Analysis of the application value of ultrasound measuring gastric sinus cross-sectional area to guide the implementation of early individualized enteral nutrition in patients with sepsis / 中华急诊医学杂志

Objective:To explore the value of ultrasound measuring gastric sinus cross-sectional area (CSA) to guide early individualized enteral nutrition implementation strategies in sepsis patients.Methods:Thirty septic patients admitted to the EICU and comprehensive ICU of The Second Affiliated Hospital of Nanjing University of Chinese Medicine between January 2021 and December 2022 each were included. EICU patients used bedside ultrasound for gastric sinus CSA to guide the implementation of early enteral nutrition in septic patients, and a routine nutritional support strategy was adopted in the integrated ICU. The correlation of CSA and feeding intolerance in patients with septic gastrointestinal dysfunction, the ROC curve and other relevant indicators of gastrointestinal dysfunction gastrointestinal dysfunction score, SOFA score, APACHEⅡ score, intra-abdominal pressure (IAP), serum protein (PA), [albumin (Alb)]. By comparing the indicators related to inflammation, nutritional status and days of ICU stay after different strategies of the two groups, the advantages of different strategies were analyzed.Results:The baseline data of the two groups were balanced and comparable; the incidence of feeding intolerance was significantly higher (36.67%) than the conventional group (10.00%), with aggressive and early individualized treatment, the incidence rate on the third day was only 10.00%, significantly lower than that in the conventional treatment group (40.00%). Treatment up to the 5th day, the related function scores (gastrointestinal dysfunction score, APACHEⅡ score, SOFA score, IAP), nutritional status indicators (5 d hot card reaching the standard rate, PA, Alb) and inflammation indicators (WBC, PCT, hs-CRP) were significantly improved compared with admission, and is better than the conventional treatment group. In addition, the ICU hospital days and the incidence of aspiration were lower in the ultrasound treatment group ( P <0.05). CSA showed favorable correlation with gastrointestinal dysfunction score, APACHEⅡ score, SOFA score, IAP, PA and Alb, correlation coefficients were 0.79、0.60、0.66、0.71、-0.6 and -0.64( P <0.05). The ROC curve for predicting feeding intolerance by CSA showed the AUC was 0.828, 95% CI was 0.737-0.919, its optimal cutoff value for predicted feeding intolerance was 7.835 cm 2, the sensitivity and specificity were 88.20% and 71.80%. Conclusions:Ultrasound measuring CSA can early and effectively found the feeding intolerance in the patients with sepsis , via giving individualized enteral nutrition implementation strategy, significantly improve the organ function score, nutritional status and inflammation index, reduce the ICU hospital days and aspiration, and correlate with the conventional evaluation index, and sensitivity and specificity are high, worthy of the clinical further promotion.

Optimization of Menin inhibitors based on artificial intelligence-driven molecular factory technology / 中国药科大学学报

@#Abstract: The new generation of artificial intelligence technology, represented by deep learning, has emerged as a crucial driving force in the advancement of new drug research and development. This article creatively proposes a workflow named “Molecular Factory” for the design and optimization of drug molecules based on artificial intelligence technology. This workflow integrates intelligent molecular generation models, high-performance molecular docking algorithms, and accurate protein-ligand binding affinity prediction methods. It has been integrated as a core module into DrugFlow, a one-stop drug design software platform, providing a comprehensive set of mature solutions for the discovery and optimization of lead compounds. Utilizing the “Molecular Factory” module, we conducted the research of second-generation inhibitors against Menin that can combat drug resistance. Through the integration of computational and experimental approaches, we rapidly identified multiple promising compounds. Among them, compound RG-10 exhibited the IC50 values of 9.681 nmol/L, 233.2 nmol/L, and 40.09 nmol/L against the wild-type Menin, M327I mutant, and T349M mutant, respectively. Compared to the positive reference molecule SNDX-5613, which has entered Phase II clinical trials, RG-10 demonstrated significantly enhanced inhibitory activity against the M327I and T349M mutants. These findings fully demonstrate the unique advantages of the "Molecular Factory" technology in practical drug design and development scenarios. It can rapidly and efficiently generate high-quality active molecules targeting specific protein structures, holding significant value and profound implications for advancing new drug discovery.

Effect of Yishen Gushu Formula on bone metabolic markers and clinical efficacyn in patients with osteoporosis of kidney deficiency and blood stasis type / 中国组织工程研究

BACKGROUND:With the variation of disease treatment modes and the in-depth research on senile osteoporosis in recent years,increasing studies have confirmed that traditional Chinese medicine has a significant effect on the prevention and treatment of senile osteoporosis. OBJECTIVE:To investigate the effect of Yishen Gushu Formula on bone metabolic markers in patients with osteoporosis of kidney deficiency and blood stasis type. METHODS:102 patients with senile osteoporosis of kidney deficiency and blood stasis type who were treated at Ruikang Hospital Affiliated to Guangxi University of Traditional Chinese Medicine from July 2020 to March 2022 were enrolled,including 32 males and 70 females,aged 71-93 years.All patients were randomly divided into two groups,with 51 patients in each group.The control group was treated with calcium carbonate D3 granules and sodium alendronate tablets,while the treatment group was treated with Yishen Gushu Formula beyond the control group.Treatments in each group lasted 3 months.Bone mineral density of the L1-4 lumbar vertebrae and left femoral neck,visual analog scale score,and serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were measured before and 3 months after treatment.Traditional Chinese medicine syndrome score and therapeutic efficiency were also assessed. RESULTS AND CONCLUSION:After 3 months of treatment,the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly increased in both two groups(P<0.05),and the bone mineral density of the lumbar vertebrae(L1-4)and left femoral neck was significantly higher in the treatment group than the control group(P<0.05).The visual analog scale scores of both groups after 3 months of treatment were lower than those before treatment(P<0.05),and the visual analog scores of the treatment group after 3 months of treatment were lower than those of the control group(P<0.05).After 3 months of treatment,the serum levels of osteocalcin,osteopontin,type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly improved in both two groups,while compared with the control group,the serum levels of osteocalcin and osteopontin were significantly higher(P<0.05)and the serum levels of type Ⅰ collagen cross-linked C-terminal peptide and tartrate resistant acid phosphatase were significantly lower in the treatment group(P<0.05).After 3 months of treatment,the Traditional Chinese medicine syndrome scores were decreased in both two groups,while the Traditional Chinese medicine syndrome scores in the treatment group were lower than those in the control group.After 3 months of treatment,no significant adverse reactions occurred in both groups.The total effective rate was 88.2%and 70.6%in the treatment and control groups respectively,and there was a significant difference between the two groups(P<0.05).To conclude,Yishen Gushu Formula combined with anti-osteoporosis drugs can significantly improve the clinical symptoms of patients with senile osteoporosis of kidney deficiency and blood stasis type and prevent disease progression by regulating bone metabolism,increasing bone mineral density,and relieving pain.

[The effect of visual-vestibular sensory input consistency on standing stability and electroencephalogram brain network characteristics in the elderly].

Aging is a crucial factor influencing postural stability control and contributing to frequent falls, yet its underlying mechanisms remain incompletely understood. This study aims to explore the effects of aging on postural stability control by comparing differences in postural stability and node strength of electroencephalogram (EEG) brain network between elderly and young people under the conditions of congruent and incongruent visual-vestibular sensory inputs. Eighteen elderly volunteers without neuromuscular disorders and eighteen young individuals participated in the present study. Virtual reality (VR) technology was employed to manipulate visual rotation stimuli (clockwise and counterclockwise), and a horizontal rotating platform was used for vestibular rotation stimuli (clockwise). Based on the directional disparity of sensory input in the horizontal plane, visual-vestibular input consistency was categorized as congruent and incongruent. Postural stability was assessed by the center of pressure (COP) trajectory, and EEG signals were collected and analyzed using directed network analysis to observe EEG brain network node connectivity strength. The results revealed that, under conditions of incongruent visual-vestibular sensory inputs, the elderly exhibited significantly inferior postural stability performance in terms of COP anterior-posterior (Y-axial) sway speed, total path length, anterior-posterior and medial-lateral sample entropy, compared to the young adults. Moreover, the node connectivity strength of visual cortex in the elderly was notably higher, while node connectivity strength of superior temporal cortex was significantly lower than that in the young adults. These findings suggest that the elderly have a heightened reliance on visual information in postural control and an impaired ability to cope with sensory conflicts arising from incongruent visual-vestibular sensory inputs, leading to compromised postural stability. The outcomes of this study hold significant implications for future assessments of balance function in the elder and fall prevention trainings.

Electrochemical trifluoroalkylation/annulation for the synthesis of CF3-functionalized tetrahydroquinolines and dihydroquinolinones.

Tuning the electronic structure of protecting groups on the nitrogen atom of substrates has emerged as an effective strategy to achieve the tandem trifluoromethylation/C(sp2)-H annulation using Langlois' reagent as the CF3 source for the electrochemical synthesis of functionalized tetrahydroquinolines and dihydroquinolinones.

Efficacy of Chinese Herbal Medicines on Pregnancy Outcomes in Patients with Endometriosis in Long-Term Management: A Multicenter Retrospective Cohort Study.

OBJECTIVE: To analyze the factors related to pregnancy of endometriosis and whether Chinese herbal medicines (CHMs) can improve pregnancy outcomes in patients with endometriosis in long-term management. METHODS: This multicenter cohort study retrospectively analyzed the clinical data of endometriosis patients with fertility needs from January 2019 to November 2019. A total of 252 patients with endometriosis from 5 level-III Grade A hospitals in Beijing were included in this study. Univariate and multivariate logistic regression analysis were performed for the relevant factors. The propensity score matching (PSM) function of SPSS software was used to match the CHMs group with the non-CHMs group. The pregnancy rate and live birth rate were analyzed. RESULTS: The results of univariate analysis showed that age, disease course, presence of infertility, presence of adenomyosis, time after surgery or use of gonadotropin-releasing hormone agonist (GnRH-a), use of CHMs and follow-up time were influencing factors of pregnancy in endometriosis patients (P<0.05). The results of multivariate analysis showed that age, presence of adenomyosis, time after surgery or use of GnRH-a, use of CHMs and follow-up time were independent factors affecting pregnancy in endometriosis patients, among which, age ⩾35 years old, presence of adenomyosis and follow-up time >6 months were independent risk factors (OR=0.445, 0.348, 0.140, respectively, P<0.05), time after surgery or use of GnRH-a ⩽6 months and use of CHMs were independent protective factors (OR=3.839, 3.842, respectively, P<0.05). After PSM, 99 pairs of two groups were matched successfully. The pregnancy rate of the CHMs group was higher than that of the non-CHMs group [55.56% (55/99) vs. 36.36% (36/99), P<0.05]. The live birth rate of the CHMs group was higher than that of the non-CHMs group [49.49% (49/99) vs. 35.35% (35/99), P<0.05]. CONCLUSION: CHMs can effectively improve clinical pregnancy rate and live birth rate of patients with endometriosis in the chronic disease management.

Effect of Cognitive Load on Anticipatory Postural Adjustment Latency and its Relationship with Pain-Related Dysfunction in Non-specific Chronic Low Back Pain: A Cross-Sectional Study.

INTRODUCTION: This study aimed to investigate the effect of cognitive load on anticipatory postural adjustment (APA) latency in patients with non-specific chronic low back pain (NCLBP) and its relationship with pain-related functional changes. METHODS: A cross-sectional study was conducted from December 15, 2022 to January 25, 2023. Participants were divided into a healthy control group (n = 29) and an NCLBP group (n = 29). Each group was assigned a single task of rapid arm raising and a dual task of rapid arm raising combined with a cognitive load. The cognitive load task was conducted using visual conflict. The APA latency for bilateral trunk muscles was observed using electromyography. The duration of electromyography recording in each task cycle was 28 s. Pain related-functional changes were evaluated using Roland-Morris Disability Questionnaire (RMDQ) before all tasks. RESULTS: The APA latency for the right multifidus was significantly delayed in the NCLBP group [25.38, 95% confidence interval (CI) 13.41-37.35] than in the healthy control group (- 5.80, 95% CI - 19.28 to 7.68) during dual task (p = 0.0416). The APA latency for the right multifidus (25.38, 95% CI 13.41-37.35) and transverse abdominis/internal oblique (29.15, 95% CI 18.81-39.50) were significantly delayed compared with on the left side in the NCLBP group during dual task (- 3.03, 95% CI - 15.18-9.13, p = 0.0220; 3.69, 95% CI - 6.81 to 14.18, p = 0.0363). The latency delay of the right and left multifidus APA in the NCLBP group under the dual-task was positively correlated with RMDQ scores (r = 0.5560, p = 0.0017; r = 0.4010, p = 0.0311). CONCLUSIONS: Cognitive load could induce APA delay in the right trunk muscles and co-activation pattern changes in bilateral trunk muscle APA in patients with NCLBP. The APA onset delay in multifidus is positively related to pain-related daily dysfunction. Trial Registration ChiCTR2300068580 (retrospectively registered in February 23, 2023).

CiteSpace knowledge map of research hotspots and frontiers of Polygalae Radix / 中国中药杂志

In this study, the Web of Science and China National Knowledge Infrastructure(CNKI) were searched comprehensively for the literature about the research on Polygalae Radix. After manual screening, 1 207 Chinese articles and 263 English articles were included in this study. Excel was used to draw the line chart of the annual number of relevant publications. CiteSpace 6.1.R3 was used for the visual analysis of author cooperation, publishing institutions, keyword co-occurrence, keyword clustering, and bursts in the research on Polygalae Radix. The results showed that the number of articles published in Chinese and English increased linearly, which indicated the rising research popularity of Polygalae Radix. WANG J and LIU X were the authors publishing the most articles in Chinese and English, respectively. Shanxi University of Chinese Medicine and Chinese Academy of Medical Sciences were the research institutions with the largest number of Chinese and English publications in this field, respectively. The institutions publishing the relevant articles in English formed a system with the Chinese Academy of Medical Sciences as the core. According to the keywords, the research hotspots of Polygalae Radix included variety selection and breeding, quality standard, extraction and identification of active chemical components, prescription compatibility, processing, clinical medication rules, and pharmacological mechanism. The research frontiers were the molecular mechanisms of Polygalae Radix and its active components in exerting the protective effect on brain nerve, regulating receptor pathways, alleviating anxiety and Alzheimer's disease, as well as data mining and clinical medication summary. This study has reference significance for the topic selection and frontier identification of the future research on Polygalae Radix.

CD301b+ macrophage: the new booster for activating bone regeneration in periodontitis treatment / 国际口腔科学杂志·英文版

Periodontal bone regeneration is a major challenge in the treatment of periodontitis. Currently the main obstacle is the difficulty of restoring the regenerative vitality of periodontal osteoblast lineages suppressed by inflammation, via conventional treatment. CD301b+ macrophages were recently identified as a subpopulation that is characteristic of a regenerative environment, but their role in periodontal bone repair has not been reported. The current study indicates that CD301b+ macrophages may be a constituent component of periodontal bone repair, and that they are devoted to bone formation in the resolving phase of periodontitis. Transcriptome sequencing suggested that CD301b+ macrophages could positively regulate osteogenesis-related processes. In vitro, CD301b+ macrophages could be induced by interleukin 4 (IL-4) unless proinflammatory cytokines such as interleukin 1β (IL-1β) and tumor necrosis factor α (TNF-α) were present. Mechanistically, CD301b+ macrophages promoted osteoblast differentiation via insulin-like growth factor 1 (IGF-1)/thymoma viral proto-oncogene 1 (Akt)/mammalian target of rapamycin (mTOR) signaling. An osteogenic inducible nano-capsule (OINC) consisting of a gold nanocage loaded with IL-4 as the "core" and mouse neutrophil membrane as the "shell" was designed. When injected into periodontal tissue, OINCs first absorbed proinflammatory cytokines in inflamed periodontal tissue, then released IL-4 controlled by far-red irradiation. These events collectively promoted CD301b+ macrophage enrichment, which further boosted periodontal bone regeneration. The current study highlights the osteoinductive role of CD301b+ macrophages, and suggests a CD301b+ macrophage-targeted induction strategy based on biomimetic nano-capsules for improved therapeutic efficacy, which may also provide a potential therapeutic target and strategy for other inflammatory bone diseases.

Study on the value of color Doppler ultrasound combined with serum miR-128-3p and DJ-1 in diagnosis and clinical staging of bladder cancer / 中国医学装备

Objective:To investigate the value of color Doppler ultrasound combined with serum miR-128-3p and DJ-1 in the diagnosis and clinical staging of bladder cancer.Methods:A total of 136 patients with suspected bladder cancer were selected and they were divided into bladder cancer group(56 cases)and benign lesion group(80 cases)according to the results of pathological examination.All patients underwent color Doppler ultrasound examination,and the levels of serum miR-128-3p and DJ-1 of them were measured.The receiver operating characteristic(ROC)curve was applied to analyze the diagnostic efficacy of color Doppler ultrasound examination combined with serum miR-128-3p and DJ-1 for bladder cancer and the clinical staging of that.Results:Compared with pathological results as the"gold standard",the sensitivities of color Doppler ultrasound in diagnosing bladder cancer and the clinical staging of that were respectively 75.00%and 80.49%,and the specificities of that for them were respectively 86.25%and 80.00%,and the accuracies of that for them were respectively 81.62%and 80.36%.Compared with benign lesion group,the serum miR-128-3p level decreased and DJ-1 level increased in bladder cancer group,the differences were statistically significant(t=8.842,t=8.844,P<0.05),respectively.In the bladder cancer group,the serum miR-128-3p level of infiltration type patients was lower than that of superficial type patients,and the serum DJ-1 level of them was higher than that of superficial type patients,and the differences were statistical significant(t=5.722,t=6.327,P<0.05),respectively.ROC curve results showed that the area under curve(AUC),sensitivity and specificity of color Doppler ultrasound combined with serum miR-128-3p and DJ-1 were respectively higher than those of single examination indicator in diagnosing bladder cancer and the clinical staging of that,and the differences were statistical significant(Z=4.028,Z=2.535,Z=3.386,Z=2.131,Z=2.137,Z=2.063,P<0.05).Conclusion:Color Doppler ultrasound combined with serum miR-128-3p and DJ-1 can improve the diagnostic efficacy for bladder cancer and the clinical staging of that,which has important clinical significance in diagnosing bladder cancer and judging the clinical staging of that.

Comparative study of dual stability constructs and modified Scott techniques for symptomatic spondylolysis in active adolescents / 中华创伤骨科杂志

Objective:To compare the efficacy between dual stability constructs and modified Scott techniques for treatment of symptomatic spondylolysis in active adolescents.Methods:A retrospective study was conducted to analyze the clinical date of 64 active adolescents who had been treated for symptomatic spondylolysis at Department of Orthopedic Surgery, The 900th Hospital of Joint Logistic Support Force from January 2017 to October 2021. There were 59 males and 5 females with an age of (24.9±5.2) years. Responsible vertebral bodies were L 3 in 2 cases, L 4 in 10 cases, L 5 in 47 cases, and L 4 to L 5 in 5 cases; spondylolisthesis was accompanied in 9 cases. Depending on the surgical methods, the patients were divided into a dual stability constructs (pedicle screws and laminar screws) group (observation group, 31 cases) and a modified Scott group (control group, 33 cases). The 2 groups were compared in terms of operative time, bleeding volume, postoperative drainage volume, isthmus healing rate, rate of internal fixation failure, visual analogue scale (VAS) for low back pain, Japanese Orthopaedic Association (JOA) score and the good and excellent rate by JOA at postoperative 1 month, 3 months, and the last follow-up, and the incidence of complications. Results:There was no statistically significant difference in the preoperative general data between the 2 groups, indicating comparability ( P>0.05). All patients were followed up. The operation time in the observation group [(94.7±14.9) min] was significantly longer than that in the control group [(84.4±16.4) min] ( P=0.011), but there was no significant difference in intraoperative bleeding volume or postoperative drainage volume ( P>0.05). The healing rate of bilateral isthmi in the observation group was 93.5% (29/31), significantly higher than that in the control group [60.6% (20/33)], and the rate of internal fixation failure in the observation group (0) was significantly lower than that in the control group (12.1%, 4/33) ( P<0.05). At postoperative 1 month, 3 months, and the last follow-up, the VAS scores were significantly lower than the preoperative value in all patients while the JOA scores significantly higher ( P<0.05). At the last follow-up, in the observation group the VAS score [0 (0, 1.0)] was significantly lower than that in the control group [1(0, 2)], and the JOA score [(27.1±1.2) points] and the excellent and good rate by JOA [93.5% (29/31)] were significantly higher than those in the control group [(25.7±2.1) points and 75.8% (25/33)] ( P<0.05). In the control group, follow-ups revealed internal fixation failure in 4 cases due to the cable cutting out of the spinous processes, yielding a failure rate of 12.1%, while no internal fixation failure was observed in the observation group. Conclusions:Both dual stability constructs and modified Scott techniques can relieve the clinical symptoms of spondylolysis in active adolescents to various extents. However, dual stability constructs with pedicle screws and laminar screws may lead to a higher isthmus healing rate and better curative effects.

Analysis of risk factors affecting the completion of postoperative adjuvant chemotherapy in elderly patients with progressive gastric cancer / 中华老年医学杂志

Objective:To investigate the risk factors affecting the completion of postoperative adjuvant chemotherapy in elderly patients with progressive gastric cancer.Methods:Clinicopathological data of patients diagnosed with gastric adenocarcinoma and treated with radical surgery at our hospital between January 2017 and December 2018 were retrospectively collected, and 96 patients were finally included in the study according to the inclusion and exclusion criteria.Patients were divided into a completed chemotherapy group and an uncompleted chemotherapy group depending on whether they had completed 6 cycles of adjuvant chemotherapy after surgery.The optimal cut-off value was derived from the receiver operating characteristic(ROC)curve, and the Youden Index was calculated.Relevant factors that might affect the completion of postoperative adjuvant chemotherapy in elderly patients with progressive gastric cancer were included in univariate and multivariate Logistic regression analyses to identify independent risk factors affecting the completion of postoperative adjuvant chemotherapy in gastric cancer patients.The Kaplan-Meier(K-M)method was used to plot the survival curves for the groups, and the log-rank test was used to compare the survival rates between the groups.Results:A total of 96 patients, aged 60-89 years, with a mean age of(70.3±7.0)years, were included.Sixteen patients completed postoperative adjuvant chemotherapy, while 80 patients did not.The following analysis was performed on clinicopathological data of patients in the two groups.Univariate Logistic regression analysis showed that patient age ≥70 years( OR=8.135, 95% CI: 1.735-38.153, P=0.008)or a preoperative prognostic nutritional index(PNI)score <49.5( OR=4.765, 95% CI: 1.549-14.656, P=0.006)affected the completion of postoperative adjuvant chemotherapy.The risk factors that might affect the completion of postoperative adjuvant chemotherapy in elderly gastric cancer patients were analyzed using multivariate Logistic regression and the results showed that age ≥70 years( OR=9.815, 95% CI: 1.947-49.485, P=0.006)and a preoperative PNI score <49.5( OR=5.895, 95% CI: 1.711-20.305, P=0.005)were independent risk factors hindering the completion of postoperative adjuvant chemotherapy. Conclusions:Age ≥70 years and PNI<49.5 are independent risk factors for the completion of postoperative adjuvant chemotherapy.Failure to complete postoperative adjuvant chemotherapy is associated with a poor prognosis.PNI is a valid predictor for whether postoperative adjuvant chemotherapy will be completed and helps to screen chemotherapy patients who need nutritional intervention.

The interpretation and review of urothelial carcinoma, 2023 EMSO / 中华泌尿外科杂志

We present a summary of important research in the field of urothelial carcinoma presented at the 2023 European Society for Medical Oncology (ESMO) conference. A total of 53 studies related to urothelial carcinoma were reported, including 6 late-breaking abstract, 7 oral presentations, and 40 poster presentations. Several new treatment options were reported in the non-muscle invasive bladder cancer (NMIBC) field, providing more choices for bacillus Calmette-Guerin (BCG) failing patients. For perioperative systemic treatment of muscle-invasive bladder cancer (MIBC), studies further explored various adaptation of neoadjuvant therapy strategies. For metastatic urothelial carcinoma (mUC), the data on CheckMate-901 and EV-302 studies provided thoughts on first-line treatment options. These studies provide important guidance for clinical practice in the field of urothelial carcinoma.

Rapid Determination of Bucinnazine in Blood by UPLC-MS/MS / 法医学杂志

OBJECTIVES@#To establish a rapid method for the analysis of bucinnazine in blood by UPLC-MS/MS and to apply the method to the practical case.@*METHODS@#After the internal standard was added to blood, the protein was precipitated with 900 μL mixed solution (Vacetonitrile∶Vwater=8∶2). After vortex and centrifugation, the protein was measured through 0.22 μm filter membrane. The separation was performed on C18 chromatography column, with acetonitrile and 5 mmol/L ammonium acetate containing 0.1% formic acid aqueous as mobile phase gradient elution at the flow rate of 0.4 mL/min. Multiple reaction monitoring scan was performed in electrospray positive ion mode, quantitative measurement was performed by internal standard method, and methodological verification was carried out.@*RESULTS@#The linear relationship of bucinnazine in blood was good in the range of 0.5-200 μg/L, the correlation coefficient (r) was 0.999 7, the limit of detection was 0.1 μg/L, the limit of quantitation was 0.5 μg/L, and the recovery was 78.3%-83.8% at 1, 10 and 100 μg/L mass concentration levels. The matrix effect was 69.4%-73.8%, the intra-day precision was 1.9%-2.8%, and the inter-day precision was 2.8%-3.2%, the accuracy was 3.1%-3.5%. The stability test results of 1 and 100 μg/L mass concentrations at -25 ℃ showed that the accuracy (bias) of 10 d was less than 4.5%.@*CONCLUSIONS@#This method has the advantages of simple pre-treatment process, fast sample processing speed, high sensitivity of instrument analysis, good stability of content determination and reliable identification results, and can meet the needs of case identification.

Advance progress and future trend of the natural origin adjuvants for tumor vaccines / 免疫学杂志

Tumor has become the major reasons cause of death,and its vaccine has become the effective tracts of treatment and prevention by enhancing the immune response of patients.However,most vaccines which are recombination subunit protein antigens are poorly immunogenic and difficult to induce a robust immune response in patients with compromised immune systems,resulting in poor marketing approval.The core component of the vaccine adjuvant can greatly enhance the strength,speed and duration of the immune response,thus becoming the key to the development of an ideal tumor vaccine.Most tumor vaccines are combined with tradition adjuvant such as aluminum,MF59 and AS adjuvant,but their products and patents are monopolized by large foreign companies.We found that natural adjuvants have many unique advantages,such as good biocompatibility and biodegradability,promoting the maturation of dendritic cell and the secretion of immune cytokines,significantly enhancing the tumor vaccine immune response,etc.In this paper,the application and future development of natural polysaccharides,saponins,flavonoid and plant virus-like particles in cancer vaccines were reviewed,which may lay a solid foundation for the development of the original and innovative adjuvants with domestic independent intellectual property rights.

Comprehensive interpretation of RCC abstracts, ASCO-GU 23 / 中华泌尿外科杂志

The ASCO-GU 23 conference was held offline as scheduled after the pandemic. A total of 167 abstracts in the field of renal cell carcinoma has been posted during the conference, covering the first PET/CT diagnostic technology targeting tumors in renal cell carcinoma, risk stratified interpretation of the previous clinical trial results, and exploring the value of tumor and serum biomarkers for precise classification therapy, as well as providing evidence for the therapeutic scheme sequencing.

Efficacy of first-line tyrosine kinase inhibitors plus immune checkpoint inhibitors in metastatic fumarate hydratase-deficient renal cell carcinoma / 中华泌尿外科杂志

Objective:To evaluate the efficacy of first-line tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors (ICI) in metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC).Methods:The data of 87 metastatic FH-deficient RCC patients from West China Hospital ( n=44), Renji Hospital ( n=27) and Sun Yat-sen University Cancer Center (n=16) from Mar 2019 to Aug 2022 were retrospectively analyzed. The median age was 37(30, 47) years, the male to female ratio was 1.9∶1. The median size of tumor was 7.5(5.0, 10.0) cm. Sixty-one patients (70.1%) had germline FH mutations, and 26 patients (29.9%) had somatic FH mutations. Forty-nine patients (56.3%) metastasis disease at initial diagnosis, and 38 patients (43.7%) had metachronous metastasis. The most common site of metastasis was lymph node (41/87, 47.1%), followed by bone (33/87, 37.9%), liver (22/87, 25.3%), and lung (14/87, 16.1%). Fifteen patients (17.2%) had weak expression of FH protein and 59 patients (67.8%) had positive PD-L1 expression. The most common treatments were sintilimab plus axitinib (52/87, 59.8%), followed by pembrolizumab plus cabozantinib (7/87, 8.0%), tirelizumab plus axitinib (6/87, 6.9%), pembrolizumab plus axitinib (5/87, 5.7%), and toripalimab plus axitinib (4/87, 4.6%). Thirteen patients (13/87, 14.9%) received other ICI plus TKI combination treatments. Statistical analysis was conducted using R 4.2.3 software. Kaplan Meier survival curve was used to evaluate survival data, and log-rank test was used to compare differences between treatment groups. Results:The overall objective response rate (ORR) and disease control rate (DCR) of first-line TKI + ICI were 39.1% and 89.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 16.5 months and 71.0 months, respectively. For first-line sintilimab plus axitinib, the ORR and DCR were 44.2% and 92.3%, respectively. The median PFS was 17.3 months and the median OS was not reached for this combination treatment. The efficacy of first-line tirelizumab plus axitinib was inferior to other treatment strategies (median PFS: 4.0 vs. 16.6 months, P<0.001; median OS: 22.0 vs. 71.0 months, P=0.043). Subgroup analyses further showed that the efficacy of ICI+ TKI combination therapy was consistent in patients with different clinicopathologic and genomic features. However, patients with liver metastasis had shorter OS than those without liver metastasis (median OS: 26.3 vs. 71.0 months, P=0.021). Conclusion:First-line TKI + ICI is effective for metastatic FH-deficient RCC and can significantly prolong the survival of the patients.

Prediction and analysis of Q-markers of Elephantopus scaber based on its UPLC fingerprint, content determination of components, and in vitro a nti-tumor activity / 中国中药杂志

This study aimed to provide scientific evidence for predicting quality markers(Q-markers) of Elephantopus scaber by establishing UPLC fingerprint of E. scaber from different geographical origins and determining the content of 13 major components, as well as conducting in vitro anti-cancer activity investigation of the main components. The chromatographic column used was Waters CORTECS UPLC C_(18)(2.1 mm×150 mm, 1.6 μm), and the mobile phase consisted of acetonitrile and 0.1% formic acid solution(gradient elution). The column temperature was set at 30 ℃, and the flow rate was 0.2 mL·min~(-1). The injection volume was 1 μL, and the detection wavelength was 240 nm. The UPLC fingerprint of E. scaber was fitted using the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine(2012 edition) to determine common peaks, evaluate similarity, identify and determine the content of major components. The CCK-8 assay was used to explore the inhibitory effect of the main components on the proliferation of lung cancer cells. The results showed that in the established UPLC fingerprint of E. scaber, 35 common peaks were identified. Thirteen major components, including neochlorogenic acid(peak 1), chlorogenic acid(peak 2), cryptochlorogenic acid(peak 3), caffeic acid(peak 4), schaftoside(peak 6), galuteolin(peak 9), isochlorogenic acid B(peak 10), isochlorogenic acid A(peak 12), isochlorogenic acid C(peak 18), deoxyelephantopin(peak 28), isodeoxyelephantopin(peak 29), isoscabertopin(peak 31), and scabertopin(peak 32) were identified and quantified, and a quantitative analysis method was established. The results of the in vitro anti-cancer activity study showed that deoxyelephantopin, isodeoxyelephantopin, isoscabertopin, and scabertopin in E. scaber exhibited inhibition rates of lung cancer cell proliferation exceeding 80% at a concentration of 10 μmol·L~(-1), higher than the positive drug paclitaxel. These results indicate that the fingerprint of E. scaber is highly characteristic, and the quantitative analysis method is accurate and stable, providing references for the research on quality standards of E. scaber. Four sesquiterpene lactones in E. scaber show significant anti-cancer activity and can serve as Q-markers for E. scaber.

Clinical study of evaluating the clinical effect of Dachengqi decoction in the treatment of sepsis complication with gastrointestinal dysfunction via gastric antrum cross-sectional area measured by bedside ultrasound / 中华危重病急救医学

OBJECTIVE@#To evaluate the clinical value of Dachengqi decoction in the treatment of sepsis complication with gastrointestinal dysfunction via gastric antrum cross-sectional area (CSA) measured by bedside ultrasound.@*METHODS@#A parallel group randomized controlled trial was conducted. A total of 80 patients with sepsis with gastrointestinal dysfunction admitted to the Second Affiliated Hospital of Nanjing University of Chinese Medicine from January 2021 to October 2022 were enrolled. According to whether patients agree to use Dachengqi decoction after admission, all patients were divided into Dachengqi decoction group (observation group) and conventional treatment group (control group) by 1 : 1 randomization, each group has 40 patients. Both groups were treated with fluid resuscitation, anti-infection, maintaining stable respiratory circulation, early nourishing feeding, promoting gastrointestinal motility, and regulating intestinal flora. The observation group was treated with Dachengqi decoction on the basis of western medicine, 30 mL decoction was taken in the morning and evening. Both groups were treated for 7 days. The CSA of the two groups was measured by bedside ultrasound before and after treatment. The gastric residual volume (GRV1 and GRV2) were calculated by formula and traditional gastric tube withdrawal method. The gastrointestinal dysfunction score, acute physiology and chronic health evaluation II (APACHE II), intraperitoneal pressure (IAP), serum preprotein (PA), albumin (Alb), white blood cell count (WBC), procalcitonin (PCT), hypersensitivity C-reactive protein (hs-CRP), length of intensive care unit (ICU) stay and incidence of aspiration were detected to evaluate the clinical efficacy of Dachengqi decoction, the correlation and advantages and disadvantages between CSA measured by bedside ultrasound and other evaluation indicators of gastrointestinal dysfunction in sepsis were also analyzed.@*RESULTS@#There were no significant differences in the indicators before treatment between the two groups, which were comparable. In comparison with the pre-treatment period, CSA, GRV, gastrointestinal dysfunction score, APACHE II score, IAP, WBC, PCT, and hs-CRP of the two groups after treatment were significantly decreased, PA and Alb were significantly increased, and the observation group decreased or increased more significantly than the control group [CSA (cm2): 4.53±1.56 vs. 6.04±2.52, GRV1 (mL): 39.85±8.21 vs. 53.05±11.73, GRV2 (mL): 29.22±5.20 vs. 40.91±8.97, gastrointestinal dysfunction score: 0.87±0.19 vs. 1.35±0.26, APACHE II score: 11.54±3.43 vs. 14.28±3.07, IAP (cmH2O, 1 cmH2O ≈ 0.098 kPa): 9.79±2.01 vs. 13.30±2.73, WBC (×109/L): 9.35±1.24 vs. 12.35±1.36, PCT (μg/L): 3.68±1.12 vs. 6.43±1.45, hs-CRP (mg/L): 24.76±5.41 vs. 46.76±6.38, PA (mg/L): 370.29±45.89 vs. 258.33±34.58, Alb (g/L): 38.83±5.64 vs. 33.20±4.98, all P < 0.05]. The length of ICU stay (days: 10.56±3.19 vs. 14.24±3.45) and incidence of aspiration (12.5% vs. 25.0%) were lower than those in the control group (both P < 0.05). Correlation analysis showed that CSA measured by bedside ultrasound was positively correlated with GRV2, gastrointestinal dysfunction score, APACHE II score, and IAP (r values were 0.84, 0.78, 0.75, 0.72, all P < 0.01) and negatively correlated with PA and Alb (r values were -0.64 and -0.62, both P < 0.01).@*CONCLUSIONS@#The Dachengqi decoction can significantly improve the clinical symptoms of septic patients with gastrointestinal dysfunction, reduce systemic inflammatory response, improve nutritional status, and shorten ICU hospital stay. Bedside ultrasound monitoring of CSA is a simple, accurate and effective means to evaluate gastrointestinal dysfunction, which is worthy of further clinical promotion.