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Effects of early-life gut microbiota on the neurodevelopmental outcomes of preterm infants: a multi-center, longitudinal observational study in China.
Zhang, D, Lan, Y, Zhang, J, Cao, M, Yang, X, Wang, X
European journal of pediatrics. 2024;(4):1733-1740
Abstract
UNLABELLED To prospectively investigate associations between the features of gut microbiota at the fourth week after birth in preterm infants and neurodevelopment from 1 month of corrected age to 6 months of corrected age (MCA). Seventy-seven preterm infants were recruited from three NICUs of three tertiary hospitals between Apr 2021 to Sep 2022. Stool samples were collected during the fourth week after birth. Illumina MiSeq high-throughput sequencing technology was used to detect the composition and diversity of gut microbiota. Neurodevelopment assessments of preterm infants were conducted at 1, 3, and 6 MCA using the Ages and Stages Questionnaire, the third edition (ASQ-3). Spearman correlation, a generalized linear mixed model (GLMM), and permutational multivariate analysis of variance (PERMANOVA) analysis were used to horizontally and prospectively explore the associations between gut microbial and ASQ-3 dimension scores at each time point. The GLMM showed no significant associations between the alpha diversity and neurodevelopmental trajectory from 1 to 6 MCA. The beta diversity was significantly associated with gross motor scores at 1, 3, and 6 MCA (R2 = 0.067, p = 0.001; R2 = 0.039, p = 0.020; R2 = 0.031, p = 0.047); communication scores at 3 MCA (R2 = 0.030, p = 0.040); and fine motor scores at 6 MCA (R2 = 0.035, p = 0.022). After adjusting for covariates, the GLMM showed that the relative abundance of Klebsiella was negatively associated with gross motor score trajectory from 1 to 6 MCA (β = - 1.449; 95% CI, - 2.275 to - 0.572; p = 0.001), while the relative abundance of Lactobacillus displayed a positive association (β = 1.421; 95% CI, 0.139 to 2.702; p = 0.030). Moreover, the relative abundance of Streptococcus was negatively associated with fine motor trajectory from 1 to 6 MCA (β = - 1.669; 95% CI, - 3.305 to - 0.033; p = 0.046). CONCLUSION Our results suggest a possible association between the neonatal gut microbial diversity; the relative abundance of Klebsiella, Streptococcus, and Lactobacillus; and neurodevelopment from 1 to 6 MCA. In the future, clinical staff can focus on the window period of gut microbiota colonization, and implement probiotics targeted at the dominant genera to improve the neurodevelopment of preterm infants. WHAT IS KNOWN • In the fields of biology and medicine, current studies suggest that gut microbiota may play an important role in the critical window period of neurodevelopment through the gut-brain axis pathway. • Extensive preclinical research has implied the vital role of the initial gut colonization in the long-term neurodevelopment of children. WHAT IS NEW • The early-life gut microbiota was associated with neurodevelopment in preterm infants within 6 months of corrected age (MCA).
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Effect of Baimai ointment on lumbar disc herniation: A multicentre, prospective, randomised, double-blind, placebo-controlled trial.
Sun, C, Sun, K, Wang, S, Wang, Y, Yuan, P, Li, Z, Yang, S, Zhang, J, Jia, Y, Wang, W, et al
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2024;:155138
Abstract
BACKGROUND Baimai ointment is a traditional Tibetan topical ointment, which is widely used for various diseases related to the skeletal muscular system and neurological rehabilitation. It has demonstrated good clinical effectiveness. However, there is currently a lack of high-quality evidence regarding the clinical effectiveness of Baimai ointment in treating lumbar disc herniation (LDH). PURPOSE In this study, we conducted a prospective, multicenter, double-blind, randomized controlled trial at eight hospitals in China to investigate the clinical effectiveness of Baimai ointment in the treatment of LDH. METHODS Participants aged 18-65 years were diagnosed as LDH and were randomly assigned to receive either Baimai ointment or placebo. The treatment duration was 2 weeks, with 1-week follow-up after treatment. The primary outcome measures included VAS and JOA score. The secondary outcome measures included Likert scale, compliance with health education and the incidence of rescue therapy. The intervention effects on these outcomes were examined by generalized estimating equations (GEE) with baseline measurement as the covariates. All statistical analysis were performed using SPSS 25.0 and Python 3.11. RESULTS In total, 228 participants were screened from August 25, 2021 to January 31, 2022 at 8 Grade-A tertiary hospitals in China. Finally, 194 eligible participants were randomly assigned to the Baimai ointment group and placebo group in a 1:1 ratio. At the end of 2-week treatment (14th day) and 1-week follow-up after treatment (21st day), the decrease of VAS reached 39.57% (95% CI: 34.29, 44.86) and 36.85% (95% CI: 32.04, 41.66), the decrease in JOA score reached 27.74% (95% CI: 23.05, 32.43) and 26.25 % (95% CI: 20.82, 31.69) in Baimai ointment group. A significant group-by-time interaction indicated a difference for VAS between intervention over time (χ2 = 26.81, p = 0.020), but JOA score and Likert scale did not reach statistical significance. The adjusted net difference of VAS was statistically significant from 10th day of treatment (p < 0.05). After 2-week treatment, the relief rate of VAS was 30.85% (21.95, 41.34) in Baimai ointment group and 22.73% (14.75, 33.13) in placebo group (χ2 = 1.53, p = 0.217). It demonstrated Baimai ointment in improving VAS and JOA score was valuable from a clinical view by measuring MCID. Moreover, the Likert scale, the incidence of rescue therapy and compliance with health education did not reach statistical significance. There was no evidence showing that Baimai ointment could cause serious adverse reactions in treating patients with LDH. CONCLUSION Baimai ointment demonstrated significantly higher rates of symptom relief compared to the placebo for LDH patients, particularly in terms of relieving pain. Moreover, further high-quality randomized controlled trials were necessary to confirm these positive results. The study protocol is registered with the Clinical Trials Registry (registration number: ISRCTN11912818).
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Machine learning identifies the risk of complications after laparoscopic radical gastrectomy for gastric cancer.
Hong, QQ, Yan, S, Zhao, YL, Fan, L, Yang, L, Zhang, WB, Liu, H, Lin, HX, Zhang, J, Ye, ZJ, et al
World journal of gastroenterology. 2024;(1):79-90
Abstract
BACKGROUND Laparoscopic radical gastrectomy is widely used, and perioperative complications have become a highly concerned issue. AIM: To develop a predictive model for complications in laparoscopic radical gastrectomy for gastric cancer to better predict the likelihood of complications in gastric cancer patients within 30 days after surgery, guide perioperative treatment strategies for gastric cancer patients, and prevent serious complications. METHODS In total, 998 patients who underwent laparoscopic radical gastrectomy for gastric cancer at 16 Chinese medical centers were included in the training group for the complication model, and 398 patients were included in the validation group. The clinicopathological data and 30-d postoperative complications of gastric cancer patients were collected. Three machine learning methods, lasso regression, random forest, and artificial neural networks, were used to construct postoperative complication prediction models for laparoscopic distal gastrectomy and laparoscopic total gastrectomy, and their prediction efficacy and accuracy were evaluated. RESULTS The constructed complication model, particularly the random forest model, could better predict serious complications in gastric cancer patients undergoing laparoscopic radical gastrectomy. It exhibited stable performance in external validation and is worthy of further promotion in more centers. CONCLUSION Using the risk factors identified in multicenter datasets, highly sensitive risk prediction models for complications following laparoscopic radical gastrectomy were established. We hope to facilitate the diagnosis and treatment of preoperative and postoperative decision-making by using these models.
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Insulin Glargine is More Suitable Than Exenatide in Preventing Muscle Loss in Non-Obese Type 2 Diabetic Patients with NAFLD.
Liu, L, Wang, R, Gao, J, Yan, J, Zhang, J, Zhang, Z, Liu, J, Lin, H, Rao, S, Yao, X, et al
Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association. 2023;(11):583-588
Abstract
AIM: This study investigated the effects of insulin glargine and exenatide on the muscle mass of patients with newly diagnosed type 2 diabetes (T2DM) and nonalcoholic fatty liver disease (NAFLD). METHODS We performed a post-hoc analysis of our previously study, a 24-week randomized controlled multicenter clinical trial (ClinicalTrials.gov, NCT02303730). Seventy-six patients were randomly assigned 1:1 to receive insulin glargine or exenatide treatment. The changes in psoas muscle area (PMA) (mm2) were obtained with the cross-sectional Dixonfat magnetic resonance images at the fourth lumber vertebra. RESULTS There were no significant differences in age, BMI, gender, and PMA in insulin glargine and exenatide groups at baseline. After treatment, PMA tended to increase by 13.13 (-215.52, 280.80) mm2 in the insulin glargine group and decrease by 149.09 (322.90-56.39) mm2 in the exenatide group (both p>0.05). Subgroup analysis showed a 560.64 (77.88, 1043.40) (mm2) increase of PMA in the insulin group relative to the Exenatide group in patients with BMI<28 kg/m2 (p0.031) after adjusting for gender, age, and research center. Interaction analysis showed an interaction between BMI and treatment (p0.009). However, no interaction was observed among subgroups with a BMI≥28 kg/m2 or with different genders and ages. CONCLUSION Compared to exenatide, insulin glargine can relativity increase PMA in patients with T2DM having BMI<28 kg/m2 and NAFLD.
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Intravenous versus super-selected intra-arterial chemotherapy in children with advanced unilateral retinoblastoma: an open-label, multicentre, randomised trial.
Wen, X, Fan, J, Jin, M, Jiang, H, Li, J, Han, M, Zhang, C, He, X, Luo, Y, Yang, J, et al
The Lancet. Child & adolescent health. 2023;(9):613-620
Abstract
BACKGROUND Super-selected intra-arterial chemotherapy has increasingly been used as conservative management for retinoblastoma during the past decade. However, the absence of evidence from randomised controlled trials engendered controversy in the administration route of chemotherapy. We aimed to assess the efficacy and safety of intra-arterial chemotherapy compared with intravenous chemotherapy. METHODS This open-label, multicentre, randomised trial was done at six hospitals in China. Patients with new-onset unilateral group D or E retinoblastoma (poorly defined, large, or very large tumours, according to the International Intraocular Retinoblastoma Classification) without high-risk clinical factors were included. Patients were randomly assigned (1:1) to receive intra-arterial chemotherapy (injections of 0·5 mg/kg [or depending on age] melphalan with 20 mg carboplatin [first and third cycles] or with 1 mg topotecan [second and fourth cycles]) or intravenous chemotherapy (0·05 mg/kg [or 1·5 mg/m2] vincristine, 5 mg/kg [or 150 mg/m2] etoposide, and 18·6 mg/kg [or 560 mg/m2] carboplatin for six cycles). After intra-arterial chemotherapy, patients received a subcutaneous injection of 0·1 mL nadroparin calcium twice at a 12 h interval. Both intra-arterial and intravenous chemotherapy cycles were completed every 4 weeks. No masking was done, except of independent statisticians, who were masked to the allocation information. The primary outcome was 2-year progression-free globe salvage rate, defined as the time from randomisation to tumour progression or enucleation, whichever occurred first, and was analysed by intention to treat. We also recorded predefined safety outcomes (myelosuppression and ophthalmic arterial stenosis or occlusion) and severe adverse events likely to be related to study treatment. The study is registered with the Chinese Clinical Trial Registry, ChiCTR-IPR-15006469, and is complete. FINDINGS Between June 1, 2015, and June 1, 2018, 234 patients with newly diagnosed retinoblastoma were screened and 143 eligible patients (median age 23·6 months [IQR 14·0-31·9]) were enrolled and randomly assigned to the intra-arterial chemotherapy group (n=72) or the intravenous chemotherapy group (n=71). At a median follow-up of 35·8 months (IQR 28·4-43·0), the 2-year progression-free globe salvage rate was 53% (38 of 72 patients) in the intra-arterial chemotherapy group and 27% (19 of 71 patients) in the intravenous chemotherapy group (risk ratio 1·97, 95% CI 1·27-3·07, p=0·0020). Myelosuppression was less common in the intra-arterial chemotherapy group than in the intravenous chemotherapy group (37 [51%] of 72 patients vs 50 [70%] of 71 patients; 0·73, 95% CI 0·56-0·96, p=0·021) and less severe (ptrend=0·0070). In the intra-arterial chemotherapy group, two (3%) of 72 patients had ophthalmic artery occlusion and 13 (18%) patients had ophthalmic artery stenosis. INTERPRETATION Our findings show that intra-arterial chemotherapy could significantly improve the globe salvage rate in children with advanced unilateral retinoblastoma compared with intravenous chemotherapy, with mild systemic complications and no difference in overall survival rate. Intra-arterial chemotherapy could be an acceptable first-line treatment in children with advanced unilateral retinoblastoma. FUNDING Scientific Research Program of the National Health and Family Planning Commission of China, the Clinical Research Plan of Shanghai Hospital Development Center, the National Natural Science Foundation of China, and the Science and Technology Commission of Shanghai Municipality.
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A Novel Risk Score Model for the Differential Diagnosis of Type 2 Diabetic Nephropathy: A Multicenter Study.
Zhao, Y, Liu, L, Zuo, L, Zhou, X, Wang, S, Gao, H, Yu, F, Zhang, X, Wang, M, Chen, L, et al
Journal of diabetes research. 2023;:5514767
Abstract
INTRODUCTION DN is a common complication of diabetes. However, diabetes combined with renal injury may involve DN or NDKD, with different treatment schemes. The purpose of our study was to determine the independent risk factors of DN and establish a risk score model to help differentiate DN and NDKD, providing a reference for clinical treatment. METHODS A total of 678 T2D patients who had undergone renal biopsy in four affiliated hospitals of Peking University were consecutively enrolled. Patients were assigned to the DN group and NDKD group according to histopathological results. Seventy percent of patients from PKUFH were randomly assigned to the training group, and the remaining 30% were assigned to the internal validation group. Patients from the other three centers were assigned to the external validation group. We used univariate and multivariate logistic regression analyses to identify independent risk factors of DN in the training group and conducted multivariate logistic regression analysis with these independent risk factors in the training group to find regression coefficients "β" to establish a risk score model. Finally, we conducted internal and external validation of the model with ROC curves. RESULTS Diabetic retinopathy, diabetes duration ≥ 5 years, eGFR < 30 ml/min/1.73 m2, 24 h UTP ≥ 3 g, and no hematuria were independent risk factors (P < 0.05), and each factor scored 2, 1, 1, 1, and 1. We assigned the patients to a low-risk group (0-1 points), a medium-risk group (2-3 points), and a high-risk group (4-6 points), representing unlikely DN, possibly DN, and a high probability of DN, respectively. The AUCs were 0.860, 0.924, and 0.855 for the training, internal validation, and external validation groups, respectively. CONCLUSION The risk score model could help differentiate DN and NDKD in a noninvasive manner, reduce the number of renal biopsies, and provide a reference for clinical treatment.
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Association between body mass index change and mortality in critically ill patients: A retrospective observational study.
Zhang, J, Du, L, Jin, X, Ren, J, Li, R, Liu, J, Li, J, Gao, Y, Wang, X, Wang, G
Nutrition (Burbank, Los Angeles County, Calif.). 2023;:111879
Abstract
OBJECTIVE Previous studies have emphasized the association between baseline body mass index (BMI) and mortality in patients during a stay in the intensive care unit (ICU). However, to our knowledge, few studies have focused on BMI change during an ICU stay. The aim of this study was to explore the prognostic value of BMI change during ICU hospitalization. METHODS This was a multicenter, retrospective cohort study with data extracted from the eICU Collaborative Research Database. Logistic regression models were used to explore the relationship between BMI change and mortality in ICU patients. BMI change was calculated as follows: {[discharge ICU weight (kg) - admission ICU weight (kg)] / height (m)2]}. Interaction and subgroup analyses were conducted for patients grouped with baseline BMI on ICU admission (≥30 versus 25-29.9 versus <25 kg/m2), Acute Physiology and Chronic Health Evaluation (APACHE) IV score (<53 versus ≥53), and ICU length of stay (≥3 versus <3 d). RESULTS Compared with those with weight loss (n = 17 134), patients with weight gain during ICU hospitalization (n = 17 436) were associated with higher hospital mortality (odds ratio [OR], 1.251; 95% confidence interval [CI], 1.155-1.356; P < 0.001) and ICU mortality (OR, 1.360; 95% CI, 1.227-1.506; P < 0.001) after multivariable adjustment. The associations remained robust in patients with different baseline BMI levels and were especially remarkable among those with higher APACHE IV score and the longer ICU stay. CONCLUSIONS The present study exposed the potential hazard of increasing BMI for hospital and ICU mortalities during ICU hospitalization and indicating that patients in the ICU may benefit from a more balanced nutritional strategy.
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Combined use of amlodipine and folic acid are significantly more efficacious than amlodipine alone in lowering plasma homocysteine and blood pressure among hypertensive patients with hyperhomocysteinemia and intolerance to ACEI: A multicenter, randomized, double-blind, parallel-controlled clinical trial.
Bao, H, Huang, X, Li, P, Sheng, C, Zhang, J, Wang, Z, Song, D, Hu, L, Ding, C, Cheng, Z, et al
Journal of clinical hypertension (Greenwich, Conn.). 2023;(8):689-699
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Abstract
Hyperhomocysteinemia with hypertension can synergistically increase the risk of stroke. The China stroke primary prevention trial showed that combining 0.8 mg folic acid (FA) with angiotensin-converting enzyme inhibitor (ACEI) can effectively lower plasma total homocysteine (tHcy) and blood pressure (BP); and reduce first stroke risk by additional 21% compared to ACEI alone. However, intolerance to ACEI is common in Asians and amlodipine can be alternative. This is a multicenter, randomized, double-blind, parallel-controlled clinical trial (RCT) which evaluated whether amlodipine combined with FA is more efficacious than amlodipine alone in lowering tHcy and BP among Chinese hypertensive with hyperhomocysteinemia and intolerance to ACEI. 351 Eligible patients were randomly assigned by 1:1:1 ratio to receive amlodipine-FA tablet daily (amlodipine 5 mg/FA 0.4 mg, A group); amlodipine 5 mg/FA 0.8 mg tablet daily (B group); amlodipine 5 mg daily (C group, control group). Follow-up was conducted at 2, 4, 6, and 8 weeks. The primary outcome was efficacy of lowering both tHcy and BP at the end of 8-week treatment. Compared with C group, A group had a significantly higher rate of lowering both tHcy and BP (23.3% vs. 6.0%; Odds Ratio [OR], 8.68; 95% CI, 3.04-24.78, P < .001); B group also had a higher rate of lowering both tHcy and BP (20.3% vs. 6.0%; OR: 5.90; 95% CI, 2.11-16.47, P < .001). This RCT showed amlodipine combined with FA compared with amlodipine alone, each had significantly higher efficacy of lowering both tHcy and BP. No difference was found in BP-lowering and occurrence of adverse events between the three groups.
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Activity of Anlotinib in the Second-Line Therapy of Metastatic Gastrointestinal Stromal Tumors: A Prospective, Multicenter, In Vitro Study.
Zhou, Y, Zeng, C, Sun, X, Zhang, J, Qu, H, Zhang, X, Zhou, Y, Liu, Z, Wu, X, Wu, X, et al
The oncologist. 2023;(4):e191-e197
Abstract
BACKGROUND Anlotinib is a multi-target tyrosine kinase inhibitor that can effectively inhibit tumor cell proliferation after receptor kinase activation caused by KIT gene mutation. METHODS We tested the inhibitory effect of anlotinib in GIST cell lines with different gene mutations and evaluated the efficacy of anlotinib for patients with metastatic GIST after imatinib failure in a multicenter, single-arm, phase II study. RESULTS In vitro, V654A mutation encoded by KIT exon 13 was intermediately sensitive to anlotinib. Moreover, anlotinib was able to partly suppress the activation loop mutation D820A from exon 17 while another activation loop mutation N822K, also from exon 17, was resistant to anlotinib. From September 2018 to October 2020, 64 patients from 9 Chinese medical centers were enrolled in this study. Seven patients had partial response and 39 patients had stable disease. The median PFS was 8.0 months. There was no statistical significance comparing with PFS of sunitinib second-line therapy at the same period. The most common adverse events related to anlotinib treatment were hypertension, neutropenia, and fatigue. CONCLUSION Anlotinib showed moderate antitumor activity in drug-resistant GIST cell lines in vitro, and good PFS and better tolerance in second-line therapy study.
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Efficacy and Safety of Chinese Herbal Medicine Compared With Losartan for Mild Essential Hypertension: A Randomized, Multicenter, Double-Blind, Noninferiority Trial.
Lai, X, Dong, Z, Wu, S, Zhou, X, Zhang, G, Xiong, S, Wu, W, Cao, R, Wang, X, Hua, Q, et al
Circulation. Cardiovascular quality and outcomes. 2022;(3):e007923
Abstract
BACKGROUND Hypertension is one of the most challenging public health problems worldwide. Previous studies suggested that the Songling Xuemaikang capsule (SXC)-a Chinese herbal formula-was effective for essential hypertension. However, the efficacy of SXC monotherapy for hypertension remains unclear. We aimed to compare the blood pressure (BP)-lowering efficacy and safety of SXC versus losartan in patients with essential hypertension. METHODS In this multicenter, randomized, double-blind, noninferiority trial in China, patients 18 to 65 years of age with mild essential hypertension were randomly allocated to receive either SXC or losartan for 8 weeks. The primary outcome was the change in sitting diastolic BP from baseline to 8 weeks, with a predefined noninferiority margin of -2.5 mm Hg. RESULTS Of the 755 patients who entered a 2-week run-in period, 628 patients (327 women and 301 men; mean [SD] age, 52.6 [9.2] years) were randomly assigned to the SXC (n=314) or losartan (n=314) group. The primary analysis based on the intention-to-treat principle showed that the change in diastolic BP from baseline to 8 weeks was similar between the SXC and losartan groups (-7.9 [8.0] versus -8.1 [7.9]). The lower boundary of 95% CI (mean difference, -0.24 [95% CI, -1.51 to 1.03]) was above the margin of -2.5 mm Hg, showing noninferiority. Results were consistent with per-protocol analysis. SXC produced greater improvements in total hypertension symptom score (-5.7 [4.2] versus -5.0 [4.0]; P=0.020) and total cholesterol (-0.1 [1.0] versus 0.1 [1.2]; P=0.025). There were no differences between groups in the other BP and patient-reported outcomes. Incidence and severity of adverse events were similar between groups. CONCLUSIONS SXC was well tolerated and demonstrated noninferior to losartan in BP lowering in patients with mild hypertension. SXC might be an alternative for mild hypertension, particularly for patients with a preference for natural medicine. REGISTRATION URL: www.chictr.org.cn; Unique identifier: ChiCTR-IPR-16008108.