Objective: To analyze the school tuberculosis (TB) outbreaks and preventive treatment in Hefei from 2022 to 2024, so as to provide reference for TB prevention and control in schools. Methods: Data were collected on all school based TB outbreaks occurring during 2022-2024 in Hefei, defined as ≥2 epidemiologically linked TB cases within the same school during a single semester. Statistical analyses were performed using the Chi square test. Results: Close contacts exhibited significantly higher TB incidence (2.88%) and latent mycobacterium tuberculosis infection (LTBI) rates (13.80%) in the school TB outbreaks, compared to non close contacts (0.12% and 2.63%, respectively). Among close contacts, secondary school students showed lower TB incidence (0.48%) and LTBI prevalence (3.42%) than both primary school or younger children (0.68%, 6.95%) and college students ( 0.78% , 6.50%), with statistically significant differences ( χ 2=360.91, 6.37; 791.71, 102.03, all P <0.05). The proportion of LTBI individuals recommended for preventive therapy was higher in primary school or younger groups (98.59%) than in secondary (95.25%) or college students (86.34%) ( χ 2=25.86, P <0.01). However, among those recommended, close contacts had higher uptake (85.82%) and completion rates (87.25%) of preventive therapy than non close contacts (69.63% and 70.57%); similarly, secondary school students demonstrated higher uptake (91.21%) and completion rates (86.45%) compared to primary school or younger (88.57%, 83.87%) and college students (57.28%, 64.08%) ( χ 2=30.52, 26.72; 125.17, 38.84, all P <0.01). Subsequent TB incidence among LTBI close contacts (13.30%) and among those who did not complete preventive therapy (22.73%) were significantly higher than among non close contacts (2.80%, 2.41%), respectively ( χ 2=32.19, 13.87, both P <0.05). Conclusions In school TB outbreaks, close contacts face higher LTBI prevalence and subsequent TB risk than non close contacts. College students show notably low adherence to preventive therapy. It is necessary to take targeted measures to improve the compliance of preventive measures among students.

ObjectiveTo compare the differences between the ultrafiltration method and the dextran gel filtration method during the purification of Tfn-modified PCL micelles by using purification efficiency and micelle purity as indicators. MethodsCoumarin-6 （C6） was used as a fluorescent probe and was loaded into HOOC-PEG-PCL to form PCL micelles by the film-dispersion method. Tfn was then conjugated to the surface of PCL micelles via an amidation reaction， resulting in two types of micelles： Tfn/PCL_H and Tfn/PCL_L. The pharmaceutical properties of the two types of micelles were characterized. The micelles were then purified through ultrafiltration method and dextran gel method respectively， and the efficiency of the two methods， along with the purity of the final micelles， was compared. The density of Tfn on the surface of PCL micelles was also calculated. ResultsThe hydrated diameter of PCL micelles was approximately 73 nm， and the C6 loading efficiency was around 0.046%. The size increased to 134 nm and 158 nm for Tfn/PCL_L and Tfn/PCL_H， respectively. The micelle population was monodisperse. The purification results showed that， for the ultrafiltration method， after two and one rounds of purification， the Tfn/C6 ratio stabilized at 23.6 and 3.4 for Tfn/PCL_H and Tfn/PCL_L， respectively. For the dextran gel filtration method， the Tfn/C6 ratio reached 23.7 for the Tfn/PCL_H group after two rounds of purification. However， for the Tfn/PCL_L group， the Tfn/C6 ratio increased during four rounds of dextran gel purification， and a significant difference （P = 0.042 4） was observed between the first and last filtrations. The density of Tfn in the final micelles were calculated. For the ultrafiltration method， the Tfn density of Tfn/PCL_H and Tfn/PCL_L were 94.9% and 13.8%， respectively. For the dextran gel filtration method， the density of the two micelles were 95.6% and 14.4%， respectively. For Tfn/PCL_L group， the density results revealing a statistically significant difference （P=0.000 2）. ConclusionThe purification efficiency of the two methods is comparable. However， the purity of the final micelles shows a significant difference， with the dextran gel filtration method resulting in higher purity， particularly for the Tfn/PCL_L micelles.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

Background: and Purpose Accurately predicting long-term functional outcomes of basilar artery occlusion (BAO) remains challenging. We compared the predictive performance of the baseline, 24-hour, and 72-hour National Institutes of Health Stroke Scale (NIHSS) scores for 90-day BAO functional outcomes using the Acute Basilar Artery Occlusion: Endovascular Thrombectomy versus Standard Medical Treatment (ATTENTION) trial data. We identified the optimal assessment time point, determined treatment-specific NIHSS cutoff values, and explored the role of early neurological function in treatment effects. Methods: This retrospective post hoc analysis included 324 patients with acute BAO with baseline NIHSS scores ≥10 and complete NIHSS assessments at each time point. The primary outcome was a favorable 90-day functional outcome (modified Rankin Scale score, 0–3). Receiver operating characteristic curve analysis was used to assess the predictive ability of NIHSS scores. The optimal 72-hour NIHSS predictive cutoff values were determined for the endovascular treatment (EVT) and best medical management (BMM) subgroups. Results: The 72-hour NIHSS score showed the highest predictive accuracy for the primary outcome (area under the receiver operating characteristic curve [AUC]: 0.954), outperforming the 24-hour (AUC: 0.903) and baseline (AUC: 0.688) scores; its optimal predictive cut-off value was ≤11 in the EVT group (sensitivity: 85.6%, specificity: 92.9%, positive predictive value [PPV]: 91.8%, negative predictive value [NPV]: 87.4%) and ≤9 in the BMM group (sensitivity: 84.6%, specificity: 95.1%, PPV: 84.6%, NPV: 95.1%). Conclusions The 72-hour NIHSS score outperformed the baseline and 24-hour scores in predicting 90-day functional outcomes and mediating the effects of EVT. Treatment-specific 72-hour NIHSS cut-off values may guide early risk stratification and prognostic assessments.

Objective To develop an ultra high performance liquid chromatography-mass spectrometry(UPLC-MS)method for quantifying serum levels of norepinephrine(NE)and 5-hydroxytryptamine(5-HT),and to monitor the dynamic changes in these neurotransmitters during the process of establishing a model of acute reserpine-induced depression-like mice.Methods By evaluating matrix effect,recovery,precision,and accuracy efficiency,an UPLC-MS method for determining the concentrations of NE and 5-HT in serum was established.Forty-eight C57 mice were randomly divided into normal control and model groups,which were intraperitoneally injected with physiological saline(10 mL/kg)and reserpine(2.5 mg/kg),respectively.At various time points after intraperitoneal injection,the degree of ptosis and decreases in body temperature of the mice were observed before orbital blood was sample for the determination of NE and 5-HT levels.Results The concentrations of NE and 5-HT showed good linearity within the range of 15.63 to 2000.00 ng/mL,with R2 values greater than 0.999.The results of methodological validation met the requirements for the analysis of biological samples,with a lower limit of quantification of 15.63 ng/mg.After intraperitoneal injection of reserpine,the model mice exhibited varying body temperature decreases and ptosis.At 1 and 2 h post-administration,the depression-like symptoms in the model group were significantly different from those of the normal control group(P＜0.01).The body temperature of mice in the model group was significantly lower than that of mice in the normal control group(P＜0.01),while the score of the eyelid ptosis was significantly higher(P＜0.001).The levels of NE and 5-HT in the serum of model mice were also significantly depleted,and were significantly different from those of the normal control group at 0.5,1 and 2 h(P＜0.05).Conclusion The study process of established a rapid and accurate method for dynamically observing the changes in NE and 5-HT levels during the process of establishing a model of acute reserpine-induced depression-like mice,which might contribute to the study of the pathogenesis of depression and the development of new antidepressant drugs.

P-glycoprotein(P-gp)is an ATP-dependent efflux transporter that is distributed in many tissues and organs.P-gp can selectively pump endogenous substrates and exogenous chemicals from the cell to the outside of the cell to maintain a stable endo-environment.However,it meanwhile restricts the entry of therapeutic drug into tissues and organs,and in particular,mediates the multidrug resistance of tumor cells to chemotherapeutic drugs.Therefore,understanding the localization of P-gp in different tissues and organs may be an important breakthrough point for disease treatment.In this paper,we mainly review the molecular structure,transport mechanism,localization,and regulation of P-gp in different tissues and organs,providing reference for the subsequent treatment of diseases.
Humans ; ATP Binding Cassette Transporter, Subfamily B, Member 1/chemistry* ; Animals ; Drug Resistance, Multiple

Objective:To investigate the clinical application effect of Zishen Yutai Pill in patients with repeated implantation failure (RIF) undergoing frozen-thawed embryo transfer (FET) cycles.Methods:A retrospective case-control study was conducted, selecting 744 cycles of patients with RIF at the Department of Female Reproductive Medicine,State Key Laboratory of Reproductive Medicine and Offspring Health, Center for Reproductive Medicine, Institute of Women, Children and Reproductive Health, Shandong University from October 2017 to April 2023. The patients were divided into experimental group (treated with Zishen Yutai Pill, n=279) and control group (treated without Zishen Yutai Pill, n=465) based on whether Zishen Yutai Pill was added to luteal support. The pregnancy outcomes between the two groups were compared. Based on the different endometrial preparation protocols in the FET cycles, the patients were used down-regulation protocol ( n=271) or non-down-regulation protocol ( n=473). The pregnancy outcomes of the two groups in each protocol were compared. Results:There were no statistically significant differences between the two groups in terms of biochemical pregnancy rate, clinical pregnancy rate, embryo implantation rate, early miscarriage rate, late miscarriage rate, and live birth rate (all P>0.05). However, the biochemical pregnancy rate [69.0% (58/84)], clinical pregnancy rate [59.5% (50/84)], and embryo implantation rate [59.4% (57/96)] in the experimental group of the down-regulated protocol were significantly higher than those in control group [56.1% (105/187), P=0.045; 46.5% (87/187), P=0.048; 44.9% (92/205), P=0.019], with statistically significant differences. In the non-down-regulated protocol, there were no statistically significant differences in pregnancy outcomes between the two groups (all P>0.05). Conclusion:In the FET down-regulated protocol, Zishen Yutai Pill can significantly improve the clinical pregnancy rate and the embryo implantation rate in patients with RIF, thereby improving pregnancy outcomes.

Objective:To investigate the predictive value of serum 25 hydroxyvitamin D3[25 (OH) D3], insulin-like growth factor 1 (IGF-1) and bone mineral density (BMD) in the occurrence of osteoporosis (OP) in postmenopausal women.Methods:A total of 87 postmenopausal women admitted to Shanxi Children’s Hospital from Jan. 2020 to Dec. 2023 were chosen and separated into OP group ( n=40) and non-OP group ( n=47) . The differences of clinical features, serum 25 (OH) D3, IGF-1 and BMD were compared, and the correlation analysis between serum 25 (OH) D3, IGF-1 and BMD (including L 1-4 BMD, femoral neck BMD and total hip BMD) was analyzed. Multivariate Logistic regression model and receiver operating characteristic (ROC) curve were used to analyze the influencing factors of OP occurrence in postmenopausal women and the predictive value of serum 25 (OH) D3 and IGF-1 combined with BMD for OP occurrence. Results:Compared with non-OP group, there were no significant differences in age, body mass index (BMI) , menopause time, serum calcium, serum phosphorus, alanine aminotransferase (ALT) , or aspartate aminotransferase (AST) levels in OP group ( t=1.42, 1.03, 1.71, 0.93, 0.76, 0.43, 0.04; P=0.161, 0.306, 0.092, 0.354, 0.452, 0.670, 0.966) , but the proportion of diabetes mellitus significantly increased ( χ2=4.37, P=0.037) . Compared with non-OP group, the levels of serum 25 (OH) D3 and IGF-1 and the values of L1-4 BMD, femoral neck BMD and total hip BMD in OP group significantly decreased ( t=5.37, 4.83, 8.31, 2.01, 3.11; P<0.001, P<0.001, P<0.001, P=0.048, P=0.003) . Correlation analysis showed that serum 25 (OH) D3 and IGF-1 were significantly positively correlated with L 1-4 BMD, femoral neck BMD and total hip BMD ( r=0.37, 0.42, 0.29, 0.33, 0.28, 0.29; P<0.001, P<0.001, P=0.024, P=0.015, P=0.032, P=0.021) . Multivariate Logistic analysis showed that serum 25 (OH) D3, IGF-1 and L 1-4 BMD were independent influencing factors for OP occurrence in postmenopausal women ( P=0.007, 0.019, 0.001) ROC curve showed that the area under the curve (AUC) values of serum 25 (OH) D3, IGF-1, L 1-4 BMD and their combination in the prediction of the occurrence of OP in postmenopausal women were 0.764, 0.752, 0.957 and 0.985, respectively. Conclusion:Serum 25 (OH) D3, IGF-1 and L 1-4 BMD can be used as predictors of OP occurrence in postmenopausal women, and the combined value of the three is higher.

Objective:To explore the mechanism by which atractylodin regulates the ROS (reactive oxygen species) /AKT signaling pathway to induce apoptosis and cell cycle arrest in endometrial cancer cells, and to provide theoretical support for its potential application in the treatment of endometrial cancer.Methods:Endometrial cancer cell lines (Ishikawa and HEC-1A) were selected as experimental models. Cells were treated with different concentrations (1, 5, 10, 20 μM) of atractylodin. Cell proliferation was assessed by CCK-8 assay, apoptosis was analyzed by flow cytometry (FCM), and protein expression levels of AKT, p-AKT, Bcl-2, Caspase-3, and other AKT signaling pathway-related proteins were detected by Western blot. ROS levels were measured by flow cytometry.Results:Atractylodin treatment significantly inhibited the proliferation of endometrial cancer cells. Flow cytometry analysis revealed a marked increase in the apoptotic cell population. Western blot results showed that atractylodin treatment significantly decreased p-AKT expression, reduced Bcl-2 protein levels, and increased Caspase-3 expression. ROS level analysis showed that atractylodin treatment significantly elevated intracellular ROS generation, suggesting that atractylodin might induce AKT pathway inhibition through ROS, leading to cell cycle arrest and apoptosis.Conclusions:Atractylodin regulates the ROS/AKT signaling pathway to induce apoptosis and cell cycle arrest in endometrial cancer cells, exhibiting potential anti-endometrial cancer effects. This study provides new theoretical evidence for the application of atractylodin in the treatment of endometrial cancer and reveals its underlying mechanisms.