miR-6881-3p contributes to diminished ovarian reserve by regulating granulosa cell apoptosis by targeting SMAD4.

BACKGROUND: In our previous investigation, we revealed a significant increase in the expression of microRNA-6881-3p (miR-6881-3p) in follicular fluid granulosa cells (GCs) from women with diminished ovarian reserve (DOR) compared to those with normal ovarian reserve (NOR). However, the role of miR-6881-3p in the development of DOR remains poorly understood. OBJECTIVE: This study aimed to elucidate the involvement of miR-6881-3p in the regulation of granulosa cells (GCs) function and the pathogenesis of DOR. MATERIALS AND METHODS: Initially, we assessed the expression levels of miR-6881-3p in GCs obtained from human follicular fluid in both NOR and DOR cases and explored the correlation between miR-6881-3p expression and clinical outcomes in assisted reproduction technology (ART). Bioinformatic predictions and dual-luciferase reporter assays were employed to identify the target gene of miR-6881-3p. Manipulation of miR-6881-3p expression was achieved through the transfection of KGN cells with miR-6881-3p mimics, inhibitor, and miRNA negative control (NC). Following transfection, we assessed granulosa cell apoptosis and cell cycle progression via flow cytometry and quantified target gene expression through quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot (WB) analysis. Finally, we examined the correlation between target gene expression levels in GCs from NOR and DOR patients and their association with ART outcomes. RESULTS: Our findings revealed elevated miR-6881-3p levels in GCs from DOR patients, which negatively correlated with ovarian reserve function and ART outcomes. We identified a direct binding interaction between miR-6881-3p and the 3'-untranslated region of the SMAD4. Transfection with miR-6881-3p mimics induced apoptosis in KGN cell. Furthermore, miR-6881-3p expression negatively correlated with both mRNA and protein levels of the SMAD4. The mRNA and protein levels of SMAD4 were notably reduced in GCs from DOR patients, and SMAD4 mRNA expression positively correlated with ART outcomes. In addition, the mRNA levels of FSHR, CYP11A1 were notably reduced after transfection with miR-6881-3p mimics in KGN cell, while LHCGR notably increased. The mRNA and protein levels of FSHR, CYP11A1 were notably reduced in GCs from DOR patients, while LHCGR notably increased. CONCLUSION: This study underscores the role of miR-6881-3p in directly targeting SMAD4 mRNA, subsequently diminishing granulosa cell viability and promoting apoptosis, and may affect steroid hormone regulation and gonadotropin signal reception in GCs. These findings contribute to our understanding of the pathogenesis of DOR.

Copper-Catalyzed Decarboxylation Cross-Coupling Cascade Reaction for Synthesis of Fused Dihydro-benzoxazinones.

A protocol for a tandem copper-catalyzed intermolecular decarboxylation cross-coupling cascade between o-bromobenzoic acids and proline or piperic acid has been disclosed. The developed protocol allows access to a variety of synthetically useful fused benzoxazinones scaffolds with high efficiency and good functional group compatibility. A mechanistically sequential approach for the decarboxylation and dehydration coupling process was presented.

Silver-Catalyzed Radical Umpolung Cross-Coupling of Silyl Enol Ethers with Activated Methylene Compounds: Access to Diverse Tricarbonyl Derivatives.

A silver-catalyzed protocol for the intermolecular radical umpolung cross-coupling protocol of silyl enol ethers with activated methylene compounds is disclosed. The protocol exhibits excellent functional group tolerance, enabling the expedient preparation of a variety of tricarbonyl compounds. Preliminary mechanistic investigations suggest that the reaction proceeds through a process involving free radicals in which silver oxide has a dual role, acting as both a catalyst and a base.

LECT2 mediates antibacterial immune response induced by Nocardia seriolae infection in the northern snakehead.

Leukocyte-derived chemotaxin-2 (LECT2) is a multifunctional immunoregulator that plays several pivotal roles in the host's defense against pathogens. This study aimed to elucidate the specific functions and mechanisms of LECT2 (CaLECT2) in the northern snakehead (Channa argus) during infections with pathogens such as Nocardia seriolae (N. seriolae). We identified CaLECT2 in the northern snakehead, demonstrating its participation in the immune response to N. seriolae infection. CaLECT2 contains an open reading frame (ORF) of 459 bp, encoding a peptide of 152 amino acids featuring a conserved peptidase M23 domain. The CaLECT2 protein shares 62%-84 % identities with proteins from various other fish species. Transcriptional expression analysis revealed that CaLECT2 was constitutively expressed in all examined tissues, with the highest expression observed in the liver. Following intraperitoneal infection with N. seriolae, CaLECT2 transcription increased in the spleen, trunk kidney, and liver. In vivo challenge experiments showed that injecting recombinant CaLECT2 (rCaLECT2) could protect the snakehead against N. seriolae infection by reducing bacterial load, enhancing serum antibacterial activity and antioxidant capacity, and minimizing tissue damage. Moreover, in vitro analysis indicated that rCaLECT2 significantly enhanced the migration, respiratory burst, and microbicidal activity of the head kidney-derived phagocytes. These findings provide new insights into the role of LECT2 in the antibacterial immunity of fish.

Effect of estrogen exposure on pregnancy outcomes in artificial frozen-thawed embryo transfer cycles.

In contemporary times, the employment of vitrification freezing technology has led to the widespread adoption of frozen-thawed embryo transfer (FET) worldwide. Meanwhile, hormone replacement therapy (HRT) is a crucial protocol for priming the endometrium during FET cycles. Estrogen is required in HRT cycles for the induction of progesterone receptors and to promote endometrial thickness. However, there is no universal consensus on the treatment duration, dosage regimen, administration route, and target serum estrogen levels. Therefore, this study aimed to offer a comprehensive review of these topics. A shorter duration of estrogen exposure may elevate the risk of early miscarriage, while prolonged exposure to estrogen does not seem to confer advantages to general population and may be attempted in individuals with thin endometrium. Moreover, excessive estrogen levels on the day of progesterone administration may be associated with higher miscarriage rates and lower live birth rates (LBR). To offer more comprehensive guidance for clinical practice, extensive and prospective studies involving a large sample size are warranted to determine the optimal concentration and duration of estrogen exposure.

Screening Nonlinear miRNA Features of Breast Cancer by Using Ensemble Regularized Polynomial Logistic Regression.

Differentiating breast cancer subtypes based on miRNA data helps doctors provide more personalized treatment plans for patients. This paper explored the interaction between miRNA pairs and developed a novel ensemble regularized polynomial logistic regression method for screening nonlinear features of breast cancer. Three different types of second-order polynomial logistic regression with elastic network penalty (SOPLR-EN) in which each type contains 10 identical models were integrated to determine the most suitable sample set for feature screening by using bootstrap sampling strategy. A single feature and 39 nonlinear features were obtained by screening features that appeared at least 15 times in 30 integrations and were involved in the classification of at least 4 subtypes. The second-order polynomial logistic regression with ridge penalty (SOPLR-R) built on screened feature set achieved 82.30% classification accuracy for distinguishing breast cancer subtypes, surpassing the performance of other six methods. Further, 11 nonlinear miRNA biomarkers were identified, and their significant relevance to breast cancer was illustrated through six types of biological analysis.

Mechanisms of mitochondrial dysfunction in ovarian aging and potential interventions.

Mitochondria plays an essential role in regulating cellular metabolic homeostasis, proliferation/differentiation, and cell death. Mitochondrial dysfunction is implicated in many age-related pathologies. Evidence supports that the dysfunction of mitochondria and the decline of mitochondrial DNA copy number negatively affect ovarian aging. However, the mechanism of ovarian aging is still unclear. Treatment methods, including antioxidant applications, mitochondrial transplantation, emerging biomaterials, and advanced technologies, are being used to improve mitochondrial function and restore oocyte quality. This article reviews key evidence and research updates on mitochondrial damage in the pathogenesis of ovarian aging, emphasizing that mitochondrial damage may accelerate and lead to cellular senescence and ovarian aging, as well as exploring potential methods for using mitochondrial mechanisms to slow down aging and improve oocyte quality.

General Approach to Amides through Decarboxylative Radical Cross-Coupling of Carboxylic Acids and Isocyanides.

Herein, we report a silver-catalyzed protocol for decarboxylative cross-coupling between carboxylic acids and isocyanides, leading to linear amide products through a free-radical mechanism. The disclosed approach provides a general entry to a variety of decorated amides, accommodating a diverse array of radical precursors, including aryl, heteroaryl, alkynyl, alkenyl, and alkyl carboxylic acids. Notably, the protocol proved to be efficient for decarboxylative late-stage functionalization of several elaborate pharmaceuticals, demonstrating its potential applications.

NONO promotes gallbladder cancer cell proliferation by enhancing oncogenic RNA splicing of DLG1 through interaction with IGF2BP3/RBM14.

Gallbladder cancer (GBC) is a highly malignant and rapidly progressing tumor of the human biliary system, and there is an urgent need to develop new therapeutic targets and modalities. Non-POU domain-containing octamer-binding protein (NONO) is an RNA-binding protein involved in the regulation of transcription, mRNA splicing, and DNA repair. NONO expression is elevated in multiple tumors and can act as an oncogene to promote tumor progression. Here, we found that NONO was highly expressed in GBC and promoted tumor cells growth. The dysregulation of RNA splicing is a molecular feature of almost all tumor types. Accordingly, mRNA-seq and RIP-seq analysis showed that NONO promoted exon6 skipping in DLG1, forming two isomers (DLG1-FL and DLG1-S). Furthermore, lower Percent-Spliced-In (PSI) values of DLG1 were detected in tumor tissue relative to the paraneoplastic tissue, and were associated with poor patient prognosis. Moreover, DLG1-S and DLG1-FL act as tumor promoters and tumor suppressors, respectively, by regulating the YAP1/JUN pathway. N6-methyladenosine (m6A) is the most common and abundant RNA modification involved in alternative splicing processes. We identified an m6A reader, IGF2BP3, which synergizes with NONO to promote exon6 skipping in DLG1 in an m6A-dependent manner. Furthermore, IP/MS results showed that RBM14 was bound to NONO and interfered with NONO-mediated exon6 skipping of DLG1. In addition, IGF2BP3 disrupted the binding of RBM14 to NONO. Overall, our data elucidate the molecular mechanism by which NONO promotes DLG1 exon skipping, providing a basis for new therapeutic targets in GBC treatment.

Concordance between three integrated scores based on prostate biopsy and grade-grouping of radical prostatectomy specimen / 中华病理学杂志

Objective: To analyze three different integrated scoring schemes of prostate biopsy and to compare their concordance with the scoring of radical prostatectomy specimens. Methods: A retrospective analysis of 556 patients with radical prostatectomy performed in Nanjing Drum Tower Hospital, Nanjing, China from 2017 to 2020. In these cases, whole organ sections were performed, the pathological data based on biopsy and radical prostatectomy specimens were summarized, and 3 integrated scores of prostate biopsy were calculated, namely the global score, the highest score and score of the largest volume. Results: Among the 556 patients, 104 cases (18.7%) were classified as WHO/ISUP grade group 1, 227 cases (40.8%) as grade group 2 (3+4=7); 143 cases (25.7%) as grade group 3 (4+3=7); 44 cases (7.9%) as grade group 4 (4+4=8) and 38 cases (6.8%) as grade group 5. Among the three comprehensive scoring methods for prostate cancer biopsy, the consistency of global score was the highest (62.4%). In the correlation analysis, the correlation between the scores of radical specimens and the global scores was highest (R=0.730, P<0.01), while the correlations of the scores based on radical specimens with highest scores and scores of the largest volume based on biopsy were insignificant (R=0.719, P<0.01; R=0.631, P<0.01, respectively). Univariate and multivariate analyses showed tPSA group and the three integrated scores of prostate biopsy were statistically correlated with extraglandular invasion, lymph node metastasis, perineural invasion and biochemical recurrence. Elevated global score was an independent prognostic risk factor for extraglandular invasion and biochemical recurrence in patients; increased serum tPSA was an independent prognostic risk factor for extraglandular invasion; increased hjighest score was an independent risk factor for perineural invasion. Conclusions: In this study, among the three different integrated scores, the overall score is most likely corresponded to the radical specimen grade group, but there is difference in various subgroup analyses. Integrated score of prostate biopsy can reflect grade group of radical prostatectomy specimens, thereby providing more clinical information for assisting in optimal patient management and consultation.

Clinicopathological features of gastric carcinomas with NTRK-rearrangement/amplification: report of four cases / 中华病理学杂志

Objective: To investigate the clinicopathological, immunohistochemical and molecular genetic characteristics of gastric carcinoma with NTRK-rearrangement/amplification. Methods: The clinicopathological data of gastric carcinoma cases with NTRK-rearrangement/amplification diagnosed from January 2011 to September 2020 at the Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, China, were collected. The clinicopathological, immunophenotypic and molecular pathological features were analyzed. The relevant literature was reviewed. Results: There were 4 cases of gastric carcinoma with NTRK-rearrangement/amplification. All 4 patients were male, aged 57-67 years (average, 63 years). Tumor sizes ranged from 3.5 to 5.2 cm (average, 4.8 cm). All tumors were in the antrum. All 4 patients underwent radical gastrectomy and were followed up after the surgery. Morphologically, all tumors showed histological features with enteroblastic-differentiated gastric carcinoma. Tumor cells showed predominantly tubular/papillary architecture, with conspicuous vesicular nuclei and pale staining or transparent cytoplasm. Immunohistochemistry showed pan-TRK expression in all cases, with various degrees of positivity in the cytoplasm. All cases were subject to NTRK1/2/3 detection using fluorescence in situ hybridization. There were NTRK translocations in 2 cases and NTRK amplifications in 2 cases. These cases were further verified by RNAseq next generation sequencing which confirmed that NTRK1 gene translocation (TPM3-NTRK1) and NTRK2 gene translocation (NTRK2-SMCHD1) occurred in two cases, respectively. Conclusions: NTRK mutation occurs less frequently in gastric cancer. In this study, the cases mainly occur in the antrum. The morphology has the characteristics of enteroblastic differentiation. The tumors have unique histological, immunophenotypic and molecular characteristics, which require much attention from pathologists to effectively guide clinicians to choose the best treatment.

Anti-fatigue effect of Lubian on kidney Yin deficiency and kidney Yang deficiency mice and mechanism based on PI3K-Akt pathway / 中国中药杂志

This study aimed to investigate the anti-fatigue effect and mechanism of Lubian(Cervi Penis et Testis) on kidney Yin deficiency and kidney Yang deficiency mice. After one week of adaptive feeding, 88 healthy male Kunming mice were randomly divided into a blank group, a kidney Yin deficiency model group, a kidney Yin deficiency-Panacis Quinquefolii Radix(PQR) group, kidney Yin deficiency-Lubian treatment groups, a kidney Yang deficiency model group, a kidney Yang deficiency-Ginseng Radix et Rhizoma(GR) group, and kidney Yang deficiency-Lubian treatment groups, with eight mice in each group. The kidney Yin deficiency model and kidney Yang deficiency model were prepared by daily regular oral administration of dexamethasone acetate and hydrocortisone, respectively, and meanwhile, corresponding drugs were provided. The mice in the blank group received blank reagent. The treatment lasted 14 days. The exhaustive swimming time was measured 30 min after drug administration on the 14th day. On the 15th day, blood was collected from eyeballs and the serum was separated to determine the content of lactic acid(LD), blood urea nitrogen(BUN), lactate dehydrogenase(LDH), cyclic adenosine monophosphate(cAMP), and cyclic guanosine monophosphate(cGMP). The liver was dissected to determine the content of liver glycogen and the protein expression of phosphoinositide 3-kinase(PI3K) and protein kinase B(Akt). Compared with the kidney Yang deficiency model group, the kidney Yang deficiency-Lubian treatment groups showed increased body weight(P<0.05), relieved symptoms of Yang deficiency, decreased cGMP content(P<0.01), increased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), reduced LD(P<0.01), elevated BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K and Akt in the liver(P<0.05). Compared with the kidney Yin deficiency model group, the kidney Yin deficiency-Lubian treatment groups showed increased body weight(P<0.01), relieved symptoms of Yin deficiency, increased content of cGMP(P<0.01), decreased cAMP/cGMP(P<0.01), prolonged exhausted swimming time(P<0.01), decreased LD(P<0.01), decreased BUN content(P<0.01), increased liver glycogen content(P<0.01), and increased protein expression of PI3K(P<0.05) and Akt in the liver(P<0.05). To sum up, Lubian can regulate Yin deficiency and Yang deficiency and increase glycogen synthesis by affecting the PI3K-Akt pathway, thereby exerting an anti-fatigue role.

Expression of GPNMB in renal eosinophilic tumors and its value in differential diagnosis / 中华病理学杂志

Objective: To investigate the expression of glycoprotein non metastatic melanoma protein B (GPNMB) in renal eosinophilic tumors and to compare the value of GPNMB with CK20, CK7 and CD117 in the differential diagnosis of renal eosinophilic tumors. Methods: Traditional renal tumor eosinophil subtypes, including 22 cases of renal clear cell carcinoma eosinophil subtype (e-ccRCC), 19 cases of renal papillary cell carcinoma eosinophil subtype (e-papRCC), 17 cases of renal chromophobe cell carcinoma eosinophil subtype (e-chRCC), 12 cases of renal oncocytoma (RO) and emerging renal tumor types with eosinophil characteristics [3 cases of eosinophilic solid cystic renal cell carcinoma (ESC RCC), 3 cases of renal low-grade eosinophil tumor (LOT), 4 cases of fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) and 5 cases of renal epithelioid angiomyolipoma (E-AML)], were collected at the Affiliated Drum Tower Hospital of Nanjing University Medical School from January 2017 to March 2022. The expression of GPNMB, CK20, CK7 and CD117 was detected by immunohistochemistry and statistically analyzed. Results: GPNMB was expressed in all emerging renal tumor types with eosinophil characteristics (ESC RCC, LOT, FH-dRCC) and E-AML, while the expression rates in traditional renal eosinophil subtypes e-papRCC, e-chRCC, e-ccRCC and RO were very low or zero (1/19, 1/17, 0/22 and 0/12, respectively); the expression rate of CK7 in LOT (3/3), e-chRCC (15/17), e-ccRCC (4/22), e-papRCC (2/19), ESC RCC (0/3), RO (4/12), E-AML(1/5), and FH-dRCC (2/4) variedly; the expression of CK20 was different in ESC RCC (3/3), LOT(3/3), e-chRCC(1/17), RO(9/12), e-papRCC(4/19), FH-dRCC(1/4), e-ccRCC(0/22) and E-AML(0/5), and so did that of CD117 in e-ccRCC(2/22), e-papRCC(1/19), e-chRCC(16/17), RO(10/12), ESC RCC(0/3), LOT(1/3), E-AML(2/5) and FH-dRCC(1/4). GPNMB had 100% sensitivity and 97.1% specificity in distinguishing E-AML and emerging renal tumor types (such as ESC RCC, LOT, FH-dRCC) from traditional renal tumor types (such as e-ccRCC, e-papRCC, e-chRCC, RO),respectively. Compared with CK7, CK20 and CD117 antibodies, GPNMB was more effective in the differential diagnosis (P<0.05). Conclusion: As a new renal tumor marker, GPNMB can effectively distinguish E-AML and emerging renal tumor types with eosinophil characteristics such as ESC RCC, LOT, FH-dRCC from traditional renal tumor eosinophil subtypes such as e-ccRCC, e-papRCC, e-chRCC and RO, which is helpful for the differential diagnosis of renal eosinophilic tumors.

Correlation of NTRK genetic fusions with mismatch repair protein deletion in patients with colorectal cancer / 中华病理学杂志

Objective: To investigate the relationship between the expression of four mismatch repair proteins (MLH1, MSH2, MSH6 and PMS2) and NTRK genetic fusions in colorectal cancer. Methods: The paraffin-embedded tissue blocks of 830 cases of colorectal cancer were collected at the Affiliated Drum Tower Hospital, Nanjing University Medical School, China, from 2015 to 2019. Immunohistochemical and fluorescence in situ hybridization(FISH) method were used respectively to detect the expression of mismatch repair proteins and the break-apart of NTRKs; and the relationship between the expression of mismatch repair proteins and the NTRK genetic fusions was analyzed. Results: The overall mismatch repair protein deficiency (dMMR) rate was 9.88% (82/830), the mismatch repair proteins proficiency (pMMR) rate was 90.12%(748/830). The total deficiency rate of MLH1 protein was 9.04% (75/830), hPMS2 protein deficiency rate was 9.04% (75/830), MSH2 protein deficiency rate was 2.53% (21/830), MSH6 protein deficiency rate was 4.10% (34/830), the deficiency rate of synchronous MLH1 and PMS2 were 8.67% (72/830) and the deficiency rate of synchronous MSH2 and MSH6 were 2.17% (18/830). The dMMR group was associated with tumor location, different histological subgroups, tumor differentiation, AJCC stage and N stage (P<0.05). There were six cases (7.32%) carrying NTRK fusion by FISH among the 82 cases of dMMR, but only seven cases (0.94%) carrying NTRK fusion among the 748 cases of PMMR. The NTRKs translocation by FISH in all 13 cases were further confirmed by next generation sequencing. Among the clinicopathological characteristics, only differentiation showed significant difference between NTRK fusion positive and negative groups (P<0.05). More importantly, NTRK fusion was enriched in dMMR group (7.32% vs. 0.94%). Conclusion: In dMMR colorectal cancer group, the prevalence of NTRK fusion is higher than that in pMMR group.

Application and prospect of organoid culture in cancer / 中国药理学通报

At present, the traditional models for cancer research include the 2D cell model, human tumor xenograft model and animal model. With the deepening of research, the traditional tumor model is unable to meet the needs of researchers. Organoid model is derived from the surgical specimens of tumor patients, which can completely preserve the histological and genomic characteristics of tumor. It can be used in the research of tumor pathogenesis, drug screening, personalized treatment of patients, etc. Compared with traditional model, it has the advantages of short modeling time, economic benefits and closer-ness to the characteristics of the original tumor. This paper mainly focuses on the research status of organoid technology in tumor, the application of organoid model in treatment, and the advantages of organoid model compared with traditional model, so as to provide reference for the follow-up research.

SWOT analysis of schistosomiasis elimination in Laos / 中国血吸虫病防治杂志

Objective To analyze the advantages, disadvantages, opportunities and challenges for schistosomiasis elimination in Laos, so as to propose the corresponding healthy policies and suggestions. Methods A SWOT analysis was performed to analyze the strength, weakness, opportunity and threat for the schistosomiasis elimination program in Laos, and the corresponding policy suggestions were proposed. Results The national schistosomiasis elimination program of Laos receives governmental emphases and great supports. A strategy based on mass drug administration was proposed and a sentinel site-bases surveillance system has been built for schistosomiasis elimination in Laos; however, there are several challenges for the national schistosomiasis elimination program in Laos, including insufficient financial supports, inadequate professional capability, weak schistosomiasis control awareness in community populations and difficulty in vector control. Conclusions Persistent governmental leadership, increasing financial supports, strengthening professional team building and improving schistosomiasis control awareness in community populations are required to facilitate the progress towards schistosomiasis elimination in Laos.

Whole-Brain Monosynaptic Inputs to Hypoglossal Motor Neurons in Mice / 神经科学通报·英文版

Hypoglossal motor neurons (HMNs) innervate tongue muscles and play key roles in a variety of physiological functions, including swallowing, mastication, suckling, vocalization, and respiration. Dysfunction of HMNs is associated with several diseases, such as obstructive sleep apnea (OSA) and sudden infant death syndrome. OSA is a serious breathing disorder associated with the activity of HMNs during different sleep-wake states. Identifying the neural mechanisms by which the state-dependent activities of HMNs are controlled may be helpful in providing a theoretical basis for effective therapy for OSA. However, the presynaptic partners governing the activity of HMNs remain to be elucidated. In the present study, we used a cell-type-specific retrograde tracing system based on a modified rabies virus along with a Cre/loxP gene-expression strategy to map the whole-brain monosynaptic inputs to HMNs in mice. We identified 53 nuclei targeting HMNs from six brain regions: the amygdala, hypothalamus, midbrain, pons, medulla, and cerebellum. We discovered that GABAergic neurons in the central amygdaloid nucleus, as well as calretinin neurons in the parasubthalamic nucleus, sent monosynaptic projections to HMNs. In addition, HMNs received direct inputs from several regions associated with respiration, such as the pre-Botzinger complex, parabrachial nucleus, nucleus of the solitary tract, and hypothalamus. Some regions engaged in sleep-wake regulation (the parafacial zone, parabrachial nucleus, ventral medulla, sublaterodorsal tegmental nucleus, dorsal raphe nucleus, periaqueductal gray, and hypothalamus) also provided primary inputs to HMNs. These results contribute to further elucidating the neural circuits underlying disorders caused by the dysfunction of HMNs.

Genetic Diversity and Association Analysis between Medicinal Components and ISSR Markers in Astragali Radix / 中国药学杂志

OBJECTIVE: To study and exploit Chinese medicine Astragali Radix, the molecular markers that relates to the phenotypic traits on medicinal components of Astragali Radix and would be detected. METHODS: The genetic diversity of 43 Astragali Radix samples was analyzed with ISSR molecular marker technique and then the population genetic structure was studied through 13 selected markers. The association analysis between ISSR markers and 4 phenotypic traits of medicinal components were performed with GLM (general linear model) programs in Tassel 2.1. Certain genetic diversity was discovered among the 43 Astragali Radix samples. RESULTS: The genetic distance varied between 0.050 6 and 0.743 8, with an average of 0.274 1. Moreover, the cultivated Astragali Radix from Ningxia and Gansu province closely related to the wild Astragali Radix collected from Liupanshan town in Ningxia. On the other hand, No. 340 had the farthest relationship with other Astragali Radix. The content of polysaccharide, total saponins, total flavonoids, and Astragaloside IV ranged between 7.693-27.840 mg•g-1, 7.167-17.579 mg•g-1, 2.212-6.164 mg•g-1 and 6.070-107.920 μg•g-1, respectively. Meanwhile, linear regression analysis indicated that there was a significant positive correlation between the content of the total saponins and that of flavonoids (r=0.650 5,P=2.3×10-6<0.01), while the content of astragaloside had no significant correlation with that of polysaccharide, total saponins and total flavonoids. The population genetic structural analysis showed that the 43 samples were divided into 4 subgroups. There were total of 34 locus in 13 ISSR markers significantly associated (P<0.01) with the content of polysaccharide,total saponins, flavonoids and astragaloside , and the rate of explanation on the phenotype of related marker ranged from 8.14% to 51.39%. Among the locus, 15 were related with astragaloside content at interpretation rates above 30%, 1 with polysaccharide content an interpretation rate reached as high as 51.39% with high threshold (P<1×10-5). CONCLUSION: These results would provide supporting evidence for identification and protection of germplasm resources as well as molecular marker-assisted breeding.

Visual-spatial neglect after right-hemisphere stroke: behavioral and electrophysiological evidence / 中华医学杂志(英文版)

BACKGROUND@#Visual-spatial neglect (VSN) is a neuropsychological syndrome, and right-hemisphere stroke is the most common cause. The pathogenetic mechanism of VSN remains unclear. This study aimed to investigate the behavioral and event-related potential (ERP) changes in patients with or without VSN after right-hemisphere stroke.@*METHODS@#Eleven patients with VSN with right-hemisphere stroke (VSN group) and 11 patients with non-VSN with right-hemisphere stroke (non-VSN group) were recruited along with one control group of 11 age- and gender-matched healthy participants. The visual-spatial function was evaluated using behavioral tests, and ERP examinations were performed.@*RESULTS@#The response times in the VSN and non-VSN groups were both prolonged compared with those of normal controls (P  0.05).@*CONCLUSIONS@#Visual-spatial attention function is impaired after right-hemisphere stroke, and clinicians should be aware of the subclinical VSN. Our findings provide neuroelectrophysiological evidence for the lateralization of VSN.