A randomized phase 2b study of subcutaneous PD-L1 antibody ASC22 in virally-suppressed, HBeAg negative chronic hepatitis B patients.

BACKGROUND AIMS: Studies have shown that blocking the PD-1/PD-L1 pathway may lead to a potential cure for HBV infections. ASC22 (Envafolimab) is a humanized, single-domain PD-L1 antibody administered subcutaneously. This study aimed to evaluate the efficacy and safety of ASC22 in virally suppressed chronic hepatitis B (CHB) patients on nucleos(t)ide analogs (NAs). APPROACH AND RESULTS: This randomized, single-blind, phase IIb trial enrolled CHB patients in two cohorts for a 24-week treatment with ASC22 or placebo (PBO) once every 2 weeks and 24-week follow-up. In total, 60, 59, and 30 patients were treated with 1.0, 2.5 mg/kg ASC22 and PBO, respectively. The mean HBsAg changes from baseline at week 24 and 24 week follow-up periods were -0.309 (p<0.001) and -0.272 (p<0.023) log10 IU/mL in the 1.0 mg/kg ASC22 group, -0.231 (p=0.007) and -0.205 (p=0.12) log10 IU/mL in the 2.5 mg/kg ASC22 group, and-0.003 and -0.063 log10 IU/mL in the PBO group, respectively (ITT population). Three out of ten patients with baseline HBsAg levels ≤100 IU/mL in the 1.0 mg/kg group obtained on-treatment HBsAg loss. Most AEs were mild (97.9%). There were no study drug-related serious AEs in the 1.0 mg/kg ASC22 group. CONCLUSIONS: Subcutaneous administration of 1.0 mg/kg ASC22 Q2W for 24 weeks was shown to be safe and well tolerated in virally suppressed CHB patients on NAs and can induce HBsAg decline, especially in patients with HBsAg ≤100 IU/mL.

Pan-histone deacetylase inhibitor vorinostat suppresses osteoclastic bone resorption through modulation of RANKL-evoked signaling and ameliorates ovariectomy-induced bone loss.

BACKGROUND: Estrogen deficiency-mediated hyperactive osteoclast represents the leading role during the onset of postmenopausal osteoporosis. The activation of a series of signaling cascades triggered by RANKL-RANK interaction is crucial mechanism underlying osteoclastogenesis. Vorinostat (SAHA) is a broad-spectrum pan-histone deacetylase inhibitor (HDACi) and its effect on osteoporosis remains elusive. METHODS: The effects of SAHA on osteoclast maturation and bone resorptive activity were evaluated using in vitro osteoclastogenesis assay. To investigate the effect of SAHA on the osteoclast gene networks during osteoclast differentiation, we performed high-throughput transcriptome sequencing. Molecular docking and the assessment of RANKL-induced signaling cascades were conducted to confirm the underlying regulatory mechanism of SAHA on the action of RANKL-activated osteoclasts. Finally, we took advantage of a mouse model of estrogen-deficient osteoporosis to explore the clinical potential of SAHA. RESULTS: We showed here that SAHA suppressed RANKL-induced osteoclast differentiation concentration-dependently and disrupted osteoclastic bone resorption in vitro. Mechanistically, SAHA specifically bound to the predicted binding site of RANKL and blunt the interaction between RANKL and RANK. Then, by interfering with downstream NF-κB and MAPK signaling pathway activation, SAHA negatively regulated the activity of NFATc1, thus resulting in a significant reduction of osteoclast-specific gene transcripts and functional osteoclast-related protein expression. Moreover, we found a significant anti-osteoporotic role of SAHA in ovariectomized mice, which was probably realized through the inhibition of osteoclast formation and hyperactivation. CONCLUSION: These data reveal a high affinity between SAHA and RANKL, which results in blockade of RANKL-RANK interaction and thereby interferes with RANKL-induced signaling cascades and osteoclastic bone resorption, supporting a novel strategy for SAHA application as a promising therapeutic agent for osteoporosis.

Predictive ability of novel and traditional anthropometric measurement indices for kidney stone disease: a cross-sectional study.

BACKGROUND: The aim of our research was to examine the association of novel anthropometric indices (a body shape index (ABSI), waist-to-height ratio (WtHR), conicity index (CI) and body roundness index (BRI)) and traditional anthropometric indices (body mass index (BMI), and waist (WC)) with prevalence of kidney stone disease (KSD) in the general population of United States (U.S.). METHODS: In this study, we conducted a cross-sectional analysis among the participants in the National Health and Nutrition Examination Survey between the years 2007 and 2020. Weighted multivariable logistic regression analysis, restricted cubic spline (RCS), receiver operating characteristic (ROC) curves, and subgroup analysis were performed to analyze the association of ABSI, BRI, WtHR, CI, BMI and WC with prevalence of KSD. RESULTS: In total, 11,891 individuals were included in our study. The RCS plot shown that the linear positive association was found between ABSI, BRI, WtHR, CI, BMI and WC and KSD risk. Additionally, the ROC curve demonstrated that the area under the curve of ABSI, BRI, WtHR, and CI was significantly higher than traditional anthropometric indices, including BMI and WC. CONCLUSIONS: Our study found that the discriminant ability of ABSI, BRI, WtHR, and CI for KSD was higher than BMI and WC. Consequently, ABSI, BRI, WtHR, and CI have the potential to become new indicators for the detection of KSD risk in clinical practice.

Application of 3D computed tomography in emphysematous parenchyma patients scheduled for bronchoscopic lung volume reduction.

Bronchoscopic lung volume reduction (BLVR) is a feasible, safe, effective and minimally invasive technique to significantly improve the quality of life of advanced severe chronic obstructive pulmonary disease (COPD). In this study, three-dimensional computed tomography (3D-CT) automatic analysis software combined with pulmonary function test (PFT) was used to retrospectively evaluate the postoperative efficacy of BLVR patients. The purpose is to evaluate the improvement of lung function of local lung tissue after operation, maximize the benefits of patients, and facilitate BLVR in the treatment of patients with advanced COPD. All the reported cases of advanced COPD patients treated with BLVR with one-way valve were collected and analysed from 2017 to 2020. Three-dimensional-CT image analysis software system was used to analyse the distribution of low-density areas <950 Hounsfield units in both lungs pre- and post- BLVR. Meanwhile, all patients performed standard PFT pre- and post-operation for retrospective analysis. We reported six patients that underwent unilateral BLVR with 1 to 3 valves according to the range of emphysema. All patients showed a median increase in forced expiratory volume in 1 second (FEV1) of 34%, compared with baseline values. Hyperinflation was reduced by 16.6% (range, 4.9%-47.2%). The volumetric measurements showed a significant reduction in the treated lobe volume among these patients. Meanwhile, the targeted lobe volume changes were inversely correlated with change in FEV1/FEV1% in patients with heterogeneous emphysematous. We confirm that 3D-CT analysis can quantify the changes of lung volume, ventilation and perfusion, to accurately evaluate the distribution and improvement of emphysema and rely less on the observer.

The Effectiveness of the Educational Model Based on "Moral and Medical Integration" in the Nursing Students' Education in the Operating Theatre.

Objective: As the reform of China's medical and healthcare system progresses and the demand for medical and healthcare services increases, the humanistic quality of medical personnel has received more attention and concern. The humanistic quality of medicine for medical staff is specifically translated into the ethics of nursing for nursing staff. In this study, we explored the effectiveness of the education model based on "moral and medical integration" in the nursing students' education in the operating room. Methods: The "moral and medical integration" education model was implemented in The Affiliated Changzhou No. 2 People's Hospital since September 1, 2021, and 50 nursing students who received the traditional education model before the implementation from May 1, 2021, to August 31, 2021, were selected as the control group. The study group was composed of 50 nursing trainees who received the traditional education model from 1 September 2021 to 30 November 2021 and 50 nursing trainees who received the education model based on the "integration of moral and medical science". The nursing theory and nursing skills scores, professional nursing practice scores, moral courage scores, and satisfaction with teaching were compared between the two groups. Results: The nursing theory scores (t = 14.36, P < .001), nursing skills scores (t = 11.27, P < .001), and teaching satisfaction of the study group (t = 4.76, P < .029) were all higher than those of the control group . After the education, all the professional nursing practice ability scores(t=9.16, P < .001; t = 12.24, P < .001; t = 10.42, P < .001; t = 10.95, P < .001) and moral courage scores(t=7.81, P < .001; t = 11.76, P < 0.001; t = 15.11, P < .001; t = 12.24, P < .001) of the study group were higher than those of the control group (P < .05). Conclusion: The education model based on "moral and medical integration" can help improve the professional nursing level of nursing students in the operating theatre.

Causal effects of PM2.5 exposure on neuropsychiatric disorders and the mediation via gut microbiota: A Mendelian randomization study.

BACKGROUND: Growing evidence has revealed the impacts of exposure to fine particulate matter (PM2.5) and dysbiosis of gut microbiota on neuropsychiatric disorders, but the causal inference remains controversial due to residual confounders in observational studies. METHODS: This study aimed to examine the causal effects of exposure to PM2.5 on 4 major neuropsychiatric disorders (number of cases = 18,381 for autism spectrum disorder [ASD], 38,691 for attention deficit hyperactivity disorder [ADHD], 67,390 for schizophrenia, and 21,982 cases for Alzheimer's disease [AD]), and the mediation pathway through gut microbiota. Two-sample Mendelian randomization (MR) analyses were performed, in which genetic instruments were identified from genome-wide association studies (GWASs). The included GWASs were available from (1) MRC Integrative Epidemiology Unit (MRC-IEU) for PM2.5, PMcoarse, PM10, and NOX; (2) the Psychiatric Genomics Consortium (PGC) for ASD, ADHD, and schizophrenia; (3) MRC-IEU for AD; and (4) MiBioGen for gut microbiota. Multivariable MR analyses were conducted to adjust for exposure to NOX, PMcoarse, and PM10. We also examined the mediation effects of gut microbiota in the associations between PM2.5 exposure levels and neuropsychiatric disorders, using two-step MR analyses. RESULTS: Each 1 standard deviation (1.06 ug/m3) increment in PM2.5 concentrations was associated with elevated risk of ASD (odds ratio [OR] 1.42, 95% confidence interval [CI] 1.00-2.02), ADHD (1.51, 1.15-1.98), schizophrenia (1.47, 1.15-1.87), and AD (1.57, 1.16-2.12). For all the 4 neurodevelopmental disorders, the results were robust under various sensitivity analyses, while the MR-Egger method yielded non-significant outcomes. The associations remained significant for all the 4 neuropsychiatric disorders after adjusting for PMcoarse, while non-significant after adjusting for NOX and PM10. The effects of PM2.5 exposure on ADHD and schizophrenia were partially mediated by Lachnospiraceae and Barnesiella, with the proportions ranging from 8.31% to 15.77%. CONCLUSIONS: This study suggested that exposure to PM2.5 would increase the risk of neuropsychiatric disorders, partially by influencing the profile of gut microbiota. Comprehensive regulations on air pollutants are needed to help prevent neuropsychiatric disorders.

Clinical Characteristics, Treatment, and Prognosis of Osteoarticular Brucellosis: A Retrospective Real-World Study in Shenyang, China, 2014-2019.

This study aimed to assess the clinical characteristics, treatment, and prognosis of osteoarticular brucellosis. We conducted a retrospective study enrolling brucellosis patients from the Sixth People's Hospital of Shenyang between September 2014 and June 2019. A total of 1917 participants were admitted during this period. After applying propensity score matching, we retrospectively analyzed 429 patients with osteoarthritis and 429 patients without osteoarthritis. The primary outcome was treatment completion. The secondary outcome was symptom disappearance and seroconversion. Brucellosis patients with osteoarthritis had longer treatment course (160 [134.3-185.7] vs. 120 [102.3-137.7] d, p = 0.008) than those without osteoarthritis. The most common involved site was lumbar vertebrae (290 [67.6%]) in brucellosis patients with osteoarthritis. Longer symptom duration (90 [83.0-97.0] vs. 42 [40.2-43.8], p < 0.001) along with no significant difference in seroconversion (180 [178.8-181.2] vs. 180 [135.1-224.9], p = 0.212) was observed in osteoarthritis patients with treatment course >90 d. Peripheral joint involvement (adjusted hazard ratio [95% confidence interval] 1.485 [1.103-1.999]; p = 0.009) had a shorter symptom duration compared with shaft joint involvement. No significant differences were observed in treatment therapy between doxycycline plus rifampin (DR) or plus cephalosporins (DRC) in treatment course (p = 0.190), symptom persistence (p = 0.294), and seroconversion (p = 0.086). Lumbar vertebra was the most commonly involved site. Even if all symptoms disappeared, Serum agglutination test potentially remained positive in some patients. Compared with peripheral arthritis, shaft arthritis was the high-risk factor for longer symptom duration. The therapeutic effects were similar between DR and DRC. In summary, our study provided important insights into the clinical characteristics, treatment, and outcomes of osteoarticular brucellosis. Clinical Trial Registration number: NCT04020536.

Enhanced Proximity of Rh1,2-Rhn Ensembles Encaged in UiO-67 Boosting Catalytic Conversion of Syngas to Oxygenates.

Maintaining high conversion under the premise of high oxygenates selectivity in syngas conversion is important but a formidable challenge in Rh catalysis. Monometallic Rh catalysts provide poor oxygenate conversion efficiency, and efforts have been focused on constructing adjacent polymetallic sites; however, the one-pass yields of C2+ oxygenates over the reported Rh-based catalysts were mostly <20 %. In this study, we constructed a monometallic Rh catalyst encapsulated in UiO-67 (Rh/UiO-67) with enhanced proximity to dual-site Rh1,2-Rhn ensembles. Unexpectedly, this catalyst exhibited high efficacy for oxygenate synthesis from syngas, giving a high oxygenate selectivity of 72.0 % with a remarkable CO conversion of 50.4 %, and the one-pass yield of C2+ oxygenates exceeded 25 %. The state-of-the-art characterizations further revealed the spontaneous formation of an ensemble of Rh single atoms/dimers (Rh1,2) in the proximity of ultrasmall Rh clusters (Rhn) confined within the nanocavity of UiO-67, providing adjacent Rh+-Rh0 dual sites dynamically during the reaction that promote the relay of the undissociated CHO species to the CHx species. Thus, our results open a new route for designing highly efficient Rh catalysts for the conversion of syngas to oxygenates by precisely tuning the ensemble and proximity of the dual active sites in a confined space.

Relationships between Size-specific Dose Estimate and Signal to Noise Ratio under Chest CT Examinations with Tube Current Modulation.

PURPOSE: Exploring the relationship between the signal-to-noise ratio (SNR) of organs and size-specific dose estimate (SSDE) in tube current modulation (TCM) chest CT examination. METHODS: Forty patients who received TCM chest CT scanning were retrospectively collected and divided into four groups according to the tube voltage and sexes. We chose to set up the region of interest (ROI) at the tracheal bifurcation and its upper and lower parts in slice images of the heart, aorta, lungs, paracranial muscles, and female breast, and the SNR of each organ was calculated. We also calculated the corresponding axial volume CT dose index (CTDIvolz) and axial size-specific dose estimate (SSDEz). RESULTS: The correlation analysis showed that the correlation between the SNR of the slice images of most organs and SSDEz was more significant than 0.8, and that between the SNR and CTDIvol was more significant than 0.7. The simple linear regression analysis results showed that when the sex is the same, the SNR of the same organ at 100kVp was higher than 120kVp, except for the lung. In multiple regression analysis, the result indicated that the determination coefficients of the SNR and SSDEz of the four groups were 0.934, 0.971, 0.905, and 0.709, respectively. CONCLUSION: In chest CT examinations with TCM, the correlation between the SNR of each organ in slice images and SSDEz was better than that of CTDIvolz. And when the SSDEz was the same, the SNR at 100 kVp was better than that at 120 kVp.

Molecular mechanism and intervention measures of microvascular complications in diabetes.

Objective: In this article, the epidemiology, molecular mechanism of occurrence and development, risk factors, and treatment of diabetic microvascular complications such as diabetic nephropathy, diabetic retinopathy, and diabetic peripheral neuropathy were discussed, providing the theoretical basis for more accurate elucidation of the pathogenesis and treatment of diabetic microvascular complications. Methods: The electronic database of PubMed was searched, and retrieved papers were screened for eligibility by two independent reviewers. Data were extracted using a standardized data extraction form and the quality of included papers was assessed. Results: Thirty-eight articles were included. Diabetes nephropathy, diabetes peripheral neuropathy, and diabetes retinopathy are the most common and serious microvascular complications of diabetes in clinical patients. Renin-angiotensin system blockers, beta drugs, statins, antivascular endothelial growth factor drugs, and antioxidants can inhibit the occurrence of microvascular complications in diabetes. Conclusions: However, there has been no breakthrough in the treatment of diabetic microvascular complications. Therefore, prevention of diabetic microvascular complications is more important than treatment.

Long-chain fatty acids - The turning point between 'mild' and 'severe' acute pancreatitis.

Acute pancreatitis (AP) is an inflammatory disease characterized by localized pancreatic injury and a systemic inflammatory response. Fatty acids (FAs), produced during the breakdown of triglycerides (TGs) in blood and peripancreatic fat, escalate local pancreatic inflammation to a systemic level by damaging pancreatic acinar cells (PACs) and triggering M1 macrophage polarization. This paper provides a comprehensive analysis of lipases' roles in the onset and progression of AP, as well as the effects of long-chain fatty acids (LCFAs) on the function of pancreatic acinar cells (PACs). Abnormalities in the function of PACs include Ca2+ overload, premature trypsinogen activation, protein kinase C (PKC) expression, endoplasmic reticulum (ER) stress, and mitochondrial and autophagic dysfunction. The study highlights the contribution of long-chain saturated fatty acids (LC-SFAs), especially palmitic acid (PA), to M1 macrophage polarization through the activation of the NLRP3 inflammasome and the NF-κB pathway. Furthermore, we investigated lipid lowering therapy for AP. This review establishes a theoretical foundation for pro-inflammatory mechanisms associated with FAs in AP and facilitating drug development.

Application of telemedicine system for older adults postoperative patients in community: a feasibility study.

Purpose: In response to the growing challenges posed by an aging society, a telemedicine system was developed specifically for older adults postoperative patients, and its effectiveness was thoroughly investigated. Methods: Between May 2020 and May 2022, a total of 88 older adults postoperative patients were enrolled and randomly allocated into an experimental group and a control group. The experimental group received telemedicine services after discharge, while the control group received conventional medical services following the traditional protocol. One month after discharge, various indicators were evaluated for both groups, including number of visits, medical expenditures, postoperative recovery, anxiety, depression and satisfaction. Results: The number of visits and medical expenditures of the experimental group were less than those of the control group [1 (0, 1) vs. 1 (1, 2), Z = -3.977, p < 0.001; 25.25 (0.00, 277.40) yuan vs. 174.65 (49.63, 446.10) yuan, Z = -2.150, p = 0.032]. In both groups, there were 2 cases of incision infection, respectively. No significant difference was observed between the two groups (Fisher χ2, p = 0.259). In both groups, there was no instance of incision bleeding, incision dehiscence, readmission, or reoperation. Additionally, there was no significant difference in physical status between the two groups at discharge and after discharge (66.06 ± 8.92 vs. 65.45 ± 7.39 t = 0.287, p = 0.775; 73.33 ± 9.97 vs. 70.91 ± 7.50, t = 1.202, p = 0.235). And there was no significant difference in the change of physical status between the two groups after discharge [10.00 (0.00, 10.00) vs. 5.00 (0.00, 10.00), Z = -1.077, p = 0.281]. There was no significant difference in body weight change between the two groups after discharge [1.05 (0.38, 1.60) Kg vs. 0.80 (0.50, 1.43) Kg, Z = -0.265, p = 0.791]. There was no significant difference in the levels of anxiety and depression between the two groups at discharge (45.64 ± 8.10 vs. 44.60 ± 8.24, t = 0.520, p = 0.604, 48.33 ± 8.46 vs. 47.50 ± 6.85, t = 0.418, p = 0.677). But the levels of anxiety and depression in the experimental group were lower than those in the control group after discharge (34.92 ± 7.38 vs. 39.03 ± 8.42, t = -2.183, p = 0.032, 37.86 ± 7.29 vs. 41.93 ± 7.13, t = -2.281, p = 0.025); The change of anxiety level and depression level of the experimental group were more than those of the control group [-10.00 (-11.25, -8.75) vs. -5.00 (-7.81, -3.75), Z = -5.277, p < 0.001; -10.00 (-12.50, -7.50) vs. -5.00 (-7.75, -3.44), Z = -4.596, p < 0.001]. The level of satisfaction regarding medical services, daily care, and psychological comfort was higher in the experimental group compared to the control group [3 (3, 3.25) vs. 2 (1, 2), Z = -5.931, p < 0.001; 3 (3, 4) vs. 3 (2, 3), Z = -2.286, p = 0.022; 2 (1, 3) vs. 1 (0.75, 2), Z = -2.081, p = 0.037]. Conclusion: In the context of an aging society, telemedicine system can offer improved healthcare to older adults postoperative patients. This includes benefits such as reducing number of visits, saving medical expenditures, enhancing psychological comfort and daily care.

AMPK Alchemy: Therapeutic Potentials in Allergy, Aging, and Cancer.

All cells are equipped with intricate signaling networks to meet the energy demands and respond to the nutrient availability in the body. AMP-activated protein kinase (AMPK) is among the most potent regulators of cellular energy balance. Under ATP -deprived conditions, AMPK phosphorylates substrates and affects various biological processes, such as lipid/glucose metabolism and protein synthesis. These actions further affect the cell growth, death, and functions, altering the cellular outcomes in energy-restricted environments. AMPK plays vital roles in maintaining good health. AMPK dysfunction is observed in various chronic diseases, making it a promising target for preventing and alleviating such diseases. Herein, we highlight the different AMPK functions, especially in allergy, aging, and cancer, to facilitate the development of new therapeutic approaches in the future.

[Research progress in the anatomy and surgical approach of the parapharyngeal space].

The parapharyngeal space, a complex fascial compartment within the head and neck region, encompasses crucial anatomical structures including blood vessels and nerves. Tumors occurring within this space are rare, with the majority being benign in nature. Surgical intervention remains the primary treatment modality; however, managing parapharyngeal space tumors poses significant challenges due to their intricate anatomical configuration. Conventional open surgical approaches have been associated with significant tissue damage and a high prevalence of postoperative complications. Recently, advancements in anatomical studies and surgical techniques have led to significant progress in understanding parapharyngeal space anatomy and improving surgical management. This article aims to provide a comprehensive overview of these developments.

[Drafâ ¢ approach to unilateral frontal sinus for contralateral drainage].

Objective:Anatomical variation or scar atresia of the drainage channel of the frontal sinus on the affected side, and opening the frontal sinus through the drainage channel of the frontal sinus on the affected side may lead to surgical failure. The purpose of this study is to explore a modified Draf Ⅲ operation to complete the drainage of the affected frontal sinus by removing the floor wall and septum of the frontal sinus and connecting the bilateral frontal sinus through the healthy side of the frontal sinus. Methods:Through the anatomical study of 2 skull bone specimens and 2 fresh frozen specimens, the surgical landmark and surgical approach were explored. Four patients with frontal sinus atresia and frontal sinusitis after DrafⅡb surgery in Eye & ENT Hospital of Fudan University were retrospectively analyzed. Descriptive method was used to analyze the data. Results:The bottom wall of bilateral frontal sinus was removed, and the bilateral frontal sinus was enlarged above the nasal septum to form a large common cavity. The uncinate process and ethmoid bubble were retained, and the midline drainage of the affected frontal sinus in the healthy side of the nasal cavity was completed. From August 2022 to April 2023, 4 patients with frontal sinus atresia and frontal sinusitis after DrafⅡb surgery for unilateral frontal sinus papilloma in Eye & ENT Hospital of Fudan University were treated with surgery. The headache symptoms disappeared after surgery, and the drainage of frontal sinus was spacious, the mucosa healed well and the drainage was unobstructed under endoscopy. There were no other postoperative complications. Conclusion:DrafⅢ approach to unilateral frontal sinus for contralateral drainage can drain the affected frontal sinus adequately. The essence of this operation is to drain the bilateral frontal sinus in the unilateral nasal cavity, and this operation has short path, less trauma, and a broader prospect, which is suitable for promotion.

Anatomical studies and early results on endoscopic transoral medial pterygomandibular fold approach to salvage retropharyngeal lymphadenectomy in nasopharyngeal carcinoma.

OBJECTIVE: Retropharyngeal lymphadenectomy is challenging. This study investigated a minimally invasive approach to salvage retropharyngeal lymphadenectomy in patients with nasopharyngeal carcinoma. METHODS: An anatomical study of four fresh cadaveric heads was conducted to demonstrate the relevant details of retropharyngeal lymphadenectomy using the endoscopic transoral medial pterygomandibular fold approach. Six patients with nasopharyngeal cancer with retropharyngeal lymph node recurrence, who underwent retropharyngeal lymphadenectomy with the endoscopic transoral medial pterygomandibular fold technique at the Eye and ENT Hospital of Fudan University from July to December 2021, were included in this study. RESULTS: The anatomical study demonstrated that the endoscopic transoral medial pterygomandibular fold approach offers a short path and minimally invasive approach to the retropharyngeal space. The surgical procedure was well tolerated by all patients, with no significant post-operative complications. CONCLUSION: The endoscopic transoral medial pterygomandibular fold approach is safe and efficient for retropharyngeal lymphadenectomy.

LC3-dependent extracellular vesicles promote M-MDSC accumulation and immunosuppression in colorectal cancer.

For a long time, myeloid-derived suppressor cells (MDSCs) dilated in circulation system of colorectal cancer (CRC) patients have been puzzling clinicians. Various evidence shows that MDSCs constitute the bulk of immunosuppression in CRC, which is related to tumor growth, adhesion, invasion, metastasis, and immune escape. However, the mechanisms underlying these cells formation remain incompletely understood. In this study, we reported that CRC cell-derived LC3-dependent extracellular vesicles (LDEVs)-mediated M-MDSCs formation via TLR2-MYD88 pathway. Furthermore Hsp60 was the LDEVs surface ligand that triggered these MDSCs induction. In clinical studies, we reported that accumulation of circulating M-MDSCs as well as IL-10 and arginase1 secretion were reliant upon the levels of tumor cell-derived LDEVs in CRC patients. These findings indicated how local tumor cell-derived extracellular vesicles influence distal hematopoiesis and provided novel justification for therapeutic targeting of LDEVs in patients with CRC.

The efficacy and safety of radial endobronchial ultrasound-guided transbronchial lung cryobiopsy in the diagnosis of lung disease.

Background: Transbronchial lung cryobiopsy (TBLC) is a novel technology in which a cryoprobe is used to obtain large tissue samples from the lungs of patients with interstitial lung diseases (ILDs) and peripheral pulmonary lesions (PPLs). We aimed to determine the efficacy and safety of TBLC in the diagnosis of peripheral lung diseases in the Endoscopy Center of Shanghai Pulmonary Hospital. Further, the application value of radial endobronchial ultrasound (R-EBUS) used to determine the optimal area for cryobiopsy was evaluated in this study. Methods: In this retrospective study, the data of patients with unclarified ILDs or PPLs who underwent TBLC guided by R-EBUS between April 2020 and December 2021 at Shanghai Pulmonary Hospital in China were analyzed. Results: A total of 137 patients [72 men, 65 women; median age, 52 years (range, 24-76 years)] were enrolled in the study. Out of the 137 patients included in the study, 123 (89.8%) were diagnosed after multidisciplinary discussions (MDDs), including 105 (85.4%) with ILD, 10 (8.1%) with tuberculosis, and 8 (6.5%) with a malignant tumor. Sixty-five (47.4%) patients had a definitive pathologic diagnosis through TBLC, including 54 (83.1%) with ILD, 5 (7.7%) with tuberculosis and 6 (9.2%) with malignant tumors. The overall pathological diagnosis rate was 47.4%. In addition to clarifying the blood supply situation of the candidate target, R-EBUS detected lesions in 44 (32.1%) patients. Mild and moderate bleeding occurred in 75.2% and 24.8% of patients, respectively. No cases of severe bleeding were observed. Pneumothorax occurred in 6 (4.4%) patients, of which 2 recovered without additional treatment, and 4 (66.7%) needed closed thoracic drainage. Hydropneumothorax and mediastinal emphysema occurred in one patient each. No patients died due to TBLC. Conclusions: R-EBUS-guided TBLC is safe and effective for the diagnosis of lung diseases, including ILDs and other PPLs. R-EBUS can guide cryobiopsy and avoid the potential risk of severe bleeding as well as radiation exposure. The pathological diagnosis rate of ILDs is relatively low, and MDD plays an important role in the diagnosis of ILDs.

CB2 regulates oxidative stress and osteoclastogenesis through NOX1-dependent signaling pathway in titanium particle-induced osteolysis.

Periprosthetic osteolysis (PPO) induced by wear particles at the interface between the prosthesis and bone is a crucial issue of periprosthetic bone loss and implant failure. After wear and tear, granular material accumulates around the joint prosthesis, causing a chronic inflammatory response, progressive osteoclast activation and eventual loosening of the prosthesis. Although many studies have been conducted to address bone loss after joint replacement surgeries, they have not fully addressed these issues. Focusing on osteoclast activation induced by particles has important theoretical implications. Cannabinoid type II receptor (CB2) is a seven-transmembrane receptor that is predominantly distributed in the human immune system and has been revealed to be highly expressed in bone-associated cells. Previous studies have shown that modulation of CB2 has a positive effect on bone metabolism. However, the exact mechanism has not yet been elucidated. In our experiments, we found that NOX1-mediated ROS accumulation was involved in titanium particle-stimulated osteoclast differentiation. Furthermore, we confirmed that CB2 blockade alleviated titanium particle-stimulated osteoclast activation by inhibiting the NOX1-mediated oxidative stress pathway. In animal experiments, downregulation of CB2 alleviated the occurrence of titanium particle-induced cranial osteolysis by inhibiting osteoclasts and scavenging intracellular ROS. Collectively, our results suggest that CB2 blockade may be an attractive and promising therapeutic scheme for particle-stimulated osteoclast differentiation and preventing PPO.