1.Research progress on strategies to target intestinal microbiota to improve drug resistance in tumor immunotherapy
Hui-ling LI ; Bi-qing LIU ; Ying-nan FENG ; Xin HU ; Lan ZHANG ; Xian-zhe DONG
Acta Pharmaceutica Sinica 2025;60(2):260-268
A growing body of research points out that gut microbiota plays a key role in tumor immunotherapy. By optimizing the composition of intestinal microbiota, it is possible to effectively improve immunotherapy resistance and enhance its therapeutic effect. This article comprehensively analyzes the mechanism of intestinal microbiota influencing tumor immunotherapy resistance, expounds the current strategies for targeted regulation of intestinal microbiota, such as traditional Chinese medicine and plant components, fecal microbiota transplantation, probiotics, prebiotics and dietary therapy, and explores the potential mechanisms of these strategies to improve patients' resistance to tumor immunotherapy. At the same time, the article also briefly discusses the prospects and challenges of targeting intestinal microbiota to improve tumor immunotherapy resistance, which provides a reference for related research to help the strategy research of reversing tumor immunotherapy resistance.
2.Neuropsychological development status and risk factors in small for gestational age infants at corrected ages 12-24 months.
Ran TAN ; Li-Ya MA ; Chang LIU ; Qian LYU ; Bi-Lan DING ; Wan-Xiang XIAO
Chinese Journal of Contemporary Pediatrics 2025;27(11):1339-1345
OBJECTIVES:
To explore the status and risk factors of neuropsychological development in small for gestational age (SGA) infants at corrected 12-24 months of age.
METHODS:
Clinical data were retrospectively collected for 754 SGA infants at corrected ages 12-24 months in Shenzhen Bao'an Women and Children's Hospital between April 2018 and December 2023. Developmental quotient (DQ) levels were analyzed. According to the presence of global developmental delay (GDD), participants were divided into a GDD group (71 cases) and a control group (683 cases), and the incidence and influencing factors of GDD were investigated.
RESULTS:
In the high-risk preterm SGA group, the total DQ and DQ in all domains were lower than in the full-term SGA group (P<0.017). The overall incidence of GDD was 9.4% (71/754) and increased with decreasing gestational age (P<0.017). Compared with the control group, the GDD group had higher proportions of males; low-risk and high-risk preterm birth; mothers with less than a bachelor's degree; multiple birth; neonatal hypoglycemia; neonatal pneumonia; neonatal respiratory distress syndrome; bronchopulmonary dysplasia; and, at corrected 12-24 months, low body weight, growth retardation, and microcephaly. The length of neonatal hospital stay was longer in the GDD group than in the control group (P<0.05). The weight-for-age Z score, length-for-age Z score, and head circumference-for-age Z score at birth and at corrected 12-24 months were lower in the GDD group than in the control group (P<0.05). Multivariable logistic regression showed that male sex and maternal education below a bachelor's degree were independent risk factors for GDD in SGA infants (P<0.05).
CONCLUSIONS
Neuropsychological development in preterm SGA infants is comparatively delayed; male SGA infants born to mothers with less than a bachelor's degree should receive priority attention.
Humans
;
Female
;
Male
;
Infant, Small for Gestational Age/psychology*
;
Risk Factors
;
Infant
;
Retrospective Studies
;
Child Development
;
Developmental Disabilities/epidemiology*
;
Infant, Newborn
;
Child, Preschool
3.Distribution and prognosis analysis of TCM syndromes elements in elderly patients with sepsis and septic shock
Fuyao NAN ; Caijun WU ; Junxi LIU ; Xiang JI ; Yuanzhen JIAN ; Lan LI ; Wei BI
International Journal of Traditional Chinese Medicine 2024;46(9):1113-1120
Objective:To analyze the distribution pattern of TCM syndrome elements in elderly patients with sepsis and septic shock, as well as the relationship between TCM syndrome elements, Sepsis Sequential Organ Failure Score (SOFA), Acute Physiology and Chronic Health Score Ⅱ (APACHE Ⅱ), and short-term mortality prognosis.Methods:A retrospective analysis was conducted on the clinical data of 58 patients treated in the Emergency Department and ICU of Dongzhimen Hospital of Beijing University of Chinese Medicine and the Third Affiliated Hospital of Beijing University of Chinese Medicine from January 1, 2021, to May 1, 2022. The patients were divided into a sepsis group of 38 cases and a septic shock group of 20 cases based on disease type. Basic information, TCM syndromes, SOFA score, and APACHE Ⅱ score of the two groups were collected. The survival and death statuses of the two groups within 28 days of admission were separately analyzed. Association rule analysis was used to investigate the distribution pattern of TCM syndromes in patients, and logistic regression analysis was performed to explore the relationship between TCM syndromes, SOFA score, APACHE Ⅱ score, and death prognosis.Results:In the sepsis group, the main TCM syndromes included yin deficiency, lung, phlegm, qi deficiency, blood stasis, heat, and yang deficiency; while in the septic shock group, the main TCM syndromes were yin deficiency, lung, yang deficiency, and qi deficiency. Multifactor logistic regression analysis showed that in the sepsis group, liver syndromes [ OR (95% CI)=0.080 (0.011, 0.578), P=0.012], meridians and collaterals [ OR (95% CI)=0.088 (0.011, 0.718), P=0.024], SOFA score [ OR (95% CI)=0.524 (0.310, 0.886), P=0.016], and APACHE Ⅱ score [ OR (95% CI)=0.426 (0.186, 0.977), P=0.044] were independent influencing factors for patient mortality prognosis. In the septic shock group, phlegm [ OR (95% CI)=0.014 (0.001, 0.267), P=0.005], meridians and collaterals [ OR (95% CI)=0.041 (0.003, 0.618), P=0.021], yang deficiency [ OR (95% CI)=0.028 (0.002, 0.427), P=0.010], SOFA score [ OR (95% CI)=0.543 (0.310, 0.950), P=0.032], and APACHE Ⅱ score [ OR (95% CI)=0.633 (0.408, 0.985), P=0.042] were independent influencing factors for patient mortality prognosis. Conclusions:The sepsis group mainly exhibits a mixture of deficiency and excess, while the septic shock group predominantly shows deficiency. Qi deficiency and yin deficiency are consistent throughout the disease progression. Meridians and collaterals, high SOFA score, and high APACHE Ⅱ score in elderly patients with sepsis and septic shock may indicate a poorer prognosis.
4.Evaluation of a prediction model for the risk of acute urinary retention in elderly hip fracture patients in the Emergency Care
Ran BI ; Xueqi LI ; Lan GUAN ; Zhaoxing TIAN
Chinese Journal of Emergency Medicine 2024;33(8):1172-1177
Objective:To establishing a clinical prediction model can assist clinicians in identifying at-risk patients early and intervening promptly to decrease AUR incidence.Methods:A retrospective collection of 313 elderly patients with hip fracture treated between 1st July and 31st August 2023 at the Emergency Department of our hospital. Patients were categorised into two groups: The AUR group (45 patients) and the non-AUR group (268 patients) based on the presence or absence of AUR. Basic characteristics, laboratory indicators and bladder volume were compared between the two groups. Factors independently associated with the incidence of AUR were analysed using Logistic regression. Analysis of the independent risk factors impacting the occurrence of AUR, development of a clinical prediction model for the risk of AUR in elderly patients with hip fractures, and internal validation of the model.Results:Comorbid psycho-behavioural symptoms of dementia ( OR=3.334, 95% CI 1.258-8.839, P=0.015), use of hypnotic sedatives ( OR=6.758, 95% CI 2.184-20.912, P=0. 001), increased heart rate ( OR=1.041, 95% CI 1.013-1.070, P=0.004), and increased bladder volume ( OR=1.005, 95% CI 1.004-1.007, P<0.01) were all identified as risk factors. The study identified independent risk factors for AUR in elderly patients who suffered a hip fracture. Based on these factors, the research team developed a prediction model which underwent internal validation using the Bootstrap method. The analysis indicated that the model’s prediction curves aligned closely with the standard model curves. The average absolute error was 0.021. The study's ROC results showed an AUC of 0.083 and a 95% CI of 0.767-0.909. Conclusions:Comorbid psycho-behavioural symptoms of dementia, the use of hypnotic sedative drugs, an increased heart rate, and an increased bladder volume are independent risk factors for the occurrence of AUR in elderly patients who have suffered a hip fracture. The creation of a chart prediction model using columns allows for a visual evaluation of the likelihood of AUR in elderly patients with hip fractures. This model provides important reference material for emergency physicians.
5.Preparation of soluble microneedles of Aconitum brachypodum alkaloids
Yao CHEN ; Bi-Li DENG ; Jing WAN ; Na-Na DONG ; Xiao-Lan CHEN ; Yong-Ping ZHANG
Chinese Traditional Patent Medicine 2024;46(3):740-747
AIM To prepare the soluble microneedles of Aconitum brachypodum Diels alkaloids.METHODS Centrifugal molding method was adopted in the preparation of soluble microneedles.With chondroitin sulfate consumption,PVP K120 consumption and 40%ethanol consumption as influencing factors,piercing rate as an evaluation index,the formulation was optimized by Box-Behnken response surface method,after which the morphology,piercing performance,drug content and in vitro transdermal performance were investigated.RESULTS The optimal formulation was determined to be 123 mg for chondroitin sulfate consumption,298 mg for PVP K120 consumption,and 2.4 mL for 40%ethanol consumption,the piercing rate was 98.3%.The soluble microneedles were yellow and square patch with conoid needle,which could pierce aluminum foil and rat skin,along with the drug content of(0.94±0.025)mg.The soluble microneedle group demonstrated the accumulative permeability rate of 91.4%within 24 h,which was higher than that in the gel ointment group,and the permeability accorded with Higuchi equation.CONCLUSION The soluble microneedles of A.brachypodum alkaloids exhibit good mechanical strength,which can achieve effective transdermal delivery of drugs.
6.Risk factors analysis for severe acute kidney injury in septic patients and establishment and validation of an hour-specific prediction model
Lan JIA ; Xueqing BI ; Jia MENG ; Hongye DONG ; Xian LI ; Lihua WANG ; Aili JIANG
Chinese Critical Care Medicine 2024;36(9):910-916
Objective:To explore the risk factors of severe acute kidney injury (AKI) in septic patients, and to establish an hour-specific prediction model.Methods:Based on the information of septic patients in the Medical Information Mart for Intensive Care-Ⅳ (MIMIC-Ⅳ) database, general information, comorbidities, vital signs, severity scoring system, laboratory indicators, invasive operations and medication use were recorded. The enrolled patients were randomized into a training set and a validation set according to a ratio of 7∶3. AKI was diagnosed according to the guidelines of Kidney Disease: Improving Global Outcome (KDIGO). Based on Lasso regression and Cox regression, the risk factors of severe AKI (AKI stage 2 and stage 3) in septic patients were analyzed and hour-specific prediction model were established. Consistency index (C-index), area under the receiver operator characteristic curve (AUC) and calibration curve were used to assess the predictive efficacy of the model.Results:A total of 20 551 septic patients were enrolled, including 14 385 patients in the training set and 6 166 patients in the validation set. Multivariate Cox regression analysis showed that atrial fibrillation [hazard ratio ( HR) = 1.266, 95% confidence interval (95% CI) was 1.150-1.393], heart failure ( HR = 1.348, 95% CI was 1.217-1.493), respiratory failure ( HR = 1.565, 95% CI was 1.428-1.715), heart rate ( HR = 1.004, 95% CI was 1.002-1.007), mean arterial pressure ( HR = 1.245, 95% CI was 1.126-1.377), lactic acid ( HR = 1.051, 95% CI was 1.025-1.077), simplified acute physiology score Ⅱ (SAPSⅡ, HR = 1.019, 95% CI was 1.016-1.023), serum creatinine ( HR = 1.171, 95% CI was 1.127-1.216), anion gap ( HR = 1.024, 95% CI was 1.010-1.038), serum potassium ( HR = 1.155, 95% CI was 1.079-1.236), white blood cell count ( HR = 1.006, 95% CI was 1.003-1.009) and furosemide use ( HR = 0.414, 95% CI was 0.368-0.467) were independently associated with severe AKI in septic patients (all P < 0.01). The above predictors were applied to construct an hour-specific prediction model for the occurrence of severe AKI in septic patients. The C-index of the prediction model was 0.723 and 0.735 in the training and validation sets, respectively. The AUC for the occurrence of severe AKI at 12, 24, and 48 hours were 0.795 (95% CI was 0.782-0.808), 0.792 (95% CI was 0.780-0.805), and 0.775 (95% CI was 0.762-0.788) in the training set, and the AUC were 0.803 (95% CI was 0.784-0.823), 0.791 (95% CI was 0.772-0.810), and 0.773 (95% CI was 0.752-0.793) in the validation set, respectively. The calibration curves of the two cohorts were in good agreement. Conclusion:The hour-specific prediction model effectively identifies high-risk septic patients for developing severe AKI within 48 hours, aiding clinicians in stratifying patients for early therapeutic interventions to improve outcomes.
7. Molecular mechanism of a Matijin-su derivative for inhibiting proliferation, invasion and migration of prostate cancer cells
Cai-Hong WU ; Jia YU ; Sha CHENG ; Lan-Lan LI ; Bi-Xue XU ; Heng LUO ; Cai-Hong WU ; Lan-Lan LI ; Jia YU ; Sha CHENG ; Bi-Xue XU ; Heng LUO ; Ming-Fei YANG
Chinese Pharmacological Bulletin 2023;39(3):453-462
Aim To investigate the effects of HXL130 on the proliferation, invasion and migration of prostate cancer PC3 cells and its molecular mechanism. Methods MTT assay was used to detect the effect of HXL130 on the proliferation of prostate cancer PC3 cells. Hoechst 33258 staining and flow cytometry were used to detect the effects on apoptosis and cell cycle of cancer cells. Transwell was used to detect the effects of compounds on the invasion and migration of cancer cells. Proteomic sequencing was employed to detect differentially expressed proteins (DEPs) induced by compound treatment of cancer cells. Bioinformatics was used to analyze the functions of DEPs and the related signaling pathways regulated by DEPs, and Western blot was used to verify the result. Results The survival rate of PC3 cells decreased with the increase of HXL130 concentration and treatment time. HXL130 could significantly induce cell apoptosis and block G
8.Relationship between Dining Place, Iodine Source, and Iodine Nutrition in School-Age Children: A Cross-Sectional Study in China.
Ting Ting QIAN ; Rong SUN ; Lan Chun LIU ; Wen Jing CHE ; Meng ZHAO ; Ling ZHANG ; Wei Dong LI ; Qing Zhen JIA ; Jian Hui WANG ; Jin Shu LI ; Zhi Hui CHEN ; Bi Yun ZHANG ; Peng LIU
Biomedical and Environmental Sciences 2023;36(1):10-23
OBJECTIVE:
This study assesses the impact of iodine-rich processed foods and dining places on the iodine nutritional status of children.
METHODS:
School-aged children (SAC) in seven provinces in China were selected by school-based multi-stage sampling. Urinary iodine, salt iodine, and thyroid volume (TVOL) were determined. Questionnaires were used to investigate dining places and iodine-rich processed foods. The water iodine was from the 2017 national survey. Multi-factor regression analysis was used to find correlations between variables.
RESULTS:
Children ate 78.7% of their meals at home, 15.1% at school canteens, and 6.1% at other places. The percentage of daily iodine intake from water, iodized salt, iodine-rich processed foods, and cooked food were 1.0%, 79.2%, 1.5%, and 18.4%, respectively. The salt iodine was correlated with the urinary iodine and TVOL, respectively (r = 0.999 and -0.997, P < 0.05). The iodine intake in processed foods was weakly correlated with the TVOL (r = 0.080, P < 0.01). Non-iodized salt used in processed foods or diets when eating out had less effect on children's iodine nutrition status.
CONCLUSION
Iodized salt remains the primary source of daily iodine intake of SAC, and processed food has less effect on iodine nutrition. Therefore, for children, iodized salt should be a compulsory supplement in their routine diet.
Humans
;
Child
;
Nutritional Status
;
Cross-Sectional Studies
;
Iodine
;
Sodium Chloride, Dietary/analysis*
;
China
;
Water
9.Effective constituents of essential oil from Gleditsiae Fructus Abnormalis and anti-cerebral ischemia/reperfusion injury mechanism: based on GC-MS, network pharmacology, and experimental verification.
Na-Na DONG ; Xiao-Lan CHEN ; Bi-Li DENG ; Shu-Cai XIE ; Juan HU
China Journal of Chinese Materia Medica 2023;48(4):1076-1086
Based on GC-MS and network pharmacology, the active constituents, potential targets, and mechanism of essential oil from Gleditsiae Fructus Abnormalis(EOGFA) against cerebral ischemia/reperfusion(I/R) injury were explored, and the effective constituents were verified by experiment. To be specific, GC-MS was used identify the constituents of the volatile oil. Secondly, the targets of the constituents and disease were predicted by network pharmacology, and the drug-constituent-target network was constructed, followed by Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment of the core targets. Molecular docking was performed to investigate the binding affinity between the active constituents and the targets. Finally, SD rats were used for experimental verification. The I/R injury model was established, and the neurological behavior score, infarct volume, and pathological morphology of brain tissue were measured in each group. The content of interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-alpha(TNF-α) was determined by enzyme-linked immunosorbent assay(ELISA), and the protein expression of vascular endothelial growth factor(VEGF) by Western blot. A total of 22 active constituents and 17 core targets were screened out. The core targets were involved in 56 GO terms and the major KEGG pathways of TNF signaling pathway, VEGF signaling pathway, and sphingolipid signaling pathway. Molecular docking showed that the active constituents had high affinity to the targets. The results of animal experiment suggested that EOGFA can alleviate the neurological impairment, decrease the cerebral infarct volume and the content of IL-1β, IL-6 and TNF-α, and down-regulate the expression of VEGF. The experiment verified the part results of network pharmacology. This study reflects the multi-component, multi-target, and multi-pathway characteristics of EOGFA. The mechanism of its active constituents is related to TNF and VEGF pathways, which provides a new direction for in-depth research on and secondary development of Gleditsiae Fructus Abnormalis.
Animals
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Rats
;
Rats, Sprague-Dawley
;
Network Pharmacology
;
Oils, Volatile
;
Gas Chromatography-Mass Spectrometry
;
Interleukin-6
;
Molecular Docking Simulation
;
Tumor Necrosis Factor-alpha
;
Vascular Endothelial Growth Factor A
;
Reperfusion Injury
;
Cerebral Infarction
10.Physical growth and neurodevelopment of preterm infants at the corrected age of 18-24 months.
Zi-Yi ZHANG ; Wan-Xiang XIAO ; Li-Ya MA ; Jing-Ru CAO ; Xiao-Li ZHAO ; Bi-Lan DING
Chinese Journal of Contemporary Pediatrics 2023;25(1):25-30
OBJECTIVES:
To investigate the levels of physical growth and neurodevelopment in preterm infants at the corrected age of 18-24 months.
METHODS:
The physical growth data and neurodevelopment data of 484 preterm infants at corrected age of 18-24 months were prospectively collected by a post-discharge follow-up system for preterm infants. The infants were regularly followed up in Shenzhen Bao'an Maternal and Child Health Hospital Affiliated to Jinan University from April 2018 to December 2021. The neurodevelopment was evaluated by the Children Neuropsychological and Behavioral Scale-Revision 2016. A total of 219 full-term infants served as controls. The infants were divided into groups (extremely preterm, very preterm, moderate late preterm, and full-term) based on gestational age, and the groups were compared in the levels of physical growth and neurodevelopment.
RESULTS:
Except that the moderate preterm group had a higher length-for-age Z-score than the full-term group (P=0.038), there was no significant difference in physical growth indicators between the preterm groups and the full-term group (P>0.05). Each preterm group had a significantly lower total developmental quotient (DQ) than the full-term group (P<0.05). Except for the social behavior domain, the DQ of other domains in the extremely preterm and very preterm groups was significantly lower than that in the full-term group (P<0.05). The <32 weeks preterm group had a significantly higher incidence rate of global developmental delay than the full-term group (16.7% vs 6.4%, P=0.012), and the incidence rate of global developmental delay tended to increase with the reduction in gestational age (P=0.026).
CONCLUSIONS
Preterm infants can catch up with full-term infants in terms of physical growth at the corrected age of 18-24 months, but with a lower neurodevelopmental level than full-term infants. Neurodevelopment monitoring and early intervention should be taken seriously for preterm infants with a gestational age of <32 weeks.
Infant
;
Child
;
Infant, Newborn
;
Humans
;
Child, Preschool
;
Infant, Premature
;
Aftercare
;
Patient Discharge
;
Gestational Age

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