Objective To establish a stable,reliable,and clinically relevant porcine model of endotoxin-induced acute respiratory distress syndrome(ARDS).Methods Ten 8-month-old male Bama minipigs were deeply sedated,followed by invasive mechanical ventilation and electrocardiographic monitoring.Lipopolysaccharide(LPS)was intravenously pumped at 600 μg/(kg·h)for 3 hours,then maintained at 15 μg/(kg·h)thereafter.Dynamic monitoring was performed at five time points after LPS injection(LPS 0,1,3,5,and 8 h),including arterial blood gas analysis and chest computed tomography(CT)scans.Pathological examination of lung tissues obtained via bronchoscopic biopsy(HE staining and transmission electron microscopy)was conducted.These indicators were comprehensively used to evaluate the success of the animal model.Results At 5 hours after LPS administration,8 minipigs developed symptoms such as skin cyanosis,elevated body temperature,and respiratory distress.The oxygenation index decreased to<300 mmHg.Chest CT scans showed diffuse pulmonary infiltrates.Histopathology revealed alveolar edema and hyaline membrane formation.Transmission electron microscopy demonstrated disruption of pulmonary blood-air barrier,depletion of lamellar bodies in type Ⅱ pneumocytes,inflammatory cell infiltration,and exudation of plasma proteins and fibrin.Compared with LPS 0 h,at LPS 8 h,the oxygenation index and arterial blood pH were significantly decreased(P<0.001),while blood lactic acid and serum potassium were significantly increased(P<0.05);serum calcium and base excess were significantly decreased(P<0.05),and the lung injury score based on HE-stained lung sections was significantly increased(P<0.01).Conclusion The porcine ARDS model established by continuous LPS injection can dynamically simulate the pathophysiological characteristics and typical pathological manifestations of clinical septic ARDS,making it an effective tool to study the pathogenesis,prevention,and treatment strategies of septic ARDS.

Idiopathic pulmonary fibrosis(IPF) is a chronic progressive interstitial lung disease characterized by a complex pathogenesis and limited treatment options. Although studies have indicated that lipid metabolism dysregulation is associated with the progression of IPF, the core regulatory mechanisms remain unclear. By integrating RNA sequencing data from the GEO database, we identified four key genes related to lipid metabolism: peroxisome proliferator-activated receptor gamma(PPARG), secreted phosphoprotein 1(SPP1), caspase 3(CASP3), and platelet endothelial cell adhesion molecule 1(PECAM1). Further validation using single-cell RNA sequencing revealed the cell-specific expression patterns of these genes. The results found that PPARG was significantly downregulated in alveolar macrophages while SPP1 was significantly upregulated. Mechanistic studies indicated that PPARG negatively regulated SPP1 expression, and the interaction between SPP1 and cluster of differentiation 44(CD44) activated intercellular signaling pathways that promoted fibrosis. Through network pharmacology and molecular docking, it was predicted that the bioactive components of the traditional Chinese medicine formula, namely Buyang Huanwu Decoction may target PPARG to modulate lipid metabolism pathways. In a bleomycin-induced rat model with IPF, this paper randomly divided the rats into six groups(control, group, model group, pirfenidone group, and low, middle, and high-dose groups of Buyang Huanwu Decoction). The results demonstrated that Buyang Huanwu Decoction treatment significantly improved tissue pathological damage, reduced collagen deposition, and alleviated lipid metabolism dysregulation. Western blot analysis confirmed that Buyang Huanwu Decoction mediated the upregulation of PPARG and inhibited the activation of the SPP1/CD44 pathway. The multi-omics study elucidated the role of the PPARG/SPP1/CD44 pathway as a key regulatory factor in lipid metabolism in IPF, providing evidence that Buyang Huanwu Decoction exerted its antifibrotic effects through this novel mechanism and thus offering new insights into the therapeutic prospects for IPF.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Signal Transduction/drug effects* ; PPAR gamma/genetics* ; Humans ; Osteopontin/genetics* ; Lipid Metabolism/drug effects* ; Idiopathic Pulmonary Fibrosis/genetics* ; Hyaluronan Receptors/genetics* ; Rats ; Male ; Rats, Sprague-Dawley ; Molecular Docking Simulation

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.
Female ; Humans ; Adolescent ; SARS-CoV-2 ; Smell ; COVID-19/complications* ; Cross-Sectional Studies ; COVID-19 Vaccines ; Incidence ; Olfaction Disorders/etiology* ; Taste Disorders/etiology* ; Prognosis

Objective:To analyze the quality of surgical specimens of rectal cancer in the Chinese transanal total mesorectal excision (taTME) registry collaborative (CTRC) database.Methods:The retrospective and descriptive study was conducted. Based on the concept of real-world research, the clinicopathological data of 1 761 patients with rectal cancer in the CTRC database who underwent taTME in 40 medical centers, including the Beijing Friendship Hospital of Capital Medical University et al, from November 15, 2017 to December 31, 2022 were collected. There were 1 212 males and 549 females, aged 62(range, 53-68)years. Observation indicators: (1) preoperative examinations; (2) neoadjuvant therapy; (3) postoperative examinations. Measurement data with skewed distri-bution were represented as M(range). Count data were described as absolute numbers. Results:(1) Preoperative examinations. Of the 1 761 patients, 1 324 patients underwent preoperative pelvic magnetic resonance imaging examination, and the results showed that 4 cases as clinical T0 stage, 30 cases as clinical T1 stage, 250 cases as clinical T2 stage, 828 cases as clinical T3 stage, 141 cases as clinical T4 stage, 11 cases as clinical Tx stage, 60 cases missing clinical T staging data, 490 cases as clinical N0 stage, 373 cases as clinical N1 stage, 311 cases as clinical N2 stage, 86 cases as clinical Nx stage, 64 cases missing clinical N staging data, 156 cases with mesorectal fascia invasion, 223 cases with extraintestinal blood vessels invasion. The distance from lower margin of tumor to anal margin of 1 324 patients was 50(range, 40-60)mm. (2) Neoadjuvant therapy. Of the 1 761 patients, 873 patients underwent neoadjuvant therapy, including 17 cases receiving radiotherapy alone, 155 cases receiving chemotherapy alone, 43 cases receiving short-course simultaneous chemoradiotherapy, 26 cases receiving short-course simultaneous chemoradiotherapy and delayed surgery, 1 case receiving contact radiotherapy, 277 cases receiving long-course simultaneous chemoradiotherapy, 9 cases receiving other treatments, and 345 cases missing neoadjuvant therapy data. (3) Postoperative examinations. Of the 1 761 patients, 1 584 cases achieved R 0 resection, 23 cases achieved R 1 resection, 1 case achieved R 2 resection, and there were 153 cases missing surgical margin data. The tumor diameter, number of lymph nodes harvest and positive rate of intravascular tumor thrombus were 30(range, 20-45)cm, 13(range, 10-17) and 20.794%(330/1 587) in 1 761 patients. There were 1 647 patients with circumferential margin records, which showed positive in 51 cases, and the minimum distance from deep part of tumor to circumferential margin was 5(rang, 3-13)mm in 1 647 patients. There were 547 cases with distal margin records, which showed positive in 4 cases, and the distance from lower margin of tumor to distal margin was 20(10-25)mm in 547 cases. There were 1 698 patients with specimen integrity records, which showed intact specimen in 1 436 cases, fair specimen in 233 cases, poor specimen in 8 cases, unevaluated specimen in 21 cases, and there were 20 cases with rectal tube perforation. Of the 1 761 patients, cases as pathological T0 stage, Tis stage, T1 stage, T2 stage, T3 stage, T4 stage was 103, 23, 145, 515, 712, 179, respectively, and there were 4 cases of pathology that could not be evaluated and 80 cases missing pathological T staging data. Of the 1 761 patients, cases as pathological N0 stage, N1a stage, N1b stage, N1c stage, N2a stage, N2b stage was 1 117, 189, 133, 66, 109, 68, respectively, and there were 79 cases missing pathological N staging data. Of the 1 761 patients, there were 79 cases with distant metastasis, 1 591 cases without distant metastasis, and 91 cases without data of tumor metastasis. Of the 873 patients undergoing neoadjuvant therapy, there were 405 patients with tumor regression grade records including 105 cases as grade 1, 142 cases as grade 2, 91 cases as grade 3, 43 cases as grade 4, 24 cases as grade 5. Conclusions:In China, the quality of surgical specimens of taTME for rectal cancer is good with low positive rate of resection margin. It is recommended that using a formatted postoperative pathological report for good quality control of pathological report of surgical specimen.

Objective:To investigate the influencing factors of refractory anastomotic stenosis after laparoscopic intersphincteric resection (Ls-ISR) for rectal cancer and construction of nomogram prediction model.Methods:The retrospective case-control study was conducted. The clinicopatho-logical data of 495 patients who underwent Ls-ISR for rectal cancer in two medical centers, including 448 patients in Peking University First Hospital and 47 patients in Cancer Hospital Chinese Academy of Medical Sciences, from June 2012 to December 2021 were collected. There were 311 males and 184 females, aged 61 (range, 20-84)years. Observation indicators: (1) incidence of anastomotic stenosis; (2) influencing factors of refractory anastomotic stenosis after Ls-ISR; (3) construction and evaluation of nomogram prediction model for refractory anastomotic stenosis after Ls-ISR. Follow-up was conducted using outpatient examination and telephone interview to detect the incidence of postoperative anastomotic leakage and anastomotic stenosis up to August 2022. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M(range). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. Univariate and multivariate analyses were conducted using the Logistic regression model. Factors with P<0.10 in univariate analysis were included in multivariate analysis. The R software (3.6.3 version) was used to construct nomogram prediction model. The receiver operating characteristic (ROC) curve was drawn and the area under curve (AUC) was used to evaluate the efficacy of nomogram prediction model. Results:(1) Incidence of anastomotic stenosis. All 495 patients underwent Ls-ISR successfully, without conversion to laparotomy, and all patients were followed up for 47(range, 8-116)months. During the follow-up period, there were 458 patients without anas-tomotic stenosis, and 37 patients with anastomotic stenosis. Of the 37 patients, there were 15 cases with grade A anastomotic stenosis, 3 cases with grade B anastomotic stenosis and 19 cases with grade C anastomotic stenosis, including 22 cases being identified as the refractory anastomotic stenosis. Fifteen patients with grade A anastomotic stenosis were relieved after anal dilation treat-ment. Three patients with grade B anastomotic stenosis were improved after balloon dilation and endoscopic treatment. Nineteen patients with grade C anastomotic stenosis underwent permanent stoma. During the follow-up period, there were 42 cases with anastomotic leakage including 17 cases combined with refractory anastomotic stenosis, and 453 cases without anastomotic leakage including 5 cases with refractory anastomotic stenosis. There was a significant difference in the refractory anastomotic stenosis between patients with and without anastomotic leakage ( χ2=131.181, P<0.05). (2) Influencing factors of refractory anastomotic stenosis after Ls-ISR. Results of multivariate analysis showed that neoadjuvant therapy, distance from tumor to anal margin ≤4 cm, clinic N+ stage were independent risk factors of refractory anastomotic stenosis after Ls-ISR ( hazard ratio=7.297, 3.898, 2.672, 95% confidence interval as 2.870-18.550, 1.050-14.465, 1.064-6.712, P<0.05). (3) Construction and evaluation of nomogram prediction model for refractory anastomotic stenosis after Ls-ISR. Based on the results of multivariate analysis, neoadjuvant therapy, distance from tumor to anal margin and clinic N staging were included to constructed the nomogram prediction model for refractory anastomotic stenosis after Ls-ISR. Results of ROC curve showed the AUC of nomogram prediction model for refractory anastomotic stenosis after Ls-ISR was 0.739 (95% confidence interval as 0.646-0.833). Conclusions:Neoadjuvant therapy, distance from tumor to anal margin ≤4 cm, clinic N+ stage are independent risk factors of refractory anastomotic stenosis after Ls-ISR. Nomogram prediction model based on these factors can predict the incidence of refractory anastomotic stenosis after Ls-ISR.

OBJECTIVE: To compare the efficacy of plerixafor (PXF) combined with granulocyte colony-stimulating factor (G-CSF) (PXF+G-CSF) and cyclophosphamide (Cy) combined with G-CSF (Cy+G-CSF) in the mobilization of peripheral blood stem cells (PBSCs) in patients with multiple myeloma (MM). METHODS: The clinical data of 41 MM patients who underwent PBSC mobilization using PXF+G-CSF (18 cases) or Cy+G-CSF (23 cases) in Shanxi Bethune Hospital from January 2019 to December 2021 were retrospectively analyzed, including the count of collected CD34⁺ cells, acquisition success rate, failure rate, and optimal rate. The correlation of sex, age, disease type, DS staging, ISS staging, number of chemotherapy cycle, disease status before mobilization, and mobilization regimen with the collection results was analyzed, and the adverse reactions, length of hospital stay, and hospitalization costs were compared between the two mobilization regimens. RESULTS: The 41 patients underwent 97 mobilization collections, and the median number of CD34⁺ cells collected was 6.09 (0-34.07)×10⁶/kg. The acquisition success rate, optimal rate, and failure rate was 90.2%, 56.1%, and 9.8%, respectively. Univariate analysis showed that sex, age, disease type, and disease stage had no significant correlation with the number of CD34⁺ cells collected and acquisition success rate (P >0.05), but the patients with better disease remission than partial remission before mobilization were more likely to obtain higher CD34⁺ cell count (P <0.05). The PXF+G-CSF group had a larger number of CD34⁺ cells and higher acquisition success rate in the first collection than Cy+G-CSF group (both P <0.05), and had lower infection risk and shorter length of hospital stay during mobilization (both P <0.05), but the economic burden increased (P <0.05). CONCLUSION PXF+G-CSF used for PBSC mobilization in MM patients has high first acquisition success rate, large number of CD34⁺ cells, less number of collection times, and short length of hospital stay, but the economic cost is heavy.
Humans ; Antigens, CD34/metabolism* ; Cyclophosphamide/therapeutic use* ; Granulocyte Colony-Stimulating Factor/therapeutic use* ; Hematopoietic Stem Cell Mobilization/methods* ; Hematopoietic Stem Cell Transplantation ; Heterocyclic Compounds/therapeutic use* ; Multiple Myeloma/drug therapy* ; Peripheral Blood Stem Cells/metabolism* ; Retrospective Studies

Aim To investigate the effects of daidzeinDD on the proliferation and apoptosis of non-small cell lung cancer cells,with a focus on the possible role of the p53 signaling pathway in this regard. Methods CCK-8 method and flow cytometry were used to detect the effects of soy isoflavone crude extract and DD on the viability and apoptosis of HELF and H1299 cells. Gene microarray was used to detect the changes in gene expression after treatment of H1299 cells with DD. GSEA and differential analysis were used to screen the major pathways and key genes. RT-qPCR and Western blot were performed to verify the differences in mRNA and protein expression of key genesp53 and CASP9 in the major pathways. After p53 inhibitor Pifithrin-α inhibited the expression of p53,the effect of DD on p53 mRNA and protein expression levels was examined,and the proliferative effect on H1299 cells was observed. Results Soy isoflavone crude extract and DD promoted proliferation and inhibited apoptosis of normal lung cells and inhibited proliferation and promoted apoptosis of lung cancer cells. p53 signaling pathway was significantly enriched in the DD-treated groupNES=1.78,P=0.000,and the expressions of p53 and CASP9 genes were found to be significantly up-regulated in the treated group. Compared with the control group,mRNA expression of CASP9 and p53 significantly increased in both HELF and H1299 cells treated with DDP<0.05,and p53 protein expression also increased in HELF cellsP<0.05. After inhibition of p53 expression,DD significantly increased the mRNA expression of p53 in H1299 and HELF cellsP<0.05 and also markedly increased the expression of p53 protein in H1299 cellsP<0.05,and it was observed that DD inhibited the proliferation of lung cancer cells. Conclusions DD inhibits the proliferation and promotes the apoptosis of lung cancer H1299 cells,and the mechanism mainly involves the p53 signaling pathway.

Aged ; Antiviral Agents/therapeutic use* ; COVID-19/drug therapy* ; China/epidemiology* ; Cohort Studies ; Female ; Hospital Mortality ; Hospitalization ; Humans ; Male ; Middle Aged ; Patient Acuity ; SARS-CoV-2 ; Treatment Outcome

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.
China ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Prescriptions ; Public Health