Phosphatase and tensin-homolog deleted on chromosome 10 (PTEN) is an important cancer suppressor gene. Its pathogenic mutation leads to PTEN hamartoma tumor syndrome (PHTS), a rare syndrome also known as Cowden syndrome, which is relevant to early-onset hereditary breast cancer (BC). In this paper, we report three patients with unilateral multicentric BC and synchronous and metachronous bilateral BC who harbored PTEN gene mutations, and summarize the clinical manifestations, pathological characteristics, diagnosis, treatment and follow-up outcomes to provide reference for management of PTEN gene mutation-related BC among the Cowden syndrome population.

Objective This study aims at establishing a teaching catalog and content for breast rare dis-eases and developing the syllabus for the breast rare disease using integrated multimodality of case-/problem-/resource-based learning(CBL+PBL+RBL).Methods By conducting bibliometrics co-occurrence analysis,we collected 6291 articles on breast rare disease published from January,1975 to June,2024.Additionally,we re-trieved the Textbook on Rare Diseases,the Catalog of Chinese Rare Disease,and Second Batch of Rare Dis-ease Catalog and then decided the teaching content.Results From 16,387 keywords,1000(6.1％)keywords were identified through co-occurrence analysis,including 50(0.3％)candidate diseases.These were classified into three categories:rare primary breast diseases,rare genetic mutation-related diseases associated with breast cancer,and rare systemic multi-system diseases involving the breast.From the candidate list,20(0.1％)rare primary breast diseases were further selected for their notable clinical teaching significance,and significant multi-systemic diseases affecting the breast,whether related to gene mutations or not.Teaching plans were draf-ted using a diversified parallel teaching approaches,taking into account the characteristics of different diseases and the focus of different teaching methods.Conclusions This study initiated the development of the teaching content for breast rare diseases and developed the teaching syllabus using the CBL+PBL+RBL integrated multi teaching model and targeting each rare breast disease for the critical point for teaching.

Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P＜0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.

Objective:To investigate the application value of single-sperm sequencing in resolving the carrier status of preim-plantation genetic testing(PGT)for chromosomal structural rearrangements in Robertsonian translocations.Methods:Haplotypes were constructed by single-sperm isolation combined with single-sperm sequencing for a patient with 45,XY,der(13;14)(q10;q10).Twenty single-sperm samples were isolated by mechanical braking and subjected to whole-genome amplification(WGA),and then the Asian Screening Array(ASA)gene chip was used to detect the 183 708 single nucleotide polymorphisms(SNP)of the WGA products.The single sperm associated with the translocation that could be used as haplotype inference was detected by copy number variation(CNV)sequencing,and the chromosomal haplotypes with normal and Robertsonian translocations were inferred.Three biopsy samples of embryonic trophoblast cells were used as the objects.After whole-genome amplification,high-throughput sequencing was employed to determine the status of the translocation chromosome carried by the embryos.The available blastocysts were selected for transfer,and the amniotic fluid samples were taken at 18 weeks of gestation to confirm whether the fetus carried the pathogenic muta-tion.Results:A total of 6 037 SNP sites were screened by single-sperm sequencing,and 30 sites selected to distinguish normal and translocation haplotypes.Preimplantation haplotype analysis showed that all the three embryos were euploids without Robertsonian translocation chromosome.Genetic testing of amniotic fluid in the second trimester confirmed that the karyotype of the fetus was 46,XN,carrying no Robertsonian translocation chromosome.Conclusion:For male carriers of Robertsonian translocation,single sperm sequencing can be used to screen SNP sites to construct haplotypes for distinguishing normal and Robertsonian translocation em-bryos,and to provide a basis for embryo selection by preimplantation chromosomal structural genetic testing.

AIM To evaluate the quality of Yanyangke Mixture.METHODS The HPLC fingerprints were established,after which cluster analysis,principal component analysis and partial least squares discriminant analysis were performed.The contents of liquiritin,rosmarinic acid,sheganoside,irisgenin,honokiol,monoammonium glycyrrhizinate,irisflorentin,isoliquiritin and magnolol were determined,the analysis was performed on a 35 ℃ thermostatic Agilent ZORBAX SB-C18 column(5 μm,250 mmx4.6 mm),with the mobile phase comprising of 0.1％phosphoric acid-acetonitrile flowing at 1 mL/min in a gradient elution manner,and multi-wavelength detection was adopted.RESULTS There were ten common peaks in the fingerprints for twelve batches of samples with the similarities of more than 0.9.Various batches of samples were clustered into three types,three principal components displayed the acumulative variance contribution rate of 87.448％,peaks 5、14(honokiol),3(liquiritin),11(monoammonium glycyrrhizinate)and 15(asarinin)were quality markers.Nine constituents showed good linear relationships within their own ranges(r＞0.999 0),whose average recoveries were 98.5％-103.6％with the RSDs of 0.92％-1.7％.CONCLUSION This stable and reliable method can provide a basis for the quality control of Yanyangke Mixture.

Aim To explore the effect of artesunate (ART) on the function of breast cancer cells during the progression of breast cancer and the possible mechanism of action. Methods MCF-7 (30 μmol • L-

ObjectiveTo compare the changes of retinal microcirculation indexes in the anterior and posterior macular areas of the eyes used at close range and to explore the possible causes of myopia affected by near work. MethodsWatching mobile phone video for 1 hour at close range was used as the method of defining near work. The OCTA technology was used to measure the superficial retinal microcirculation indexes within 6 by 6 mm macular area before and after near work， including the superficial retinal VLD from the nerve fiber layer to the inner boundary of the outer plexiform layer， the VPD， nonperfusion area of FAZ， FAZ-P and FAZ circulation，. The FAZ was divided int center， inner layer， outer layer and overall according to the region， and 11 microcirculation indexes were obtained to compare the differences between before and after near work. ResultsThe indexes of superficial retinal microcirculation in the macular area generally decreased after near work， except for FAZ-A and FAZ-P（P = 0.148， 0.975）. The largest differences among both VLD and VPD occurred between the central and inner layer（Difference = 1.00， 0.80， 0.02， 0.02，P = 0.001， 0.008， 0.001， 0.008）. No differences in microcirculation indexs were observed in the macular area after near work with different diopters and axial lengths. ConclusionNear work may affect the occurrence and development of myopia by affecting the changes of retinal microcirculation in the superficial layer of macula， leading to ischemia and hypoxia.

Diabetic peripheral neuropathy(DPN) is a chronic complication resulted from peripheral nerve injury in the late stage of diabetes. It involves a variety of pathological changes such as oxidative stress, endoplasmic reticulum stress, neuroinflammation, and apoptosis of Schwann cells(SCs). DPN is the main factor leading to lower limb disability or amputation in diabetic patients, with high incidence, long disease course, and poor prognosis. The modern medicine treatment of DPN mainly focuses on controlling blood glucose and improving microcirculation and nerve nutrition, which can only mitigate the clinical symptoms and not fundamentally reverse the pathological changes of peripheral nerves. Autophagy is a self-clearing mechanism that maintains cellular homeostasis by removing excess metabolites. Traditional Chinese medicine(TCM), featuring the holistic concept and syndrome differentiation, can treat chronic diseases in a multi-target, multi-pathway, and wide-range manner. Modern studies have shown that the occurrence and development of DPN are related to a variety of pathological changes, and autophagy is a key mechanism associated with DPN. The environment with persistent high glucose can lead to the inhibition or over-activation of peripheral nerve cells, which causes irreversible damage of nerve cells and the occurrence and development of DPN. Therefore, restoring autophagy balance and reducing nerve damage is one of the key ways to treat DPN. The recent studies have confirmed that some active ingredients in traditional Chinese medicines and TCM compound prescriptions can inhibit the oxidative stress, endoplasmic reticulum stress, mitochondrial damage, inflammation, and apoptosis of SCs in DPN by regulating the autophagy pathway, thus playing a role in the prevention and treatment of DPN. However, the systematic induction in this field remains to be carried out. This paper reviewed the relevant literature, explained the mechanism of TCM in the prevention and treatment of DPN by regulating autophagy, and summarized the potential targets of TCM in the treatment of DPN, with a view to providing new ideas for clinical research and drug development.
Humans ; Autophagy ; Diabetes Mellitus ; Diabetic Neuropathies/complications* ; Medicine, Chinese Traditional ; Oxidative Stress ; Schwann Cells/pathology*

OBJECTIVE: The study explores the effects of electroacupuncture (EA) at the governing vessel (GV) on proteomic changes in the hippocampus of rats with cognitive impairment. METHODS: Healthy male rats were randomly divided into 3 groups: sham, model and EA. Cognitive impairment was induced by left middle cerebral artery occlusion in the model and EA groups. Rats in the EA group were treated with EA at Shenting (GV24) and Baihui (GV20) for 7 d. Neurological deficit was scored using the Longa scale, the learning and memory ability was detected using the Morris water maze (MWM) test, and the proteomic profiling in the hippocampus was analyzed using protein-labeling technology based on the isobaric tag for relative and absolute quantitation (iTRAQ). The Western blot (WB) analysis was used to detect the proteins and validate the results of iTRAQ. RESULTS: Compared with the model group, the neurological deficit score was significantly reduced, and the escape latency in the MWM test was significantly shortened, while the number of platform crossings increased in the EA group. A total of 2872 proteins were identified by iTRAQ. Differentially expressed proteins (DEPs) were identified between different groups: 92 proteins were upregulated and 103 were downregulated in the model group compared with the sham group, while 142 proteins were upregulated and 126 were downregulated in the EA group compared with the model group. Most of the DEPs were involved in oxidative phosphorylation, glycolipid metabolism and synaptic transmission. Furthermore, we also verified 4 DEPs using WB technology. Although the WB results were not exactly the same as the iTRAQ results, the expression trends of the DEPs were consistent. The upregulation of heat-shock protein β1 (Hspb1) was the highest in the EA group compared to the model group. CONCLUSION EA can effect proteomic changes in the hippocampus of rats with cognitive impairment. Hspb1 may be involved in the molecular mechanism by which acupuncture improves cognitive impairment.
Rats ; Male ; Animals ; Rats, Sprague-Dawley ; Electroacupuncture ; Proteomics ; Cognitive Dysfunction/therapy* ; Hippocampus

Objective: To investigate the association between metabolically healthy obesity and the incident risk of stroke in people aged ≥40 years from rural areas of Henan Province. Methods: During 2007 to 2008, 20 194 residents aged ≥18 years were selected for baseline examination by random cluster sampling and 17 265 participants were followed up during 2013 to 2014. According to the aim of current study, a total of 11 864 eligible subjects were included in this post-hoc analysis. Depending on body mass index and metabolic status, subjects were divided into four groups: metabolically healthy normal weight, metabolically healthy obesity, metabolically abnormal normal weight and metabolically abnormal obesity. Multivariate logistic regression model was used to analyze the relationship between metabolically healthy obesity and the risk of stroke. Results: The median (Q₁, Q₃) age of study participants was 54(46, 61) years, and 4 526 participants were men. During the mean follow-up of 6 years, the cumulative incidence of stroke was 7.16%. The incidence of stroke in metabolically healthy normal weight, metabolically healthy obesity, metabolically abnormal normal weight, and metabolically abnormal obesity were 3.73%, 4.61%, 8.99% and 9.38%, respectively (χ²=117.458, P<0.001). After adjusting possible confounding factors, compared with metabolically healthy normal weight, the risk of stroke was significantly increased in the metabolically healthy obesity group, metabolically abnormal normal weight group and metabolically abnormal obesity group with the odds ratio (OR) and 95% confidence interval (CI) of 1.52(1.10-2.12), 2.11(1.61-2.77) and 2.78(2.18-3.55), respectively. Stratified analysis showed that the risk of stroke was significantly higher in metabolically healthy obesity people aged 40-59 years compared with metabolically healthy normal weight group (OR=2.12, 95%CI: 1.36-3.30). Conclusion: Metabolically healthy obesity, metabolically abnormal normal weight and metabolically abnormal obesity are positively associated with the risk of stroke.
Adolescent ; Adult ; Body Mass Index ; Humans ; Male ; Middle Aged ; Obesity/complications* ; Obesity, Metabolically Benign/epidemiology* ; Risk Factors ; Stroke/epidemiology*