sample gene set enrichment analysis (ssGSEA), LUAD specimens were assigned scores based on glutamine metabolism-related genes, and the shared common glutamine metabolism-related lncRNAs in three different LUAD data cohorts were identified. ConsensusClusterPlus was used to perform unsupervised clustering analysis in patients with LUAD. Key glutamine metabolism-related lncRNAs were identified by first-order partial correlation analysis. Results: A total of 11 shared glutamine metabolism-associated lncRNAs were identified in three LUAD data cohorts, and LUAD patients were classified into three glutamine metabolism subtypes based on the expressions of the related genes. C1 exhibited shorter overall survival (OS), poor genomic instability, and inadequate infiltration of immune cell types in the tumor microenvironment (TME) and was representative of the immunodeficiency phenotype. C2 represented the immunosuppressive phenotype while C3 represented the immune activation phenotype, exhibiting the highest sensitivity to immunotherapy. Nine of the 11 lncRNAs were localized to the nucleus. Finally, three key lncRNAs, significantly enriched in multiple metabolic pathways, were screened and found to be remarkably related to the OS of LUAD. Conclusion: We identified three glutamine metabolism subtypes of LUAD, which reflected different OS, genomic, and TME features, and identified three key glutamine metabolism-associated lncRNAs may contribute to further study of lncRNAs in cancer metabolism.

HPLC and high-throughput sequencing revealed higher tea-leaves quality, soil fertility and microbial community diversity in ancient tea plantations: compared with modern tea plantations.

BACKGROUND: Ancient tea plantations with an age over 100 years still reserved at Mengku Town in Lincang Region of Yunan Province, China. However, the characteristic of soil chemicophysical properties and microbial ecosystem in the ancient tea plantations and their correlation with tea-leaves chemical components remained unclear. Tea-leaves chemical components including free amino acids, phenolic compounds and purine alkaloids collected from modern and ancient tea plantations in five geographic sites (i.e. Bingdao, Baqishan, Banuo, Dongguo and Jiulong) were determined by high performance liquid chromatography (HPLC), while their soil microbial community structure was analyzed by high-throughput sequencing, respectively. Additionally, soil microbial quantity and chemicophysical properties including pH, cation exchange capacity (CEC), soil organic matter (SOM), soil organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), total potassium (TK), alkali-hydrolyzable nitrogen (AN), available phosphorous (AP) and available potassium (AK) were determined in modern and ancient tea plantations. RESULTS: Tea-leaves chemical components, soil chemicophysical properties and microbial community structures including bacterial and fungal community abundance and diversity evaluated by Chao 1 and Shannon varied with geographic location and tea plantation type. Ancient tea plantations were observed to possess significantly (P < 0.05) higher free amino acids, gallic acid, caffeine and epigallocatechin (EGC) in tea-leaves, as well as soil fertility. The bacterial community structure kept stable, while fungal community abundance and diversity significantly (P < 0.05) increased in ancient tea plantation because of higher soil fertility and lower pH. The long-term plantation in natural cultivation way might significantly (P < 0.05) improve the abundances of Nitrospirota, Methylomirabilota, Ascomycota and Mortierellomycota phyla. CONCLUSIONS: Due to the natural cultivation way, the ancient tea plantations still maintained relatively higher soil fertility and soil microbial ecosystem, which contributed to the sustainable development of tea-leaves with higher quality.