The mechanism of action of mitochondrial dysfunction in the development of non-alcoholic fatty liver disease / 临床肝胆病杂志

Nonalcoholic fatty liver disease （NAFLD） has gradually become the main reason affecting human liver health， and many factors are involved in the development and progression of NAFLD. Mitochondria， as the “energy factory” of cells， plays an important role in maintaining normal physiological functions. Studies have shown that hepatic mitochondrial dysfunction promotes the development and progression of NAFLD. This article briefly introduces the latest research advances in the basic characteristics and physiological function of liver mitochondria and reviews new research findings in the association of mitochondrial dysfunction with obesity， simple fatty liver disease， and nonalcoholic steatohepatitis， in order to provide new ideas for the research on targeted mitochondrial therapy for NAFLD.

Challenges in the study of self-assembled aggregates in decoction of traditional Chinese medicine: A preliminary review / 药学学报

Decoction is the most commonly used dosage form in the clinical treatment of traditional Chinese medicine (TCM). During boiling, the violent movement of various active ingredients in TCM creates molecular forces such as hydrogen bonding, π-π stacking, hydrophobic interactions and electrostatic interactions, which results in the formation of self-assembled aggregates in decoction (SADs), including particles, gels, fibers, etc. It was found that SADs widely existed in decoction with biological activities superior to both effective monomers and their physical mixtures, providing a new idea to reveal the pharmacodynamic material basis of Chinese herbal medicine from the perspective of component interactions-phase structure. Recently, SADs have become a novel focus of research in TCM. This paper reviewed their relevant studies in recent years and found some issues to be concerned in the research, such as the polydispersity of decoction system, instability of active ingredient interactions during boiling, uncertainty of the aggregates self-assembly rules, and stability, purity, yield of the products. In this regard, some solutions and new ideas were presented for the integrated development and clinical application of SADs.

Optimization of on-site supervision strategy based on big data of quality risk in drug enterprises / 中国药房

On-site supervision is a risk-based regulatory system that requires the scientific development of supervision plans for quality risks and hidden dangers in pharmaceutical enterprises， the rational allocation of supervision resources based on their risk levels， and the implementation of classified supervision measures. In this study， the quality risk monitoring business support system is set up for pharmaceutical enterprises by establishing the quality risk expert database and quality risk monitoring index system for pharmaceutical enterprises based on the difficulty analysis of on-site drug supervision. Based on this support system， the quality risk classification method， the differentiated spot check strategy and business auxiliary visualization system are established. This support system is used to learn the risk level of pharmaceutical enterprises， so as to innovate supervision methods and optimize monitoring strategies. Taking Jiangxi Province as an example， it is verified that the support system can guide the risk assessment of sample enterprises， can improve the targeting of on-site drug supervision in the process of technical review， scheme editing， on-site implementation and comprehensive evaluation， and can effectively improve the quality and efficiency of supervision.

Definition， Framework and Connotation of Modernization of Traditional Chinese Medicine Theories / 中医杂志

The modernization of traditional Chinese medicine （TCM） theories is not only a prerequisite for the modernization of TCM but also a way to deal with the external environment and the difficulties of its development. The modernization of TCM is based on the premise of maintaining its own characteristics and advantages， and along with the progress of modern science and technology， the entire TCM has undergone new changes and improvements from theory to practice， and has become a scientific system with modern scientific level that adapts to the needs of the times. In the context of the unprecedented profound changes in contemporary TCM academics， this paper puts forward the definition of modernization of TCM theory and argues that the modernized theoretical system of TCM should maintain originality to build the foundation of TCM inheritance， clarify the frontier of the discipline and establish the conceptual system， form an open network to be compatible with multi-disciplinary interaction， incorporate the falsification and establish self-renewal system， creatively transform and innovatively develop， and modernize the interpretation and update the discourse system.

Intervention of Traditional Chinese Medicine in NLRP3 Signaling Pathway for Prevention and Treatment of Alzheimer's Disease： A Review / 中国实验方剂学杂志

Alzheimer's disease （AD） is a neurodegenerative disease often characterized by cognitive impairment in clinical practice. The main pathogenesis includes β amyloid protein （Aβ） excessive deposition， neuroinflammatory response， Tau protein hyperphosphorylation， and other factors， and currently only a few chemical drugs have been approved for clinical treatment of AD. The mechanism of action is relatively single， so it is imperative to find new treatment strategies. Traditional Chinese medicine theory believes that the loss of nourishment in the brain and marrow， as well as the loss of vital energy， is the internal mechanisms underlying the occurrence and development of AD， which runs through the entire treatment process. The pathogenesis of AD is closely related to the inflammasome signaling pathway of nucleotide binding oligomerization domain-like receptor protein 3 （NLRP3）. Activating the NLRP3 signaling pathway increases neuroinflammatory response， intervenes in microglial polarization， and regulates Aβ sedimentation， cellular autophagy， brain homeostasis， etc. This article takes the NLRP3 signaling pathway as the starting point to sort out and summarize the upstream and downstream targets under the AD mechanism in the past five years， as well as the research on the NLRP3 signal pathway targets with the participation of the relevant traditional Chinese medicine compounds， such as Danggui Shaoyaosan， modified Shuyu Wan， Qingxin Kaiqiao prescription， Kaixin San， Jiedu Yizhi prescription， and modified Buwang San， traditional Chinese medicine monomer extracts， such as silibinin， Lycium barbarum polysaccharides， liquiritigenin， salidroside， baicalin， cinnamaldehyde， betaine， acacetin， and Hericium erinaceus， and acupuncture and moxibustion. It also reviews the latest achievements in the prevention and treatment of AD. This study provides ideas and directions for in-depth research on the prevention and treatment of cognitive dysfunction related diseases with traditional Chinese medicine.

Effect of Rhei Radix et Rhizoma and Eupolyphaga Steleophaga on liver protection mechanism based on pharmacokinetics and metabonomics / 中草药·英文版

OBJECTIVE@#Based on metabonomics technology of high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) and hydrogen nuclear magnetic resonance spectroscopy (1H NMR), the pharmacokinetic characteristics and therapeutic mechanism of Rhei Radix et Rhizoma (RhRR, Dahuang in Chinese), Eupolyphaga Steleophaga (EuS, Tubiechong in Chinese) combined with RhRR acting on acute liver injury were explored.@*METHODS@#Models of acute liver injury were established, and the pharmacokinetic methods of five components of RhRR-EuS in rats were found by HPLC-MS/MS. The liver tissues of different groups of mice were analyzed by 1H NMR spectroscopy combined with multivariate statistical analysis to investigate the metabolomics of RhRR-EuS and RhRR.@*RESULTS@#Pharmacokinetic results showed there were different levels of bimodal phenomenon in different groups, and the absorption of free anthraquinone in RhRR increased after compatibility with EuS. In addition, the pathological state of acute liver injury in rats can selectively promote the absorption of emodin, chrysophanol, physcion and aloe emodin. Through 15 differential metabolites in the liver tissue of acute liver injury mice, it was revealed that RhRR-EuS and RhRR could protect the liver injury by regulating the metabolism of glutamine and glutamic acid, alanine, aspartic acid and glutamic acid, and phosphoinositide. However, the regulation of RhRR was weaker than that of RhRR-EuS.@*CONCLUSION@#For the first time, we studied the pharmacokinetics and metabolomics differences of RhRR-EuS and RhRR in rats and mice with acute liver injury, in order to provide theoretical reference for clinical treatment of liver disease by DHZCP.

Identification of overlay differentially expressed genes in both rats and goats with blast lung injury through comparative transcriptomics / 中华创伤杂志(英文版)

PURPOSE@#To identify the potential target genes of blast lung injury (BLI) for the diagnosis and treatment.@*METHODS@#This is an experimental study. The BLI models in rats and goats were established by conducting a fuel-air explosive power test in an unobstructed environment, which was subsequently validated through hematoxylin-eosin staining. Transcriptome sequencing was performed on lung tissues from both goats and rats. Differentially expressed genes were identified using the criteria of q ≤ 0.05 and |log2 fold change| ≥ 1. Following that, enrichment analyses were conducted for gene ontology and the Kyoto Encyclopedia of Genes and Genomes pathways. The potential target genes were further confirmed through quantitative real-time polymerase chain reaction and enzyme linked immunosorbent assay.@*RESULTS@#Observations through microscopy unveiled the presence of reddish edema fluid, erythrocytes, and instances of focal or patchy bleeding within the alveolar cavity. Transcriptome sequencing analysis identified a total of 83 differentially expressed genes in both rats and goats. Notably, 49 genes exhibited a consistent expression pattern, with 38 genes displaying up-regulation and 11 genes demonstrating down-regulation. Enrichment analysis highlighted the potential involvement of the interleukin-17 signaling pathway and vascular smooth muscle contraction pathway in the underlying mechanism of BLI. Furthermore, the experimental findings in both goats and rats demonstrated a strong association between BLI and several key genes, including anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4, which exhibited up-regulation.@*CONCLUSIONS@#Anterior gradient 2, ankyrin repeat domain 65, bactericidal/permeability-increasing fold containing family A member 1, bactericidal/permeability-increasing fold containing family B member 1, and keratin 4 hold potential as target genes for the prognosis, diagnosis, and treatment of BLI.

Association of outdoor artificial light at night exposure with overweight and obesity among children and adolescents aged 9 to 18 years in China / 北京大学学报(医学版)

OBJECTIVE@#To analyze the association between outdoor artificial light-at-night (ALAN) exposure and overweight and obesity among children and adolescents aged 9 to 18 years in China.@*METHODS@#Using follow-up data of 5 540 children and adolescents aged 9 to 18 years conducted from November 2019 to November 2020 in eight provinces of China, latitude and longitude were determined based on school addresses, and the mean monthly average nighttime irradiance at the location of 116 schools was extracted by the nearest neighbor method to obtain the mean outdoor ALAN exposure [unit: nW/(cm2·sr)] for each school. Four indicators of overweight and obesity outcomes were included: Baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence. Mixed effects Logistic regression was used to explore the association between ALAN exposure levels (divided into quintiles Q1-Q5) and baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence. In addition, a natural cubic spline function was used to explore the exposure response association between ALAN exposure (a continuous variable) and the outcomes.@*RESULTS@#The prevalence of baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence among the children and adolescents in this study were 21.6%, 16.3%, 2.9% and 12.8%, respectively. The OR value for the association between ALAN exposure and baseline overweight and obesity was statistically significant when ALAN exposure levels reached Q4 or Q5, 1.90 (95%CI: 1.26-2.86) and 1.77 (95%CI: 1.11-2.83), respectively, compared with the children and adolescents in the Q1 group of ALAN exposure. Similar to the results for baseline overweight and obesity, the OR values for the association with persistent overweight and obesity were 1.89 (95%CI: 1.20-2.99) and 1.82 (95%CI: 1.08-3.06) when ALAN exposure levels reached Q4 or Q5, respectively, but none of the OR values for the association between ALAN and overweight and obesity progression and overweight and obesity incidence were statistically significant. Fitting a natural cubic spline function showed a non-linear trend between ALAN exposure and persistent overweight and obesity.@*CONCLUSION@#There is a positive association between ALAN exposure and overweight and obesity in children and adolescents, and the promotion of overweight obesity in children and adolescents by ALAN tends to have a cumulative effect rather than an immediate effect. In the future, while focusing on the common risk factors for overweight and obesity in children and adolescents, there is a need to improve the overweight and obesity-causing nighttime light exposure environment.

Perioperative management and operative treatment of malignant tumor of anal canal merging severe abdominal protuberance / 中华胃肠外科杂志

Objective: To report the perioperative management and robot-assisted minimally invasive surgery results of one case with malignant tumor of anal canal combined with severe abdominal distention. Methods: A 66-year-old male suffer from adenocarcinoma of anal canal (T3N0M0) with megacolon, megabladder and scoliosis. The extreme distention of the colon and bladder result in severe abdominal distention. The left diaphragm moved up markedly and the heart was moved to the right side of the thoracic cavity. Moreover, there was also anal stenosis with incomplete intestinal obstruction. Preoperative preparation: fluid diet, intravenous nutrition and repeated enema to void feces and gas in the large intestine 1 week before operation. Foley catheter was placed three days before surgery and irrigated with saline. After relief of abdominal distention, robotic-assisted abdominoperineal resection+ subtotal colectomy+colostomy was performed. Results: Water intake within 6 hours post-operatively; ambulance on Day 1; anal passage of gas on Day 2; semi-fluid diet on Day 3; safely discharged on Day 6. Conclusion: Robotic-assisted minimally invasive surgery is safe and feasible for patients with malignant tumor of anal canal combined with severe abdominal distention after appropriate and effective preoperative preparation to relieve abdominal distention.

Classification system of radical surgery for rectal cancer based on membrane anatomy / 中华胃肠外科杂志

Because the classification system of radical surgery for rectal cancer has not been established, it is impossible to select the appropriate surgical method according to the clinical stage of the tumor. In this paper, we explained the theory of " four fasciae and three spaces " of pelvic membrane anatomy and then combined this theory with the membrane anatomical basis of Querleu-Morrow classification for radical cervical cancer resection. Based on this theory and the membrane anatomy of Querleu-Morrow classification of radical cervical cancer resection, we proposed a new classification system of radical rectal cancer surgery based on membrane anatomy according to the lateral lymph node dissection range of the rectum. This system classifies the surgery into four types (ABCD) and defines corresponding subtypes based on whether the autonomic nerve was preserved. Among them, type A surgery is total mesorectal excision (TME) with urogenital fascia preservation, type B surgery is classical TME, type C surgery is extended TME, and type D surgery is lateral extended resection. This classification system unifies the anatomical terminology of the pelvic membrane, validates the feasibility of using the " four fasciae and three fascial spaces " theory to classify rectal cancer surgery, and lays the theoretical foundation for the future development of a unified and standardized classification of radical pelvic tumor surgery.

Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH) / 中华胃肠外科杂志

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.

Cirrhosis recompensation: clinical complications / 中华肝脏病杂志

Cirrhosis recompensation is a new concept proposed in recent years to describe the clinical stage of the overall reversal of patients with decompensated cirrhosis. The recompensation of cirrhosis is discussed here from the perspective of clinical complications.

Clinical study of serum human-βeta-defensin-1 level for evaluating short-term prognosis in patients with acute-on-chronic liver failure / 中华肝脏病杂志

Objective: To evaluate the diagnostic value of serum human-βeta-defensin-1 level (HBD-1) for short-term (28-day) prognosis in patients with acute-on-chronic liver failure (ACLF). Methods: Fifty cases diagnosed with ACLF were selected. 20 cases with decompensated cirrhosis and 20 cases with compensated cirrhosis who were admitted at the same time were included. Age, gender, serum HBD-1 level, C-reactive protein (CRP), procalcitonin (PCT), neutrophil count/lymphocyte ratio (NLR), blood routine, coagulation function, liver function, kidney function, and other indicators from the three groups of patients were collected. Patients with ACLF were screened for indicators related to the short-term (28-day) prognosis. Patients were divided into an improvement group and a worsening group according to the 28-day disease outcome. The serum HBD-1 level and other above-mentioned indicators were compared between the two patient groups. The receiver operating characteristic (ROC) curve was used to analyze the diagnostic efficacy of serum HBD-1 levels for short-term prognosis in patients with ACLF. PCT, NLR, and prothrombin activity (PTA) application as a mono indicator and HBD-1 in combination with NLR, PCT, and PTA were compared to evaluate diagnostic efficacy for short-term prognosis in patients with ACLF. The intergroup mean of measurement data was determined using a t-test or analysis of variance. χ (2) test was used for comparison of count data. Spearman's rank correlation analysis was used for correlation analysis. Results: There was no statistically significant difference in age and gender among the three groups: ACLF, decompensated cirrhosis, and compensated cirrhosis (P > 0.05). The expression levels of serum HBD-1 in the ACLF group, decompensated cirrhosis group, and compensated cirrhosis group were (319.1 ± 44.4) ng/ml, (264.5 ± 46.5) ng/ml and (240.1 ± 35.4) ng/ml, respectively, while the ACLF group expression levels were significantly increased, with statistical significance (P < 0.01).The serum HBD-1 level was significantly higher in the ACLF worsening group (346.2 ± 43.6) ng/ml than that in the improvement group (308.5 ± 40.6) ng/ml, and the difference was statistically significant (P < 0.05). Correlation analysis showed that HBD-1, NLR, PCT, prothrombin time (PT), and international standardized ratio (INR) were negatively correlated with the 28-day disease outcome (improvement) of patients (P < 0.05). PTA was positively correlated with 28-day disease outcome (improvement) (P < 0.05). The area under the receiver operating characteristic curve (AUC) for evaluating HBD-1's diagnostic efficacy for short-term prognosis in patients with ACLF was 0.774, with a sensitivity of 0.750, a specificity of 0.786, and a cut-off point of 337.96 ng/ml. PCT, NLR, and PTA had greater diagnostic efficacy. HBD-1 combined with PTA had the highest diagnostic efficacy, with an AUC of 0.802, a sensitivity of 0.778, and a specificity of 0.786. The diagnostic efficacy of HBD-1+PCT, HBD-1+NLR and HBD-1, PCT, and NCR was superior to PTA mono. Conclusion: The serum HBD-1 level gradually increases with the aggravation of liver function injury and is negatively correlated with the short-term prognosis in patients with ACLF. Serum HBD-1 level has high sensitivity and specificity in predicting short-term prognosis in patients with ACLF, and its diagnostic efficacy is superior to that of PCT, NLR, and PTA. The combined application of HBD-1 and PTA has higher diagnostic efficacy; however, when the serum HBD-1 level is greater than 337.96ng/ml, it indicates poor prognosis in patients.

Analysis of risk factors for depth of invasion and angiolymphatic invasion for circumferential superficial esophageal squamous cell carcinoma and precancerous lesion / 中华肿瘤杂志

Objective: To analyze clinicopathological features of circumferential superficial esophageal squamous cell carcinoma and precancerous lesions and investigate the risk factors for deep submucosal invasion and angiolymphatic invasion retrospectively. Methods: A total of 116 cases of esophageal squamous epithelial high-grade intraepithelial neoplasia or squamous cell carcinoma diagnosed by gastroscopy, biopsy pathology and endoscopic resection pathology during November 2013 to October 2021 were collected, and their clinicopathological features were analyzed. The independent risk factors of deep submucosal invasion and angiolymphatic invasion were analyzed by logistic regression model. Results: The multivariate logistic regression analysis showed that drinking history (OR=3.090, 95% CI: 1.165-8.200; P<0.05), The AB type of intrapapillary capillary loop (IPCL) (OR=11.215, 95% CI: 3.955-31.797; P<0.05) were the independent risk factors for the depth of invasion. The smoking history (OR=5.824, 95% CI: 1.704-19.899; P<0.05), the presence of avascular area (AVA) (OR=3.393, 95% CI: 1.285-12.072; P<0.05) were the independent factors for the angiolymphatic invasion. Conclusions: The risk of deep submucosal infiltration is greater for circumferential superficial esophageal squamous cell carcinoma patients with drinking history and IPCL type B2-B3 observed by magnifying endoscopy, while the risk of angiolymphatic invasion should be vigilant for circumferential superficial esophageal squamous cell carcinoma patients with smoking history and the presence of AVA observed by magnifying endoscopy. Ultrasound endoscopy combined with narrowband imagingand magnification endoscopy can improve the accuracy of preoperative assessment of the depth of infiltration of superficial squamous cell carcinoma and precancerous lesions and angiolymphaticinvasion in the whole perimeter of the esophagus, and help endoscopists to reasonably grasp the indications for endoscopic treatment.

Effects of Tanreqing Injection on ICU Mortality among ICU Patients Receiving Mechanical Ventilation: Time-Dependent Cox Regression Analysis of A Large Registry / 中国结合医学杂志

OBJECTIVE@#To assess whether the use of Tanreqing (TRQ) Injection could show improvements in time to extubation, intensive care unit (ICU) mortality, ventilator-associated events (VAEs) and infection-related ventilator associated complication (IVAC) among patients receiving mechanical ventilation (MV).@*METHODS@#A time-dependent cox-regression analysis was conducted using data from a well-established registry of healthcare-associated infections at ICUs in China. Patients receiving continuous MV for 3 days or more were included. A time-varying exposure definition was used for TRQ Injection, which were recorded on daily basis. The outcomes included time to extubation, ICU mortality, VAEs and IVAC. Time-dependent Cox models were used to compare the clinical outcomes between TRQ Injection and non-use, after controlling for the influence of comorbidities/conditions and other medications with both fixed and time-varying covariates. For the analyses of time to extubation and ICU mortality, Fine-Gray competing risk models were also used to measure competing risks and outcomes of interest.@*RESULTS@#Overall, 7,685 patients were included for the analyses of MV duration, and 7,273 patients for the analysis of ICU mortality. Compared to non-use, patients with TRQ Injection had a lower risk of ICU mortality (Hazards ratios (HR) 0.761, 95% CI, 0.581-0.997), and was associated with a higher hazard for time to extubation (HR 1.105, 95% CI, 1.005-1.216), suggesting a beneficial effect on shortened time to extubation. No significant differences were observed between TRQ Injection and non-use regarding VAEs (HR 1.057, 95% CI, 0.912-1.225) and IVAC (HR 1.177, 95% CI, 0.929-1.491). The effect estimates were robust when using alternative statistic models, applying alternative inclusion and exclusion criteria, and handling missing data by alternative approaches.@*CONCLUSION@#Our findings suggested that the use of TRQ Injection might lower mortality and improve time to extubation among patients receiving MV, even after controlling for the factor that the use of TRQ changed over time.

Choice of medical treatment for renal colic: A survey of Chinese urologists / 北京大学学报(医学版)

OBJECTIVE@#To investigate the status quo of recognition and management of renal colic among urological surgeons in China.@*METHODS@#From November 2021 to March 2022, 725 urological surgeons in China were surveyed in the form of a questionnaire, including their province, hospital grade, professional title, the number of patients with renal colic treated per week, the preferred drugs and the cognition of the disease. This study was approved by the Medical Ethics Committee of Peking University People's Hospital, and all respondents completed informed consent online.@*RESULTS@#During November 2021 and March 2022, urological surgeons across China were surveyed in the form of a questionnaire, and the reliability and validity of the questionnaire were verified before the study was carried out. In the study, 720 valid questionnaires were collected (accounting for 99.31% of the total number), in which 42.4% of the doctors' preferred drugs were non-steroidal anti-inflammatory drugs (NSAIDs), and 40.0% of the doctors' preferred antispasmodic drugs. Opioids were the first choice of 11.0% of the physicians and other treatments were preferred by 6.6% of physicians. In addition, 61.1% of the doctors thought that the mechanism of renal colic was elevated prostaglandin, 32.2% thought it was ureteral spasm, 5.0% thought it was calculi irritation, and 1.7% thought the mechanism was unclear. The doctor of the cognition of the generation mechanism of renal colic pain had a significant influence on the preferred treatment option (χ2=54.399, P < 0.001) that the "elevated prostaglandins" doctor more often preferred NSAIDs than the doctor who thought cramps and ureter stones caused renal colic (51.6% vs. 28.0%, χ2=34.356, P < 0.001;51.6% vs. 19.4%, χ2=13.759, P < 0.001). In addition, hospital class, physician title, and the number of weekly consultations by physicians influenced the choice of medications for renal colic (P < 0.05), tertiary hospitals, middle and senior professional titles and weekly patients with renal colic > 8 cases generally preferred NSAIDs.@*CONCLUSION@#There are deficiencies in the cognition and drug treatment of renal colic among urological surgeons in China. The choice of the preferred drug was related to the doctor's cognition of the disease, the grade of the hospital, the doctor's professional title and the weekly treatment volume.

Effects of delayed ureteral stents removal during the COVID-19 pandemic on the quality of life and psychological status of postoperative patients with urinary calculi / 北京大学学报(医学版)

OBJECTIVE@#To explore the impacts of delayed ureteral stent removal on the quality of life (QoL) and mental health of urinary calculi postoperative patients due to the corona virus disease 2019(COVID-19) pandemic.@*METHODS@#The demographic and clinical data of patients with ureteral stent placement after urinary endoscopic lithotripsy and returned to Peking University People's Hospital for stent removal from December 2019 to June 2020 were collected. Ureteral stent symptoms questionnaire (USSQ) score and the outcome 20-item self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were collected to estimate the QoL and mental status. The USSQ consisted of 44 questions in 6 domains (including urinary symptom, physical pain, general health, work performance, sexual function, and ureteral stent related infection). For most questions in each domain, its score was a five-point Likert-type scale from 1 to 5, and a small proportion of questions was quantified by 1 to 4 or 1 to 7 scale. SAS and SDS both contained 20 questions used to assess a patient's level of anxiety and depression. Its scoring for each item was on a four-point Likert-type scale from 1 to 4. A total score (ranging from 20 to 80) was the main statistical indicator. The level of clinical anxiety and depression was quantified by using standard scores (total score multiplied by 1.25 to produce integers). And the multi-group structural equation model was constructed by analysis of moment structure (AMOS) analysis.@*RESULTS@#Overall, 71 patients were enrolled for analysis. It was found that the median duration of ureteral stent time differed significantly between the control and delayed groups for 32 (30, 33) d and 94.5 (88, 103) d, respectively. The delayed group resulted in higher scores in the USSQ multidimensional, which included urinary symptoms, general health, work performance and ureteral stent related infections. Anxiety and depression were also significantly serious in the delayed group than in the control group. A longer indwelling time of a ureteral stent could exacerbate the effects of urinary symptoms and physical pain on work performance (P=0.029 < 0.05). Among them, the patients with severe urinary symptoms leading to poor work performance were most significantly affected by prolonged ureteral stent duration time (CR=2.619>1.96).@*CONCLUSION@#Patients with delayed ureteral stent removal due to the COVID-19 had resulted in worse QoL and mental status. Stents related symptoms are more severe in patients with higher anxiety and depression degree during COVID-19. To improve the QoL and mental health of patients after urinary calculi surgery during COVID-19, it is still not recommended to prolong the stent duration time or corresponding intervention measures should be taken.

Preliminary Study on the Effect of Silencing Nucleostemin Com- bined with Rapamycin on Autophagy and Apoptosis of HL-60 Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effects of knocking down nucleostemin ( NS) combined with rapamycin (RAPA) on autophagy and apoptosis in HL-60 cells , and to explore its role in HL-60 cells .@*METHODS@#The expression of NS protein was detected using Western blot , after transfection of HL-60 cells was achieved by the recombinant lentviral vector NS -RNAi-GV248 . Flow cytometry was used to detect changes in cells apoptosis after NS silencing/ rapamycin for 24 , 48 hours , and the expressions of NS , LC3 , p62 , BCL-2 and Bax proteins in cells were detected by Western blot.@*RESULTS@#The expression of NS in HL-60 cells was successfully down-regulated by recombinant lentiviral vector. After treatment with rapamycin for 24 and 48 h , the apoptosis rate of cells in each group increased (P < 0.05) , and the apoptosis was more obvious at 48 hours . Compared with the NS silencing group or rapamycin group , after treated with NS down-regulation combined with rapamycin for 48 hours , the apoptosis of HL-60 cells was significantly increased ( P < 0.05 ) , LC3 -II/LC3 -I ratio was significantly increased ( P < 0.05 ) , p62 protein expression was significantly decreased (P < 0.05) , and BCL-2/Bax ratio was significantly decreased ( P < 0.05) .@*CONCLUSION@#NS down-regulation combined with rapamycin can enhance the apoptosis and autophagy of HL-60 cells , and the induction of apoptosis of HL-60 cells may be related to the expression of BCL-2 and Bax proteins .

Advances on pentraxin 3 in osteoporosis and fracture healing / 中国骨伤

Pentaxin 3 (PTX3), as a multifunctional glycoprotein, plays an important role in regulating inflammatory response, promoting tissue repair, inducing ectopic calcification and maintaining bone homeostasis. The effect of PTX3 on bone mineral density (BMD) may be affected by many factors. In PTX3 knockout mice and osteoporosis (OP) patients, the deletion of PTX3 will lead to decrease of BMD. In Korean community "Dong-gu study", it was found that plasma PTX3 was negatively correlated with BMD of femoral neck in male elderly patients. In terms of bone related cells, PTX3 plays an important role in maintaining the phenotype and function of osteoblasts (OB) in OP state;for osteoclast (OC), PTX3 in inflammatory state could stimulate nuclear factor κ receptor activator of nuclear factor-κB ligand (RANKL) production and its combination with TNF-stimulated gene 6(TSG-6) could improve activity of osteoclasts and promote bone resorption;for mesenchymal stem cells (MSCs), PTX3 could promote osteogenic differentiation of MSCs through PI3K/Akt signaling pathway. In recent years, the role of PTX3 as a new bone metabolism regulator in OP and fracture healing has been gradually concerned by scholars. In OP patients, PTX3 regulates bone mass mainly by promoting bone regeneration. In the process of fracture healing, PTX3 promotes fracture healing by coordinating bone regeneration and bone resorption to maintain bone homeostasis. In view of the above biological characteristics, PTX3 is expected to become a new target for the diagnosis and treatment of OP and other age-related bone diseases and fracture healing.

The incidence of intestinal colonization of carbapenem-resistant Enterobacterales and its risk factors for bloodstream infection / 中华检验医学杂志

Objective:The aim of this study was to determine the colonization rate of carbapenem-resistant Enterobacterales (CRE) and identify the proportion and risk factors for bloodstream infection.Methods:This was a retrospective study conducted at the Department of Clinical Laboratory, Peking University People′s Hospital from January 2018 to December 2021. A total of 4 993 patients underwent rectal swab CRE screening for CRE, of which 137 were found to be positive. Clinical and laboratory data of the positive patients were collected, and the following parameters were analyzed: the positive rate of CRE screening in high-risk population, the species of colonized bacteria, antimicrobial resistance and the risk factors of CRE bloodstream infection in colonized patients. Statistical analysis was performed using SPSS 26.0 software. Univariate analysis was conducted using the chi-square (χ 2) test, while multivariate analysis was performed using binary logistic regression. The results were expressed as relative risk (odds ratio, OR) and 95% confidence interval ( CI). A significance level of 0.05 was considered statistically significant. The drug resistance rate of pathogen was analyzed by WHONET 5.6 software. Results:During the study period, a total of 4 991 patients who underwent rectal swab screening were eligible for inclusion, of which 137 patients were screened positive, resulting in a positive rate of 2.7% (137/4 991). The positive rates were higher in the intensive care ward and hematology ward, with rates of 5.5% (27/493) and 3.3% (109/3 321), respectively. A total of 145 colonization strains were isolated from patients with positive CRE screening, including 63 strains of Klebsiella pneumoniae (43.4%, 63/145), 52 strains of Escherichia coli (35.9%, 52/145), 16 strains of Enterobacter cloacae (11.0%, 16/145) and 14 strains of other Enterobacterales (9.7%, 14/145). The metal β-lactamase production type was the main component of CRE positive colonizing bacteria. The antimicrobial resistance of 145 strains to 22 antibacterial agents revealed that amikacin and tigacycline were the most sensitive. Among 137 CRE screening-positive patients, 14 (10.2%, 14/137) developed bloodstream infection. The isolated pathogenic bacteria included 10 Klebsiella pneumoniae strains and 4 Escherichia coli strains, with a predominant serine carbapenemase producing. Notably, the enzyme type and antimicrobial resistance of the bloodstream infection isolates in the same patient were highly consistent with those of the previous screening strains. Comparison was made between patients with positive CRE screening and those with CRE conversion to bloodstream infection. The unifactor analysis revealed significant differences in surgical history, neutropenia, hematopoietic stem cell transplantation, history of antibiotic use before rectal swab screening, screening within 48 hours after admission, and serine carbapenemase production by strains ( P<0.05). The multivariate analysis indicated that surgical history ( OR 24.659, 95% CI 2.540-239.411, P=0.006) and neutropenia ( OR 93.796, 95% CI 6.294-1 397.804, P=0.001) remained significantly associated with the risk of CRE bloodstream infection ( P<0.05). Conclusions:The CRE colonization rate was low in our hospital, but the proportion of patients with positive screening converted to bloodstream infection was high. Surgical history and neutropenia are risk factors for bloodstream infection transmission. Thus, it is essential to enhance monitoring in high-risk areas and susceptible patients.