Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

AIM:To construct a recombinant adenovirus vector carrying the mouse ubiquitin-like with plant homeodomain and RING finger domains 1(Uhrf1)gene,validate the expression of Uhrf1 in neonatal mouse cardiomyo-cytes and explored its role in hydrogen peroxide(H2O2)-induced DNA damage.METHODS:The mouse Uhrf1 gene cod-ing sequence was amplified by polymerase chain reaction(PCR),digested,and inserted into the pADM-CMV-C-FH vec-tor to create the recombinant adenoviral plasmid ADM-Uhrf1.Following transfection into HEK293T cells,we generated re-combinant adenoviral particles,amplified,purified,and determined the titer.Neonatal mouse cardiomyocytes were infect-ed at an multiplicity of infection(MOI)of 50,UHRF1 protein expression was validated via Western blot and immunofluo-rescence staining.H2O2-induced DNA damage was explored along with adenovirus-mediated Uhrf1 overexpression to inves-tigate its role in DNA damage repair.RESULTS:ADM-Uhrf1 virus titer,determined by capsid immunofluorescence as-say,was 1.8×1013 pfu/L.Western blot confirmed a significant increase in UHRF1 protein expression(P＜0.05),with im-munofluorescence indicating predominant nuclear localization.Uhrf1 overexpression effectively inhibited the expression of the DNA damage marker,phosphorylated H2AX protein(γH2AX)(P＜0.01).CONCLUSION:We successfully con-structed a recombinant adenoviral vector carrying the mouse Uhrf1 gene,facilitating Uhrf1 overexpression in neonatal mouse cardiomyocytes.Furthermore,this overexpression effectively alleviated DNA damage in cardiomyocytes.

Objective:To construct an explainable artificial intelligence(AI) model of risk characteristics of papillary thyroid carcinoma(PTC), and to explore its value of it combined with clinical features in predicting cervical lymph node metastasis(CLNM) in PTC patients.Methods:From January 2021 to September 2022, 422 patients(422 nodules) with pathologically confirmed PTC underwent thyroidectomy and neck lymph node dissection in the Second Affiliated Hospital of Xi′an Jiaotong University were retrospectively collected, the patients were randomly divided into training set and test set according to the ratio of 7∶3. Ultrasonographic features highly correlated with PTC risk characteristics were extracted by traditional machine learning method, and an intelligent prediction model with optimal probability of risk characteristics was established. Then, a risk model for predicting CLNM of PTC patients was constructed in combination with clinical features. The diagnostic effectiveness of the model was evaluated by drawing a ROC curve and calculating the area under curve (AUC).Results:In the AI explaineable model of PTC risk characteristics in the test set, the intelligent diagnosis model of calcification based on logistic regression classification showed the highest diagnostic efficiency, with an AUC of 0.87 ( P<0.05). Compared with the probability model of risk characteristic of PTC alone, the comprehensive model combined with clinical characteristics showed higher diagnostic efficiency in predicting CLNM of PTC patients, with AUC of 0.97, diagnostic critical value of 0.15, corresponding accuracy, sensitivity and specificity of 92.65%, 92.76% and 92.54%, respectively (all P<0.05). Conclusions:The explaineble risk characteristics of PTC AI model combined with clinical features can effectively predict the cervical lymph node metastasis of PTC, and then provide effective information for clinical decision-making of PTC patients.

Peak picking is one of the essential steps in non-targeted metabolomics data preprocessing based on liquid chromatography-mass spectrometry.Among various peak-picking algorithms,centWave algorithm based on continuous wavelet transform has been widely adopted in high-resolution mass spectrometry.In this study,the optimization effects of two centWave parameter optimization algorithms,IPO and centWave Sweep,were compared.Two datasets including metabolite standards and urine were used for comprehensive evaluation of these two algorithms with respect to three indicators:good peak shape ratio,reliable peak ratio,and repeatable peak ratio.To quickly and accurately distinguish good and bad peak shapes,three ensemble learning algorithms,random forest,adaboost and gradient boosting decision tree,were selected to establish a model for distinguishing chromatographic peak shape.Finally,according to the accuracy and F1 score,random forest was selected to establish a discrimination model(Accuracy 93.5%,F1 score 0.938).Compared with recommended parameters of XCMS Online,the proportion of reliable peaks and the proportion of repeatable peaks of two parameter optimization algorithms were improved in different datasets.However,when it came to the proportion of peaks with good shape,there was no significant difference between the optimized parameters and the parameters recommended by XCMS Online in different datasets.Furthermore,all three parameter settings resulted in relatively low proportions of peaks with good shape.The results indicated that the current parameter optimization algorithm was unable to improve the proportion of peaks with good shape.An excessive number of bad shape peaks could not only decrease the statistical power of analysis but also generate false positive results.Therefore,it was critical to perform additional confirmation of potential markers in the practical application of metabolomics researches.

Objective To explore the feasibility and safety of submucosal tunneling endoscopic resection(STER)for the treatment of giant(long diameter≥3.5 cm)symptomatic submucosal tumors(SMT)originating from the esophageal and cardiac muscularis propria layer.Methods A retrospective analysis was conducted on patients with giant symptomatic SMT of the esophagus and cardia treated with STER at the Endoscopy Center of Zhongshan Hospital,Fudan University from January 2017 to January 2020.Clinical characteristics and follow-up data of patients were collected.The efficacy of STER was evaluated by complete resection rate,recurrence rate,and residual rate.The safety of the procedure was assessed by the occurrence of procedure-related complications.Results A total of 111 patients with SMT were included,including 65 males and 46 females,with an average age of(43.2±11.6)years old.Among them,11 patients(9.9％)presented with typical symptoms.Leiomyomas accounted for 105 cases,gastrointestinal stromal tumors for 2 cases,and schwannoma for 4 cases.The median long diameter of the tumors was 5 cm,and the median short diameter was 3 cm.The median operation time was 70 minutes,and the median time of hospital stay was 3 days.The success rate of STER was 100％,with a complete resection rate of 73.9％.Intraoperative mucosal injury was observed in 18 cases(16.2％),postoperative complications occurred in 16 cases(14.4％),including severe pneumothorax/pleural effusion requiring drainage in 10 cases(9.0％),delayed bleeding in 1 case(0.9％),moderate or severe fever in 4 cases(3.6％),and infection in tunnel in 1 case(0.9％).Follow-up at 1-18 months showed no tumor residue,recurrence,esophageal stenosis,diverticula or other long-term complications.Conclusions STER is a safe and effective treatment for giant symptomatic SMT of the esophagus and cardia.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To analyze the clinical features of gastritis cystica profunda (GCP) and investigate the risk factors associated with its coexistence with gastric cancer.Methods:Data of 149 patients with pathologically confirmed GCP at Zhongshan Hospital of Fudan University between January 2015 and March 2022 were retrospectively analyzed for basic information, clinical data, lesion manifestations and pathological results, of which 106 were pathologically confirmed GCP after endoscopic resection and 43 others were pathologically confirmed GCP after surgical procedures. Among 149 patients, 56 were in the simple GCP group, and 93 in the GCP combined with gastric cancer group.Results:In the simple GCP group of 56 patients, 62.5% (35/56) were male and the mean age was 58.8 years. The predominant site of involvement was in the upper gastric segment (cardia and fundus) (51.8%,29/56), with manifestations primarily of the polypoid bulge type (41.1%,23/56) and submucosal bulge type (35.7%,20/56). Clinical symptoms were mostly atypical. In the group where GCP was combined with gastric cancer (93 cases), males accounted for 90.3% (84/93), the median age was 66.9 years, the upper gastric segment was predominantly affected (75.3%, 70/93), with differentiated cancer being the most common histological type (91.4%, 85/93). For 76 cases of early gastric cancer combined with GCP, mucosal lesions were the main presentation (73.7%, 56/76) with atypical clinical symptoms. Furthermore, in 17 cases of progressive gastric cancer combined with GCP, the manifestations were mainly bulging ulcers (88.2%, 15/17), and most of them were referred to the doctor because of abdominal pain and black stools (100.0%, 17/17). Binary logistic regression analysis showed that being male ( P=0.004, OR=4.411, 95% CI: 1.621-12.002), age ( P=0.001, OR=1.085, 95% CI: 1.036-1.136) and endoscopic manifestations of mucosal lesions ( P<0.001, OR=5.080, 95% CI: 2.162-11.939) were risk factors for GCP combined with gastric cancer, but involvement of the upper gastric segment was not related to combination with gastric cancer ( P=0.430, OR=0.707, 95% CI: 0.299-1.672). Among 106 patients with endoscopic resection, 57 cases of early gastric cancer combined with GCP had a median lesion length of 2.50 cm; 49 cases of GCP alone had a median lesion length of 1.20 cm, with significant difference ( Z=-5.503, P<0.001). All upper gastric GCP combined with early gastric cancer in endoscopically treated patients were cancers of the cardia, most of which were superficial elevation with the concave type (0-Ⅱa+Ⅱc) (44.7%, 21/47). 75.4% (43/57) patients with gastric cancer combined with GCP were graded as curative resection (eCuraA) after endoscopic surgery , and none of those who had additional surgery after endoscopic surgery had lymph node metastasis. There were 8 cases with history of gastric surgery, 7 of esophageal cancer, and 10 of multiple neoplastic gastric lesions in the 149 patients with GCP. Conclusion:GCP often occurs in the upper gastric region and is not inherently associated with the presence of gastric cancer. However, when coexisting with gastric cancer, it tends to affect elderly men, present with mucosal lesions of a differentiated histological type, and may be accompanied by esophageal or other gastric cancers. Notably, GCP is frequently identified as para-cancerous lesion, and endoscopic treatment emerges as a safe and effective approach, characterized by a high rate of curative endoscopic resections and a low incidence of lymphatic metastases.

Objective To compare the value of two-dimensional high-frequency ultrasound, acoustic pulsed radiant force imaging (ARFI)-acoustic palpation tissue quantification (VTQ) technology, and strain elastography alone and their combination in diagnosis of benign and malignant thyroid micronodules. Methods A retrospective analysis was conducted in 99 patients (107 thyroid micro-solid nodules with diameters ≤ 10.0 mm) who were treated at Baoji People's Hospital in Shaanxi Province from June 2021 to June 2023. All patients underwent two-dimensional high-frequency ultrasound, ARFI-VTQ technology, and strain elastography to obtain ultrasound data scores and data. Using biopsy and surgical pathology as the diagnostic "gold standard", the diagnostic efficacy of the three ultrasound methods alone and their combination was compared for thyroid micro-nodules. Results A total of 62 patients (68 nodules) underwent fine-needle aspiration biopsy (FNAB), and 37 patients (39 nodules) underwent surgery. Among 107 thyroid micro-nodules, 45 were diagnosed as malignant, and 62 as benign. Significant differences were observed between malignant micro-nodules and benign micro-nodules in terms of internal echo (isoechoic and hyperechoic echo, very hypoechoic and hypoechoic echo), boundary, microcalcification, aspect ratio >1, blood supply, and resistance index (RI) of the artery (P < 0.05). When the critical value of the C-TIRADS score for diagnosing thyroid micro-nodules using two-dimensional high-frequency ultrasound was ≥ 2 points (C-TIRADS 4b), the diagnostic sensitivity was 73.33%, specificity was 79.03%, and the area under the curve (AUC) was 0.762[95%CI, 0.670 to 0.839]. In ARFI-VTQ technology, the SWV values ranged from 0.52 to 7.55 m/s, with an average of (2.62 ± 0.61) m/s. The mean SWV of malignant micro-nodules was (5.24±2.23) m/s, which was higher than (2.11±0.70) m/s of benign micro-nodules (t=10.258, P < 0.05). When the critical SWV value was 3.19 m/s, the diagnostic sensitivity was 77.78%, specificity was 80.65%, and the AUC (95%CI) was 0.792(95%CI, 0.703 to 0.865). In strain elastography, when the critical score was ≥3, the diagnostic sensitivity was 75.56%, specificity was 77.42%, and the AUC (95%CI) was 0.765 (95%CI, 0.673 to 0.841). Combined detection of the three methods showed that there were 44 positive micro-nodules, 63 negative micro-nodules, the diagnostic sensitivity was 93.33%, specificity was 96.77%, and the AUC (95%CI) was 0.951 (95%CI, 0.891 to 0.983). There was statistical significance in the diagnostic efficacy of combined application compared with that of 2D high-frequency ultrasonography, ARFI-VTQ technology and strain-elasticity imaging alone (Z=4.861, 4.393, 4.842, P < 0.05). Conclusion The combination of two-dimensional high-frequency ultrasound, ARFI-VTQ technology, and strain elastography can improve the diagnostic accuracy of benign and malignant thyroid micro-nodules.

【Objective:】 To preliminary construct a scientific, systematic and applicable evaluation index system of the interest conflict for medical institutions ethics committee. 【Methods:】 Literature retrieval, interpretation of laws and regulations, expert group discussion and Delphi expert letter inquiry were used to screen indicators and determine the evaluation index system of interest conflict and the weight of various indicators. 【Results:】 The response rates of the two rounds of correspondence questionnaire were both 100%, the authority coefficient Cr values of the two rounds were 0.855 and 0.865, and the coordination coefficient W values of the two rounds were 0.817 and 0.826, which were statistically significant (P<0.05). The final formed system included 3 first-level indicators, 10 second-level indicators and 25 third-level indicators. 【Conclusion:】 The evaluation index system of interest conflict for medical institution ethics committee is scientific and reliable.

Objective:To explore the applicability of the distance between facial marks classification in evaluating the severity of androgenic alopecia in men.Methods:From June to December 2019, the male Chinese with diagnosis of androgenic alopecia were evaluated in the specific clinic of alopecia of Hangzhou First People’s Hospital according to the distance between facial marks and BASP(basic and specific) classification. The classification based on the distance between facial marks measures the distance from the facial marks of the anterior hairline to the horizontal line of the eyebrow and the longest radius of hair loss in the hair rotation center, the hair recession of the patient’s forehead (F), temporal (M) and vertex (V) parts. The hair loss in each region is rated as 0-3 grade from light to heavy, and the final hair loss grading is expressed as FnMnVn, such as F1M2V0. The highest grade of hair loss in F, M and V is the overall grade of hair loss. SPSS 25.0 software was used to statistically analyze the general data of patients, and Kappa test was used to evaluate the consistency between the results of the distance classification and BASP classification. The repeatability of the distance classification was tested by the repetition rate of three hair loss specialists. When two or more specialists gave the same evaluation among the three hair loss specialists, the result was regarded as the standard result. The ease of use of the distance between facial marks classification was tested by the consistency rate between the grading results of two temporary trained general doctors and the standard results.Results:A total of 150 male patients, aged (32.8±7.9) years (19-58 years), were included, of which 99 patients were 24-35 years old, accounting for 66.00%. It can be observed that the onset age was earlier. As assessed in this classification, the patients who participated in the study were graded as mild in 65 cases(43.33%), severe in 58 cases(38.67%), and moderate, which was consistency with the results obtained by BASP classification ( κ=0.573, P<0.001). Three experienced alopecia specialists evaluated 150 patients through the distance between facial marks. The results showed that the repetition rates of frontal, temporal and parietal classification results were 98.00%(147/150), 97.33%(146/150) and 96.00%(144/150), respectively. The repetition rate of the final alopecia classification was 92.00%(138/150), and the repetition rate of the overall alopecia classification was 98.00%(147/150). The consistency rate between the overall alopecia classification results of two temporary trained general doctors and the standard results was 95.92%(141/147) and 96.60%(142/147), respectively, and the consistency rate of the other results was higher than 90.00% except for one general doctor who was 89.86%(124/138) in the final classification. Conclusion:The distance between facial marks classification is a comparatively accurate and easy-to-learn grading method designed for Chinese male androgenic hair loss patients based on objective measurement data.