ObjectiveThis study aims to explore the mechanism by which Yishen Huoxue Tongqiao Formula improves metabolism-neuroplasticity and treats unilateral vestibular labyrinth destruction by regulating the metabolic balance of glutamate （Glu）/γ-aminobutyric acid （GABA）. Methods48 Sprague-Dawley （SD） adult rats were randomly divided into the sham operation group， model group， Yishen Huoxue Tongqiao Formula groups with low， medium， and high doses （9.20， 18.39， 36.78 g·kg^-1）， and betahistine group （1.62 mg·kg^-1）. A unilateral vestibular labyrinth destruction （vestibular dysfunction） model was established by intratympanic injection of chloroform into the right ear， while the control group received intratympanic injection of normal saline. Drugs were administered once daily for seven consecutive days. During the period， behavioral tests were performed to evaluate the behaviors of rats after unilateral vestibular labyrinth destruction. Hematoxylin-eosin （HE） staining and Nissl staining were used to observe the neuronal morphology in the medial vestibular nucleus. Golgi staining was employed to assess the number of dendritic spines of neurons in the medial vestibular nucleus. Ultra-performance liquid chromatography-tandem mass spectrometry （LC-ESI-MS/MS） was utilized to detect Glu/GABA. Immunofluorescence and immunohistochemistry were used to detect the expressions of neuronal nuclei （NeuN）， growth-associated protein 43 （GAP-43）， and glial fibrillary acidic protein （GFAP）. Western blot and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） were applied to determine the expressions of glutamate-immunoreactive （Glu-IR）， GABA， GFAP， postsynaptic density protein 95 （PSD-95）， and GAP-43. ResultsCompared with the sham operation group， the model group presented with head deviation， balance disorder， increased tail suspension score， nuclear consolidation of medial vestibular nerve neurons， and decreased Nissl bodies （P<0.01）. The number of dendritic spines in neurons and NeuN-positive cells decreased. The content of Glu decreased. The content of GABA increased （Glu/GABA decreased）. The expression of GAP-43 was down-regulated， and GFAP was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PSD-95， and GAP-43 proteins， as well as Glu-IR mRNA decreased， while the expressions of GABA and GFAP proteins and mRNA increased （P<0.05， P<0.01）. Compared with those in the model group， the head deviation， imbalanced behavior， and tail suspension scores in each treatment group decreased， with alleviated neuronal injury and recovered Nissl bodies （P<0.01）. The number of dendritic spines of neurons increased， and the number of NeuN-positive cells rebounded. The content of Glu increased， and the content of GABA decreased （Glu/GABA increased）. GFAP was down-regulated， and GAP-43 was up-regulated （P<0.05， P<0.01）. The expressions of Glu-IR， PMD-95， and GAP-43 proteins， as well as Glu-IR mRNA increased， while the expressions of GABA and GFAP proteins and mRNA decreased. The effect was more significant in the high-dose group （P<0.01）. ConclusionThe Yishen Huoxue Tongqiao Formula can alleviate vestibular dysfunction， and its mechanism may be associated with regulating the metabolic balance of Glu/GABA， mitigating neural damage， improving synaptic plasticity （promoting GAP-43 expression and inhibiting GFAP expression）， and facilitating vestibular compensation.

In this paper, two cases of primary familial and congenital polycythemia (PFCP) were reported, and the literature was reviewed. PFCP is a rare autosomal dominant inherited disease caused by a gain-of-function mutation in the EPOR gene, resulting in a loss of negative regulation of erythrocyte proliferation. The two patients were young women with simple polycythemia and clear family history, and identified to carry the truncated mutation c.1316G>A (p.W439*) of EPOR gene. At present, there is no unified treatment plan for PFCP. Currently, there is no standardized treatment for PFCP; management primarily aligns with guidelines for polycythemia vera, focusing on preventing thrombotic complications. This article discusses the clinical features of PFCP, EPOR gene mutations, and their pathogenic mechanisms, while providing diagnostic and therapeutic recommendations based on existing literature.

In this paper, two cases of primary familial and congenital polycythemia (PFCP) were reported, and the literature was reviewed. PFCP is a rare autosomal dominant inherited disease caused by a gain-of-function mutation in the EPOR gene, resulting in a loss of negative regulation of erythrocyte proliferation. The two patients were young women with simple polycythemia and clear family history, and identified to carry the truncated mutation c.1316G>A (p.W439*) of EPOR gene. At present, there is no unified treatment plan for PFCP. Currently, there is no standardized treatment for PFCP; management primarily aligns with guidelines for polycythemia vera, focusing on preventing thrombotic complications. This article discusses the clinical features of PFCP, EPOR gene mutations, and their pathogenic mechanisms, while providing diagnostic and therapeutic recommendations based on existing literature.

High-voltage pulsed electric field(HV-PEF)ablation technology has demonstrated promising applications in the clinical treatment of chronic obstructive pulmonary disease(COPD).However,its use has been limited to exploratory applications in a small number of cases,and the underlying mechanisms remain largely undefined.To facilitate broader clinical implementation,comprehensive molecular mechanism studies via extensive animal experimentation are essential.Rats,due to their ease of modeling COPD and the availability of comprehensive molecular reagents,serve as an optimal model for such studies.Consequently,the development of electrodes specifically designed for HV-PEF respiratory ablation in SD rats is of significant importance.In this study,we meticulously examined the anatomical structure of rat airways and investigated various equipment parameters,including material composition,rigidity,diameter,electrode ring dimensions,spacing between positive and negative poles,insulation coating for the catheters,welding techniques between the guidewire and electrode ring,and the design of vent holes in the catheter.Based on these considerations,we fabricated PVC ablation electrode catheters with integrated ventilation functionality.Subsequently,we employed finite element simulation to estimate the field strengths that could be applied by these electrodes.The simulation results were then validated in normal rats to assess the electrical safety and efficacy of the electrodes.These findings laid the groundwork for further investigation into the mechanisms of HV-PEF treatment for COPD.

OBJECTIVE: To investigate the anti-invasion efficacy of the ethanol extract of Oldenlandia diffusa Will. (EEOD) on a three-dimensional (3D) human malignant glioma (MG) cell invasion and perfusion model based on microfluidic chip culture and the possible mechanism of action of Oldenlandia diffusa Will. (OD). METHODS: The comprehensive pharmacodynamic analysis method in this study was based on microfluidic chip 3D cell perfusion culture technology, and the action mechanism of Chinese medicine (CM) on human MG cells was investigated through network pharmacology analysis. First, the components of EEOD were analyzed by ultraperformance liquid chromatography with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). Then, cell viability and apoptosis were assessed to determine the optimum concentration of EEOD for invasion experiments, and two-dimensional (2D) migration and invasion abilities of U87 and U251 MG cells were evaluated using scratch wound and Transwell assays. The possible mechanism underlying the effects of EEOD on glioma was analyzed through a network pharmacology approach. RESULTS: Thirty-five compounds of EEOD were detected by UPLC-Q-TOF/MS. EEOD suppressed the viability of MG cells, promoted their apoptosis, and inhibited their migratory and invasive potentials (all P<0.05). Network pharmacology analysis showed that OD inhibited the invasion of MG cells by directly regulating MAPK and Wnt pathways through MAPK, EGFR, MYC, GSK3B, and other targets. The anti-invasion effect of OD was also found to be related to the indirect regulation of microtubule cytoskeleton organization. CONCLUSIONS ]EEOD could inhibit the invasion of human MG cells, and the anti-invasion mechanism of OD might be regulating MAPK and Wnt signaling pathways and microtubule cytoskeleton organization.

Since the implementation of drug registration in China, the classification of Chinese medicine has greatly met the needs of public health and effectively guided the transformation, inheritance, and innovation of research achievements on traditional Chinese medicine(TCM). In the past 30 years, the development of new Chinese medicine has followed the registration transformation model of " one prescription for single drug". This model refers to the R&D and registration system of modern drugs, and approximates to the " law-abiding" medication method in TCM clinic, while it rarely reflects the sequential therapy of syndrome differentiation and comprehensive treatment with multiple measures. In 2017, Opinions on Deepening the Reform of Review and Approval System and Encouraging the Innovation of Drugs and Medical Devices released by the General Office of the CPC Central Committee and the General Office of the State Council pointed out that it is necessary to " establish and improve the registration and technical evaluation system in line with the characteristics of Chinese medicine, and handle the relationship between the traditional advantages of Chinese medicine and the requirements of modern drug research". Therefore, based on the development law and characteristics of TCM, clinical thinking should be highlighted in the current technical requirements and registration system of research and development of Chinese medicine. Based on the current situation of registration supervision of Chinese medicine and the modern drug research in China, the present study analyzed limitations and deficiency of " one prescription for single drug" in the research and development of Chinese medicine. Additionally, a new type of " series prescriptions" was proposed, which was consistent with clinical thinking and clinical reality. This study is expected to contribute to the independent innovation and high-quality development of the TCM industry.
China ; Drugs, Chinese Herbal/therapeutic use* ; Medicine, Chinese Traditional ; Prescriptions ; Public Health

Objective: To analyze the post distribution of dust concentration in ferrous metal foundry enterprises and evaluate the occupational health risks, and provide basis for policies of the formulation of pneumoconiosis prevention and control. Methods: From August to September in 2020, the basic information, dust hazard information and occupational health management information of 59 ferrous metal casting enterprises were investigated, the dust concentration distribution was analyzed, and the risk assessment was carried out by using the quantitative assignment model. The dust concentration is tested by LSD method after logarithmic treatment. The 3 times time weighted average allowable exposure concentration of dust is taken as the peak concentration limit of dust; The time weighted average allowable exposure concentration of dust converted by exposure time is taken as the time weighted average exposure concentration limit of dust, and whether the time weighted average exposure concentration and peak concentration of dust at the same post exceed the limit is taken as the basis for exceeding the limit of dust post concentration to calculate the post exceeding the limit rate. Results: The dust hazards were mainly distributed in the posts of sand treatment, molding, sand falling, sand cleaning and cutting and grinding. Dust exposure time weighted average concentration was 0.44 (0.03, 5.11) mg/m(3), peak exposure concentration was 1.30 (0.18, 10.94) mg/m(3), and the over standard rate of Posts was 38.92% (79/203) . Weighted average exposure concentration of other dust (total dust) in the cutting and grinding post is 1.50 (0.15, 7.40) mg/m(3), peak exposure concentration is 0.90 (0.07, 12.48) mg/m(3), and the post exceedance rate is 4.88% (2/41) . Weighted average exposure concentration of silica dust (exhaling dust) in dust operation posts of investment casting enterprises is 0.43 (0.05, 6.35) mg/m(3), peak exposure concentration is 0.90 (0.12, 8.28) mg/m(3), and the post over standard rate is 35.77% (49/137) ; Weighted average exposure concentration of other dust (total dust) at the cutting and grinding post is 2.00 (11.00, 21.00) mg/m(3), and the post exceedance rate is 2.50% (2/80) . There was no significant difference in the concentration of respirable dust between sand casting and investment casting (P>0.05) . The concentration of respirable dust in sand casting was higher than that in sand treatment, molding and sand cleaning posts (P<0.05) . The concentration of silica dust in investment casting was higher than that in sand treatment and molding posts, and that in sand cleaning posts was higher than that in sand treatment posts (P<0.05) . 98.48% (454/461) of the dust operation posts have an occupational health risk value greater than or equal to 400, and 1.52% (7/461) of the dust operation posts have an occupational health risk value of 200~399. Conclusion: there is a high rate of exceeding the standard in the dust work posts in the ferrous metal foundry enterprises in Ningbo, and the workers have a high occupational health risk of pneumoconiosis or metal and its compound pneumoconiosis. Targeted measures should be taken to reduce the occupational health risk.
Air Pollutants, Occupational/analysis* ; Dust/analysis* ; Humans ; Occupational Exposure/analysis* ; Pneumoconiosis ; Sand ; Silicon Dioxide/analysis*

Objective:To investigate the relationship between the serum alkaline phosphatase (ALP), prostate specific antigen (PSA) and bone metastasis in initially diagnosed prostate cancer (PCa) patients in different ISUP(International Society of Urological Pathology)groups.Methods:The 368 initial diagnosed prostate cancer patients recruited from January 2013 to December 2018 were retrospectively analyzed, including 247 cases in the Third Affiliated Hospital of Sun Yat-sen University, 111 cases in the Yuebei People's Hospital Affiliated to Medical College of Shantou University and 10 cases in Shenzhen Hospital of Southern Medical University. According to whether there was bone metastasis at the initial diagnosis, it was divided into 230 cases in the bone metastasis group and 138 cases in the non bone metastasis group. There was no significant difference between the two groups in age [(71.9±9.4) years and (71.2±8.7) years], body mass index (BMI) [(23.1±3.7) kg/m 2 and (23.7±2.6) kg/m 2]. There were significant differences in PSA [(307.3±847.0) ng/ml and (84.5±257.3) ng/ml] and ALP [(174.5±270.8) U/L and (71.0±23.2) U/L] between the two groups. In different PSA subgroups, there were 45 cases in PSA <10 ng/ml, 35 cases in PSA 10-20 ng/ml and 288 cases in PSA >20 ng/ml. The differences of ALP and PSA between bone metastasis group and non-bone metastasis group based on different ISUP stratification were analyzed, ROC curves were used to predict their risks of bone metastasis. Results:There were 3(1.3%), 22(9.6%), 34(14.8%), 85(37.0%) and 86 (37.4%) prostate cancer patients with bone metastasis from ISUP group 1 to 5, and 14(10.1%), 19(13.8%), 29(21.0%), 32(23.2%) and 44(31.9%) without bone metastasis, respectively. There was significant difference in the serum ALP levels between the bone metastasis group and the boneless metastasis group in the ISUP group 4(157.6±207.7 vs. 66.5±17.0) and 5(189.4±257.5 vs. 69.2±18.4)( P<0.001) and PSA levels had difference in the ISUP group 3(240.3±313.0 vs. 42.4±42.1), 4(152.3±184.5 vs. 44.7±33.3) and 5(435.2±1006.3 vs. 60.8±84.8)( P<0.001). There was statistically significant between the bone metastasis group and the without(336.1±882.2 vs. 139.3±328.1) when PSA>20 ng/ml( P=0.006). ROC curve analysis: the cut-off values of ALP were 115.5, 109.0, 75.5 and 86.0 U/L from ISUP group 2 to 5 respectively, the sensitivity was 23.8%, 56.5%, 66.4% and 50.6% respectively, the specificity was 99.7%, 93.4%, 78.3% and 89.2% respectively, and the accuracy were 59.4%, 73.1%, 69.7% and 63.3%, respectively. The cut-off values of PSA were 39.5, 93.1, 54.2 and 28.9 ng/ml from ISUP group 2 to 5 respectively, the sensitivity was 64.4%, 68.4%, 87.4% and 88.3% respectively, and the specificity was 79.5%, 90.6%, 63.7% and 61.6% respectively, and the accuracy were 71.6%, 78.1%, 80.1% and 79.2%, respectively. Conclusion:ALP increased significantly in ISUP group ≥4 and PSA in ISUP group ≥3, which related to bone metastasis in patients with initial diagnosed prostate cancer.

AIM: To observe the anesthetic effect of nalbuphine used in ultrasound-guided transvaginal oocyte retrieval and its effect on embryo quality and pregnancy outcome. METHODS: Four-hundred patients who underwent ultrasound-guided transvaginal oocyte retrieval were randomly divided into two groups (n=200): nalbuphine group (N group) and control group (C group). The patients were in the bladder lithotomy position. Patients in N group were given nalbuphine 0.1 mg/kg intravenously 2 minutes before induction of anesthesia, patients in C group were given normal saline intravenously, and patients in both groups were induced with propofol 1.5 mg/kg. The patients were kept breathing spontaneously, and they were given intravenous injections of propofol (2 mg•kg

OBJECTIVE： To explore the mechanism of Lysimachia christinae in the treatment of cholecyst related diseases by network pharmacology. METHODS： The active ingredients of L. christinae were screened through TCMSP database with “Lipinski rule” and “Oral bioavailability ＞30％” rules， and their related targets were predicated correspondingly， then compound-target network were constructed by Cytoscape 3.2.1 software. Disease related targets were predicted by searching TTD database， OMIM database， PharmGKB database， DrugBank database and GAD database with “cholelithiasis” “gallstones” “cholecystitis” and “cholangitis” as keywords. Then， the network of disease-target was constructed and merged with active ingredient target to obtain therapeutic target. After pathway enrichment analysis of therapeutic target were performed by utilizing the DAVID database， molecular docking between target and active ingredient was also conducted in order to screen the main active ingredients of L. christinae. RESULTS： Twenty-seven active ingredients with good oral absorption and drug-like properties were screened from L. christinae. Thirty-three targets were attained after constructing and merging the network. Seven pathways， mainly related to cancer pathway and ABC transporter pathway were achieved. Top 4 active ingredients of L. christinae in the list of docking score were kaempferin， acacia， hesperetin and isorhamnetin， which acted on ABCC3， ABCB1， ABCC2， ABCB4 target. CONCLUSIONS： L. christinae treat cholecyst related diseases through ABC transporter pathway.