A Phase 3, Multicenter, Randomized, Double-Blind, Placebo-Controlled 14-Week Study of Mirogabalin in Chinese Patients with Diabetic Peripheral Neuropathic Pain.

INTRODUCTION: There is no approved effective drug for diabetic peripheral neuropathic pain (DPNP) in China. Gabapentinoids including mirogabalin have shown promise, although data in Chinese patients are scarce. METHODS: This phase 3, multicenter, randomized, double-blind, placebo-controlled trial investigated the efficacy and safety of mirogabalin for treating DPNP in China. Mirogabalin was administered at 5 mg twice daily for the first week and uptitrated to 15 mg twice daily for a total duration of 14 weeks. The primary efficacy endpoint was the change from baseline in weekly average daily pain score (ADPS) at week 14; secondary endpoints included the ADPS responder rate, Short-Form McGill Pain Questionnaire visual analogue scale score, patient global impression of change (PGIC), average daily sleep interference score (ADSIS), EuroQol 5-dimensions 5-levels (EQ-5D-5L), and incidence of treatment-emergent adverse events (TEAEs). RESULTS: Of 393 patients (mirogabalin, n = 196; placebo n = 197), the mean age was 58.2 years (mirogabalin, 58.7 years; placebo, 57.7 years) and 54.2% were male (mirogabalin, 56.1%; placebo, 52.3%). Mirogabalin elicited a greater change from baseline in the weekly ADPS vs. placebo at week 14: least-squares mean difference (95% confidence interval) vs. placebo - 0.39 (- 0.74, - 0.04), p = 0.0301. PGIC, ADSIS, and EQ-5D-5L data reflected significantly better improvements for patients receiving mirogabalin vs. placebo. The incidence of TEAEs was 75.0% and 75.1% in the mirogabalin and placebo groups, respectively. Most TEAEs were mild or moderate, and the incidence of TEAEs leading to treatment discontinuation was 2.6% in the mirogabalin group and 1.5% in the placebo group. CONCLUSIONS: Although the effect size of mirogabalin was reduced due to the placebo effect, mirogabalin is a safe and effective treatment option for Chinese patients with DPNP. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04094662.

Enhanced Plastic Stability: Achieving High Performance in a Al6xxx Alloy Fabricated by Additive Manufacturing.

Additive manufacturing (AM) facilitates the creation of materials with unique microstructural features and distinctive phenomena as compared to conventional manufacturing methods. Among the various well-fabricated AM alloys, aluminum alloys garner substantial attention due to their extensive applications in the automotive and aerospace industries. In this work, an Al6xxx alloy is successfully fabricated with outstanding performance. A nucleation agent is introduced to diminish the susceptibility to cracking during the AM process, thereby inducing a heterogeneous microstructure in this alloy. However, the introduction of ultrafine grains induces plastic instability, evidenced by the presence of Lüders band. This work investigates the evolution of the Lüders band and the strategy to reduce their undesirable effect. The heterogeneity destabilizes the band propagation and thus deteriorates the ductility. Through a T6 heat treatment, the local Lüders strain decreases from 10.0% to 6.2%, leading to a substantial enhancement in plastic stability. With the increase in grain growth and the enlargement of coarse grain regions, the mismatch between the local and macroscopic Lüders strain disappears. Importantly, the strength and the thermal conductivity are concurrently increased. The findings demonstrate the significance of ensuring plastic stability to achieve improved strength-ductility trade-off in AM alloys with heterogeneous microstructures.

Fraxin Ameliorates Ulcerative Colitis by Modulating Oxidative Stress, Inflammation and TLR4/NF-κB and MAPK Signaling Pathways.

Objective: UC is a chronic gastrointestinal disorder of uncertain etiology. However, effective therapeutic drug options for UC are relatively limited. Fraxin represents a principal active constituent within the traditional Chinese medicinal herb known as Cortex Fraxini or Qinpi. Nevertheless, the impact of Fraxin on UC remains uncharted. This study aims to explore the potential of Fraxin, a key component of Cortex Fraxini, in inhibiting DSS-induced intestinal inflammation in mice and to unravel the underlying mechanisms. Methods: In vitro experiment,the RAW264. 7 cells were induced by LPS as the model.In vivo experiment,the mice were induced by DSS as the animal model for a ten day experiment.The ELISA, western blots, measurement of oxidative stress markers and other relevant methods were used to discuss the effect of Fraxin on LPS-induced RAW264.7 cells and the inhibitory effect of Fraxin on intestinal inflammation induced by DSS in mice and underlying mechanisms. Results: Our findings indicated that Fraxin significantly reduced symptoms of UC, such as body weight loss, colonic length shortening, and histological damage. At the molecular level, it inhibited ROS generation, reduced pro-inflammatory cytokines, and regulated key pathways including TLR4/NF-κB and MAPK.The findings indicated that Fraxin diminished the expression of p-NF-κB and p-IκB, downregulated iNOS and COX-2 expression, and lessened p38, JNK and ERK phosphorylation. Conclusion: Taken together, Fraxin ameliorates UC by regulating oxidative stress, inflammation, and TLR4/NF-κB and MAPK pathways, and Fraxin may be a new treatment for UC. Our findings suggest that Fraxin could offer a novel therapeutic approach for UC, targeting oxidative stress and key inflammatory pathways.

Injectable hydrogels as promising in situ therapeutic platform for cartilage tissue engineering.

Injectable hydrogels are gaining prominence as a biocompatible, minimally invasive, and adaptable platform for cartilage tissue engineering. Commencing with their synthesis, this review accentuates the tailored matrix formulations and cross-linking techniques essential for fostering three-dimensional cell culture and melding with complex tissue structures. Subsequently, it spotlights the hydrogels' enhanced properties, highlighting their augmented functionalities and broadened scope in cartilage tissue repair applications. Furthermore, future perspectives are advocated, urging continuous innovation and exploration to surmount existing challenges and harness the full clinical potential of hydrogels in regenerative medicine. Such advancements are crucial for validating the long-term efficacy and safety of hydrogels, positioning them as a promising direction in regenerative medicine to address cartilage-related ailments.

Reaction of cyclamate with hypochlorous acid in vitro and formation of chlorcyclohexylamine and cyclohexylamine.

In this work, we investigated the reaction of cyclamate with hypochlorous acid (HOCl) in simulated gastric juice. The reaction products were detected by high-performance liquid chromatography diode array detection (HPLC-DAD) and ultra-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS). We also explored the changes in product concentration as a function of reaction time, cyclamate and HOCl concentrations. Cyclamate reacted with hypochlorous acid instantly in the simulated gastric fluid. N, N-dichlorcyclohexylamine and cyclohexylamine were both detected when the HOCl concentration was at millimole. Cyclohexylamine can only be found when HOCl concentration was at micromole. N, N-dichlorcyclohexylamine and cyclohexylamine concentrations both increased when cyclamate concentration increased under the millimole level of HOCl. As an important reactive oxygen species, hypochlorous acid (HClO) is produced in various physiological processes. The abnormal rise of the HClO level is associated with many inflammatory diseases. Chronic gastritis associated with Helicobacter pylori is a multistep, progressive, life-long inflammation. So, chronic gastritis infected with H. pylori may cause cyclamate metabolizing into cyclohexylamine in vivo.

Additive manufacturing of alloys with programmable microstructure and properties.

In metallurgy, mechanical deformation is essential to engineer the microstructure of metals and to tailor their mechanical properties. However, this practice is inapplicable to near-net-shape metal parts produced by additive manufacturing (AM), since it would irremediably compromise their carefully designed geometries. In this work, we show how to circumvent this limitation by controlling the dislocation density and thermal stability of a steel alloy produced by laser powder bed fusion (LPBF) technology. We show that by manipulating the alloy's solidification structure, we can 'program' recrystallization upon heat treatment without using mechanical deformation. When employed site-specifically, our strategy enables designing and creating complex microstructure architectures that combine recrystallized and non-recrystallized regions with different microstructural features and properties. We show how this heterogeneity may be conducive to materials with superior performance compared to those with monolithic microstructure. Our work inspires the design of high-performance metal parts with artificially engineered microstructures by AM.

Recommendations and considerations for speeding the collapse of the non-ventilated lung during single-lung ventilation in thoracoscopic surgery: a literature review.

Video-assisted thoracoscopic thoracic surgery has the advantages of less physical damage, less postoperative pain, and a rapid recovery. Therefore, it is widely used in the clinic. The quality of nonventilated lung collapse is the key point of thoracoscopic surgery. Poor lung collapse on the operative side damages surgical exposure and prolongs the process of surgery. Therefore, it is important to achieve good lung collapse as soon as possible after opening the pleura. Over the past two decades, there have been reports of advances in research on the physiological mechanism of lung collapse and several kinds of techniques for speeding up lung collapse. This review will inform the advances of each technique, make recommendations for reasonable implementation and discuss their controversies and considerations.

Effect of combination of pressure biofeedback therapy and Flexi-bar in sitting on chronic non-specific low back pain / 中国康复理论与实践

ObjectiveTo explore the immediate and short-term effects of pressure biofeedback therapy combined with Flexi-bar exercise in the sitting position on chronic non-specific low back pain (CNSLBP). MethodsFrom June to September, 2022, 27 CNSLBP students in Xuzhou Medical University and other universities around were randomly divided into pressure biofeedback unit (PBU) group (n = 9), Flexi-bar group (n = 9) and combined group (n = 9). On the basis of routine rehabilitation guidance, the PBU group accepted pressure biofeedback therapy, the Flexi-bar group accepted active vibration therapy, and the combined group accepted pressure biofeedback therapy and active vibration therapy, for three weeks. They were measured core stability with Stabilizer, lumbar joint repositioning error (LJRE) with iHandy, and bilateral transverse abdominis thickness and multifidus muscle cross-sectional area with ultrasonography; and assessed with Visual Analogue Scale for pain (VAS), Oswestry Disability Index (ODI) before and after treatment; and the core stability were measured immediately after the first treatment. ResultsThe indexes of core stability improved after the first treatment (|t| > 3.000, P < 0.05) in all groups, and improved the most in the combined group (F > 10.909, P < 0.001). All the indexes improved after three weeks of treatment (|t| > 2.604, P < 0.05), except for LJRE in PBU group; and they were the best in the combined group (|F| > 4.061, P < 0.05), except LJRE was not significantly different from the Flexi-bar group (P > 0.05). ConclusionPressure biofeedback therapy combined with Flexi-bar exercise in the sitting position can more effectively improve core stability and core muscles, proprioception, and pain for patients with CNSLBP.

Research progress in prevention and treatment of radiation-induced intestinal injury by traditional Chinese medicine active components / 中国中药杂志

Radiation-induced intestinal injury(RIII), a common complication of radiotherapy for pelvic malignancies, affects the quality of life and the radiotherapy efficacy for cancer. Currently, the main clinical approaches for the prevention and treatment of RIII include drug therapy, hyperbaric oxygen therapy, and surgical treatment. Among these methods, drug therapy is cost-effective. Traditional Chinese medicine(TCM) containing a variety of active components demonstrates mild side effects and good efficacy in preventing and treating RIII. Studies have proven that TCM active components, such as flavonoids, terpenoids, phenylpropanoids, and alkaloids, can protect the intestine against RIII by inhibiting oxidative stress, regulating the expression of inflammatory cytokines, modulating the mitochondrial apoptosis pathway, adjusting intestinal flora, and suppressing cell apoptosis. These mechanisms can help alleviate the symptoms of RIII. The paper aims to provide a theoretical reference for the discovery of new drugs for the prevention and treatment of RIII by reviewing the literature on TCM active components in the last 10 years.

Efficacy and Safety of Allogeneic Hematopoietic Stem Cell Transplantation with Decitabine-containing Regimen in Myelodysplastic Syndromes and Myelodysplastic Syndromes Transformed Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To evaluate the efficacy and safety of allogeneic hematopoietic stem cell transplantation (allo-HSCT) with decitabine (Dec)-conditioning regimen in the treatment of myelodysplastic syndrome (MDS) and MDS transformed acute myeloid leukemia (MDS-AML).@*METHODS@#The characteristics and efficacy data of 93 patients with MDS and MDS-AML who received allo-HSCT in our center from April 2013 to November 2021 were retrospectively analyzed. All patients were administered by myeloablative conditioning regimen containing Dec (25 mg/m2 /d×3 d).@*RESULTS@#Among the 93 patients, 63 males and 30 females, were diagnosed as MDS（n ＝77）, MDS-AML（n ＝16）. The incidence of I/II grade regimen-related toxicity (RRT) was 39.8%, and III grade RRT was only found in 1 patient (1%). Neutrophil engraftment was successful in 91 (97.8%) patients after a median neutrophil engraftment time of 14 (9-27) days; Successful platelet engraftment was achieved in 87 (93.5%) patients, with a median engraftment time of 18 (9-290) days. The incidence of acute graft versus host disease（aGVHD） and grade III-IV aGVHD was 44.2% and 16.2%, respectively. The incidence of chronic graft versus host disease（cGVHD） and moderate-to-severe cGVHD was 59.5% and 37.1%, respectively. Of the 93 patients, 54 (58%) developed posttransplant infections, among which lung infection (32.3%) and bloodstream infection (12.9%) were the most common. The median follow-up after transplantation was 45 (0.1-108) months. The 5-year overall survival (OS) rate, disease-free survival (DFS) rate, treatment-related mortality, and cumulative incidence of relapse were 72.7%, 68.4%, 25.1%, and 6.5%, respectively. And the 1-year graft-versus-host disease/relapse-free survival rate was 49.3%. The patients in different group of relative high-risk prognostic scoring or low-risk prognostic scoring, with or without poor-risk mutation(s), with mutations number ≥3 or <3 had similar 5-year OS rate (more than 70%). Multivariate analysis showed that the incidence of grade III-IV aGVHD was the independent risk factor affecting OS（P =0.008）and DFS (P =0.019).@*CONCLUSION@#Allo-HSCT with Dec-conditioning regimen is feasible and effective in the treatment of patients with MDS and MDS-AML, especially those in high prognostic risk and with poor-risk mutations.

Meta analysis of the prevalence and influencing factors of WMSDs among dentists in China / 中华劳动卫生职业病杂志

Objective: To explore the relevant factors of work-related musculoskeletal disorders (WMSDs) among dentists through Meta analysis, providing a basis for the prevention and control of WMSDs among dentists. Methods: In April 2022, cross-sectional research literatures on the prevalence correlation of WMSDs among Chinese dentists were searched in databases such as China National Knowledge Infrastructure, Wanfang, VIP, PubMed, Web of Science, and Em Base database. The search was conducted from the establishment of the database until April 2022, literatures were selected using keywords such as musculoskeletal disorders and dentists. To extract gender, age, length of service, disease classification and other related influencing factors as indicator, and prevalence was selected as the outcome indicator. After evaluating the quality of the literatures, RevMan 5.3 software was used to calculate the combined RD (95%CI) values of the included literatures. Results: A total of 15 articles were included, with a total sample size of 3646 people. Meta analysis results showed that the prevalence of WMSDs among dentists in China was 80%, and the top three parts of the incidence rates were 65% of the waist, 58% of the neck, and 50% of the back. Gender, age, length of service, region and disease classification all increased the risk of WMSDs, and the combined effect size were 75%, 78%, 71%, 77% and 82% respectively (P<0.05) . Conclusion: The occurrence of WMSDs among dentists in China is related to multiple factors such as gender, age, length of service and disease classification. The above risk factors should be taken into account in the workplace and preventive measures should be actively implemented to prolong the working life of dentists.

Clinical and genetics characteristics of adult-onset cerebrotendinous xanthomatosis: analysis of a Chinese pedigree / 中华内科杂志

Objective: Clinical manifestations, imaging findings, pathologic features, and genetic mutations of Chinese adult patients with cerebrotendinous xanthomatosis (CTX) were analyzed in order to achieve a greater understanding of CTX that can improve early detection, diagnosis, and treatment. Methods: Clinical data including medical history, neurologic and auxiliary examinations, imaging findings, and genetic profile were collected for an adult patient with CTX admitted to the Sixth Medical Center of Chinese People's Liberation Army General Hospital in August 2020. Additionally, a systematic review of genetically diagnosed Chinese adult CTX cases reported in major databases in China and other countries was performed and age of onset, first symptoms, common signs and symptoms, pathologic findings, imaging changes, and gene mutations were analyzed. Results: The proband was a 39-year-old female with extensive, early-onset nervous system manifestations including cognitive dysfunction and ataxia. Systemic lesions included juvenile cataract and a tendon mass. Cranial magnetic resonance imaging revealed cerebral atrophy, symmetric white matter changes predominantly in the pyramidal tract, and lesions in the cerebellar dentate nucleus. A novel homozygous mutation in the sterol-27-hydroxylase (CYP27A1) gene (c.1477-2A>C) was identified. There were no family members with similar clinical presentation although some were carriers of the c.1477-2A>C mutation. The patient showed a good response to deoxycholic acid treatment. Totally there were 56 cases of adult CTX patients in China, mostly in East China (31/56, 55.4%), at a male-to-female ratio of 1.8 to 1. Multiple organs and tissues including nervous system, tendon, lens, lung, and skeletal muscle were affected in these cases. The most common neurologic manifestations were cognitive dysfunction (44/52, 84.6%) and ataxia (44/51, 86.3%). The cases were characterized by early onset, chronic progressive damage of multiple systems, long disease course, and delayed diagnosis, making the disease difficult to manage clinically and resulting in poor prognosis. The 2 most common genetic mutations in Chinese adult CTX patients were c.1263+1G>A and c.379C>T. Exon 2 of the CYP27A1 gene was identified as a mutation hot spot. Conclusions: Chinese adult patients with CTX have complex clinical characteristics, a long diagnostic cycle, and various CYP27A1 gene mutations. Early diagnosis and intervention can improve the prognosis of these patients.

New progress and challenges in the diagnosis and treatment of cosmetic allergy-related adverse reactions / 中华预防医学杂志

In China, the current standard for cosmetic adverse reactions related skin disease (GB/T 17149.1-1997) was jointly issued by the Ministry of Health and the State Bureau of Technical Supervision in 1997, cosmetic-allergic adverse reactions include allergic contact dermatitis and photo-allergic contact dermatitis according to this standard. The increasing use and changes in cosmetic ingredients or formula lead to a significant increase for the incidence of adverse reactions as the cosmetics industry is developing rapidly in the last 20 years. In the meantime, the clinical manifestations have become more diverse. In recent years, there have been many reports on the special manifestations for cosmetic allergy and allergen test, which provide a reference for the subsequent improvement of the diagnosis and prevention.

Cholesterol paradox in the community-living old adults: is higher better? / 老年心脏病学杂志（英文版）

OBJECTIVE@#To evaluate the associations of lipid indicators and mortality in Beijing Elderly Comprehensive Health Cohort Study.@*METHODS@#A prospective cohort was conducted based on Beijing Elderly Comprehensive Health Cohort Study with 4499 community older adults. After the baseline survey, the last follow-up was March 31, 2021 with an average 8.13 years of follow-up. Cox proportional hazard model was used to estimate the hazard ratios (HR) with 95% CI for cardiovascular disease (CVD) death and all-cause death in associations with baseline lipid indicators.@*RESULTS@#A total of 4499 participants were recruited, and the mean levels of uric acid, body mass index, systolic blood pressure, diastolic blood pressure, fasting plasma glucose, total cholesterol (TC), triglyceride, and low-density lipoprotein cholesterol (LDL-C) showed an upward trend with the increasing remnant cholesterol (RC) quarters (Ptrend < 0.05), while the downward trend was found in high-density lipoprotein cholesterol (HDL-C). During the total 36,596 person-years follow-up, the CVD mortality and all-cause mortality during an average 8.13 years of follow-up was 3.87% (95% CI: 3.30%-4.43%) and 14.83% (95% CI: 13.79%-15.86%) with 174 CVD death participants and 667 all-cause death participants. After adjusting for confounders, the higher level of TC (HR = 0.854, 95% CI: 0.730-0.997), LDL-C (HR = 0.817, 95% CI: 0.680-0.982) and HDL-C (HR = 0.443, 95% CI: 0.271-0.724) were associated with lower risk of CVD death, and the higher level of HDL-C (HR = 0.637, 95% CI: 0.501-0.810) were associated with lower risk of all-cause death. The higher level of RC (HR = 1.276, 95% CI: 1.010-1.613) increase the risk of CVD death. Compared with the normal lipid group, TC ≥ 6.20 mmol/L group and LDL-C ≥ 4.10 mmol/L group were no longer associated with lower risk of CVD death, while RC ≥ 0.80 mmol/L group was still associated with higher risk of CVD death. In normal lipid group, the higher levels of TC, LDL-C and HDL-C were related with lower CVD death.@*CONCLUSIONS@#In community older adults, higher levels of TC and HDL-C were associated with lower CVD mortality in normal lipid reference range. Higher RC was associated with higher CVD mortality, which may be a better lipid indicator for estimating the CVD death risk in older adults.

Clinical features of portal biliopathy / 临床肝胆病杂志

ObjectiveThis article aims to investigate the clinical features of portal biliopathy （PB） patients， in order to improve the understanding of PB. MethodsClinical data were collected from 22 patients who were diagnosed with PB in recent years in The First Hospital of Jilin University， and an analysis was performed for their clinical manifestations， liver function， abdominal color Doppler ultrasound， abdominal CT， and hepatobiliary magnetic resonance imaging. The imaging manifestations of biliary tract abnormalities were described， as well as the type of collateral circulation and the location of thrombosis. ResultsAs for the initial symptom in these 22 patients， three were 11 patients with gastrointestinal bleeding， 5 with abdominal distension， 3 with abdominal pain， 1 with fever， 1 with abdominal discomfort， and 1 with gingival bleeding. There were 3 patients with an increase in aspartate aminotransferase， 4 with an increase in alanine aminotransferase， 4 with an increase in gamma-glutamyl transpeptidase， 7 with an increase in alkaline phosphatase， 8 with a reduction in cholinesterase， 9 with a reduction in albumin， 2 with an increase in globulin， and 5 with an increase in total bilirubin. Among the 22 patients， 20 had cavernous transformation of the portal vein， and 2 had portal vein thrombosis without cavernous transformation. All 22 patients had bile duct abnormalities， among whom 2 had extrahepatic bile duct abnormalities alone， 12 had intrahepatic bile duct dilatation alone， and 8 had dilatation of both intrahepatic and extrahepatic bile ducts. Varices at different sites were observed in 20 patients， among whom 19 had esophageal and gastric varices and 1 had peri-gallbladder varices， and no varices was observed in the superior mesenteric vein or the splenic vein. ConclusionThere are no typical clinical symptoms and changes in liver function parameters in patients with PB， but radiological examination may show dilatation， stenosis， or malformation of the bile ducts at different parts. Therefore， it is necessary to expand the sample size to further explore the diagnosis and treatment of PB.

An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique (version 2023) / 中华创伤杂志

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.

Impact of Coronary Plaque on the Precision of Computational Fractional Flow Reserve Derived from CTA / 中山大学学报(医学科学版)

ObjectiveThe fractional flow reserve （FFR） computed from coronary computed tomographic （CT） angiograms makes it possible to noninvasively assess coronary artery disease， but the impact of plaque on FFR derived from computed tomography angiography （CTA） is still unknown. The study used invasive FFR as the reference standard to analyze the impact of plaque on coronary computed tomography angiography （CCTA）-based quantitative flow ratio （CT-QFR）. MethodsThe retrospective study included 108 patients with suspected coronary heart disease （CHD） who underwent both CCTA and FFR within 60 days. CCTA images were analyzed by the software. We obtained the CT-QFR of target vessels， perfomed the quantitative and qualitative analyses on target vascular plaques， including total plaque volume （TPV）， plaque burden， calcified plaque volume （CPV）， fibrous plaque volume （FPV）， lipid plaque volume （LPV）， and the presence or absence of high-risk plaque. ResultsAccording to the difference between CT-QFR and FFR at blood vessel level， 137 target vessels of 108 patients were divided into the overestimated group （difference＞0.03， n＝29）， reference group （-0.03≤difference≤0.03， n＝88） and underestimated group （difference＜-0.03， n＝20）. The underestimated group （14.81mm3） presented higher LPV than overestimated group （1.97mm3， P < 0.05）. There was a negative correlation between LPV and the difference （P＜0.05）. ConclusionsWhen CT-QFR is used to estimate hemodynamics of coronary artery stenosis， the presence of lipid plaque may underestimate the virtual FFR.

IgG3 subclass antibodies recognize antigenically drifted influenza viruses and SARS-CoV-2 variants through efficient bivalent binding

The constant domains of antibodies are important for effector functions, but less is known about how they can affect binding and neutralization of viruses. Here we evaluated a panel of human influenza virus monoclonal antibodies (mAbs) expressed as IgG1, IgG2 or IgG3. We found that many influenza virus-specific mAbs have altered binding and neutralization capacity depending on the IgG subclass encoded, and that these differences result from unique bivalency capacities of the subclasses. Importantly, subclass differences in antibody binding and neutralization were greatest when the affinity for the target antigen was reduced through antigenic mismatch. We found that antibodies expressed as IgG3 bound and neutralized antigenically drifted influenza viruses more effectively. We obtained similar results using a panel of SARS-CoV-2-specific mAbs and the antigenically advanced B.1.351 strain of SARS-CoV-2. We found that a licensed therapeutic mAb retained neutralization breadth against SARS-CoV-2 variants when expressed as IgG3, but not IgG1. These data highlight that IgG subclasses are not only important for fine-tuning effector functionality, but also for binding and neutralization of antigenically drifted viruses. SignificanceInfluenza viruses and coronaviruses undergo continuous change, successfully evading human antibodies elicited from prior infections or vaccinations. It is important to identify features that allow antibodies to bind with increased breadth. Here we examined the effect that different IgG subclasses have on monoclonal antibody binding and neutralization. We show that IgG subclass is a determinant of antibody breadth, with IgG3 affording increased neutralization of antigenically drifted variants of influenza virus and SARS-CoV-2. Future studies should evaluate IgG3 therapeutic antibodies and vaccination strategies or adjuvants that may skew antibody responses toward broadly reactive isotypes.

Changes of mercury and methylmercury content and mercury methylation in Suaeda salsa soil under different salinity.

In this paper, we studied the changes of Hg and MeHg contents in Liaohe estuarine Suaeda salsa soils under anaerobic conditions by simulated indoor incubation at constant temperature and whether the changes of salinity (CK, 0.5%, 1.0%, 1.5%, 2.0%) affected SRB and dominated the formation of MeHg. The lowest Hg content is found in the subsurface Suaeda salsa soils at 2.0% salinity. The MeHg content in the soil also showed a general trend of increasing and then decreasing with increasing flooding salinity, and the MeHg content was higher at 0.5-1.0% flooding salinity. SRB was present in the soil under all salinity conditions and reached the maximum value at 15 days of incubation. The SRB content was higher under CK, S1 and S2 conditions, and the soil MeHg content showed a significant positive correlation with the number of SRB bacteria, indicating that the formation of MeHg was related to SRB which is of great significance to the study of estuarine wetlands.

Efficacy of hardware maintenance after fracture-related infection / 中华创伤骨科杂志

Objective:To investigate the efficacy of internal fixation maintenance after fracture-related infection (FRI).Methods:Retrospectively analyzed were the data of 81 patients with deep FRI after 6 weeks of internal fixation who had been treated with hardware maintenance at Department of Orthopedics, The Second Hospital Affiliated to School of Medicine, Zhejiang University between 2013 and 2021. They were 61 males and 20 females, aged from 11 to 73 years (average, 11 years). After admission, the patients received bacterial culture, thorough debridement, negative pressure suction, soft tissue repair, and local and intravenous antibiotics. If a joint was affected by FRI, its cavity was cleaned and drained. Infection control and fracture healing were regularly observed in all patients. A treatment was considered successful when the internal fixation was maintained until fracture union, and considered as unsuccessful when the internal fixation was removed before fracture union. Risk factors associated with treatment failure were identified from gender, age, smoking, diabetes, fracture type, methicillin-resistant Staphylococcus aureus (MRSA) infection, methicillin-susceptible staphylococcus (MSSA) infection, Pseudomonas aeruginosa infection, Escherichia coli infection, infection by two kinds of bacteria, negative bacterial culture, early infection (within 2 weeks) and local use of antibiotics.Results:All patients were followed up for an average of 30 months (from 6 to 84 months). Fracture union was achieved in 62 (76.5%) patients with infection control and internal fixation retained. Masquelet technique was used to treat bone defects in 2 patients; a muscle flap or skin flap was used to reconstruct soft tissue coverage in 11 cases; fracture union was achieved by antibiotics and dressing changes in 2 patients with sinus tract. Amputation was performed in one unsuccessful case due to uncontrollable infection, and internal fixation was changed to external fixation in the other 18 unsuccessful cases, of which 3 achieved final bone union after application of Masquelet technique, 7 achieved final bone union after application of bone transfer technique, and 3 achieved soft tissue coverage after reconstruction with flap technique. Pseudomonas aeruginosa infection, open fractures and FRI for more than 2 weeks were high risk factors for failure in internal fixation maintenance ( P<0.05). Conclusions:If internal fixation is still stable and effective, hardware maintenance should be tried first in the patients with FRI within 6 weeks after fracture internal fixation. Muscle flap or skin flap surgery should be performed as soon as possible to effectively control infection and promote fracture union in the patients with soft tissue defects after thorough and effective debridement. History of open fracture, Pseudomonas aeruginosa infection, and FRI for over 2 weeks may be risk factors for failure in internal fixation maintenance.