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.

ObjectiveTo analyze the microbial diversity in the rhizosphere soil of Gastrodia elata with different yields and explore the influence of soil microorganisms on the yield of G. elata. MethodThe experiment adopted the 16S DNA and ITS high-throughput sequencing technologies to study the diversity of the bacterial and fungal community in the rhizosphere soil of G. elata with high yield （GC） and low yield （DC）. ResultProteobacteria， Firmicutes， and other unidentified Bacteria were dominant in the rhizosphere soil of G. elata. The dominant rhizosphere fungi were Ascomycota， Basidiomycota， and Mortierellomycota. There was no significant difference in microbial community abundance in the high-yield and low-yield rhizosphere soil of G. elata， but there was a significant difference in species composition. Thirty-eight microbes such as Bradyrhizobium， Schleiferilactobacillus， and Archaeorhizomyces were gathered in large numbers in the high-yield rhizosphere soil， and thirty microbes such as Fusarium， Coprinellus， and Nitrosotalea were gathered in large numbers in the low-yield rhizosphere soil. At the level of genus and species， there were six different species in the high-yield and low-yield rhizosphere soil of G. elata， among which Russula mariae， Archeaeorhizomyces， and Ilyonectria were gathered in the high-yield rhizosphere soil of G. elata， while Nitrosotalea， Coprinellus disserminatus， and Fusarium were gathered in the low-yield rhizosphere soil of G. elata. ConclusionThere are different microorganisms in the rhizosphere soil of G. elata with different yields， and it is speculated that these microorganisms are related to the yields of G. elata. The research results are expected to provide a vital theoretical basis for the follow-up study of the high yield of G. elata.

This study aimed to evaluate the therapeutic potential of inhibiting protein arginine methyltransferase 5(PRMT5)in cisplatin-induced hearing loss.The effects of PRMT5 inhibition on cisplatin-induced auditory injury were determined using immunohistochemistry,apoptosis assays,and auditory brainstem response.The mechanism of PRMT5 inhibition on hair cell survival was assessed using RNA-seq and Cleavage Under Targets and Tagment-quantitative polymerase chain reaction(CUT&Tag-qPCR)analyses in the HEI-OC1 cell line.Pharmacological inhibition of PRMT5 significantly alleviated cisplatin-induced damage to hair cells and spiral ganglion neurons in the cochlea and decreased apoptosis by protecting mitochondrial function and preventing the accumulation of reactive oxygen species.CUT&Tag-qPCR analysis demonstrated that inhibition of PRMT5 in HEI-OC1 cells reduced the accumulation of H4R3me2s/H3R8me2s marks at the promoter region of the Pik3ca gene,thus activating the expression of Pik3ca.These findings suggest that PRMT5 inhibitors have strong potential as agents against cisplatin-induced ototoxicity and can lay the foundation for further research on treatment strategies of hearing loss.

Cisplatin-related ototoxicity is a critical side effect of chemotherapy and can lead to irreversible hearing loss. This study aimed to assess the potential effect of the DNA methyltransferase (DNMT) inhibitor RG108 on cisplatin-induced ototoxicity. Immunohistochemistry, apoptosis assay, and auditory brainstem response (ABR) were employed to determine the impacts of RG108 on cisplatin-induced injury in murine hair cells (HCs) and spiral ganglion neurons (SGNs). Rhodamine 123 and TMRM were utilized for mitochondrial membrane potential (MMP) assessment. Reactive oxygen species (ROS) amounts were evaluated by Cellrox green and Mitosox-red probes. Mitochondrial respiratory function evaluation was performed by determining oxygen consumption rates (OCRs). The results showed that RG108 can markedly reduce cisplatin induced damage in HCs and SGNs, and alleviate apoptotic rate by protecting mitochondrial function through preventing ROS accumulation. Furthermore, RG108 upregulated BCL-2 and downregulated APAF1, BAX, and BAD in HEI-OC1 cells, and triggered the PI3K/AKT pathway. Decreased expression of low-density lipoprotein receptor-related protein 1 (LRP1) and high methylation of the LRP1 promoter were observed after cisplatin treatment. RG108 treatment can increase LRP1 expression and decrease LRP1 promoter methylation. In conclusion, RG108 might represent a new potential agent for preventing hearing loss induced by cisplatin via activating the LRP1-PI3K/AKT pathway.

Autosomal recessive congenital ichthyosis (ARCI) is a rare hereditary cornification disorder presented with abnormal skin scaling. In this paper, we used next-generation sequencing to determine the variants in a Chinese ARCI patient. We used sanger sequencing to verify bidirectionally the DNA from the proband and her parents. Results showes that two compound heterozygous variants (c.235G > T and c.641delG) in CYP4F22 gene, and both of the mutations are novel. The parents were heterozygous carriers. The two variants are classified as pathogenic variants based on interpretation guidelines. The compound heterozygous mutations in CYP4F22 gene were the causative mutations responsible for ARCI in proband.

Objective To investigate an outbreak of norovirus GII gastroenteritis in a school, and explore the causes, transmission routes and risk factors of the outbreak, and to provide a scientific basis and experience for effective control of outbreaks of acute gastroenteritis in schools. Methods A case study of an acute gastroenteritis outbreak in a school in Wujin District, Changzhou was conducted by field epidemiological investigation. Anal swab samples of patients and controls were collected, and enterovirus nucleic acid was detected by real-time fluorescent PCR. Results From December 12 to December 17, 2019, a total of 185 cases were identified, all of them from students of the school, with an incidence rate of 3.84% (185/4,822). All of the cases were distributed in three (7^th/8^th/9^th) grades of the school, with attack rates of 5.38% (31 / 576), 18.71% (104 / 556) and 9.06% (50 / 552) in 7^th, 8^th and 9^th grade, respectively, showing a significant difference among the grades (χ²=54.47，P＜0.05). The attack rate of each floor of the teaching building from the first to fifth floor was 2.17% (5/230), 7.51% (26/346), 15.77% (53/336), 17.11% (65/380), and 6.38% (25/392), respectively, showing a statistically significant difference among different floors (χ²=55.66，P＜0.05). A total of 32 anal swabs were collected, including 12 patients, 10 control students and 10 workers in the canteen. Of them, 9 specimens of the patients and 1 specimen of the workers were positive for norovirus type GII. Conclusion The school outbreak of acute gastroenteritis was caused by norovirus GII. Close contact between students was the main mode of transmission. A hidden infection of canteen staff may be related to this outbreak. It is important to promote popular science of norovirus prevention and to enhance the awareness of the risks of the virus.

Objective:To study the safety and effectiveness of endoscopic full-thickness resection(EFR) in the treatment of large gastric stromal tumors with diameter of 5-7 cm.Methods:Data of 36 patients with large gastric stromal tumors (5-7 cm) who received EFR or surgery (including laparoscopic and open surgery) in the First Affiliated Hospital of Zhengzhou University and confirmed by postoperative histopathology from January 2017 to October 2018 were retrospectively analyzed. Patients were divided into endoscopic group (9 cases) and surgical group (27 cases) according to different resection methods. The perioperative indicators and the total incidence of complications in the two groups were compared.Results:In terms of perioperative indicators, the median operation time of the endoscopic group was significantly longer than that of the surgical group (4.0 hours VS 2.0 hours, P<0.01), and the postoperative fasting time (4.55±0.88 days VS 6.22±2.24 days, t=-2.15, P=0.03) and hospital stay (6.88±1.26 days VS 10.03±2.90 days, t=-3.13, P<0.01) were significantly shorter than those of the surgical group. The median visual analogue scores (VAS) of abdominal pain of the endoscopic group on the first postoperative day (3 VS 6, P<0.01)and the third postoperative day (1 VS 3, P<0.01) were significantly lower than those of the surgical group. The hospitalization cost was significantly less than that of the surgical group (55±14.7 thousand yuan VS 73±24.3 thousand yuan, t=-2.11, P=0.04). In term of the total incidence of complications, the endoscopic group was 11.1% (1/9), which was higher than that of the surgical group [7.4% (2/27)], but there was no statistically significant difference( P=1.00). Conclusion:EFR is safe and effective in the treatment of large gastric stromal tumors (5-7 cm), and has the advantages of less invasiveness, rapid postoperative recovery, and lower hospitalization cost. But how to shorten the operation time is an urgent problem to be solved.

This article teases out the main regulatory incentives for innovative drugs in China and US, including optimizing the processes, setting time limits for registration, expedited programs, R&D and evaluation communication and receiving clinical data from overseas. Meanwhile, case study method is used to analyze the impact of these regulatory incentives on BeiGene's zanubrutinib, which is the first drug from Chinese Innovation Company simultaneously developed in US and China. The results show that regulatory incentives are key factors to realize simultaneous development of zanubrutinib by shortening the time of registration in both countries and reducing the costs and risks of drug development. Other domestic companies can learn from the experience of zanubrutinib, to target unmet clinical needs, to rationally use domestic and foreign regulatory policies, and to enhance communication with regulators. Domestic regulator also can provide more suggestion to companies who have the intention to develop products abroad, so that more innovative drugs developed by local companies can be on the world stage.

Objective To explore the correlation between childhood obesity and adult metabolic diseases. Methods A total of 3 542 people who underwent physical examination in the General Hospital of Fuming from January 2018 to January 2019 were selected as research subjects. They were divided into childhood obesity group and control group according to the childhood body mass index (BMI). Single factor and multivariate logistic regression analysis were performed on relevant factors that may affect adult metabolic diseases by comparing clinical data with laboratory parameters. Results A total of 113 adult patients with metabolic diseases were found in the control group, with an incidence rate of 4.56%. In the childhood obesity group, 322 adult patients with metabolic diseases were found, with an incidence rate of 30.32%. The incidence of adult metabolic diseases in the childhood obesity group was significantly higher than that of the control group, while the HDL-C level in the childhood obesity group was significantly lower than that in the control group. The differences were statistically significant (P<0.05). Univariate analysis showed that the gender and childhood obesity were significantly correlated to adult metabolic diseases (P<0.05). Multivariate logistic regression analysis showed that the childhood obesity was an independent risk factor for adult metabolic diseases (P<0.05). Conclusion There was a difference in the incidence of adult metabolic diseases and laboratory indicators in the adulthood between childhood obese patients and childhood non-obese patients. Childhood obesity is an independent risk factor for adult metabolic diseases.

OBJECTIVE: To assess the value of Ploton silver staining and phalloidin-iFlour 488 staining in observation of the morphology of osteocyte dendrites of mice at different developmental stages. METHODS: The humerus and femurs were harvested from mice at 0 (P0), 5 (P5), 15 (P15), 21 (P21), 28 (P28), and 35 days (P35) after birth to prepare cryo-sections and paraffin sections. HE staining of P35 mouse femur sections served as a reference for observing osteocytes in the trabecular bone and cortical bone. The humeral sections at different developmental stages were stained with Ploton silver staining to observe the morphology of osteocytes and canaliculi, and the canalicular lengths in the cortical and trabecular bones of the humerus of the mice in each developmental stage were recorded. The cryo-sections of the humerus from P10 and P15 mice were stained with phalloidin iFlour-488 to observe the morphology of osteocytes and measurement of the length of osteocyte dendrites in the cortical bone. RESULTS: In the trabecular bone of the humerus of P0-P15 mice, Ploton silver staining only visualized the outline of the osteocytes, and the morphology of the canaliculi was poorly defined. In P21 or older mice, Ploton silver staining revealed the morphology of the trabecular bone osteocytes and the canaliculi, which were neatly arranged and whose lengths increased significantly with age (P21 CONCLUSIONS Mouse osteocyte dendrites elongate progressively and their arrangement gradually becomes regular with age. Ploton silver staining can clearly visualize the morphology of the osteocytes and the canaliculi in adult mice but not in mice in early stages of development. Phalloidin iFlour-488 staining for labeling the cytoskeleton can be applied for mouse osteocytes at all developmental stages and allows morphological observation of mouse osteocytes in early developmental stages.
Animals ; Bone and Bones ; Dendrites ; Mice ; Osteocytes ; Phalloidine ; Silver Staining