Objective To investigate the comparative neuroprotective effects of human umbilical cord mesenchymal stem cells(hUC-MSCs-Exos)administered via different routes on hypoxic ischemic brain damage(HIBD)in neonatal mice.Methods Healthy one-week-old SPF-grade BALB/c mice were randomly divided into 4 groups:sham operation group(n=6),model group(n=6),exosome group 1(n=8),exosome group 2(n=8).HIBD was induced using the Rice-Vannucci method.Exosome group 1 and Exosome group 2 were intraperitoneal injection/intranasal drip of phosphate buffer(PBS)100 μl containing 10 μl exosomes within 24 h after successful modeling,respectively.Sham operation and model groups were intraperitoneal injection of PBS 100 μl.On the 7th day after the intervention,neuromotor function was assessed using the horizontal grid test and pole climbing test.On the 2nd day after the evaluation,all mice were killed and their brains were removed by decapitation.HE staining was used to observe the pathological injury of brain tissue,toluidine blue staining was used to observe the survival of neurons in cerebral cortex,and TUNEL staining was used to observe the apoptosis of cerebral cortex cells.Results Compared with sham operation group,model group,exosome group 1 and exosome group 2 exhibited increased hind limb drops in horizontal grid test and climbing scores(P<0.05).No significant difference was found in model group,exosome group 1 and exosome group 2 in these measures(P<0.05).Significant pathology was observed in model group,exosome group 1 and exosome group 2 compared to sham operation group(P<0.05),with significantly reduced damage in exosome group 1 and exosome group 2 compared to model group(P<0.05).Compared with sham operation group,Nissl body count was lower in model group and exosome group 1 and exosome group 2,with a higher count in exosome group 2 compared to exosome group 1(P<0.05).Compared with sham operation group,apoptotic cells were higher in model group and exosome group 1 and exosome group 2,with a significant reduction in exosome group 1 and exosome group 2 compared to model group,and the lowest in exosome group 2(P<0.05).Conclusions hUC-MSCs-Exos can improve the neuronal motor function,promote neuron repair and inhibit apoptosis in HIBD mice.Intranasal administration of hUC-MSCs-Exos is more effective than intraperitoneal administration for reducing neuronal apoptosis in HIBP neonatal mice,offering a convenient and rapid method suitable for clinical application.

Objective:To investigate the effect of intradialytic cerebral blood flow (CBF) fluctuation on cognitive decline in middle-aged and elderly maintenance hemodialysis (MHD) patients.Methods:It was a prospective cohort study. MHD patients aged ≥50 years from Beijing Shijitan Hospital were enrolled from January 2023 to June 2023. Middle cerebral artery mean flow velocity (MFV) was serially monitored via transcranial Doppler (TCD) during dialysis sessions. Cognitive function was assessed at baseline and after 12-month follow-up using standardized neuropsychological tests: montreal cognitive assessment (MoCA), auditory verbal learning test (AVLT 5), complex figure test (CFT), trail making test-B (TMT-B), Stroop color and word test (SCWT), and symbol digit modalities test (SDMT). ΔMFV was calculated as pre-to-post dialysis MFV difference. Multivariable linear regression was used to analyze the association of ΔMFV and cognition.Results:A total of 121 MHD patients were recruited with an age of (63.63±8.44) years. There were 97 males (80.2%), and the dialysis vintage was (55.08±54.73) months. Significant intradialytic MFV reductions were observed ( P<0.05). At 12 months, cognitive decline manifested in global cognition (MoCA), memory (CFT-memory), executive function (TMT-B, SCWT-C, SCWT-T), attention (SDMT), visuospatial ability (CFT-copy)(all P<0.05). Multivariable linear regression analysis revealed ΔMFV independently predicted declines in: MoCA ( B=0.066, 95% CI 0.018-0.113, P=0.007), AVLT5 ( B=0.050, 95% CI 0.004-0.097, P=0.035), TMT-B ( B=-1.955, 95% CI -3.453--0.457, P=0.011), SCWT-C ( B=0.298, 95% CI 0.112-0.484, P=0.002), SCWT-T ( B=-1.371, 95% CI -2.303--0.439, P=0.004). Conclusions:Hemodialysis induces acute CBF reductions detectable by TCD. Cumulative intradialytic CBF fluctuations may accelerate cognitive deterioration in middle-aged and elderly MHD populations, particularly affecting memory and executive domains.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To evaluate the value of ultrasound radiomics combined with machine learning for early diagnosis of seronegative Hashimoto’s thyroiditis (SN-HT) .Methods:This retrospective study included 164 patients from Liaoning Provincial People’s Hospital , Lixin County People’s Hospital, Linghai Dalinghe Hospital, Fengcheng Phoenix Hospital, who underwent thyroidectomy for solitary nodules with normal thyroid function between Nov. 2016 and Jan. 2024. Postoperative pathology confirmed Hashimoto’s thyroiditis (HT) in some cases, who were further categorized into antibody-positive and antibody-negative groups based on serum antibody status. Patients without Hashimoto’s thyroiditis served as the control group. A total of 298 ultrasound images were analyzed. Radiomics features were extracted from hypoechoic non-nodular areas within 0.5 cm surrounding the tumor. Two senior pathologists and two senior ultrasound physicians independently assessed lymphocytic infiltration, eosinophilic changes of follicular epithelium, and the proportion of hypoechoic areas in pathology and ultrasound images, respectively. A machine learning model, CCH-NET, was developed using linear regression and t-distributed stochastic neighbor embedding (t-SNE) techniques. The dataset was divided into a training set (80%) and a validation set (20%) to compare the diagnostic accuracy of CCH-NET with that of senior ultrasound physicians. Results:In internal validation, CCH-NET achieved a diagnostic accuracy of 88.89% for both antibody-positive and antibody-negative groups, significantly higher than the 66.67% accuracy of senior ultrasound physicians ( P<0.01). In external validation, CCH-NET achieved 75.00% and 66.67% accuracy for the two groups, compared to 50.00% by senior ultrasound physicians. For the control group, both methods achieved 93.33% accuracy. The AUC of CCH-NET was 0.848, outperforming senior ultrasound physicians (0.681) ,demonstrating superior diagnostic performance. Conclusion:The radiomics-based CCH-NET model, using non-nodular hypoechoic areas as a specific indicator, can accurately identify early SN-HT in euthyroid patients. It significantly outperforms senior ultrasound physicians, improving diagnostic accuracy and reducing missed diagnoses.

Objective:To investigate the effect of intradialytic cerebral blood flow (CBF) fluctuation on cognitive decline in middle-aged and elderly maintenance hemodialysis (MHD) patients.Methods:It was a prospective cohort study. MHD patients aged ≥50 years from Beijing Shijitan Hospital were enrolled from January 2023 to June 2023. Middle cerebral artery mean flow velocity (MFV) was serially monitored via transcranial Doppler (TCD) during dialysis sessions. Cognitive function was assessed at baseline and after 12-month follow-up using standardized neuropsychological tests: montreal cognitive assessment (MoCA), auditory verbal learning test (AVLT 5), complex figure test (CFT), trail making test-B (TMT-B), Stroop color and word test (SCWT), and symbol digit modalities test (SDMT). ΔMFV was calculated as pre-to-post dialysis MFV difference. Multivariable linear regression was used to analyze the association of ΔMFV and cognition.Results:A total of 121 MHD patients were recruited with an age of (63.63±8.44) years. There were 97 males (80.2%), and the dialysis vintage was (55.08±54.73) months. Significant intradialytic MFV reductions were observed ( P<0.05). At 12 months, cognitive decline manifested in global cognition (MoCA), memory (CFT-memory), executive function (TMT-B, SCWT-C, SCWT-T), attention (SDMT), visuospatial ability (CFT-copy)(all P<0.05). Multivariable linear regression analysis revealed ΔMFV independently predicted declines in: MoCA ( B=0.066, 95% CI 0.018-0.113, P=0.007), AVLT5 ( B=0.050, 95% CI 0.004-0.097, P=0.035), TMT-B ( B=-1.955, 95% CI -3.453--0.457, P=0.011), SCWT-C ( B=0.298, 95% CI 0.112-0.484, P=0.002), SCWT-T ( B=-1.371, 95% CI -2.303--0.439, P=0.004). Conclusions:Hemodialysis induces acute CBF reductions detectable by TCD. Cumulative intradialytic CBF fluctuations may accelerate cognitive deterioration in middle-aged and elderly MHD populations, particularly affecting memory and executive domains.

Objective:To investigate the association between peripheral immune function status and lung cancer metastasis,and to identify peripheral blood immune biomarkers for'Deficiency of Vital Qi'assessment in lung cancer metastasis.Methods:A retrospective analysis was conducted on peripheral blood immune markers collected before treatment from lung cancer patients admitted into Shanghai Municipal Hospital of Traditional Chinese Medicine,affiliated to Shanghai University of Traditional Chinese Medicine,between March 2023 and April 2025.Patients were categorized into the non-metastatic and the metastatic groups based on the presence of distant metastasis,and the differences in the expressions of immune cells and cytokines between groups were compared.Peripheral blood immune markers with P<0.05 in univariate analysis were incorporated into a multivariate binary logistic regression model to identify independent predictors of lung cancer metastasis.Results:A total of 193 lung cancer patients were included(101 in the non-metastatic group and 92 in the metastatic group).There were no statistically significant differences between the two groups in terms of gender,age,smoking history,drinking history,or pathological type(all P>0.05).Univariate analysis revealed significant differences in multiple immune markers between the non-metastatic and metastatic groups(all P<0.05),including:lymphocyte count,CD3+,CD4+,and CD8+T,CD19+B cells,absolute counts of CD3-CD16+CD56+NK cells,percentages of Treg cells,CD8+CD28+Treg cells,G-MDSC,and CD3-CD16+CD56+dim NK cells,and levels of cytokine IL-1β,IL-6,and IL-10.Binary logistic regression analysis of differential indicators suggested that the percentage of Treg cells and CD8+CD28+Treg cells in peripheral blood were independent predictors of distant metastasis in lung cancer(OR=1.193,95%CI[1.047,1.36],P<0.01;OR=0.978,95%CI[0.957,0.999],P<0.05).Conclusion:Peripheral blood immune dysfunction is the biological basis for'qi deficiency'in lung cancer metastasis.This study quantitatively demonstrates the correlation between peripheral immune function status and lung cancer metastasis,providing empirical evidence for the theories of'qi deficiency and hidden toxicity'and'metastatic state of tumors'.

Objective:To identify the gene mutation types of 4 suspected β-thalassemia patients in Yunnan Province,and to analyze the genotypes and hematological phenotypes.Methods:Whole genome sequencing was performed on the samples of 4 suspected β-thalassemia patients from the Dai ethnic group in a thalassemia endemic area of Yunnan Province,whose hematological phenotypes were not consistent with the results of common thalassemia gene mutations.The mutations of β-globin gene clusters were confirmed by polymerase chain reaction(PCR)and Sanger DNA sequencing technology.Results:The 3.5 kb deletion in β-globin gene cluster(NC_000011.10:g.5224302-5227791 del3490bp)was detected in 4 patients'samples,of which 1 case was also detected with HbE mutation and 1 case with CD17 mutation.These 2 patients displayed moderate anemia phenotype,while the two patients with only the 3.5 kb deletion presented with other mild anemia phenotype.Conclusion:Heterozygous carriers with rare 3.5 kb deletion of the β-globin gene cluster may develop mild anemia,compound mutations of the 3.5 kb deletion with other mutations may led to intermediate thalasemia with moderate to sever anemia.In areas with a high incidence of thalassemia,suspected patients should undergo genetic testing to avoid missing or misdiagnosing rare mutations.

BACKGROUND: The effects of acupuncture have varied in different randomized controlled trials (RCTs), and there are many factors that influence treatment effect of acupuncture in different outcomes, with conflicting results. OBJECTIVE: To identify factors and their impact on the treatment effect of acupuncture in different outcomes. METHODS: Acupuncture RCTs were searched from 7 databases including Medline (PubMed), Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, Wanfang Database, VIP Database, and China Biology Medicine disc between January 1st, 2015 and December 31st, 2019. Eligible studies must compare acupuncture to no acupuncture, sham acupuncture, or waiting lists, and report at least 1 patient-important outcome. A multi-level meta-regression was conducted using a 3-level robust mixed model and univariate analyses were performed for all independent variables, even those excluded from the multivariable model due to collinearities. We used thresholds of 0.2 and 0.4 for the difference of standardized mean differences (SMDs), categorising them as small (<0.2), moderate (0.2-0.4), or large (>0.4) effects. RESULTS: The pain construct analysis involved 211 effect estimates from 153 studies and 14 independent variables. High-frequency acupuncture treatment sessions produced larger effects compared to low-frequency sessions [large magnitude, the difference of adjusted SMDs 0.46, 95% confidence interval (CI) 0.07 to 0.84; P=0.02]. The non-pain symptoms construct analysis comprised 323 effect estimates from 231 studies and 15 independent variables. Penetrating acupuncture showed moderately larger effects when compared to non-penetrating acupuncture (0.30, 95% CI 0.06 to 0.53; P=0.01). The function construct analysis included 495 effect estimates from 274 studies and 14 independent variables. Penetrating acupuncture and the flexible acupuncture regimen showed moderately larger effects, compared to non-penetrating acupuncture and fixed regimen, respectively (0.40, 95% CI 0 to 0.80; P=0.05; 0.29, 95% CI 0.06 to 0.53; P=0.01). CONCLUSIONS High-frequency acupuncture sessions appear to be a more effective approach to managing painful symptoms. Penetrating acupuncture demonstrated greater effect in relieving non-painful symptoms. Both penetrating acupuncture type and flexible acupuncture regimen were linked to significant treatment effects in function outcomes. Future studies should consider the factors that are significantly associated with the effects of acupuncture in patient-important outcomes.
Humans ; Randomized Controlled Trials as Topic ; Acupuncture Therapy/methods* ; Pain ; Pain Management ; China

Objective To investigate the effect of nobiletin on platelet-activating factor(PAF)metabolism in diabetic rats with renal injury.Methods Totally 72 rats were randomly divided into control group(n=10)and modeling group(n=62).The modeling group rats were induced to develop a diabetic rat model with renal injury and then further divided into the model group,aspirin group(20 mg/kg),and nobiletin low(50 mg/kg),medium(100 mg/kg),and high-dose(200 mg/kg)groups,each with 10 rats.After continuous oral administration for 6 weeks,rat body weight,kidney weight,and kidney index were measured.Histopathological assessments were conducted by using HE,periodic acid-Schiff staining(PAS),Masson staining,and transmission electron microscopy.Blood glucose levels,renal function,inflammatory factors,PAF and its regulatory factors were detected.Expression levels of PAF metabolism-related proteins,PAF-acetylhydrolase(PAFAH),PAF receptor(PAFR),and cholinephosphotransferase 1(CHPT1)in kidney tissues were assessed using Western blotting and immunohistochemistry.Results Following nobiletin intervention,rat body weight increased while kidney weight and kidney index decreased.Improvement in renal tissue pathology was observed,with reduced interstitial fibrosis and thinner basement membrane.Fasting blood glucose and glycated hemoglobin decreased,while fasting insulin showed no significant improvement.Urea nitrogen,blood creatinine,cystatin C,and 24-hour urinary protein excretion were reduced.Levels of interleukin(IL)-1α,IL-6,IL-8,and tumor necrosis factor(TNF-α)were lowered.PAF and its regulatory factors decreased.PAFR and CHPT1 expression decreased,while PAFAH increased.Conclusion Nobiletin can alleviate renal injury in diabetic rats with renal injury,improve kidney function,regulate blood glucose,and mitigate inflammatory response.Its mechanism may be associated with the modulation of platelet-activating factor metabolism.

Bone organoids can simulate the complex structure and function of the bone tissues, which makes them a frontier technology in organoid researches. Bone organoids show a tremendous potential of applications in bone disease modeling, bone injury repair, and medicine screening. Although advancements have been made so far in constructing bone organoids with functional structures like mineralization, bone marrow, trabecular bone, callus, woven bone, etc, the researches in this field are confronted with numerous challenges such as lack of standardized construction strategies and unified evaluation criteria, which limits their further promotion and application. To standardize researches in bone organoids, the Orthopedic Expert Committee of Geriatric Branch of Chinese Association of Gerontology and Geriatrics, the Youth Osteoporosis Group of Orthopedic Branch of Chinese Medical Association, the Osteoporosis Group of Orthopedic Surgeon Branch of Chinese Medical Doctor Association, and the Osteoporosis Committee of Shanghai Association of Integrated Traditional Chinese and Western Medicine organized related experts to formulate Expert consensus on the construction, evaluation, and application of bone organoids ( version 2024) based on an evidence-based approach. A total of 17 recommendations were put forth, aiming to standardize researches and clinical applications of bone organoids and enhance their value in scientific research and clinical practice.