Aim To investigate the role and potential mechanism of methyltransferase-like 5 (METTL5) in triple-negative breast cancer (TNBC) . Methods The expression of METTL5 in TNBC tumor tissues and cell lines was detected by immunohistochemistry and Western blot. After shRNA targeting METTL5 (shRNAMETTL5) was transfected into TNBC cells, cell proliferation, migration and invasion were detected by CCK-8, colony formation, wound healing and Transwell assays, respectively. Western blot was used to detect the expression of Wnt/p-catenin signaling-related key proteins. A xenograft tumor model was constructed to verify the effect of METTL5 knockdown on the growth of TNBC cells and Wnt/p-catenin signaling activity in vivo. Results The expression of METTL5 was up-regulated in TNBC tumor tissues and cell lines (P < 0. 01) . Knockdown of METTL5 significantly inhibited the proliferation, migration and invasion of TNBC cells and reduced the expression of Wnt/p-catenin signaling molecules (3-catenin, cyclin Dl, matrix metalloproteinase (MMP) -2 and MMP-7 (all P < 0. 01) . Knockdown of METTL5 reduced tumor growth and Wnt/pcatenin signaling activity in vivo. Conclusions Knockdown of METTL5 can inhibit the proliferation, migration and invasion of TNBC cells, which may be related to the inhibition of Wnt/p-catenin signaling pathway.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective To explore the diagnostic efficacy of American Thyroid Association(ATA)guidelines,American College of Radiology Thyroid Imaging Report and Data System(ACR-TIRADS),and Chinese Thyroid Imaging Reporting and Data System(C-TIRADS)alone and combined with BRAF^V600E mutation in atypia of undetermined significance/follicular lesion of undetermined significance(AUS/FLUS).Methods A total of 138 patients who underwent ultrasound-guided fine needle aspiration(FNA)in the Chinese PLA General Hospital from January 2020 to May 2023 were selected.The clinicopathological and ultrasound characteristics were retrospectively analyzed for each nodule.Each nodule underwent preoperative BRAF^V600E mutation testing and was diagnosed according to the ATA guidelines,ACR-TIRADS,and C-TIRADS.The diagnostic efficacy of ATA guidelines,ACR-TIRADS,and C-TIRADS alone and combined with BRAF^V600E mutation was assessed based on the results of histopathological diagnosis.Results The 138 AUS/FLUS thyroid nodules included 45(32.6%)benign ones and 93(67.4%)malignant ones.The patient age(t=1.444,P=0.151),gender(χ²=0.259,P=0.611),and location of nodules(χ²=2.055,P=0.358)had no statistical significance for the differentiation between benign and malignant nodules,while nodule size(Z=2.500,P=0.012),echo(χ²=14.693,P<0.001),composition(χ²=17.075,P<0.001),aspect ratio ≥1(χ²=9.477,P=0.002),and microcalcification(χ²=6.892,P=0.009)were of significance for the differentiation.When applied alone,BRAF^V600E mutation showed high specificity(95.56%)and positive predictive value(95.65%).Among the three ultrasound grading systems,ACR-TIRADS had the highest sensitivity(χ²=37.923,P<0.001;χ²=40.462,P<0.001)and accuracy(χ²=81.595,P<0.001;χ²=76.912,P<0.001),while C-TIRADS had the highest specificity(χ²=11.746,P<0.001;χ²=21.235,P<0.001).However,the three systems showed no statistically significant difference in the diagnostic efficiency when applied alone(Z=1.177,P=0.239;Z=0.213,P=0.831;Z=1.016,P=0.310).The combination of BRAF^V600E mutation with ACR-TIRADS or C-TIRADS improved the diagnostic efficacy of BRAF^V600E mutation in distinguishing the benign and malignant AUS/FLUS nodules(Z=2.107,P=0.035;Z=2.752,P=0.006).The combination of ATA guidelines with BRAF^V600E mutation increased the diagnostic accuracy of BRAF^V600E mutation(χ²=20.679,P<0.001),while it had no statistically significant difference in distinguishing the benign and malignant AUS/FLUS nodules(Z=1.321,P=0.186).The combination of ATA guidelines,ACR-TIRADS,or C-TIRADS with BRAF^V600E mutation improved the diagnostic efficacy of ultrasound grading systems for AUS/FLUS nodules(Z=2.770,P=0.006;Z=2.770,P=0.006;Z=2.890,P=0.004).Specifically,ACR-TIRADS combined with BRAF^V600E mutation showed the highest sensitivity(χ²=4.712,P=0.030;χ²=4.712,P=0.030),while C-TIRADS combined with BRAF^V600E mutation showed the highest accuracy(χ²=77.627,P<0.001;χ²=85.827,P<0.001).However,there were no statistically significant differences in diagnostic performance between the combinations(Z=1.276,P=0.202;Z=0.808,P=0.419;Z=1.615,P=0.106).Conclusion ATA guidelines,ACR-TIRADS,and C-TIRADS combined with BRAF^V600E mutation can improve the diagnostic efficacy of BRAF^V600E mutation or ultrasound grading system alone in AUS/FLUS nodules,which can facilitate the further management and treatment of such patients.
Humans ; United States ; Infant ; Thyroid Neoplasms/genetics* ; Proto-Oncogene Proteins B-raf/genetics* ; Adenocarcinoma, Follicular/pathology* ; Retrospective Studies ; Data Systems ; Thyroid Nodule/genetics* ; Ultrasonography/methods* ; Mutation ; China ; Radiology

OBJECTIVE: To observe the effect of thumb-tack needles based on "Biaoben acupoint compatibility" on sequela symptoms, mental state and pulmonary ventilation function in patients with coronavirus disease 2019 (COVID-19) during recovery period. METHODS: Fifty cases of COVID-19 during recovery period were randomly divided into an observation group and a control group, 25 cases in each group. The patients in the observation group were treated with thumb-tack needles at Guanyuan (CV 4), Zusanli (ST 36) and Taiyuan (LU 9). The patients in the control group were treated with sham thumb-tack needles at identical acupoints as the observation group. The treatment in the two groups was given once a day, 7-day treatment was taken as a course of treatment, and totally two courses of treatment were given. The TCM symptom score, Hamilton anxiety scale (HAMA) score, Hamilton depression scale (HAMD) score, pulmonary function (forced vital capacity [FVC], forced expiratory volume in the first second [FEV1], peak expiratory flow [PEF]), the severity of pulmonary ventilation dysfunction and pulmonary imaging changes in the two groups were compared before and after treatment. RESULTS: Compared before treatment, the total scores and each item scores of TCM symptom scale, HAMA scores and HAMD scores in the two groups were reduced after treatment (P<0.05). Except for the symptom scores of dry throat and dry stool, the total score and each item score of TCM symptom scale, HAMA score and HAMD score in the observation group were lower than those in the control group (P<0.05). Compared before treatment, FVC, FEV1 and PEF in the two groups were increased after treatment (P<0.05), and those in the observation group were higher than the control group (P<0.05). The severity of pulmonary ventilation dysfunction in the two groups was reduced after treatment (P<0.05), and the severity in the observation group was better than that in the control group (P<0.05). After treatment, the lung shadow area in the two groups was decreased (P<0.05), and that in the observation group was smaller than the control group (P<0.05). The improvement of imaging change in the observation group was better than that in the control group (P<0.05). CONCLUSION The thumb-tack needles based on "Biaoben acupoint compatibility" could significantly reduce the sequela symptoms, anxiety and depression in patients with COVID-19 during recovery stage, and improve the pulmonary ventilation function.
Acupuncture Points ; Anxiety/etiology* ; COVID-19/therapy* ; Depression/etiology* ; Humans ; Needles ; Respiratory Function Tests ; Thumb

Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ² test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 μg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) μg; t=9.98, -1.98, Z=-4.89, all P<0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P<0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t=-2.34, P<0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.
Ceruloplasmin/metabolism* ; Child ; Child, Preschool ; Copper/metabolism* ; Copper-Transporting ATPases/genetics* ; Female ; Hepatolenticular Degeneration/genetics* ; Humans ; Male ; Mutation ; Phenotype ; Retrospective Studies

ObjectiveTo retrospectively analyze the clinical data of 52 patients with coronavirus disease-2019 （COVID-19） and explore the clinical efficacy of modified Sanxiaoyin on mild/moderate COVID-19 patients. MethodThe propensity score matching method was used to collect the clinical data of mild or moderate COVID-19 patients enrolled in the designated hospital of the Second Hospital of Jingzhou from December 2019 to May 2020. A total of 26 eligible patients who were treated with modified Sanxiaoyin were included in the observation group， and the 26 patients treated with conventional method were the regarded as the control. The disappearance of clinical symptoms， disappearance time of main symptoms， efficacy on traditional Chinese medicine （TCM） symptoms， hospitalization duration， laboratory test indicators， and CT imaging changes in the two groups were compared. ResultThe general data in the two groups were insignificantly different and thus they were comparable. After 7 days of treatment， the disappearance rate of fever， cough， fatigue， dry throat， anorexia， poor mental state， and poor sleep quality in the observation group was higher than that in the control group （P<0.05）， and the difference in the disappearance rate of expectoration and chest distress was insignificant. For the cases with the disappearance of symptoms， the main symptoms （fever， cough， fatigue， dry throat， anorexia， chest distress） disappeared earlier in the observation group than in the control group （P<0.01）. After 7 days of treatment， the scores of the TCM symptom scale of both groups decreased （P<0.01）， and the decrease of the observation group was larger that of the control group （P<0.01）. All patients in the two groups were cured and discharged. The average hospitalization duration in the observation group ［（12.79±2.68） d］ was shorter than that in the control group ［（15.27±3.11） d］ （P<0.01）. The effective rate in the observation group （92.31%， 24/26） was higher than that in the control group （76.92%， 20/26） . After 7 days of treatment， the lymphocyte （LYM） count increased （P<0.05）， and white blood cell （WBC） count and neutrophil （NEUT） count decreased insignificantly in the two groups. Moreover， levels of C-reactive protein （CRP）， erythrocyte sedimentation rate （ESR）， and procalcitonin （PCT） reduced in the two groups after treatment （P<0.01） and the reduction in the observation group was larger than that in the control group （P<0.01）. Through 7 days of treatment， the total effective rate on pulmonary shadow in the observation group （90.00%， 18/20） was higher than that in the control group （77.27%， 17/22） （P>0.05） and the improvement of lung shadow in the observation group was better than that in the control group （P<0.01）. ConclusionModified Sanxiaoyin can significantly alleviate fever， cough， fatigue， anorexia， chest distress， poor sleep quality， and other symptoms of patients with mild or moderate COVID-19， improve biochemical indicators， and promote the recovery of lung function. This paper provides clinical evidence for the application of modified Sanxiaoyin in the treatment of mild or moderate COVID-19.

OBJECTIVE: To observe the clinical efficacy of dynamic qi acupuncture for acute lumbar sprain, and to explore the differences of different needle retention time on the improvement of pain, lumbar mobility and lumbar dysfunction. METHODS: A total of 160 patients with acute lumbar sprain were randomly divided into an observation group A (40 cases, 4 cases dropped off), an observation group B (40 cases, 2 cases dropped off), an observation group C (40 cases, 4 cases dropped off) and a medication group (40 cases, 6 cases dropped off). The patients in the observation group A, the observation group B and the observation group C were treated with acupuncture at "lumbago point" and Sanjian (LI 3) on the left side, and during the needles were kept for 10, 20 and 30 min respectively, the patients were required to take tolerable lumbar active activities, once a day; the patients in the medication group were treated with celecoxib capsules, 0.2 g each time, twice a day. All the patients were treated for 5 d. Before and after treatment, the scores of numerical rating scale-11 (NRS-11), lumbar range of motion (ROM) and modified Oswestry disability index (ODI) were observed, and the clinical efficacy of each group was evaluated. RESULTS: After treatment, the scores of NRS-11, ROM and ODI in each group were decreased compared before treatment (P<0.01). The decreased degree of NRS-11, ROM and ODI in each observation group was greater than that in the medication group (P<0.05), and the decreased degree of ROM and ODI in the observation group B and the observation group C was greater than that in the observation group A (P<0.05). The total effective rates were 94.4% (34/36) in the observation group A, 94.7% (36/38) in the observation group B and 97.2% (35/36) in the observation group C, respectively, which were higher than 79.4% (27/34) in the medication group (P<0.05). CONCLUSION Dynamic qi acupuncture with needle retention for 10, 20 and 30 min all could effectively improve the pain, lumbar mobility and lumbar dysfunction in patients with acute lumbar sprain. If the lumbar dysfunction is severe, needle retention for 20 min or more is recommended.
Humans ; Treatment Outcome ; Pain

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

OBJECTIVE: To observe the clinical therapeutic effect of filiform-fire needling of "Biaoben acupoint combination" on the sequelae of patients with coronavirus disease 2019 (COVID-19) during the recovery period. METHODS: A total of 33 patients with COVID-19 during the recovery period were treated with filiform-fire needling at the acupoints of Mingmen (GV 4), Shenzhu (GV 12), Gaohuang (BL 43), Zusanli (ST 36) and Shangjuxu (ST 37), etc., once every other day, 3 times a week, and 3 times was one course of treatment and totally 2 courses of treatment were required. The TCM symptom, Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) scores, pulmonary function indexes (forced vital capacity [FVC], forced expiratory volume in one second [FEV1], peak expiratory flow [PEF]) and chest CT imaging change were observed before and after treatment, and the therapeutic effect was evaluated. RESULTS: After treatment, the scores of TCM symptom, HAMA and HAMD were decreased compared with those before treatment (P<0.05), and the levels of FVC, FEV1 and PEF were increased compared with those before treatment (P<0.05), and the recovery rate of 22 patients with pulmonary ventilation dysfunction was 86.4% (19/22). After treatment, the lung shadow area was smaller than that before treatment (P<0.05). The effective rate of 25 patients with lung CT abnormalities was 84.0% (21/25). After treatment, 23 cases were cured, 5 cases were markedly effective, 4 cases were effective, 1 case was ineffective, the cured and markedly effective rate was 84.8%. CONCLUSION The filiform-fire needling of "Biaoben acupoint combination" could significantly reduce the sequelae of cough, fatigue, chest tightness, etc. and mental symptoms such as anxiety and depression in patients with COVID-19 during the recovery period, and promote inflammatory exudation absorption of pulmonary lesion and improve lung ventilation function.
Acupuncture Points ; Acupuncture Therapy ; COVID-19/therapy* ; Humans ; Lung ; Vascular Surgical Procedures

Objective: To observe the clinical efficacy of 'Tong Du Yun Pi' (Governor Vessel-unblocking and spleen-promoting) manipulation in treating infantile diarrhea in autumn. Methods: Eighty-four kids were divided into a control group and an observation group using the random number table method, with 42 cases in each group. The control group was intervened by oral administration of montmorillonite powder, and the observation group was given additional 'Tong Du Yun Pi' pediatric massage (tuina) treatment. After treatment, the traditional Chinese medicine (TCM) symptoms scores, symptom improvement time, clinical efficacy and immune function indicators were compared between the two groups. Results: After treatment, the total effective rate was 95.2％ in the observation group versus 76.2％ in the control group, and the between-group difference was statistically significant (P<0.05); each item score in TCM symptoms was notably lower in the observation group than in the control group (all P<0.05); among the effective cases, the times to restore normal defecation, relieve abdominal bloating, arrest vomiting, and bring down the fever were markedly shorter in the observation group than in the control group, and the between-group differences were statistically significant (all P<0.05); the levels of immunoglobulin (Ig) G, IgM, CD4+ and CD4+/CD8+ were significantly higher and CD8+ was significantly lower in the observation group than in the control group (all P<0.05). Conclusion: In the treatment of infantile diarrhea in autumn, based on oral administration of montmorillonite powder, 'Tong Du Yun Pi' manipulation can notably improve diarrheal symptoms, shorten disease duration, and strengthen the immunity of kids, producing more significant efficacy than oral administration of montmorillonite powder.