[Clinical features and prognostic analysis of checkpoint inhibitor pneumonitis in patients with non-small cell lung cancer].

Objective: To describe the clinical characteristics of patients with non-small cell lung cancer (NSCLC) who developed checkpoint inhibitor pneumonitis (CIP) and to explore potential prognostic factors. Methods: NSCLC patients who were complicated with CIP after immune checkpoint inhibitors (ICIs) therapy in our institute were enrolled in this study from 1 July 2018 to 30 November 2022. Clinical data of NSCLC-CIP patients were collected, including clinical and radiological features and their outcomes. Results: Among the 70 enrolled NSCLC-CIP patients, there were 57 males (81%) and 13 females (19%). The mean age at the diagnosis of CIP was (65.2±6.3) years. There were 46 smokers (66%), 26 patients (37%) with emphysema, 19 patients (27%) with previous interstitial lung disease, and 26 patients (37%) with a history of thoracic radiation. The mean interval from the first application of checkpoint inhibitor to the onset of CIP was (122.7±106.9) days (range: 2-458 days). The main chest CT manifestations were coincided with non-specific interstitial pneumonia (NSIP) pattern and organizing pneumonia (OP) pattern. Most patients had grade 2 (21 cases) or grade 3 (34 cases) CIP. Seventeen patients had been concurrent with other immune-related adverse events such as rash, hepatitis, colitis, and thyroiditis. Half of the enrolled patients (36 patients/51%) had fever, and most patients had elevated C-reactive protein (52 patients/72%) and all patients had elevated erythrocyte sedimentation rate (70 patients/100%). Serum lactate dehydrogenase was elevated in 34 CIP patients. Prednisone≥1 mg·kg-1·d-1 (or equivalent) was the most commonly used initial treatment in CIP patients (50 patients/71.4%). Complications with pulmonary infections (OR=4.44, P=0.03), use of anti-fungal drugs (OR=5.10, P=0.03) or therapeutic dose of sulfamethoxazole (OR=4.86, P=0.04), longer duration of prednisone≥1 mg·kg-1·d-1 (or equivalent) (Z=-2.33, P=0.02) were probable potential risk factors for poor prognosis. Conclusions: Older males with smoking history might be predisposed to develop NSCLC-CIPs after ICIs therapy. NSIP pattern and OP pattern were common chest CT manifestations. Complications with pulmonary infections (especially fungal infection or Pneumocystis jirovecii pneumonia), longer duration, longer duration of high-dose corticosteroids were likely potential risk factors for poor prognosis.

Mitochondrial complex I activity in microglia sustains neuroinflammation.

Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis1. Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells2. However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system3.

[Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases].

Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Dynamics of the Deformable Fluid Interface Interacting with an Approaching Solid under the Electrostatic Field.

A theoretical model was developed to describe the dynamics of a deformable fluid interface interacting with an approaching solid without contact by both the attractive electrostatic and van der Waals (i.e., vdW) interaction, analogous to the situation in the experiments by electric force microscopy (i.e., EFM) or electric-surface force apparatus (i.e., E-SFA) involved in the soft fluid interface. On the basis of this model, a numerical study of the deformation of the fluid interface, the force-vs-separation behavior, and the critical limiting conditions of contact has systematically been carried out. Our results show that the surface pressure induced by the electrostatic interaction plays a more prominent role in the deformation of the fluid interface than the vdW interaction does, and there exists a principal length scale associated with the relative strength of the electrostatic field to the surface tension, affecting the fluid interface shape under the electrostatic field. It was also shown that both the force-distance curves and the corresponding curves of fluid interface deformation peak versus distance for various electrostatic fields satisfy the universal scaling power law. Moreover, an analytical solution to the Euler-Lagrange differential equation governing the deformation of the fluid interface under the external electric field is obtained, and two extended formulas for explicitly describing the principal length scales that respectively characterize the lateral and longitudinal deformations of the fluid interface were determined.

[Incidence of postoperative complications in Chinese patients with gastric or colorectal cancer based on a national, multicenter, prospective, cohort study].

Objective: To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications. Methods: This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression. Results: The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion: Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

[Efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation in the treatment of secondary acute myeloid leukemia].

Objective: To evaluate the efficacy and prognostic factors of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in patients with secondary acute myeloid leukemia (sAML) . Methods: In this multicenter, retrospective clinical study, adult patients aged ≥18 years who underwent allo-HSCT for sAML at four centers of the Zhejiang Hematopoietic Stem Cell Transplantation Collaborative Group from January 2014 to November 2022 were included, and the efficacy and prognostic factors of allo-HSCT were analyzed. Results: A total of 95 patients were enrolled; 66 (69.5%) had myelodysplastic syndrome-acute myeloid leukemia (MDS-AML) , 4 (4.2%) had MDS/MPN-AML, and 25 (26.3%) had therapy-related AML (tAML) . The 3-year CIR, LFS, and overall survival (OS) rates were 18.6% (95% CI 10.2%-27.0%) , 70.6% (95% CI 60.8%-80.4%) , and 73.3% (95% CI 63.9%-82.7%) , respectively. The 3-year CIRs of the M-AML group (including MDS-AML and MDS/MPN-AML) and the tAML group were 20.0% and 16.4%, respectively (P=0.430) . The 3-year LFSs were 68.3% and 75.4%, respectively (P=0.176) . The 3-year OS rates were 69.7% and 75.4%, respectively (P=0.233) . The 3-year CIRs of the groups with and without TP53 mutations were 60.0% and 13.7%, respectively (P=0.003) ; the 3-year LFSs were 20.0% and 76.5%, respectively (P=0.002) ; and the 3-year OS rates were 40.0% and 77.6%, respectively (P=0.002) . According to European LeukmiaNet 2022 (ELN2022) risk stratification, the 3-year CIRs of patients in the low-, intermediate-, and high-risk groups were 8.3%, 17.8%, and 22.6%, respectively (P=0.639) . The three-year LFSs were 91.7%, 69.5%, and 65.6%, respectively (P=0.268) . The 3-year OS rates were 91.7%, 71.4%, and 70.1%, respectively (P=0.314) . Multivariate analysis revealed that advanced disease at allo-HSCT and TP53 mutations were independent risk factors for CIR, LFS, and OS. Conclusion: There was no significant difference in the prognosis of patients who underwent allo-HSCT among the MDS-AML, MDS/MPN-AML, and tAML groups. Advanced disease at transplantation and TP53 mutations were poor prognostic factors. ELN2022 risk stratification had limited value for predicting the prognosis of patients with sAML following allo-HSCT.

The top 100 most cited articles on intramedullary nail fixation from 2018-2022: a bibliometric and visualized analysis.

OBJECTIVE: Intramedullary nails are commonly used for the purposes of internal fixation in the repair of tubular bone fractures, allowing for optimal fixation while minimizing intraoperative bleeding, surgical incision size, and associated stress. These nails are thus often utilized to repair hip and peripheral fractures, femur fractures, tibial fractures, humerus fractures, and clavicle fractures. Recent life expectancy increases, rising economic standards, and technological innovations have led to the application of a wider range of materials and techniques in the context of orthopedic device production, further expanding the clinical indications for intramedullary nailing. Despite the growing importance of this technique, there is currently a lack of any bibliometric or visual analyses that provide a robust overview of recent progress in the intramedullary nailing research space. Accordingly, this study was developed to succinctly and comprehensively summarize the current research status and major hotspots in this field through a bibliometric review of major relevant scientific articles focused on intramedullary nailing published in recent years. MATERIALS AND METHODS: For this analysis, the top 100 most-cited articles focused on intramedullary nails published between 2018 and 2022 were identified through a search of the Web of Science Core Collection database. Countries, institutions, journals, and other specific parameters associated with these articles were then analyzed using tools including CiteSpace, VOS-viewer, Origin, and SCImago Graphica in an effort to more clearly define the latest trends in the intramedullary nail-related research space. RESULTS: The top 3 most-cited articles related to intramedullary nailing over the past five years were "Antibacterial and immunogenic behavior of silver coatings on additively manufactured porous titanium", "Diaphyseal long bone nonunions - types, etiology, economics, and treatment recommendations", and "Epidemiology, treatment, and mortality of trochanteric and subtrochanteric hip fractures: data from the Swedish fracture register", all of which were published in 2018, respectively exhibiting 93, 83, and 81 citations. Of the 100 most-cited intramedullary nailing-related articles, 38, 20, and 12 were respectively published by researchers from the USA, China, and the UK, while research groups from Italy and Spain each published 7 articles. Four of this field's most highly cited articles were published by individuals affiliated with the US-based University of California System and the University System of Ohio. Of the 15 journals that published the largest number of these top 100 articles, the "Injury International Journal of The Care of The Injured" and the "Journal of Orthopaedic Trauma" published 9 manuscripts each, which was more than any other journal, while the "Journal of Orthopaedic Surgery" and the "Journal of Pediatric Orthopaedics" published 7 each. In total, 73 highly cited articles focused on utilizing intramedullary nailing in orthopedic applications. Rozbruch SR from the USA published 3 high-quality articles in this research space, while the Chinese researchers Chang Shi Min, Du Shou Chao, Hou Zhi Yong, and Hu Sun Jun exhibited a total linkage strength of 21 in global interaction analyses. The most common keywords associated with intramedullary nail-related research identified in these analyses included "Hip fracture", "Nonunion", "Limb lengthening", "Proximal humeral fractures", "Additive manufacturing", "Induced membrane", and "Endoprosthetic replacement". Promising areas of potential future research focus may include "Limb reconstruction", "Pediatric deformity", and "Congenital femoral deficiency". CONCLUSIONS: This analysis revealed that the highest volume of high-impact research output focused on intramedullary nailing over the past 5 years has been produced by the USA, followed by China and the UK. The most influential journals in this research space were Injury International Journal of The Care of The Injured and the Journal of Orthopaedic Trauma, while the institutions associated with the most highly cited articles were the University of California System and the University System of Ohio. Intramedullary nailing is commonly utilized to treat intertrochanteric fractures and other tubular bone fractures. In the future, the application of augmented and virtual reality technologies may help shorten the learning curve for orthopedic surgeons and trauma surgeons who are learning intramedullary nailing-related techniques, and the combination of intramedullary nailing with antibacterial drugs, metal alloys, 3D navigation, and sensor devices may help improve patient outcomes.

[Clinical analysis of COVID-19 in patients with preexisting interstitial lung abnormalities].

Objective: To describe the clinical characteristics of SARS-CoV-2 infected patients with interstitial lung abnormalities (ILA) during the COVID-19 pandemic. Methods: We respectively enrolled ILA patients who had been regularly followed up in Peking Union Medical College Hospital for more than six months since January 2021. Clinical data of these ILA patients were collected after the outbreak of COVID-19 pandemic (from December 2022 to January 2023), thirty-eight patients with preexisting ILA were enrolled. Among them, there were 34 ILA patients (20 males and 14 females) who were infected with SARS-CoV-2 during this period, with an average age of (64.0±8.8) years old (range: 41-80). There were 12 (35.3%) ILA patients who were suffered from COVID-19(pneumonia group) and others were the non-pneumonia group. The clinical characteristics, including vaccination status, features of COVID-19 and outcomes of the two groups were compared. Results: Regarding the subcategories of ILA, there were 7 cases of subpleural fibrotic ILA, 10 cases of subpleural non-fibrotic ILA, and 17 cases of non-subpleural ILA. Before SARS-CoV-2 infection, the average pulse oxygen saturation at rest was (97.38±0.87)% (range: 96%-99%); average forced vital capacity (FVC) was (97.6±18.1)% predicted (range: 65%-132%); and average diffusion capacity for carbon monoxide (DLCO) was (76.2±16.3)% predicted (range: 53%-108%). Nineteen patients had been vaccinated with 3 doses of SARS-CoV-2 vaccines, and 5 of them developed COVID-19. One patient had received one dose of vaccine and did not develop COVID-19. The other 14 patients had not been vaccinated, and seven of them developed COVID-19. Of the 12 patients with COVID-19, six were diagnosed with severe COVID-19, and the other 6 ILA patients were diagnosed with moderate COVID-19. Among them, 1 patient was complicated by deep vein thrombosis of left lower limb. All 6 patients with severe COVID-19 who were cured after systemic corticosteroids. As for the other six moderate COVID-19 patients, all were cured and/or improved greatly: two were treated with short-term oral corticosteroids, one was prescribed a dose of compound betamethasone, and the other two were not treated with systemic corticosteroids. Conclusion: Patients with ILA were predisposed to develop COVID-19 after infection with SARS-CoV-2, and more than half of them had severe COVID-19.

Evaluation of postoperative outcomes in palatoplasty with three soft palate cleft repairs.

The aim of this study was to compare the postoperative clinical and functional outcomes of palatoplasty with three soft palate cleft repairs and analyse the factors potentially impacting these outcomes. A retrospective analysis was conducted on a consecutive series of 337 patients who underwent primary cleft palate repair by palatoplasty modified with either Furlow Z-plasty (P-FZP, n = 77), intravelar veloplasty (P-IVV, n = 110), or combined intravelar veloplasty-Furlow Z-plasty (P-IVV-FZP, n = 150). The postoperative outcomes evaluated included wound healing (complete closure/fistula) and velopharyngeal function. Demographic and surgical data were analysed using both univariate and multivariate analysis. There was no significant difference between the groups with regard to the sex distribution, age at repair, cleft width, cleft type, or follow-up duration. However, relaxing incisions were significantly more common with P-FZP (26.0%) and P-IVV (29.1%) compared to P-IVV-FZP (10%) (P = 0.002 and <0.001, respectively). The complete wound closure rate was significantly higher with P-IVV-FZP (97.3%) compared to P-FZP (88.3%) (P = 0.012) and P-IVV (90%) (P = 0.015). The normal velopharyngeal function rate was comparable for P-IVV-FZP (86.7%) and P-FZP (83.1%), and both rates were significantly better than the rate with P-IVV (73.6%) (P = 0.039 and 0.029, respectively). The cleft type and width were identified as factors influencing postoperative outcomes. In conclusion, it may be appropriate to prioritize the palatoplasty with combined intravelar veloplasty-Furlow Z-plasty whenever feasible.

[Application effect of a dual release system of androgen and its antagonist in the repair of full-thickness burn wounds in mice].

Objective: To explore the optimal ratio of dihydrotestosterone and hydroxyflutamide (hereinafter referred to as DH), construct a dual release system of androgen and its antagonist, and analyze the application effect of this system in the repair of full-thickness burn wounds in mice. Methods: This study was an experimental study. The HaCaT cells were divided into blank group (without drug culture), low baseline group, medium baseline group, and high baseline group according to the random number table (the same grouping method below), and the last three groups of cells were cultured by adding three different ratios of DH. Under a medium ratio, the mass of dihydrotestosterone in the three baseline groups from low to high was 1.4, 2.8, and 4.0 µg, respectively, and the mass of hydroxyflutamide was 1.2, 1.6, and 2.0 µg, respectively. On this basis, under a small ratio, the mass of dihydrotestosterone was reduced by half and the mass of hydroxyflutamide was increased by half; under a large ratio, the mass of dihydrotestosterone was increased by half and the mass of hydroxyflutamide was reduced by half. After culture of 2 days, the cell proliferation level was detected by cell counting kit 8 (n=4). Sixteen 6-8-week-old male BALB/c mice were used to establish a full-thickness burn wound on the back and divided into blank group, small ratio group, medium ratio group, and large ratio group, with 4 mice in each group. On post injury day (PID) 7, normal saline containing different ratios of DH was locally dropped to the wounds of mice in the last three groups of mice (the total mass of DH in the three ratio groups from small to large was 127.5, 165.0, and 202.5 µg, respectively, and the mass ratios of dihydrotestosterone to hydroxyflutamide (hereinafter referred to as drug mass ratio) were 8∶9, 8∶3, and 8∶1, respectively), afterwards, the administration was repeated every 48 hours until PID 27; normal saline was dropped to the wound of mice in blank group at the aforementioned time points. The wound healing status on PID 0 (immediately), 7, 14, 21, and 28 was observed, and the wound healing rates on PID 7, 14, 21, and 28 were calculated (n=4). On PID 28, the wound tissue was taken, which was stained with hematoxylin and eosin for observing re-epithelialization and with Masson for observing collagen fibers, and the proportion of collagen fibers was analyzed (n=3). Twenty 6-8-week-old male BALB/c mice were used to establish a full-thickness burn wound on the back and divided into ordinary scaffold group, small proportion scaffold group, medium proportion scaffold group, and large proportion scaffold group (with 5 mice in each group). On PID 7, the wound was continuously dressed with a polycaprolactone scaffold without drug and a polycaprolactone scaffold containing DH with a drug mass ratio of 1∶3, 1∶1, or 3∶1 (i.e. the dual release system of androgen and its antagonist, with total mass of DH being about 1.7 mg) prepared by using electrospinning technology until the end of the experiment. Histopathological analyses of tissue (n=3) at the same time points as those in the previous animal experiment were performed. On PID 7 and 14, the wound exudates were collected and the relative abundance of bacterial communities was analyzed using 16S ribosomal RNA high-throughput sequencing (n=3). Results: After culture of 2 days, under a small ratio, the proliferation levels of HaCaT cells in low baseline group and high baseline group were significantly higher than the level in blank group (P<0.05). As the time after injury prolonged, the wounds of all four groups of mice continued to shrink. On PID 14, the wound healing rate of mice in large ratio group was 72.5% (61.7%, 75.1%), which was close to 53.3% (49.5%, 64.4%) in blank group (P>0.05); the wound healing rates of mice in small and medium ratio groups were 74.2% (71.0%, 84.2%) and 70.4% (65.1%, 74.4%), respectively, which were significantly higher than the rate in blank group (with both Z values being -2.31, P<0.05). On PID 21, the wound healing rate of mice in small ratio group was significantly higher than that in blank group (Z=-2.31, P<0.05). On PID 28, the wounds of mice in the three ratio groups were completely re-epithelialized and the epidermis was thicker than that in blank group; compared with that in blank group, the collagen fiber content in the wound tissue of mice in the three ratio groups was higher and arranged more orderly, and the proportions of collagen fibers in the wound tissue of mice in small and large ratio groups were significantly increased (P<0.05). On PID 28, the wounds of mice in ordinary scaffold group were partially epithelialized, while the wounds of mice in the three proportion scaffold groups were almost completely epithelialized. Among them, the wounds of mice in small proportion scaffold group had the thickest epidermis. The proportion of collagen fibers in the wound tissue of mice in small proportion scaffold group was significantly increased compared with that in ordinary scaffold group (P<0.05). On PID 7, the bacterial communities with high relative abundance in the wound exudation of mice in the four groups included bacteria of Corynebacterium, Staphylococcus, and Rhodococcus. On PID 14, the bacterial communities with high relative abundance in the wound exudation of mice in the four groups included bacteria of Stenotrophomonas, Rhodococcus, and Staphylococcus, and the number of bacterial species in the wound exudation of mice in the three proportion scaffold groups was more than that in ordinary scaffold group. Conclusions: When the drug mass ratio is relatively small, DH has the effect of promoting the proliferation of HaCaT cells. The ratio of 8∶9 is the optimal mass ratio of dihydrotestosterone to hydroxyflutamide, and DH with this mass ratio can promote re-epithelialization and collagen deposition of full-thickness burn wounds in mice, and promote wound healing. The constructed dual release system of androgen and its antagonist with DH in a 1∶3 drug mass ratio contributes to the re-epithelialization and collagen deposition of the full-thickness burn wounds in mice, and can improve the diversity of wound microbiota.

Severity of abdominal obesity and cardiometabolic diseases in US adults.

OBJECTIVES: To determine the prevalence of cardiometabolic diseases (CMDs) among adults with abdominal obesity and to evaluate the necessity of differentiating severity of abdominal obesity. STUDY DESIGN: Cross-sectional study and prospective cohort study. METHODS: National Health and Nutrition Examination Survey (NHANES) data between 2011 and 2020 were included for cross-sectional analyses. Class I, II and III abdominal obesity were created by dividing waist circumference within sex-specific abdominal obesity range into tertiles. Age-standardized prevalence of CMDs was estimated and differences by severity of abdominal obesity were compared using Poisson regressions. Prospective analyses were performed using NHANES data between 1988 and 2018 with linked mortality data. Cox proportional hazards models were used to assess the association between severity of abdominal obesity and mortality. RESULTS: Among 23,168 adults included (mean age: 47.8 years, 49.3% men), 13,307 (57.4%) had abdominal obesity. Among adults with abdominal obesity, the estimated prevalence of diabetes was 17.3% (95% confidence interval: 16.3%, 18.2%), hypertension 39.3% (38.2%, 40.3%), dyslipidemia 59.5% (58.0%, 61.1%), cardiovascular disease 9.0% (8.3%, 9.8%), chronic kidney disease 16.8% (15.9%, 17.7%) and non-alcoholic fatty liver disease 39.9% (38.4%, 41.4%). The estimated prevalence was 55.5% (53.8%, 57.2%) for having ≥2 CMDs. Compared with class I abdominal obesity, class III abdominal obesity was related to a 43%-184% higher prevalence of CMDs and a 44% higher risk of all-cause mortality. CONCLUSIONS: The prevalence of CMDs was high and multimorbidity of CMDs was common among US adults with abdominal obesity. The prevalence of CMDs and risk of mortality differed significantly by severity of abdominal obesity.

[Clinical characteristics of posterior malleolus fracture in adults].

Objective: To explore the latest clinical characteristics and development trends of posterior malleolus fracture. Methods: Clinical information of inpatients with posterior malleolus fracture in Shanghai Tongji Hospital and Karamay Central Hospital from January 2014 to December 2022 were reviewed and collected. The imaging data of patients were acquired using the Picture Archiving and Communication Systems. A statistical analysis was performed as to gender, current age, year of admission, injury mechanism, fracture type, and posterior malleolus fracture classification. Moreover, a comparative analysis was conducted on the injury mechanisms and morphological differences of posterior malleolus fracture at different periods, regions, and age groups. Results: A total of 472 patients (210 patients from Shanghai Tongji Hospital and 262 patients from Karamay Central Hospital) with posterior malleolus fracture with a mean age of (48.7±15.6) years were included in this study. The peak of posterior malleolus fracture occurs in the age group of 50-59 years. The injury mechanisms mainly involve low-energy fall and sprain (411 cases, 87.1%), followed by traffic accidents (52 cases, 11.0%), and fall injury from height (9 cases, 1.9%). The number of cases according to different fracture types showed the following descending order: trimalleolar fracture-supination extorsion (335 cases, 71.0%), bimalleolar fracture (60 cases, 12.7%), trimalleolar fracture-pronation extorsion (43 cases, 9.1%), posterior malleolus+tibial shaft fracture (19 cases, 4.0%), simple posterior malleolus fracture (15 cases, 3.2%). The numbers of cases corresponding to the Haraguchi Ⅰ, Ⅱ and Ⅲ type of posterior malleolus fractures was 369 (78.2%), 49 (10.4%), and 54 (11.4%), respectively. The Tongji ⅡA type represented the highest number of cases (249 cases, 52.8%), followed by the ⅡB type (120 cases, 25.4%), Ⅰ type (54 cases, 11.4%), ⅢB type (36 cases, 7.6%), and ⅢA type (13 cases, 2.8%). However, no obvious statistical difference was observed in the injury mechanism, Haraguchi classification, and Tongji classification of posterior malleolus fractures among different years and regions from the year of 2014 to 2022 (all P>0.05). Conclusions: The injury mechanism of posterior malleolus fracture mainly involves low-energy fall and sprain cases. The trimalleolar fracture-supination extorsion, Haraguchi Ⅰ type and Tongji ⅡA type of posterior malleolus fracture are predilection fracture types, and all present an obvious incidence peak in the age group of 50-59 years. There has been no significant change in the development trend of clinical characteristics of posterior malleolus fractures in recent years.

[Cost-effectiveness of pharmaceutical smoking cessation intervention in China primary cancer prevention].

Objectives: To evaluate the cost-effectiveness of typical pharmaceutical smoking cessation intervention strategies in China in the context of primary cancer prevention. Methods: Markov cohort simulation models were established to simulate the burden of 12 smoking caused cancer, including lung cancer, oral cancer, nasopharyngeal cancer, laryngeal cancer, esophageal cancer, gastric cancer, pancreatic cancer, liver cancer, kidney cancer, bladder cancer, cervical cancer, and acute myeloid leukemia. Taking incremental cost effectiveness ratio (ICER) as the main indicator, the model sets one year as the cycling period for 50 periods and simulates the cohort of 10 000 thirty-five-year-old current smokers with various smoking cessation strategies. To ensure the robustness of conclusion, univariate sensitivity analysis, probability sensitivity analysis, and age-group sensitivity analysis were conducted. Results: The results showed that varenicline intervention was the most cost-effective intervention. Compared to the next most effective option, incremental cost of each additional quality-adjusted life year is 11 140.28 yuan, which is below the threshold of willingness to pay (1 year GDP per capita). The value of ICER increased as the increasing age group of adopting intervention, but neither exceeded the threshold of willingness to pay. One-way sensitivity analysis showed that the value of discount rate, the hazard ratio and cost of intervention strategy had a greater impact on the result of ICER. Conclusion: In China, the use of varenicline to quit smoking is highly cost effective in the context of cancer primary prevention, especially for younger smokers.

Mitochondrial reverse electron transport in myeloid cells perpetuates neuroinflammation.

Sustained smouldering, or low grade, activation of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis (MS) 1 . Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells 2 . However, how these metabolic features act to perpetuate neuroinflammation is currently unknown. Using a multiomics approach, we identified a new molecular signature that perpetuates the activation of myeloid cells through mitochondrial complex II (CII) and I (CI) activity driving reverse electron transport (RET) and the production of reactive oxygen species (ROS). Blocking RET in pro-inflammatory myeloid cells protected the central nervous system (CNS) against neurotoxic damage and improved functional outcomes in animal disease models in vivo . Our data show that RET in myeloid cells is a potential new therapeutic target to foster neuroprotection in smouldering inflammatory CNS disorders 3 .

[Update in interstitial lung disease 2023].

The notable advances in interstitial lung disease (ILD) published in Chinese and international authoritative journals from November 2022 to October 2023 were systematically reviewed in our annual review. The year 2023 brought significant advances about mechanism, diagnosis and treatment of idiopathic pulmonary fibrosis, connective tissue diseases associated ILD, sarcoidosis, progressive pulmonary fibrosis and rare ILDs. The related global and/or Chinese commentaries and guidelines were also reviewed in our paper. We also highlighted the important findings of epidemiologic and health economic data on idiopathic pulmonary fibrosis and sarcoidosis.

The application of quantitative perfusion analysis of golden-angle radial sparse parallel MRI and R2∗ value for predicting pathological prognostic factors in rectal cancer.

AIM: To investigate the diagnostic value of golden-angle radial sparse parallel magnetic resonance imaging (MRI) (GRASP) and R2∗ in predicting the prognostic factors of resectable rectal cancer. MATERIALS AND METHODS: A total of 108 patients with rectal adenocarcinoma were included in this retrospective study. The volume transfer constant (Ktrans), rate constant (Kep), plasma volume fraction (Ve), and R2∗ were obtained. Univariate and multivariate logistic regression were conducted. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of the imaging parameters. RESULTS: The Ktrans was found to be significantly higher in rectal cancers with positive lymph node metastasis (LNM), higher tumour grade, positive lymphovascular invasion (LVI), and higher ki-67 (all p<0.05). The Kep was also significantly higher in the LNM-positive group (p<0.001), while the R2∗ was higher in rectal cancers with LNM-positive, higher tumour grade, LVI-positive, and higher ki-67 (all p<0.05). Combining the Ktrans and R2∗ provided the highest area under the ROC curve (AUC) for LNM-positive and higher ki-67 tumours differentiation (0.790 and 0.823, respectively). DISCUSSION: Combining quantitative parameters of the Ktrans and R2∗ could be used to non-invasively predict pathological prognostic factors preoperatively.