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.

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

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.

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.

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.

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.

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

The phenylpropanoid pathway is one of the important pathways for synthesizing plant secondary metabolites, which can produce lignin, flavonoid, and sinapoylmalate. These compounds can not only affect the plant growth, development, and stress response, but also be used to produce perfume, pesticide, dye, medicine, feed, and biomass energy. R2R3-MYBs play important roles in regulating plant secondary metabolism, organ development, and in responding to environmental stresses. Wheat (Triticum aestivum L.) is an important food crop, but lots of straw will be produced accompanied by grain yields. Therefore, elucidating the function and regulatory mechanism of R2R3 MYBs of wheat is crucial for the effective utilization of the wheat straw. RT-PCR results showed that TaMYB1A was highly expressed in the wheat stems, and the GFP-TaMYB1A fusion protein was mainly localized in the nucleus of the N. benthamiana epidermal cells. TaMYB1A has transcriptional repressive activity in yeast cells. In this study, TaMYB1A-overexpressed transgenic Arabidopsis lines were generated to elucidate the effect of overexpression of TaMYB1A on the biosynthesis of lignin and flavonoid. Our results suggested that overexpression of TaMYB1A inhibited the plant height (P < 0. 05) and decreased the lignin (P < 0. 05) and flavonoid (P < 0. 05) biosynthesis of the transgenic Arabidopsis plants significantly. TaMYB1A could bind to the promoters of the Arabidopsis At4CL1, AtC4H, AtC3H, and AtCHS as well as the wheat Ta4CL1 and TaC4H1 revealed by yeast one-hybrid (Y1H) assasy, the transcriptional repressive effect of TaMYB1A on At4CL1, AtC4H, AtC3H, and AtCHS was confirmed by dual-luciferase reporter systems and also on Ta4CL1 and TaC4H1 by a genetic approach. Gene chip and quantitative RT-PCR (qRT-PCR) results showed that overexpression of TaMYB1A down-regulated the expression of most of the key genes involved in the phenylpropanoid metabolism and decreased the 4CL activity (P < 0. 05) of the transgenic Arabidopsis plants significantly. As suggested above, the wheat TaMYB1A belongs to the subgroup 4 R2R3 MYB transcription factors. TaMYB1A could bind to the promoters of the key genes involved in phenylpropanoid metabolism, repress their expression and negatively regulate the phenylpropanoid metabolism pathway and plant height.

Objective: To investigate the factors influencing total bilirubin elevation and its correlation with UGT1A1 gene polymorphism in the early postoperative period of transjugular intrahepatic portosystemic shunt (TIPS). Methods: 104 cases with portal hypertension and esophageal variceal hemorrhage (EVB) treated with elective TIPS treatment were selected as the study subjects and were divided into a bilirubin-elevated group and a normal bilirubin group according to the total bilirubin elevation level during the early postoperative period. Univariate analysis and logistic regression were used to analyze the factors influencing total bilirubin elevation in the early postoperative period. PCR amplification and first-generation sequencing technology were used to detect the polymorphic loci of the UGT1A1 gene promoter TATA box, enhancer c.-3279 T > G, c.211G > A, and c.686C > A. Logistic regression was used to analyze the correlation of four locus alleles and genotypes with elevated total bilirubin in the early postoperative period. Results: Among the 104 cases, 47 patients were in the bilirubin elevated group, including 35 males (74.5%) and 12 females (25.5%), aged (50.72 ± 12.56) years. There were 57 cases in the normal bilirubin group, including 42 males (73.7%) and 15 females (26.3%), aged (51.63 ± 11.10) years. There was no statistically significant difference in age (t = -0.391, P = 0.697) and gender (χ(2) = 0.008, P = 0.928) between the two groups of patients. Univariate analysis revealed that preoperative alanine transaminase (ALT) level (χ(2) = 5.954, P = 0.015), total bilirubin level (χ(2) = 16.638, P < 0.001), MELD score (χ(2) = 10.054, P = 0.018), Child-Pugh score (χ(2) = 6.844, P = 0.022), and postoperative portal vein branch development (χ(2) = 6.738, P = 0.034) were statistically significantly different between the two groups. Logistic regression analysis showed that preoperative ALT level, total bilirubin level, and portal vein branch development after TIPS were correlated with the elevated total bilirubin in the early postoperative period. The polymorphism of the c.211G > A locus of the UGT1A1 gene correlation had elevated total bilirubin in the early postoperative period of TIPS. The risk of elevated total bilirubin was increased in the population carrying allele A (P = 0.001, OR = 4.049) in the early postoperative period. Allelic polymorphisms in the TATA box promoter region and enhancer c.-3279 T > G and c.686C > A had no statistically significant difference between the bilirubin-elevated group and the normal bilirubin group. Conclusion: The preoperative ALT level, total bilirubin level, and portal vein branch development are correlated with the elevated total bilirubin in early postoperative patients. The polymorphisms of the UGT1A1 gene and enhancer c.211G > A are correlated with the occurrence of elevated total bilirubin in the early postoperative period of TIPS. Allele A carrier may have a higher risk of elevated total bilirubin in the early postoperative period.
Female ; Humans ; Male ; Bilirubin ; Esophageal and Gastric Varices ; Gastrointestinal Hemorrhage/surgery* ; Portasystemic Shunt, Transjugular Intrahepatic ; Postoperative Period ; Retrospective Studies ; Treatment Outcome ; Adult ; Middle Aged ; Glucuronosyltransferase/genetics*

Objective:To analyze the risk factors of acute kidney injury (AKI) in hip fracture patients with serious underlying diseases and establish a prediction nomogram.Methods:Clinical information of hip fracture patients admitted to the intensive care unit (ICU) of Beth Israel Deaconess Medical Center (BIDMC) was analyzed using the Medical Information Mart for Intensive Care (MIMIC)-IV. Patient comorbidities, disease scores, vital signs and laboratory tests, surgical modalities, invasive procedures, and drug use were recorded. According to the diagnostic criteria of AKI in the Kidney Disease Improving Global Outcome (KDIGO) guideline, the enrolled patients were randomly divided into training set and validation set. Based on logistic regression analysis, least absolute shrinkage and selection operator (LASSO) logistic regression algorithm was used to analyze the risk factors of AKI after admission, and the corresponding prediction model was calculated.Results:A total of 474 patients were enrolled, including 331 in the training set and 143 in the validation set. According to the diagnostic criteria of AKI of KDIGO guidelines, the patients were divided into AKI group (159 cases) and non-AKI group (172 cases). Univariate analysis showed that age ( t=2.61, P=0.009), coronary heart disease (χ 2=2.08, P=0.038), heart failure (χ 2=2.60, P=0.009), hemoglobin ( t=1.89, P=0.059), platelets ( t=1.81, P=0.070), urea nitrogen ( t=2.83, P=0.005), blood creatinine ( t=3.65, P<0.001), blood sodium ( t=2.55, P=0.011), blood glucose ( t=2.52, P=0.012), anion gap ( t=3.44, P=0.001), diastolic blood pressure ( t=2.72, P=0.007), mean arterial pressure ( t=2.16, P=0.031), SOFA score ( t=3.69, P<0.001), simplified acute physiological function score II (SAPSII) score ( t=2.95, P=0.003), as well as furosemide (χ 2=2.03, P=0.042), vancomycin (χ 2=1.70, P=0.089), vasoactive medications (χ 2=3.74, P<0.001) and use of invasive mechanical ventilation (χ 2=4.81, P<0.001) were risk factors associated with the development of AKI in hip fracture patients. Multivariate logistic regression analysis showed that age ( OR=1.03, P<0.001), coronary heart disease ( OR=2.05, P=0.069), hemoglobin ( OR=0.88, P=0.050), blood creatinine ( OR=1.37, P=0.009), blood sodium ( OR=1.07, P=0.026), anion gap ( OR=1.09, P=0.028) and vasoactive medications ( OR=3.83, P=0.018) and the use of invasive mechanical ventilation ( OR=6.56, P<0.001) were independent predictors of the development of AKI in hip fracture patients with serious underlying diseases. The area under the curve of the nomogram prediction model constructed by the above 8 predictors was 0.789, and the calibration curve of the nomogram was close to the ideal diagonal. Decision curve analysis showed that the net benefit of the model was significant. Conclusion:The incidence of AKI is high in hip fracture patients with serious underlying diseases. Age, coronary heart disease, hemoglobin, serum creatinine, serum sodium, anion gap, vasoactive drugs, and invasive mechanical ventilation can predict the occurrence of AKI to a certain extent. Combined with the risk factors, the construction of the corresponding prediction model can predict and manage the diagnosis and treatment of AKI in patients with hip fracture complicated with severe underlying diseases.