The synergistic effect of withaferin A combined with cisplatin on cervical cancer and its mechanism / 中国药理学通报

Aim To study the synergistic effect of withaferin A (WA) combined with cisplatin (DDP) on cervical cancer and its mechanism. Methods MTT assay was employed to detect the synergistic effect of WA on DDP in cervical cancer cell lines. Annexin V-FITC/PI staining, TUNEL assay and immunoblotting were used to investigate the effect of WA combined with DDP on apoptosis of cervical cancer cells. Immunofluorescence and immunoblotting were used to detect NF-kB/MDR1 pathway related proteins. DCFH-DA and MitoSOX were applied to determine the intracellular reactive oxygen species (ROS) levels. A xenograft model was also used to evaluate the synergistic effect of WA on DDP. Results The combination of WA and DDP could inhibit the survival of cervical cancer cells, promote apoptosis, and inhibit the growth of tumor in mice. WA could inhibit DDP-induced NF-kB/MDR1 signaling pathway and promote ROS production. Conclusions WA plays a synergistic role in anti-cervical cancer by inhibiting DDP-induced NF-kB/MDR1 pathway activation and enhancing DDP induced ROS production.

Clinical feature difference between juvenile amyotrophic lateral sclerosis with SPTLC1 and FUS mutations / 中华医学杂志(英文版)

BACKGROUND@#Juvenile amyotrophic lateral sclerosis (JALS) is an uncommon form of amyotrophic lateral sclerosis whose age at onset (AAO) is defined as prior to 25 years. FUS mutations are the most common cause of JALS. SPTLC1 was recently identified as a disease-causative gene for JALS, which has rarely been reported in Asian populations. Little is known regarding the difference in clinical features between JALS patients carrying FUS and SPTLC1 mutations. This study aimed to screen mutations in JALS patients and to compare the clinical features between JALS patients with FUS and SPTLC1 mutations.@*METHODS@#Sixteen JALS patients were enrolled, including three newly recruited patients between July 2015 and August 2018 from the Second Affiliated Hospital, Zhejiang University School of Medicine. Mutations were screened by whole-exome sequencing. In addition, clinical features such as AAO, onset site and disease duration were extracted and compared between JALS patients carrying FUS and SPTLC1 mutations through a literature review.@*RESULTS@#A novel and de novo SPTLC1 mutation (c.58G>A, p.A20T) was identified in a sporadic patient. Among 16 JALS patients, 7/16 carried FUS mutations and 5/16 carried respective SPTLC1 , SETX , NEFH , DCTN1 , and TARDBP mutations. Compared with FUS mutation patients, those with SPTLC1 mutations had an earlier AAO (7.9 ± 4.6 years vs. 18.1 ± 3.9 years, P  < 0.01), much longer disease duration (512.0 [416.7-607.3] months vs. 33.4 [21.6-45.1] months, P  < 0.01), and no onset of bulbar.@*CONCLUSION@#Our findings expand the genetic and phenotypic spectrum of JALS and help to better understand the genotype-phenotype correlation of JALS.

Research progress of microparticles in traditional Chinese medicine decoction / 药学学报

Decoction is a classical dosage form of traditional Chinese medicines. In the process of decocting, various complex components produce physical interactions and chemical reactions, among which physical interactions include van der Waals force, hydrogen bond, electrostatic interaction, π-π stacking, etc., and chemical reactions include Maillard reaction, oxidation reaction, hydrolysis reaction, degradation reaction, polymerization reaction, etc. New substances and original ingredients from chemical reactions can be further activated. These effects form the basis of particle formation in the broth. The sizes of the particles in decoctions range from nanoscale to micron scale, mostly composed of polysaccharide, protein matrix, wrapped in water insoluble molecules, can increase the dispersion of insoluble components and the stability of unstable components, as well as reduce the volatile components and toxic components of volatile components, and ultimately achieve the purpose of efficient absorption and toxicity reduction. From the angle of physical change and chemical reaction in the process of decoction, this paper expounds the formation mechanism of particles in decoction, expounds the research method of particles, analyzes the components in particles and the interaction between components, and then explains the pharmacodynamic characteristics of traditional Chinese medicine decoction, which provides the foundation for the modernization of Chinese decoction.

Efficacy of optimal pulse technology in the treatment of demodex blepharitis and its effect on ocular surface function / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the efficacy of optimal pulse technology(OPT)in the treatment of demodex blepharitis and its influence on ocular surface function.METHODS: A retrospective study was conducted from February 2018 to October 2020. A total of 127 patients(254 eyes)with demodex blepharitis were assigned to the observation group and the control group according to the treatment method. The control group(63 patients, 126 eyes)were given conventional hot compress, eye cleansing and drug therapy. On this basis, the observation group(64 patients, 128 eyes)was treated with OPT. Both groups were given 6wk of continuous treatment. Demodex count, Marx's line scores, meibum character scores, ocular surface disease index(OSDI)scores, non-invasive tear break-up time(NIBUT), non-invasive tear meniscus height(NITMH)and lipid layer thickness(LLT)were compared between the two groups, and safety was evaluated.RESULTS: After 6wk of treatment, demodex count, Marx's line scores, meibum character scores and OSDI scores of the two groups decreased. NIBUT, NITMH and LLT increased. Meanwhile, demodex count, Marx's line scores, meibum character scores and OSDI scores of the observation group were significantly lower than those in the control group. NIBUT, NITMH and LLT were longer/larger than those in the control group(P<0.001). No obvious abnormality of intraocular pressure or conjunctival/corneal injury was observed in either group.CONCLUSION:OPT is effective and safe in the treatment of demodex blepharitis.

Relationship between atherogenic index of plasma and childhood asthma / 中国当代儿科杂志

OBJECTIVES@#To explore the relationship between atherogenic index of plasma (AIP) and childhood asthma.@*METHODS@#This retrospective study included 86 children with asthma admitted to the Changzhou Second People's Hospital Affiliated to Nanjing Medical University from July 2020 to August 2022 as the asthma group and 149 healthy children undergoing physical examination during the same period as the control group. Metabolic parameters including total cholesterol, triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and blood glucose, as well as general information of the children such as height, weight, body mass index, presence of specific dermatitis, history of inhalant allergen hypersensitivity, family history of asthma, and feeding history, were collected. Multivariable logistic regression analysis was used to study the relationship between AIP, triglycerides, and high-density lipoprotein cholesterol and asthma. The value of AIP, triglycerides, and high-density lipoprotein cholesterol for predicting asthma was assessed using receiver operating characteristic (ROC) curve analysis.@*RESULTS@#The AIP and triglyceride levels in the asthma group were significantly higher than those in the control group, while high-density lipoprotein cholesterol was significantly lower (P<0.05). However, there was no significant difference in total cholesterol and low-density lipoprotein cholesterol between the two groups (P>0.05). Before and after adjusting for height, weight, presence of specific dermatitis, history of inhalant allergen hypersensitivity, family history of asthma, feeding method, and blood glucose, multivariable logistic regression analysis showed that AIP, triglycerides, and high-density lipoprotein cholesterol were associated with asthma (P<0.05). ROC curve analysis showed that the optimal cutoff value for predicting asthma with AIP was -0.333, with a sensitivity of 80.2%, specificity of 55.0%, positive predictive value of 50.71%, and negative predictive value of 82.85%. The area under the curve (AUC) for AIP in predicting asthma was significantly higher than that for triglycerides (P=0.009), but there was no significant difference in AUC between AIP and high-density lipoprotein cholesterol (P=0.686).@*CONCLUSIONS@#AIP, triglycerides, and high-density lipoprotein cholesterol are all associated with asthma. AIP has a higher value for predicting asthma than triglycerides and comparable value to high-density lipoprotein cholesterol.

Intestinal and pharyngeal microbiota in early neonates: an analysis based on high-throughput sequencing / 中国当代儿科杂志

OBJECTIVES@#To investigate the distribution characteristics and correlation of intestinal and pharyngeal microbiota in early neonates.@*METHODS@#Full-term healthy neonates who were born in Shanghai Pudong New Area Maternal and Child Health Hospital from September 2021 to January 2022 and were given mixed feeding were enrolled. The 16S rRNA sequencing technique was used to analyze the stool and pharyngeal swab samples collected on the day of birth and days 5-7 after birth, and the composition and function of intestinal and pharyngeal microbiota were analyzed and compared.@*RESULTS@#The diversity analysis showed that the diversity of pharyngeal microbiota was higher than that of intestinal microbiota in early neonates, but the difference was not statistically significant (P>0.05). On the day of birth, the relative abundance of Proteobacteria in the intestine was significantly higher than that in the pharynx (P<0.05). On days 5-7 after birth, the relative abundance of Actinobacteria and Proteobacteria in the intestine was significantly higher than that in the pharynx (P<0.05), and the relative abundance of Firmicutes in the intestine was significantly lower than that in the pharynx (P<0.05). At the genus level, there was no significant difference in the composition of dominant bacteria between the intestine and the pharynx on the day of birth (P>0.05), while on days 5-7 after birth, there were significant differences in the symbiotic bacteria of Streptococcus, Staphylococcus, Rothia, Bifidobacterium, and Escherichia-Shigella between the intestine and the pharynx (P<0.05). The analysis based on the database of Clusters of Orthologous Groups of proteins showed that pharyngeal microbiota was more concentrated on chromatin structure and dynamics and cytoskeleton, while intestinal microbiota was more abundant in RNA processing and modification, energy production and conversion, amino acid transport and metabolism, carbohydrate transport and metabolism, coenzyme transport and metabolism, and others (P<0.05). The Kyoto Encyclopedia of Genes and Genomes analysis showed that compared with pharyngeal microbiota, intestinal microbiota was more predictive of cell motility, cellular processes and signal transduction, endocrine system, excretory system, immune system, metabolic diseases, nervous system, and transcription parameters (P<0.05).@*CONCLUSIONS@#The composition and diversity of intestinal and pharyngeal microbiota of neonates are not significantly different at birth. The microbiota of these two ecological niches begin to differentiate and gradually exhibit distinct functions over time.

Dihydromyricetin Alleviates H9C2 Cell Apoptosis and Autophagy by Regulating CircHIPK3 Expression and PI3K/AKT/mTOR Pathway / 中国结合医学杂志

OBJECTIVE@#To investigate the effect and potential mechanism of dihydromyricetin (Dmy) on H9C2 cell proliferation, apoptosis, and autophagy.@*METHODS@#H9C2 cells were randomly divided into 7 groups, namely control, model, EV (empty pCDH-CMV-MCS-EF1-CopGFP-T2A-Puro vector), IV (circHIPK3 interference), Dmy (50 µ mol/L), Dmy+IV, and Dmy+EV groups. Cell proliferation and apoptosis were detected by cell counting kit-8 assay and flow cytometry, respectivley. Western blot was used to evaluate the levels of light chain 3 II/I (LC3II/I), phospho-phosphoinositide 3-kinase (p-PI3K), protein kinase B (p-AKT), and phospho-mammalian target of rapamycin (p-mTOR). The level of circHIPK3 was determined using reverse transcriptase polymerase chain reaction. Electron microscopy was used to observe autophagosomes in H9C2 cells.@*RESULTS@#Compared to H9C2 cells, the expression of circHIPK in H9C2 hypoxia model cells increased significantly (P<0.05). Compared to the control group, the cell apoptosis and autophagosomes increased, cell proliferation rate decreased significantly, and the expression of LC3 II/I significantly increased (all P<0.05). Compared to the model group, the rate of apoptosis and autophagosomes in IV, Dmy, and Dmy+IV group decreased, the cell proliferation rate increased, and the expression of LC3 II/I decreased significantly (all P<0.05). Compared to the control group, the expressions of p-PI3K, p-AKT, and p-mTOR in the model group significantly reduced (P<0.05), whereas after treatment with Dmy and sh-circHIPK3, the above situation was reversed (P<0.05).@*CONCLUSION@#Dmy plays a protective role in H9C2 cells by inhibiting circHIPK expression and cell apoptosis and autophagy, and the mechanism may be related to PI3K/AKT/mTOR pathway.

Meta-analysis of Ac-SDKP inhibition of Pulmonary fibrosis in animal models / 中华劳动卫生职业病杂志

Objective: To systematically study the anti-fibrotic effect of N-acetyl-seryl-as partyl-lysyl-proline (Ac-SDKP) on pulmonary fibrosis. Methods: In May 2021, a computer search was performed on CNKI, Wanfang Knowledge Service Platform, VIP.com, China Biomedical Literature Database, Pubmed, OVID and other databases. The retrieval time was from January 2008 to May 2021. Randomized controlled experiments on the inhibition of pulmonary fibrosis by Ac-SDKP were screened. The control group was the pulmonary fibrosis model group and the experimental group was the Ac-SDKP treatment group. The quality of the literature was assessed using the syrcle risk of bias assessment tool, and data were extracted. Data analysis was Performed using revman 5.4 software. Results: 18 papers were included, with a total of 428 animal models. The results of meta analysis showed that the contents of α-smooth muscle actin (α-SMA), type I collagen, type Ⅲ collagen, transforming growth factor-β (TGF-β) and Nodule area in the exPerimental group were lower than those in the control grouP. [SMD=-2.44, 95%CI (-3.71--1.17), P=0.000][SMD=-5.36, 95%CI (-7.13--3.59), P=0.000] [SMD=-3.07, 95%CI (-4.13--2.02), P<0.000][SMD=-2.88, 95%CI (-3.63--2.14), P=0.000] [SMD=-1.80, 95%CI (-2.42--1.18), P=0.000], the content of hydroxy proline in the experimental group was higher than that in the control group [SMD=7.62, 95%CI (4.90-10.33), P=0.000], all indexes included in the literature were statistically significant. Conclusion: Ac-SDKP has obvious inhibitory effect on the process of pulmonary fibrosis, and may become a new clinical drug for the treatment of pulmonary fibrosis.

Surgical treatment strategies for pancreatic cancer with simultaneous liver metastasis / 中华外科杂志

Objective: To explore the outcome of different treatment strategies in patients with pancreatic cancer with synchronous liver metastasis (sLMPC). Methods: A retrospective analysis of the clinical data and treatment results of 37 patients with sLMPC treated in China-Japan Friendship Hospital was performed from April 2017 to December 2022. A total of 23 males and 14 females were included,with an age(M(IQR)) of 61 (10) years (range: 45 to 74 years). Systemic chemotherapy was carried out after pathological diagnosis. The initial chemotherapy strategy included modified-Folfirinox, albumin paclitaxel combined with Gemcitabine, and Docetaxel+Cisplatin+Fluorouracil or Gemcitabine with S1. The possibility of surgical resection (reaching the standards of surgical intervention) was determined after systemic treatment,and the chemotherapy strategy was changed in the cases of failed initial chemotherapy plans. The Kaplan-Meier method was used to estimate the overall survival time and rate,while Log-rank and Gehan-Breslow-Wilcoxon tests were used to compare the differences of survival curves. Results: The median follow-up time for the 37 sLMPC patients was 39 months,and the median overall survival time was 13 months (range:2 to 64 months) with overall survival rates of 1-,3-,and 5-year of 59.5%,14.7%,and 14.7%,respectively. Of the 37 patients,97.3%(36/37) initially received systemic chemotherapy, 29 completed more than four cycles,resulting in a disease control rate of 69.4% (partial response in 15 cases,stable disease in 10 cases,and progressive disease in 4 cases). In the 24 patients initially planned for conversion surgery,the successful conversion rate was 54.2% (13/24). Among the 13 successfully converted patients,9 underwent surgery and their treatment outcomes were significantly better than those (4 patients) of those who did not undergo surgery (median survival time not reached vs. 13 months,P<0.05). Regarding the 9 patients whose conversion was unsuccessful, no significant differences were observed in median survival time between the surgical group (4 cases) and the non-surgical group (5 cases) (P>0.05). In the allowed-surgery group(n=13),the decreased in pre-surgical CA19-9 levels and the regression of liver metastases were more significant in the successful conversion sub-group than in the ineffective conversion sub-group;however, no significant differences were observed in the changes in primary lesion between the two groups. Conclusion: For highly selective patients with sLMPC who achieve partial response after receiving effective systemic treatment,the adoption of an aggressive surgical treatment strategy can significantly improve survival time;however, surgery dose not provide such survival benefits in patients who do not achieve partial response after systemic chemotherapy.

Effects of CD73 on proliferation and function of rat cardiomyocytes in vitro / 解剖学报

Objective To investigate the effect of CD73 on the proliferation and function of rat cardiac myocytes (CMs) in vitro. Methods The primary rat CMs and H9C2 cells were cultured in vitro, and lentivirus CD73 overexpression vector and empty vector group were constructed and transfected into CMs and H9C2 respectively. Experimental groups: CD73 overexpression group (OE group) including CMs-OE group and CMs-NC group, and negative control group (NC group) including H9C2-OE grop and H9C2-NC group, 5 in each group. After transfection, the expression of CD73 gene was detected by Real-time PCR method, and the proliferation ability was detected by MTT method, and the proliferation curve, doubling time and pulsatility of CMs were detected by non-destructive cardiomyocyte function analyzer. Results After 72 hours of lentivirus transfection, CD73 mRNA level in the over expression group was significantly higher than that in the control group (P<0. 05); the proliferation ability of CMs and H9C2 at 3-4 days after transfection in OE group was larger than that in NC group (P<0. 05); the proliferation curve of CMs and H9C2 cells in OE group was higher than that in NC group, and the doubling time of CMs and H9C2 in OE group was lower than that in NC group 72 hours after CMs transfection, the beating rate of OE group was higher than that of NC group, the expression of T-box 5(TBX5) and the secretion of vasuular endothelial growth factor VEGF) in OE group were higher than those in NC group, while the secretion of hypoxia iducible factor-1α(HIF-1α) and tumor necrosis factor-α(TNF-α) was lower than that of NC group. Conclusion CD73 can promote the proliferation of CMs and H9C2, promote CMs pulsation, TBX5 expression and VEGF secretion, and inhibit the secretion of HIF-α and TNF-α.

Regulatory effect of Ac-SDKP on phosphorylated heat shock protein 27/SNAI1 pathway in silicotic rats / 中华劳动卫生职业病杂志

Objective: To study the effect of anti-fibrotic tetrapeptide N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) on phosphorylated heat shock protein 27 (P-HSP27) and zinc finger family transcriptional repressor 1 (SNAI1) expression to explore the anti-silicosis fibrosis effect of Ac-SDKP. Methods: In December 2014, the rat silicosis animal model was prepared by one-time bronchial infusion of silicon dioxide (SiO(2)) dust. 80 SPF healthy adult Wistar rats were selected, and the rats were divided into 8 groups according to the random number table method, 10 in each group. Model control group for 4 weeks (feeding for 4 weeks) , model control group for 8 weeks (feeding for 8 weeks) : bronchial perfusion with normal saline 1.0 ml per animal. Silicosis model group for 4 weeks (feeding for 4 weeks) and silicosis model group for 8 weeks (feeding for 8 weeks) : bronchial perfusion of 50 mg/ml SiO(2) suspension 1.0 ml per animal. Ac-SDKP administration group for 4 weeks (feeding for 4 weeks) , Ac-SDKP administration group for 8 weeks (feeding for 8 weeks) : Ac-SDKP 800 μg·kg(-1)·d(-1) was administered by intraperitoneal pump. Ac-SDKP preventive treatment group: 48 h after Ac-SDKP 800 μg·kg(-1)·d(-1) administration, bronchial perfusion of SiO(2) suspension 1.0 ml per animal, raised for 8 weeks. Ac-SDKP anti-fibrosis treatment group: after bronchial perfusion of 1.0 ml of SiO(2) suspension for 4 weeks, Ac-SDKP 800 μg·kg(-1)·d(-1) was administered for 4 weeks. Western blotting was used to detect the expression of P-HSP27, SNAI1, α-smooth muscle actin (α-SMA) , and collage typeⅠ and Ⅲ in each group. The expression of P-HSP27 and SNAI1 was detected by immunohistochemistry, and the co-localized expression of P-HSP27 and α-SMA was detected by laser confocal microscopy. Results: Compared with the model control group, the expressions of P-HSP27, SNAI1, α-SMA, and collage typeⅠ and Ⅲ in the silicosis fibrosis area of the rats in the silicosis model group were enhanced, and the differences were statistically significant (P<0.05) . After Ac-SDKP intervention, compared with silicosis model group for 8 weeks, the expressions of P-HSP27, SNAI1 α-SMA, and collage typeⅠ and Ⅲ in the Ac-SDKP preventive and anti-fibrosis treatment groups were significantly decreased, and the differences were statistically significant (P<0.05) . However, the expressions of P-HSP27 SNAI1, and collage typeⅠ and Ⅲ between the Ac-SDKP administration group and the model control group did not change significantly, and the differences were not statistically significant (P>0.05) . Laser confocal results showed that the positive cells expressing P-HSP27 and α-SMA in the lung tissue of the silicosis model group were more than those in the model control group. Compared with the silicosis model group, the Ac-SDKP prevention and anti-fibrosis treatment groups expressing the positive cells of P-HSP27 and α-SMA decreased. Compared with the model control group for 8 weeks, there were some double-positive cells expressing P-HSP27 and α-SMA in the nodules of the silicosis model group for 8 weeks. Conclusion: Ac-SDKP may play an anti-silicic fibrosis effect by regulating the P-HSP27/SNAI1 pathway.

Bioinformatics and expressional analysis of WRKY transcription factor family in Baphicacanthus cusia / 药学学报

WRKY, a class of conserved transcription factors in plants, plays important roles in plant growth, development and secondary metabolism. In the present study, 65 WRKY members were identified from de novo transcriptome sequencing data of three different tissues (root, stems and leaves) of Baphicacanthus cusia. BcWRKY proteins contained from 221 to 706 amino acids and the isoelectric point is from 4.68 to 9.68. Molecular weights range from 25 711.8 to 75 475 Da. The main secondary structures of BcWRKYs protein are random coil. A subcellular localization prediction indicated that the putative BcWRKY proteins were enriched in the nuclear region. Phylogenetic analysis showed that BcWRKYs could be categorized into three groups and five subgroups (Group IIa, Group IIb, Group IIc, Group IId and Group IIe) in Group II. Structural analysis found that all BcWRKY proteins contained a highly conserved motif WRKYGQK. Finally, the transcriptional profiles of ten BcWRKY genes highly expressed in root, stem and leaf tissues under abscisic acid (ABA), methyl jasmonate (MeJA), or salicylic acid (SA) treatment were systematically investigated using qRT-PCR analysis. Results showed that a total of ten BcWRKY genes were differentially expressed in response to ABA, MeJA, and SA treatment. This work would be provided a basis for further elucidating the molecular mechanism of WRKY transcription factors in the biosynthesis of indole alkaloids in B. cusia.

Mechanism of Dahuang Zhechongwan Against Multiple Organ Fibrosis： A Review / 中国实验方剂学杂志

Dahuang Zhechongwan （DHZCW） is a classic prescription from the Jingui Yaolue（《金匮要略》） by ZHANG Zhong-jing，with the effects of tonifying deficiency， relaxing the middle， promoting regeneration， and resolving stasis. It has been widely used in the clinical treatment of various diseases with definite efficacy achieved. The research on multiple organ fibrosis has shown that DHZCW can slow down the development of organ fibrosis in the heart， liver， kidney， lung， etc.， and good results in both clinical practice and experimental research have been obtained. The present study reviewed the previous investigations on the experimental mechanism of DHZCW in the treatment of multiple organ fibrosis and revealed that the pathogenesis was closely related despite different disease sites. From the perspective of traditional Chinese medicine （TCM），these diseases shared a common pathogenesis，which was manifested by deficiency. Long-term diseases led to the formation of "dried blood". From the perspective of modern medicine， the diseases all showed pathological changes in the deposition of extracellular matrix （ECM）， and their occurrence and development were all based on certain effector cells ［such as hepatic stellate cell （HSC） and pancreatic stellate cell （PSC）］， with same cytokines ［such as tumor necrosis factor-α （TNF-α），interleukin-6 （IL-6），IL-1β，and α-smooth muscle actin （α-SMA）］ and some key pathways ［transforming growth factor-β1 （TGF-β1）/Smad， phosphatidylinositol-3-kinase （PI3K）/protein kinase B （Akt）， and lipopolysaccharide （LPS） paracrine and autocrine mechanisms］ involved. As a classic prescription for "deficiency-induced dry blood"， DHZCW was effective in treating fibrosis， which was presumedly related to the inhibition of ECM deposition by intervening in the above-mentioned mechanisms， thereby delaying the disease progression. This study is expected to provide literature support to clarify the scientific connotation of DHZCW in the treatment of multiple organ fibrosis and lay a foundation for further experimental and clinical research.

Three-Dimensional Heterogeneity of Cerebellar Interposed Nucleus-Recipient Zones in the Thalamic Nuclei / 神经科学通报·英文版

The cerebellum is conceptualized as a processor of complex movements and is also endowed with roles in cognitive and emotional behaviors. Although the axons of deep cerebellar nuclei are known to project to primary thalamic nuclei, macroscopic investigation of the characteristics of these projections, such as the spatial distribution of recipient zones, is lacking. Here, we studied the output of the cerebellar interposed nucleus (IpN) to the ventrolateral (VL) and centrolateral (CL) thalamic nuclei using electrophysiological recording in vivo and trans-synaptic viral tracing. We found that IpN stimulation induced mono-synaptic evoked potentials (EPs) in the VL but not the CL region. Furthermore, both the EPs induced by the IpN and the innervation of IpN projections displayed substantial heterogeneity across the VL region in three-dimensional space. These findings indicate that the recipient zones of IpN inputs vary between and within thalamic nuclei and may differentially control thalamo-cortical networks.

Three-Dimensional Heterogeneity of Cerebellar Interposed Nucleus-Recipient Zones in the Thalamic Nuclei / 神经科学通报·英文版

The cerebellum is conceptualized as a processor of complex movements and is also endowed with roles in cognitive and emotional behaviors. Although the axons of deep cerebellar nuclei are known to project to primary thalamic nuclei, macroscopic investigation of the characteristics of these projections, such as the spatial distribution of recipient zones, is lacking. Here, we studied the output of the cerebellar interposed nucleus (IpN) to the ventrolateral (VL) and centrolateral (CL) thalamic nuclei using electrophysiological recording in vivo and trans-synaptic viral tracing. We found that IpN stimulation induced mono-synaptic evoked potentials (EPs) in the VL but not the CL region. Furthermore, both the EPs induced by the IpN and the innervation of IpN projections displayed substantial heterogeneity across the VL region in three-dimensional space. These findings indicate that the recipient zones of IpN inputs vary between and within thalamic nuclei and may differentially control thalamo-cortical networks.

Penetrance estimation of PRRT2 variants in paroxysmal kinesigenic dyskinesia and infantile convulsions / 医学前沿

Proline-rich transmembrane protein 2 (PRRT2) is the leading cause of paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), and infantile convulsions with choreoathetosis (ICCA). Reduced penetrance of PRRT2 has been observed in previous studies, whereas the exact penetrance has not been evaluated well. The objective of this study was to estimate the penetrance of PRRT2 and determine its influencing factors. We screened 222 PKD index patients and their available relatives, identified 39 families with pathogenic or likely pathogenic (P/LP) PRRT2 variants via Sanger sequencing, and obtained 184 PKD/BFIE/ICCA families with P/LP PRRT2 variants from the literature. Penetrance was estimated as the proportion of affected variant carriers. PRRT2 penetrance estimate was 77.6% (95% confidence interval (CI) 74.5%-80.7%) in relatives and 74.5% (95% CI 70.2%-78.8%) in obligate carriers. In addition, we first observed that penetrance was higher in truncated than in non-truncated variants (75.8% versus 50.0%, P = 0.01), higher in Asian than in Caucasian carriers (81.5% versus 68.5%, P = 0.004), and exhibited no difference in gender or parental transmission. Our results are meaningful for genetic counseling, implying that approximately three-quarters of PRRT2 variant carriers will develop PRRT2-related disorders, with patients from Asia or carrying truncated variants at a higher risk.

Historical evolution of Salviae Miltiorrhizae Radix et Rhizoma processing methods / 中国中药杂志

China has a long history of Salviae Miltiorrhizae Radix et Rhizoma processing with multiple methods available. The pre-sent study collated and summarized the Salviae Miltiorrhizae Radix et Rhizoma processing methods recorded in 23 related herbal medicine books, all editions of Chinese Pharmacopoeia, the 1988 edition of National Regulations for Processing of Chinese Medicine, and 20 current local processing specifications and standards. The results demonstrated various processing methods of Salviae Miltiorrhizae Radix et Rhizoma, such as removing residual part of stem, plantlet, or soil, smashing, filing, cutting, decocting, washing with wine, soaking in wine, and stir-frying with wine or blood from pig heart, while raw and wine-processed products are mainly used in modern times. Due to the lack of unified standards, the phenomena of multiple methods adopted in one place and different methods in different places have led to uneven quality of Salviae Miltiorrhizae Radix et Rhizoma pieces, even affecting the safety and effectiveness of its clinical medication. This study is expected to provide a reference for the development of Salviae Miltiorrhizae Radix et Rhizoma processing and its rational medication.

A novel nomogram provides improved accuracy for predicting biochemical recurrence after radical prostatectomy / 中华医学杂志(英文版)

BACKGROUND@#Various prediction tools have been developed to predict biochemical recurrence (BCR) after radical prostatectomy (RP); however, few of the previous prediction tools used serum prostate-specific antigen (PSA) nadir after RP and maximum tumor diameter (MTD) at the same time. In this study, a nomogram incorporating MTD and PSA nadir was developed to predict BCR-free survival (BCRFS).@*METHODS@#A total of 337 patients who underwent RP between January 2010 and March 2017 were retrospectively enrolled in this study. The maximum diameter of the index lesion was measured on magnetic resonance imaging (MRI). Cox regression analysis was performed to evaluate independent predictors of BCR. A nomogram was subsequently developed for the prediction of BCRFS at 3 and 5 years after RP. Time-dependent receiver operating characteristic (ROC) curve and decision curve analyses were performed to identify the advantage of the new nomogram in comparison with the cancer of the prostate risk assessment post-surgical (CAPRA-S) score.@*RESULTS@#A novel nomogram was developed to predict BCR by including PSA nadir, MTD, Gleason score, surgical margin (SM), and seminal vesicle invasion (SVI), considering these variables were significantly associated with BCR in both univariate and multivariate analyses (P < 0.05). In addition, a basic model including Gleason score, SM, and SVI was developed and used as a control to assess the incremental predictive power of the new model. The concordance index of our model was slightly higher than CAPRA-S model (0.76 vs. 0.70, P = 0.02) and it was significantly higher than that of the basic model (0.76 vs. 0.66, P = 0.001). Time-dependent ROC curve and decision curve analyses also demonstrated the advantages of the new nomogram.@*CONCLUSIONS@#PSA nadir after RP and MTD based on MRI before surgery are independent predictors of BCR. By incorporating PSA nadir and MTD into the conventional predictive model, our newly developed nomogram significantly improved the accuracy in predicting BCRFS after RP.

Regulatory effect of mild moxibustion on P2X3 receptors in spinal cord, anterior cingulate cortex and thalamic ventral posterolateral nucleus of rats with IBS visceral hyperalgesia / 针灸推拿医学（英文版）

Objective: To observe the therapeutic effect of mild moxibustion on irritable bowel syndrome (IBS) visceral hyperalgesiamodel rats and its regulatory effect on P2X3 receptors in the spinal cord, anterior cingutate cortex (ACC) and thalamic ventral posterolateral nucleus (VPL). Methods: Thirty 8-day-old newborn rats were randomly divided into a normal group (n=6) and a modeling group (n=24) according to the completely random number table method. Rats in the normal group were bred routinely, and those in the modeling group were subjected to preparing IBS chronic visceral hyperalgesia model using colorectal distention (CRD) in stimulation method. Rats successfully modelled were re-divided into a model group, a mild moxibustion group, a P2X3 receptor antagonist group, and a normal saline group according to the completely random number table method with 6 rats in each group. Rats in each group received corresponding interventions from the 37-day old, once a day for 7 consecutive days. Immunohistochemistry and Western blot assays were used to detect P2X3 protein expressions in the spinal cord, ACC and VPL of rats. Results: Under different intensities of CRD stimulation, the abdominal withdrawal reflex (AWR) scores of the model group were significantly increased versus the normal group (all P<0.05); the AWR scores of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group (all P<0.01). The P2X3 protein expressions in rat spinal cord, ACC and VPL tissues of the model group were significantly increased versus the normal group (all P<0.01); the P2X3 protein expressions in rat spinal cord, ACC and VPL tissues of the mild moxibustion group and the P2X3 receptor antagonist group were significantly reduced versus the model group (all P<0.01). Conclusion: Mild moxibustion can inhibit the P2X3 receptor expressions in the spinal cord, ACC, and VPL tissues of IBS visceral hyperalgesia model rats, which may be the mechanism of mild moxibustion in relieving the central sensitization of rats with IBS visceral hyperalgesia.

Effectiveness evaluation of peer-group level care and management mode in HIV infected patients / 上海预防医学

Objective To introduce and conduct effectiveness evaluation of peer-group level care and management mode in people living with HIV and AIDS(PLHAs)in Jing'an District, Shanghai. Methods We recruited PLHAs who were managed by Jing'an District and participated in the peer-group care activities from 2015 to 2016, and collected their data of general conditions, behavior, antiretroviral therapy, life quality, social support, mental status and medical modes, and then conducted effectiveness evaluation of the mode by multivariate logistic regression model and linear regression model. Results A total of 300 PLHAs were included with 150 cases in each group. PLHAs in target group had higher proportion of antiretroviral therapy[82.7%(124/150)and 64.7%(97/150)]. In addition, they got higher scores in mental health(48.5±9.2 and 43.9±10.6)and social support(28.7±8.2 and 24.8±6.6), and lower scores in depressive severity index(0.5±0.1)and avoidance of medical modes(16.1±3.0 and 17.0±2.5). Multivariate analysis showed that PLHAs in target group had less sex partners(zero partner, OR = 2.1, 95%CI:1.1-3.9;one partner, OR = 3.6, 95%CI:1.9-6.8)and increased condom use(no sex, OR = 5.3, 95%CI:2.4-11.7;complete use, OR = 10.6, 95%CI:4.7-24.1;random miss, OR = 5.1, 95%CI:1.8-14.8)in the last 12 months. Conclusion The effect of peer-group level care and management mode is significantly good in promoting behavior change, enhancing health concern and increasing antiretroviral therapy.