Classification of bladder cancer based on immune cell infiltration and construction of a risk prediction model for prognosis / 浙江大学学报·医学版

OBJECTIVES@#To classify bladder cancer based on immune cell infiltration score and to construct a risk assessment model for prognosis of patients.@*METHODS@#The transcriptome data and data of breast cancer patients were obtained from the TCGA database. The single sample gene set enrichment analysis was used to calculate the infiltration scores of 16 immune cells. The classification of breast cancer patients was realized by unsupervised clustering, and the sensitivity of patients with different types to immunotherapy and chemotherapy was analyzed. The key modules significantly related to the infiltration of key immune cells were identified by weighted correlation network analysis (WGCNA), and the key genes in the modules were extracted. A risk scoring model and a nomogram for risk assessment of prognosis for bladder cancer patients were constructed and verified.@*RESULTS@#The immune cell infiltration scores of normal tissues and tumor tissues were calculated, and B cells, mast cells, neutrophils, T helper cells and tumor infiltrating lymphocytes were determined to be the key immune cells of bladder cancer. Breast cancer patients were clustered into two groups (Cluster 1 and Custer 2) based on immune cell infiltration scores. Compared with patients with Cluster 1, patients with Cluster 2 were more likely to benefit from immunotherapy (P<0.05), and patients with Cluster 2 were more sensitive to Enbeaten, Docetaxel, Cyclopamine, and Akadixin (P<0.05). WGCNA screened out 35 genes related to key immune cells, and 4 genes (GPR171, HOXB3, HOXB5 and HOXB6) related to the prognosis of bladder cancer were further screened by LASSO Cox regression. The areas under the ROC curve (AUC) of the bladder cancer prognosis risk scoring model based on these 4 genes to predict the 1-, 3- and 5-year survival of patients were 0.735, 0.765 and 0.799, respectively. The nomogram constructed by combining risk score and clinical parameters has high accuracy in predicting the 1-, 3-, and 5-year overall survival of bladder cancer patients.@*CONCLUSIONS@#According to the immune cell infiltration score, bladder cancer patients can be classified. And the bladder cancer prognosis risk scoring model and nomogram based on key immune cell-related genes have high accuracy in predicting the prognosis of bladder cancer patients.

Electroacupuncture Promotes Functional Recovery after Facial Nerve Injury in Rats by Regulating Autophagy via GDNF and PI3K/mTOR Signaling Pathway / 中国结合医学杂志

OBJECTIVE@#To explore the mechanism of electroacupuncture (EA) in promoting recovery of the facial function with the involvement of autophagy, glial cell line-derived neurotrophic factor (GDNF), and phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) signaling pathway.@*METHODS@#Seventy-two male Sprague-Dawley rats were randomly allocated into the control, sham-operated, facial nerve injury (FNI), EA, EA+3-methyladenine (3-MA), and EA+GDNF antagonist groups using a random number table, with 12 rats in each group. An FNI rat model was established with facial nerve crushing method. EA intervention was conducted at Dicang (ST 4), Jiache (ST 6), Yifeng (SJ 17), and Hegu (LI 4) acupoints for 2 weeks. The Simone's 10-Point Scale was utilized to monitor the recovery of facial function. The histopathological evaluation of facial nerves was performed using hematoxylin-eosin (HE) staining. The levels of Beclin-1, light chain 3 (LC3), and P62 were detected by immunohistochemistry (IHC), immunofluorescence, and reverse transcription-polymerase chain reaction, respectively. Additionally, IHC was also used to detect the levels of GDNF, Rai, PI3K, and mTOR.@*RESULTS@#The facial functional scores were significantly increased in the EA group than the FNI group (P<0.05 or P<0.01). HE staining showed nerve axons and myelin sheaths, which were destroyed immediately after the injury, were recovered with EA treatment. The expressions of Beclin-1 and LC3 were significantly elevated and the expression of P62 was markedly reduced in FNI rats (P<0.01); however, EA treatment reversed these abnormal changes (P<0.01). Meanwhile, EA stimulation significantly increased the levels of GDNF, Rai, PI3K, and mTOR (P<0.01). After exogenous administration with autophagy inhibitor 3-MA or GDNF antagonist, the repair effect of EA on facial function was attenuated (P<0.05 or P<0.01).@*CONCLUSIONS@#EA could promote the recovery of facial function and repair the facial nerve damages in a rat model of FNI. EA may exert this neuroreparative effect through mediating the release of GDNF, activating the PI3K/mTOR signaling pathway, and further regulating the autophagy of facial nerves.

The evolution and application progress of non-modified drug target discovery CETSA technology / 药学学报

Understanding the research methods for drug protein targets is crucial for the development of new drugs, clinical applications of drugs, drug mechanisms, and the pathogenesis of diseases. Cellular thermal shift assay (CETSA), a target research method without modification, has been widely used since its development. Now, there are various CETSA-based technology combinations, such as mass spectrometry-based cellular thermal shift assay (MS-CETSA), isothermal dose response-cellular thermal shift assay (ITDR-CETSA), amplified luminescent proximity homogeneous assay-cellular thermal shift assay (Alpha-CETSA), etc., which combine their respective advantages and further expand the application scope of CETSA. These technologies are suitable for the entire drug development chain, from drug screening to monitoring the target binding and off-target toxicity of drugs in patients. Based on the author's research experience, this paper reviews the principles of CETSA and related binding technologies, their application in target discovery, and the progress of data processing and analysis in recent years, aiming to provide reference and reference for the further application of CETSA.

Recent advances in small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase / 药学学报

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Investigation of the current situation of pharmaceutical clinics in medical institutions in China / 中国药房

OBJECTIVE To investigate the current situation of pharmaceutical clinic service in medical institutions in China and provide experience and suggestions for promoting the development of pharmaceutical clinics. METHODS Questionnaire survey was used to investigate the development of pharmaceutical clinics in medical institutions of 31 provinces （autonomous regions and municipalities directly under the central government） in March to April 2023， and the descriptive analysis was conducted. The regression analysis was carried out for the influential factors of pharmaceutical clinic service. RESULTS A total of 1 368 questionnaires were distributed in this survey and 1 304 valid questionnaires were collected with the effective response rate of 95.32%. A total of 463 medical institutions carried out pharmaceutical clinic service， the rate of which was 35.51% （463/1 304）； the rates of pharmaceutical clinics in tertiary， secondary， primary and other medical institutions were 52.80%， 17.18% and 5.88%， respectively. The frequency of opening pharmaceutical clinics was 3.17 days per week on average， with an average of 5.99 visiting pharmacists in each medical institution. Among the visiting pharmacists， clinical pharmacists accounted for the vast majority （88.68%， 2 459/2 773）. There were various categories of pharmaceutical clinics， including joint clinics and pharmacist-independent clinics； among pharmacist-independent clinics， pharmaceutical specialty/specialty disease clinics were the main ones， accounting for 89.72% of the total number of pharmaceutical clinics. The value of pharmacists in pharmaceutical clinics was manifested in various forms， among which the proportion of medical institutions charging pharmaceutical clinics was 10.80%. The main experiences in developing pharmaceutical clinics were to attach importance to discipline construction and personnel training. The main difficulties in developing pharmaceutical clinics were low compensation levels and a shortage of talent.The number of clinical pharmacists， the number of visiting pharmacists in pharmaceutical clinics and additional compensation were positively correlated with the amount of pharmaceutical clinic services（P＜0.05）. CONCLUSIONS In recent years， pharmaceutical clinics have made significant progress； in the future， it is still necessary to further strengthen discipline construction and talent cultivation， pay attention to the value embodiment of pharmacists， to promote the healthy development of pharmaceutical clinics.

Application value of liver/spleen CT value， controlled attenuation parameter， and magnetic resonance imaging-proton density fat fraction in chronic hepatitis B patients with hepatic steatosis / 临床肝胆病杂志

ObjectiveTo investigate the application value of liver/spleen CT value （CTL/S）， controlled attenuation parameter （CAP）， and magnetic resonance imaging-proton density fat fraction （MRI-PDFF） in chronic hepatitis B （CHB） patients with hepatic steatosis. MethodsA retrospective analysis was performed for the clinical data of 213 CHB patients who underwent liver CT， CAP， and MRI-PDFF examinations in Affiliated Hospital of Yan’an University from October 2018 to December 2022. According to MRI-PDFF， the 213 patients were divided into CHB group with 111 patients （MRI-PDFF<5%） and CHB+hepatic steatosis group with 102 patients （MRI-PDFF≥5%）， among whom there were 69 patients with mild hepatic steatosis and 33 patients with moderate to severe hepatic steatosis. The independent-samples t test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The Bland-Altman plot was used to evaluate the consistency in MRI-PDFF measurement between two physicians. The Spearman’s correlation coefficient was used to analyze the correlation between CTL/S and MRI-PDFF and between CAP and MRI-PDFF. The receiver operating characteristic （ROC） curve was plotted and the area under the ROC curve （AUC） was calculated to investigate the value of CTL/S and CAP in the diagnosis of different degrees of hepatic steatosis， and the DeLong test was used to compare the AUCs of the two radiological examinations. ResultsMRI-PDFF had relatively high repeatability and stability in CHB patients. There is a significant negative correlation between CTL/S and MRI-PDFF （r=-0.800， P<0.001） and a significant positive correlation between CAP and MRI-PDFF （r=0.692， P<0.001）. Both CTL/S and CAP had a relatively high accuracy in the diagnosis of hepatic steatosis in CHB patients， with an AUC of 0.951 and 0.902， respectively， and CTL/S had a better accuracy than CAP （P<0.05）. In the diagnosis of mild and moderate-to-severe hepatic steatosis， CTL/S had an AUC of 0.921 and 0.895， respectively， and CAP had an AUC of 0.859 and 0.825， respectively， suggesting that CTL/S had a slightly higher diagnostic efficiency than CAP. ConclusionMRI-PDFF has high repeatability and stability in CHB patients， and CTL/S and CAP have a high diagnostic value for different degrees of hepatic steatosis in CHB patients.

Effects of blue light on the development of the dioptric system in guinea pigs / 眼科新进展

Objective To investigate the effect of blue light on the dioptric development of the eyes of lens-induced myopia(LIM)guinea pigs.Methods Three-week-old trichromatic guinea pigs were randomly divided into three groups:control group,white light LIM(WL)group,and blue light LIM(BL)group(420 nm LED light,with an illuminance of 700 lx);guinea pigs in the latter two groups wore-10.00 D lenses in their right eyes to induce myopia.All guinea pigs under-went a 12 h light/12 h dark treatment cycle.Before and 2,4 weeks after the intervention,the diopter,axial length,retinal thickness and choroidal thickness were measured in all groups.After 4 weeks of intervention,the corneal fluorescent stai-ning and retinal Hematoxylin and Eosin(HE)staining were conducted.Results Compared with the control group,from week 0 to week 2 of the intervention(changes in weeks 0-2),the eyes in the WL group drifted(-2.22±1.28)D towards myopia,the axial length lengthened by(0.40±0.05)mm,and the retinal and choroidal thicknesses reduced by(-7.42± 7.04)μm and(-6.29±4.66)μm,respectively;compared with the WL group,in the BL group,the eyes drifted toward hyperopia by(0.48±1.16)D,the axial length increased by(0.20±0.10)mm,and retinal and choroidal thicknesses in-creased by(1.36±7.46)μm and(8.05±8.08)μm,respectively(all P＜0.05).From week 2 to week 4(changes in weeks 2-4),compared with the control group,the diopter in the WL and BL groups progressed towards myopia,with changes of(-4.64±0.50)D and(-2.11±2.02)D,respectively(both P＜0.05);the axial length lengthened,and reti-nal and choroidal thicknesses reduced in the WL group,with changes of(0.44±0.06)mm,(-7.35±5.87)μm and(-4.84±2.61)μm,while the choroidal thickness and the retinal thickness decreased in the BL group,with changes of(-0.33±5.95)μm and(-4.78±4.96)μm,respectively.Observations of corneal fluorescence staining and retinal HE staining indicated that prolonged blue light exposure could lead to damage to corneal and retinal cells.Conclusion Blue light may influence the development of myopia through choroid-related mechanisms,but its inhibitory effect is not positive-ly correlated with time.Prolonged exposure to blue light can damage the cornea and retina,thereby reducing the inhibitory effect.

Research progress on the parvalbumin-positive inhibitory interneurons and visual developmental plasticity / 眼科新进展

The complex function of the brain depends on the interaction of its intrinsic neurons and neural network systems,in which glutamatergic projection neurons and GABAergic inhibitory interneurons play an important role.There is a critical period in the postnatal development of the visual system when it is susceptible to the external environment,which may affect visual plasticity.Changes in the visual environment can lead to adaptive adjustment in neural connections and synaptic structures among visual cortexes,and the perineural network in the extracellular matrix has been proven to play an essential role in this process.The parvalbumin-positive inhibitory interneurons(PV+INs)contained in the perineural net-works are also involved in regulating plasticity during the critical period of visual development.PV+INs are a kind of inter-neurons that express the parvalbumin found in various parts of the brain.Recent studies have demonstrated that specific modulation of these neurons not only reveals some potential therapeutic mechanisms for disorders such as amblyopia,de-pression and autism but also provides a more precise treatment for these diseases.In this paper,various regulatory factors of PV+INs from their origin to the end of the critical period of visual development and their involvement in visual develop-mental plasticity were reviewed,with the aim of providing some guidance for basic research on visual cortical plasticity.

Research progress in SARS-CoV-2 nucleic acid detection based on microfluidic platforms / 医疗卫生装备

The detection principle of microfluidic microfluidic technology was introduced.The current research status of microfluidic platform-based SARS-CoV-2 nucleic acid detection technologies were reviewed such as reverse transcription quantitative real-time polymerase chain reaction(RT-qPCR),digital PCR,isothermal amplification and clustered regularly interspaced palindromic repeats/CRISPR-associated protein.The deficiencies of microfluidic platform-based SARS-CoV-2 nucleic acid detection were analyzed.It's pointed out microfluidic platform-based SARS-CoV-2 nucleic acid detection had to be optimized and validated clinically in specialty,sensitivity,detection limit,reproducibility,informatization,quality control and reagent cost.[Chinese Medical Equipment Journal,2024,45(1):101-107]

The effect of intraspinal blocking analgesia on delivery quality and puerperal pelvic floor function of primipara / 中国医师进修杂志

Objective:To explore the effects of intraspinal blocking analgesia on the delivery quality and puerperal pelvic floor function of primiparas.Methods:A total of 99 primiparas who delivered in the Second People′s Hospital of Wuhu City from January 2021 to April 2022 were enrolled in this study, 54 patients received intraspinal blocking analgesia (study group) and 45 patients received conventional treatment, without intraspinal blocking analgesia (control group). The delivery quality between the two groups was compared, and the pelvic floor function was evaluated and compared by pelvic floor rehabilitation therapy instrument and pelvic floor ultrasound at 6-8 weeks after delivery.Results:Vaginal delivery were successful in both groups. The total labor duration in the study group was longer than that in the control group: (8.03 ± 2.94) h vs. (6.89 ± 3.49) h, there was statistical difference ( P<0.05). The maximum value of pelvic floor rapid contraction stage, rising time and average value of continuous contraction stage in the study group were higher than those in the control group: (32.85 ± 10.13) μV vs. (14.73 ± 3.25) μV, (0.28 ± 0.06) s vs. (0.22 ± 0.05) s, (30.26 ± 5.24) μV vs. (16.74 ± 4.00) μV, there were statistical differences ( P<0.05). There were no statistical differences in other indicators such as the pre-resting stage, rapid contraction phase recovery time and post-resting stage between the two groups ( P>0.05). The rate of pelvic floor class Ⅰ and class Ⅱ muscle abnormalities at 6-8 weeks after delivery in the study group were lower than those in the control group, but there were no statistical differences ( P>0.05). The maximum Valsalva state hiatus area of levator ani muscle, maximum Valsalva state bladder posterior urethral angle, hiatus area of levator ani muscle at rest state and bladder neck degree in the study group were smaller than those in the control group: (19.09 ± 4.82) cm 2 vs. (23.00 ± 5.34) cm 2, (138.59 ± 23.14)° vs. (148.47 ± 20.38)°, (9.96 ± 2.63) cm 2 vs. (11.60 ± 2.75) cm 2, (20.13 ± 4.37) mm vs. (28.05 ± 6.52) mm, there were statistical differences ( P<0.05). Conclusions:Although intraspinal block analgesia can prolong the total labor time of primipara, but it can reduce the damage of pelvic floor function, possibly by increasing systolic period to protect pelvic floor muscles.

Analysis and research of online teaching supervision based on the characteristics of medical disciplines / 中华医学教育探索杂志

Given the systematic, rigorous, and practical characteristics of medical disciplines, ensuring the teaching quality of online courses has become a significant focus. In traditional teaching models, teaching supervision is an important method to guarantee instructional quality, and introducing teaching supervision into online teaching activities is of great significance. This article systematically reviews and summarizes the domestic and international experience of conducting online medical courses. We explore the instructional supervision of online medical courses from the following perspectives: the meaning of supervision, the necessity of online supervision, online supervision methods and technical approaches, the feedback and application of supervision information, and the establishment of a standardized online supervision process.

Transfer learning enhanced graph neural network for aldehyde oxidase metabolism prediction and its experimental application

Aldehyde oxidase (AOX) is a molybdoenzyme that is primarily expressed in the liver and is involved in the metabolism of drugs and other xenobiotics. AOX-mediated metabolism can result in unexpected outcomes, such as the production of toxic metabolites and high metabolic clearance, which can lead to the clinical failure of novel therapeutic agents. Computational models can assist medicinal chemists in rapidly evaluating the AOX metabolic risk of compounds during the early phases of drug discovery and provide valuable clues for manipulating AOX-mediated metabolism liability. In this study, we developed a novel graph neural network called AOMP for predicting AOX-mediated metabolism. AOMP integrated the tasks of metabolic substrate/non-substrate classification and metabolic site prediction, while utilizing transfer learning from 13C nuclear magnetic resonance data to enhance its performance on both tasks. AOMP significantly outperformed the benchmark methods in both cross-validation and external testing. Using AOMP, we systematically assessed the AOX-mediated metabolism of common fragments in kinase inhibitors and successfully identified four new scaffolds with AOX metabolism liability, which were validated through in vitro experiments. Furthermore, for the convenience of the community, we established the first online service for AOX metabolism prediction based on AOMP, which is freely available at https://aomp.alphama.com.cn.

Development and influential factor analysis of pharmacy outpatient departments in 714 Chinese tertiary healthcare institutions / 中国药房

OBJECTIVE To investigate the basic situation of developing pharmacy outpatient departments in Chinese tertiary medical institutions and analyze the influencing factors. METHODS The research targeted the pharmacy outpatient department managers of hospitals and conducted a survey through Sojump in March 2023. Various independent variables were selected from the hospital’s own characteristics， the management of the pharmacy outpatient departments， and the construction of the pharmacist team for Logistic and linear regression analysis， with the aim of separately analyzing the factors influencing the establishment of pharmacy outpatient departments and the factors affecting the total number of patients served by these departments throughout the year 2022. RESULTS & CONCLUSIONS A total of 1 304 medical institutions of different levels nationwide participated in this survey， with 714 tertiary hospitals. Among the tertiary hospitals， 377 （52.80%） had established pharmacy outpatient departments， including 321 grade-A tertiary hospitals， 48 grade-B tertiary hospitals and 8 other tertiary hospitals. The 377 tertiary hospitals collectively operated 1 739 pharmacy outpatient departments， covering 19 specialized fields， with the highest proportion found in the cardiovascular field （including anticoagulation） at 16.45%. Tertiary hospitals in North China， Central China， East China and South China regions had more pharmacy outpatient departments. The establishment of pharmacy outpatient departments was found to be influenced by tertiary grade-B status （P＝0.010） and the annual outpatient volume of the hospital （P＝0.008）， although the impact was relatively small. The factors influencing the number of patients served by pharmacy outpatient departments were the annual outpatient volume of the hospital （P＝0.042） and the number of pharmacists engaged in clinical pharmacy work （P＝0.004）. The proportion of tertiary hospitals in China that have established pharmacy outpatient departments is insufficient. It is necessary to further accelerate the construction of pharmacy outpatient departments and appropriately expand the talent pool of hospital pharmacy teams based on the needs of pharmacy outpatient departments and patients， in order to meet the requirements of medical practice and patient care.

Usage and Dosage Analysis and Countermeasures for Development of Compound Preparations of Han Dynasty Famous Classical Formulas / 中国实验方剂学杂志

In order to provide a reference basis for the development of relevant compound preparations， this article takes a comprehensive analysis of the usage and dosage of famous classical formulas in Han dynasty from various perspectives， and gives corresponding countermeasures on this basis. Through the comprehensive analysis of the classification and statistics of Zhongjing's medication characteristics， decoction methods， administration and dosage， and combining conversion methods of weights and measures by ancient medical practitioners， along with the dosage and administration of the listed Han dynasty famous classical formulas， it was found that the "Jiangxi method" served as a general guideline for administration according to Zhongjing's original text. This method allowed for flexible dosing based on the conversion of the ancient measurements to modern equivalents［13.8 g per Liang（两）］， ensuring the safe and effective medication of these formulas. After combing， it is found that although the dosage of single medicine is large in famous classical formulas from Han dynasty， the administration is flexible. The crude drug amount per administration serves as the foundational dose， with the frequency of administration adjusted flexibly according to the condition. This dosing approach becomes the key for the rational development of compound formulations of famous classical formulas. Based on the conclusions of the study， it is recommended that when developing compound formulations of famous classical formulas in Han dynasty， the original administration method and dosage should be respected. The original crude drug amount per administration should be considered as the daily foundational dose， with the frequency of administration described within a range（1 to N times per day， where N is the maximum number of administrations as per the original text）. The specific frequency of administration can be adjusted flexibly by clinical practitioners based on the individual condition. This approach should also be adopted in toxicological studies， where the dosage per administration serves as the basis for toxicity research， and the toxicity profile at the maximum administration frequency should be observed， providing guidance on the clinical safety range. Corresponding drug labels should provide information within a range to indicate toxicological risk intervals.

Clinical application value of a predictive model for the efficacy of third-generation cephalosporin in treatment of community-acquired spontaneous bacterial peritonitis / 临床肝胆病杂志

ObjectiveTo investigate the clinical application value of a predictive model for the efficacy of third-generation cephalosporin in the treatment of community-acquired spontaneous bacterial peritonitis （CASBP）. MethodsThis prospective study was conducted among 50 patients with liver cirrhosis and CASBP who were admitted to The Ninth Hospital of Nanchang from January 2021 to June 2022， and the patients were randomly divided into optimized treatment group and traditional treatment group， with 25 patients in each group. The patients in the optimized treatment group received ceftazidime or imipenem for initial treatment based on the above predictive model， and those in the traditional treatment group received ceftazidime for initial treatment， with the subsequent use of antibiotics adjusted based on the efficacy of initial treatment. The two groups were compared in terms of the response rate of initial treatment， cure rate on day 5， and 30-day mortality rate. The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups， and the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. ResultsAll patients completed the study. The optimized treatment group had a significantly higher response rate of initial treatment than the traditional treatment group （88.0% vs 60.0%， χ2=5.094， P=0.024）， while there was no significant difference in the cure rate on day 5 between the two groups （80.0% vs 56.6%， χ2=3.309， P=0.069）. As for the patients who received ceftazidime for initial treatment， the optimized treatment group had a significantly higher response rate of initial treatment than the traditional treatment group （88.9% vs 60.0%， χ2=4.341， P=0.037）， while there was no significant difference in the cure rate on day 5 between the two groups （83.3% vs 56.0%， χ2=2.425， P=0.119）. There was no significant difference in 30-day mortality rate between the two groups （8.0% vs 20.0%， χ2=0.664， P=0.415）. For all patients， there was a significant association between response of initial treatment and cure on day 5 （odds ratio ［OR］=9.643， 95% confidence interval ［CI］： 2.292‍ — ‍40.564） and between cure on day 5 and 30-day mortality （OR=0.138， 95%CI： 0.023‍ — ‍0.813）. ConclusionThis predictive model for efficacy helps clinicians to identify the patients who can benefit from third-generation cephalosporin treatment and improve the efficacy of third-generation cephalosporin in the initial empirical treatment of CASBP.

Role and mechanism of DCLK1 in gastric cancer stem cells / 中国病理生理杂志

AIM:To investigate the effect of doublecortin-like kinase 1(DCLK1)on the biological properties of gastric cancer stem cells,and to explore its possible mechanism.METHODS:Serum-free suspension culture of gastric cancer stem cells and targeted inhibition of DCLK1 activity in gastric cancer stem cells with DCLK1 inhibitor DCLK1-IN-1 were performed.The expression levels of DCLK1,stemness-related proteins(SOX2 and OCT4),proliferation-related pro-teins(cyclin D1 and c-MYC),drug resistance-related proteins(ABCG2 and TOP2A),epithelial-mesenchymal transition-related proteins(E-cadherin,vimentin and Snail),and PI3K/AKT/mTOR signaling pathway-related proteins in gastric cancer stem cells were examined by Western blot.The effects of DCLK1 on viability and drug resistance of gastric cancer stem cells were determined by CCK-8 assay,and the effects of DCLK1 on self-renewal of gastric cancer stem cells were de-termined by methylcellulose spheroid-forming assay.Wound-healing and Transwell assays were performed to assess the ef-fect of DCLK1 on the migration and invasion of gastric cancer stem cells.RESULTS:The expression levels of DCLK1 and stemness-related proteins SOX2 and OCT4 in gastric cancer stem cells were significantly higher than those in parental cells(P＜0.01).The proliferation,drug resistance,migration and invasion of gastric cancer stem cells in DCLK1 inhibi-tion group were significantly lower than those in Sphere cell group(P＜0.01).The expression levels of proliferation-related proteins(c-MYC and cyclin D1)and drug resistance-related proteins(TOP2A and ABCG2)were down-regulated,the ex-pression of epithelial marker E-cadherin was up-regulated,the expression of mesenchymal markers vimentin and Snail was down-regulated,and the expression levels of PI3K/AKT/mTOR signaling pathway-related proteins and their phosphoryla-tion levels were reduced in DCLK1 inhibition group(P＜0.05).CONCLUSION:DCLK1 is highly expressed in gastric cancer stem cells,which may be involved in the proliferation,drug resistance and invasion of gastric cancer stem cells by regulating PI3K/AKT/mTOR signaling pathway.It suggests that DCLK1 can be used as a potential target for gastric cancer stem cells.

Predictive value of preoperative aspartate aminotransferase to alanine aminotransferase ratio for early postoperative recurrence in patients with small hepatocellular carcinoma / 中国基层医药

Objective:To investigate the predictive value of preoperative aspartate aminotransferase to alanine aminotransferase ratio (AAR) for early recurrence after radical resection of single small hepatocellular carcinoma.Methods:A retrospective cohort study was conducted to analyze the clinical data of 137 patients who underwent radical resection of liver cancer at the General Hospital of Ningxia Medical University from January 2017 to July 2021. These patients were categorized into a recurrence group ( n = 72) and a non-recurrence group ( n = 65) based on early postoperative recurrence. Univariate and multivariate logistic regression analyses were conducted in the training cohort to identify independent risk factors for early recurrence of small hepatocellular carcinomas. Subsequently, the AARs were grouped, and patients with similar propensity scores estimated by the logistic model were matched 1:1 using the Propensity Score Match method with a caliper value of 0.02 to eliminate confounders. Logistic regression analysis was then repeated to assess the predictive value of the matched AAR for postoperative recurrence in patients with single small hepatocellular carcinoma. Results:Univariate analysis revealed that age ( χ2 = 4.22, P = 0.040), the ratio of fibrinogen to albumin ( χ2 = 8.26, P = 0.004), and the AAR ( χ2 = 5.83, P = 0.016) were significantly associated with early recurrence of small liver cancer after radical resection. Multivariate logistic regression analysis further identified age ( P = 0.042), the ratio of fibrinogen to albumin ( P = 0.024), and the AAR ( P = 0.018) as independent risk factors for early recurrence of single small hepatocellular carcinoma following radical surgery. After excluding confounding factors using the Propensity Score Match method, 25 patient pairs were successfully matched. Post-matching logistic regression analysis revealed that an AAR > 0.74 ( P = 0.005) and age > 60 years ( P = 0.024) were independent risk factors for early recurrence in patients with single small hepatocellular carcinoma following radical resection. Conclusion:Preoperative AAR is an independent risk factor for early recurrence in patients with single small hepatocellular carcinoma following surgery, demonstrating excellent predictive value.

One case of coronary intervention treatment for acute occlusion of the left circumflex artery with rare abnormal origin / 中国介入心脏病学杂志

Abnormal origin of coronary artery is a rare clinical manifestation in cardiovascular disease,among which the abnormal origin of left circumflex artery accounts for 0.022％-0.024％of all coronary angiography patients.Cases of abnormal origin of the left circumflex artery combined with acute occlusion are even rarer.Timely and effective strategies and methods for finding abnormal openings during surgery are crucial for completing interventional treatment.This case reports a rare left circumflex artery anomaly originating from the absence of coronary sinus and acute occlusion of the left circumflex artery leading to myocardial infarction during coronary intervention treatment.The patient experienced sudden chest pain and was admitted to the hospital.The electrocardiogram showed elevated ST segments in the lower and posterior walls.The acute coronary angiography showed only the left main trunk,left anterior descending branch,and right coronary artery(thrombolysis in myocardial infarction blood flow grade Ⅲ),but no left circumflex branch No left circumflex branch was found in the left and right coronary sinuses.Non selective angiography was performed at the root of the ascending aorta,and an abnormal opening of the left circumflex branch was finally discovered in the non coronal sinus.This case discusses common sites of abnormal origin of the left circumflex branch,strategies,methods,and interventional treatments for finding abnormal openings.

Correlation study of age,gender and lumbar vertebral marrow fat in adults based on MRI iterative decomposition of water and fat with echo asymmetry and least-squares estimation image quantitation imaging technique / 中国脊柱脊髓杂志

Objectives:To investigate the relationships between vertebral marrow fat in lumbar spine and age and gender in adults using iterative decomposition of water and fat with echo asymmetry and least-squares estimation image quantitation(IDE AL-IQ)magnetic resonance imaging technology.Methods:The IDEAL-IQ fat fraction images from 298 subjects(Male:138,Female:160,age range:20-69 years old)were collected.All the patients were divided into 5 groups based on age,with each group spanning a range of 10 years:age range 20-29 years(Twenties):24 males,20 females;30-39 years(Thirties):47 males,39 females;40-49 years(Forties):36 males,47 females;50-59 years(Fifties):20 males,37 females;60～69 years(Sixties):11 males,17 females.The bone marrow proton density fat fration(PDFF)were measured using GE ADW4.6 processing work station.Results:In the same age group,there were differences in vertebral bone marrow PDFF between gen-ders.PDFF of L1-L5 vertebrae was significantly higher in males than females in twenties,thirties and forties(P＜0.05).In the fifties,there was no statistically significant difference in the L1-L5 vertebrae PDFF between males and females(P＞0.05);while in the sixties,the PDFF of the L1-L5 vertebrae was lower in males than that in females(P＜0.05).The PDFF of lumbar vertebral bone marrow was positively correlated with age,with a higher correlation observed in females(r=0.72,P＜0.05)than that in males(r=0.32,P＜0.05).From the age of 20 to 69,the L4 vertebra PDFF in males had the highest growth rate(21.08％),while the L1 vertebra PDFF in female had the highest growth rate(65.68％).For males,the growth of PDFF was primarily concentrated in the thirties and fifties;The PDFF of L1,L4,and L5 vertebrae showed the largest increase in the fifties,while that of L2 and L3 vertebrae had the highest increase rate in the thirties.For females,vertebral PDFF showed a slight decrease trend in the group of thirties,which gradually increased subsequently in all vertebare in the group of forties,fifties,and sixties,with the largest increase rate observed in the fifties.Conclusions:There are differences in vertebral fat distribution between males and females across different age groups,and the growth rates of vertebral PDFF also vary;the PDFF of vertebral bodies in different segments of the lumbar spine is positively correlated with age.

Influence of different hardness surfaces on gait coordination in functional ankle instability / 中国康复理论与实践

Objective To explore the influence of different hardness surfaces on gait coordination in patients with functional ankle instability(FAI). Methods Qualisys Infrared Optical Motion Capture System was used to test the coordination and variability of 15 FAI patients on the right side at Nanjing Normal University from May to July,2023.The gait cycle data were collect-ed and intercepted,and coupling angle(CA)and standard deviation of coupling angle(SDCA)were calculated by Matlab to compare the differences on different hardness surfaces. Results On coronal plane,CA of hip-ankle joint was higher on the hard surface than on the soft surface during middle stage of support and early stage of swing,and lower on its rest stages and the gait stages of hip-knee joint and knee-ankle joint than on the soft surface(P<0.01).On sagittal plane,CA of hip-ankle joint and knee-ankle joint was smaller on the hard surface than on the soft surface during middle and late stages of support,and larger than on the soft surface during their rest stages,and the gait stages of hip-knee joint(P<0.01).On horizontal plane,CA of hip-knee joint was lower on the hard surface than on the soft surface during the late stage of support,and higher than on the soft surface during its early stage of swing and bearing stage of hip-ankle joint(P<0.01).Compared with the hard surface,SDCA was smaller on the soft surface than on the hard surface only in the hip-ankle on the sagittal plane and during bearing stage of hip-knee joint,and was greater than on the hard surface for the rest(P<0.01). Conclusion FAI patients showed more distal dominance on soft surface than on hard surface during most gait cycle on 3D plane,i.e.,advantage of ankle varus and plantar flexion increased,and advantage of hip joint decreased;the coordination variability was generally higher on soft surface than on hard surface.These findings suggested that FAI patients may increase the risk of recurrent lateral ankle sprain walking on soft surface.