BACKGROUND:Grape seed extract has been shown to be effective in inhibiting the growth of androgen-dependent tumors(e.g.,breast cancer),and thus grape seed extract could theoretically inhibit epiphyseal closure induced by estrogen in late adolescence. OBJECTIVE:To screen the effects of grape seed extract on apoptosis of growth plate chondrocytes and epiphyseal closure in rats. METHODS:(1)In vitro experiment:Growth plate chondrocytes from rat large tibia and femur at logarithmic growth stage were obtained and cultured in groups:normal control group,model control group(adding 17β-estradiol to induce apoptosis),positive control group(adding letrozole and 17β-estradiol),grape seed extract group(adding 17β-estradiol and 10 μg/mL grape seed extract),Caspase-9 inhibitor group(adding 17β-estradiol and Caspase-9 inhibitor),Caspase-9 agonist group(adding 17β-estradiol and Caspase-9 agonist).Cell apoptosis was detected by flow cytometry after 48 hours of culture.(2)In vivo experiment:Thirty 3-month-old Sprague-Dawley rats were randomly divided into model control group,positive control group and low-,medium-and high-dose groups,with five rats in each group.All rats were injected subcutaneously with 17β-estradiol(3 times per week)to establish epiphyseal closure models,followed by intragastric administration of letrozole in positive control group and 0.05,0.2 and 0.8 g/kg grape seed extract in low-,medium-and high-dose groups,respectively,once a day until over 2/3 of the epiphyseal plate in the model control group was closed.The length of the tibia was then observed.Another 18 Sprague-Dawley rats were randomly divided into model control group,positive control group,and medium-dose group,with 6 rats in each group,treated as above for 1.5 continuous months.The expression of Caspase-9 protein in rat growth plate cartilage was detected by western blot. RESULTS AND CONCLUSION:(1)In vitro experiment:17β-estradiol could induce apoptosis in growth plate chondrocytes,and letrozole,grape seed extract,and caspase-9 inhibitors could all inhibit apoptosis in growth plate chondrocytes.(2)In vivo experiment:When more than 2/3 of the epiphyseal plate in the model control group was closed,the number of rats with epiphysis closure in the positive control and medium-dose groups was less than that in the model control group(P＜0.05),and the tibial length was longer than that in the model control group(P＜0.05),and the Caspase-9 protein expression in the tibial growth plate was lower than that in the model control group(P＜0.05).To conclude,the appropriate dose of grape seed extract can effectively inhibit the apoptosis of growth plate chondrocytes and delay epiphyseal closure,which has the potential to promote bone growth.

Objective To analyze the epidemiological characteristics of hand-foot-mouth disease(HFMD)in Gan-zhou.Methods The epidemiological data of HFMD reported by the Infectious Disease Surveillance System,a sub-system of China Disease Prevention and Control Information System,from 2017 to 2020 were analyzed by descriptive methods.Enterovirus(EV)nucleic acid and typing detections via throat swabs,anal swabs or herpes fluid of patients was detected by real-time fluo-rescent polymerase chain reaction.The change in HFMD epidemic characteristics was compared between 2020 and 2017-2019.Results The incidence of HFMD in Ganzhou in 2020 was significantly lower than that from 2017 to 2019(x2=50.587,P＜0.05).In 2020,the incidence of HFMD in counties and districts of Ganzhou(except Huichang County)signifi-cantly decreased compared with that in 2017-2019(P＜0.05).From 2017 to 2019,the incidence of HFMD was obviously seasonal,with a high incidence in summer and autumn,and two significant incidence peaks were formed in June and September in 2017 and 2018,respectively.In 2019,there was a summer peak in June.The epidemic trend in 2020 was different,with a very low epidemic trend in summer and autumn,and a peak in winter.The incidence of HFMD in men,women and all ages in 2020 significantly decreased compared with that in 2017-2019(P＜0.05),and the age of onset was mainly distributed in 1-5 years,especially in children aged 1 to 3 years.There was a significant difference in the incidence of HFMD among different ages(P＜0.05).The positive rate of EV in Ganzhou in 2020 was lower than that from 2017 to 2019(x2=47.273,P＜0.05).The positive rate of EV in January,March to September in 2020 was significantly lower,and the positive rate of EV in November,December 2020 was significantly higher than that in the same period in 2017 to 2019(P＜0.05).Strain CA16 showed an increasing trend year by year from 2017 to 2019,and became the dominant strain in 2019.The proportion of patients infected with CA6 strain was on the fise from 2018 to 2020,and CA6 became the dominant strain in 2020.Conclusion The HFMD in Ganzhou has obvious population characteristics and seasonality,and the pathogen spectrum is constantly changing.

Objective:To learn about the epidemiological and clinical characteristics of children with brucellosis, in order to provide reference for clinical diagnosis and treatment of brucellosis in children.Methods:Clinical data of children with brucellosis (aged ≤14 years) who visited the Department of Infectious Diseases at Beidahuang Industry Group General Hospital from December 2020 to December 2022 were retrospectively collected, and their epidemiological characteristics, clinical characteristics, laboratory tests, treatment and outcome were summarized and analyzed.Results:A total of 34 children with brucellosis were included, including 25 males (73.53%) and 9 females (26.47%), with a gender ratio of 2.78 ∶ 1.00. The median age was 8 years and 1 month, mainly in the age group of 6 to 14 years (19 cases, 55.88%). Epidemiological investigation showed that most of the affected children were rural residents (25 cases, 73.53%), with more contact with cattle/sheep (26 cases, 76.47%). The onset time was mainly concentrated in summer (15 cases, 44.12%) and spring (13 cases, 38.24%). The clinical symptoms were mainly fever (97.06%, 33/34) and arthralgia (64.71%, 22/34). In the laboratory tests, 25 cases (73.53%) had positive blood cultures, and the white blood cell count (WBC) of 30 cases (88.24%) was (4 - 10) × 10 9/L. Among the abnormalities of liver function, aspartate aminotransferase (AST) increased in 19 cases (55.88%), alanine aminotransferase (ALT) increased in 14 cases (41.18%) and γ-glutamyl transpeptidase (GGT) increased in 6 cases (17.65%). Among the myocardial enzymatic abnormalities, α-hydroxybutyrate dehydrogenase (HBDH) increased in 29 cases (85.29%), lactate dehydrogenase (LDH) increased in 27 cases (79.41%), and creatine kinase isoenzyme (CK-MB) increased in 8 cases (23.53%). After treatment, 25 children with positive blood culture turned negative. Conclusions:Children with brucellosis are mainly male, older and rural residents. The clinical manifestations are mainly fever and arthralgia. Doctors in relevant departments should conduct detailed epidemiological investigations and laboratory tests for such children in clinical work, in order to achieve early detection, diagnosis and treatment of pediatric brucellosis.

Objective:To retrospectively analyze the clinical characteristics of 193 Chinese patients with McCune-Albright syndrome (MAS).Methods:By using keywords " McCune-Albright syndrome", " Albright syndrome", or " fibrous dysplasia " as the search terms, 193 cases of MAS reported in China from January 1990 to November 2022 from the Wanfang data, CNKI, VIP, PubMed, and Embase databases were obtained, and their clinical data was retrospectively analyzed. Intergroup comparisons were carried out by using t test, Mann-Whitney U test, and χ2 test. Results:The 193 MAS patients had included 42 males and 151 females, with the median first-visit age of females being younger than males. The typical triad group had accounted for 46.1% of patients, and the middle first-visit and diagnosis age was younger than the atypical group. The primary reason for first-visit in males of MAS was fibrous dysplasia (FD), whilst that in females of MAS was peripheral precocious puberty (PPP). FD has occurred in 84.5% of the patients, with an average age of onset age being 6.1 years old, and 90% was ≤ 16 years of age. Endocrine hyperfunction was found in 79.3% of the patients, with a higher proportion in females compared with males ( P<0.05). Pituitary involvement was seen in 21.8% of the patients, and the incidence of craniofacial FD and cranial nerve compression was significantly higher in those with elevated growth hormone (GH) than without ( P<0.05). Café-au-Lait Spots were noted in 86.5% of the patients, and 28.3% (28/99) had located on the different side of FD. Conclusion:Most MAS patients had atypical manifestations and multi-systemic involvement. It is more common and occurs earlier in females. The most common reasons for initial diagnosis in male and female patients were FD and PPP, respectively. Patients with elevated GH should be examined for cranial nerve compression.

Objective To investigate the value of novel coagulation and fibrinolysis markers in the diag-nosis and prognosis of septic coagulation disease (SIC).Methods A total of 153 patients with sepsis admitted and treated in this hospital from July 2022 to March 2023 were retrospectively analyzed.According to the SIC diagnostic criteria issued by the International Society of Thrombosis and Hemostasis (ISTH) in 2017,the pa-tients were divided into the SIC group (n=55) and the general sepsis group (the SA group,n=98).The basic data and follow up situation of the patients were collected.The multivariate logistic regression was adopted to analyze the influencing factors of SIC occurrence in the patients with sepsis.The receiver operating character-istic (ROC) curve was used to analyze the predictive efficiency of the related indicators for the SIC occurrence in the patients with sepsis.The included 66 patients with sepsis from April to July 2023conducted the verifica-tion.The Kaplan-Meier survival curve was used to analyze the survival situation of the patients.Results The acute physiological and chronic health status scoring system (APACHEⅡ) score,assessment of sequential or-gan failure (SOFA) score,prothrombin time (PT),PLT,D-dimer (D-D),thrombin antithrombin complex-Ⅲ (AT-Ⅲ),tissue plasminogen activator-plasminogen activator inhibitor-1 complex (t-PAIC),thrombomodulin (TM) had statistical differences between the two groups (P<0.05).The multivariate logistic regression anal-ysis showed that PT,PLT,D-D,t-PAIC and TM were the independent influencing factors for the SIC occur-rence in the patients with sepsis (P<0.05).The combined detection of PT,PLT,D-D,t-PAIC and TM could increase the predictive efficiency[area under the curve (AUC)=0.914].This model had good fitting goodness (x2=12.593,P=0.127);the verification group showed that it had good predictive efficiency (AUC=0.888),and this model had good fitting goodness (x2=7.996,P=0.333).The median overall survival time in the t-PAIC<19.27 μg/mL group was longer than that in the t-PAIC≥19.27 μg/mL group,which in the TM<16.11 TU/mL group was longer than that in the TM≥16.11 TU/mL group (P<0.05).Conclusion The model con-structed based on the influencing factors has good predictive efficiency for the SIC occurrence in the patients with sepsis.t-PAIC and TM have high value for the prognosis judgment in the patients with sepsis.

Objective To investigate the effects of Yitangkang on browning of white adipose and PINK1/Parkin pathway of mitophagy in adipose tissue of db/db mice.Methods Totally 30 six-week db/db mice were randomly divided into model group,Yitangkang Group(30 g/kg)and liraglutide group(200 μg/kg),and another 10 C57BL/6 mice of the same age were set as normal group.All groups were treated with corresponding drugs or normal saline for 5 weeks.During the period of administration,the body mass and fasting blood glucose(FBG)of mice in each group were detected regularly,the samples of liver,white and brown adipose of mice were weighed,the contents of serum triglyceride cholesterol(TC),triacylglycerol(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C)were detected by biochemical analyzer,HE staining was used to observe the pathological changes of inguinal white adipose tissue(iWAT),immunohistochemical staining was used to detect the expression of browning marker protein uncoupling protein-1(UCP1)in iWAT,Western blot was used to detect the expressions of browning-related proteins UCP1,PRDM16,PGC-1α and mitophagy-related proteins PINK1,Parkin,Beclin-1,p62 in iWAT.Results Compared with the normal group,the body mass,liver,white adipose and brown adipose mass of the model group significantly increased(P<0.01),the FBG and serum TG,TC and LDL-C contents significantly increased(P<0.01),and the content of HDL-C significantly decreased(P<0.01);large vacuoles in iWAT adipocytes,the diameter of adipocytes increased obviously,some adipocytes were extruded and deformed,and the edge of adipocytes was not clear,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins decreased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins increased(P<0.01).Compared with the model group,the body mass,liver and white adipose mass significantly decreased in Yitangkang group and the liraglutide group(P<0.01),FBG and serum contents of TC,TG and LDL-C were significantly decreased(P<0.05,P<0.01),while HDL-C content significantly increased(P<0.01);the diameter of iWAT adipocytes decreased,the number increased,and the morphology was regular,the expressions of iWAT UCP1,PRDM16,PGC-1α and p62 proteins increased(P<0.01),while the expressions of PINK1,Parkin and Beclin-1 proteins decreased(P<0.05,P<0.01).Conclusion Yitangkang can improve glucose and lipid metabolism and promote browning of white adipose in db/db mice,which may be related to mitophagy mediated by PINK1/Parkin pathway.

Objective:To investigate the risk factors and clinical significance of lymph nodes metastasis between sternocleidomastoid and sternohyoid muscle lymph node (LNSS) metastasis in thyroid cancer patients, so as to guide the reasonable dissection of LNSS region and lateral cervical lymph node in patients with papillary thyroid carcinoma (PTC) .Methods:We selected 111 PTC patients with lateral cervical lymph node metastasis who underwent radical thyroidectomy and lateral cervical lymph node dissection from Nov. 2018 to Dec. 2021 in China-Japan Union Hospital of jilin university. All patients were treated with low collar arc incision. Radical thyroidectomy and lateral cervical lymph node dissection were performed according to the guidelines, and lymph nodes in each district were grouped for pathological examination. According to whether LNSS metastasis occurred, they were divided into two groups: LNSS positive group (LNSS metastasis occurred) and LNSS negative group (LNSS metastasis did not happen). We collected the basic information of all 111 PTC patients with lateral lymph node metastasis (LLNM), preoperative color Doppler ultrasound examination and paraffin-embedded pathology and other related clinical case data. Then we described the clinicopathological features of cervical lymph node metastasis. Independent sample t test and Mann-Whitney U test were used for continuous variables, and Fisher exact test was used for data analysis for classified variables. Correlation analysis adopted binary logistics regression model, and analyzed the regularity and risk factors of LNSS metastasis. Results:In this study, the detection rate of LNSS was 64.9% (72/111), the overall LNSS metastasis rate was 7.2% (8/111), and the number of lymph node metastasis was 0-5. Univariate analysis showed that the location of LNSS metastasis was related with the cancer focus ( P<0.001), the preoperative serum thyroglobulin (Tg) level ( P=0.002), the number of lymph node metastasis in lateral cervical level Ⅳ ( P=0.001), the longest diameter of the cancer focus ( P=0.003) and the longest diameter of metastatic lymph nodes ( P=0.001) However, age, sex, whether there is lymph node metastasis in the central region (central lymph node metastasis ,CLNM), and whether there is multifocal cancer were not related to LNSS metastasis ( P≥0.05). Further multivariate analysis and work curve analysis of subjects showed that the tumor located in the lower pole ( P=0.014) and the number of lymph node metastasis in level Ⅳ more than 3 ( P=0.027) were independent risk factors for LNSS metastasis. It was found that the risk of LNSS metastasis increased when the cancer focus was located at the lower pole relative to the upper pole or middle part of the cancer focus ( OR=74.508, 95% CI: 2.373-2339.544). The number of lymph node metastasis in level Ⅳ had a positive effect on LNSS metastasis. The more lymph node metastasis in level Ⅳ, the higher the risk of LNSS metastasis ( OR=1.556; 95% CI=1.051-2.303) . Conclusions:In PTC patients with LLNM, the LNSS metastasis rate was 7.2%, and the advantages of LNSS cleaning outweigh the disadvantages. When the cancer focus is located at the lower pole and the number of lymph node metastasis in region Ⅳ is more than 3, it is necessary to pay attention to the dissection of this group of lymph nodes.

Mitochondrial DNA (mtDNA) mutations result in a variety of genetic diseases. As an emerging therapeutic method, mtDNA editing technology recognizes targets more based on the protein and less on the nucleic acid. Although the protein recognition type mtDNA editing technology represented by zinc finger nuclease technology, transcription activator like effector nuclease technology and base editing technology has made some progress, the disadvantages of complex recognition sequence design hinder further popularization. Gene editing based on nucleic acid recognition by the CRISPR system shows superiority due to the simple structure, easy design and modification. However, the lack of effective means to deliver nucleic acids into mitochondria limits application in the field of mtDNA editing. With the advances in the study of endogenous and exogenous import pathways and the deepening understanding of DNA repair mechanisms, growing evidence shows the feasibility of nucleic acid delivery and the broad application prospects of nucleic acid recognition type mtDNA editing technology. Based on the classification of recognition elements, this article summarizes the current principles and development of mitochondrial gene editing technology, and discusses its application prospects.
Genes, Mitochondrial ; Gene Editing ; Mitochondria/genetics* ; DNA, Mitochondrial/genetics* ; Nucleic Acids ; Technology

Objective:To explore the effect of fully automatic image segmentation of adenoid and nasopharyngeal airway by deep learning model based on U-Net network. Methods:From March 2021 to March 2022, 240 children underwent cone beam computed tomography（CBCT） in the Department of Otolaryngology, Head and Neck Surgery, General Hospital of Shenzhen University. 52 of them were selected for manual labeling of nasopharynx airway and adenoid, and then were trained and verified by the deep learning model. After applying the model to the remaining data, compare the differences between conventional two-dimensional indicators and deep learning three-dimensional indicators in 240 datasets. Results:For the 52 cases of modeling and training data sets, there was no significant difference between the prediction results of deep learning and the manual labeling results of doctors（P>0.05）. The model evaluation index of nasopharyngeal airway volume: Mean Intersection over Union（MIOU） s （86.32±0.54）%; Dice Similarity Coefficient（DSC）: （92.91±0.23）%; Accuracy: （95.92±0.25）%; Precision: （91.93±0.14）%; and the model evaluation index of Adenoid volume: MIOU: （86.28±0.61）%; DSC: （92.88±0.17）%; Accuracy: （95.90±0.29）%; Precision: （92.30±0.23）%. There was a positive correlation between the two-dimensional index A/N and the three-dimensional index AV/（AV+NAV） in 240 children of different age groups（P<0.05）, and the correlation coefficient of 9-13 years old was 0.74. Conclusion:The deep learning model based on U-Net network has a good effect on the automatic image segmentation of adenoid and nasopharynx airway, and has high application value. The model has a certain generalization ability.
Child ; Humans ; Adolescent ; Adenoids/diagnostic imaging* ; Image Processing, Computer-Assisted/methods* ; Pharynx ; Cone-Beam Computed Tomography ; Nose

Objective:To discuss the application of virtual endoscopy in the diagnosis of adenoid hypertrophy and the morphologic classification of adenoid. Methods:The clinical data of 97 children with adenoid hypertrophy admitted to Department of Otorhinolaryngology Head and Neck Surgery, Shenzhen University General Hospital from July 2022 to December 2022 were collected. The virtual endoscopic reconstruction of the nasopharynx was performed by cone beam computed tomography. The results of virtual endoscopic adenoid size measurement were compared with the results of nasopharyngeal CT median sagittal position and nasopharyngeal endoscopy. Virtual endoscopic classification of adenoid based on the size of the adenoids and their relationship with the torus tubarius. Results:The t-test results of the size of adenoids measured by virtual endoscopy and nasopharyngeal CT were t=1.699 and P=0.093, and the results of intra-group correlation coefficient（ICC） analysis were ICC=0.921 and P<0.01. The proportion of adenoids measured by virtual endoscopy and nasopharyngeal CT was highly consistent. The t-test results of the size of adenoids measured virtual endoscopy and nasopharyngeal endoscopy were t=1.543 and P=0.15, and the results of intra-group correlation coefficient（ICC） analysis were ICC=0.900 and P<0.01. The proportion of adenoids measured by virtual endoscopy and nasopharyngeal endoscopy was highly consistent. Among the 97 children, the morphological classification results of adenoids were 48 cases of overall hypertrophy type, 47 cases of central bulge type, and 2 cases of flat thickening type. Conclusion:The diagnosis of adenoid hypertrophy by virtual endoscopy has high accuracy, which not only avoids the invasive operation of traditional nasopharyngeal endoscopy, but also can observe the adenoid condition and its relationship with the torus tubarius from multiple angles. And, the morphological classification of adenoids using virtual endoscopy has guiding significance for perioperative preparation.
Child ; Humans ; Adenoids/surgery* ; Nasopharynx/diagnostic imaging* ; Adenoidectomy ; Endoscopy/methods* ; Hypertrophy/surgery*