After being treated with acupuncture, some patients with idiopathic tinnitus may experience a short-term aggravation of tinnitus symptoms on the original basis. These symptoms can be gradually relieved and the overall condition fluctuates towards recovery. This phenomenon has brought some difficulties to patients and clinicians. Based on the academic view of TCM, "destroying pathogens and re-building balance", and in association with the existing understanding of acupuncture in modern medicine for tinnitus, this paper briefly discusses the mechanism and influencing factors of symptom fluctuation in patients with idiopathic tinnitus after acupuncture treatment in terms of both TCM and modern medicine, and proposes the future direction in the research of symptom fluctuation, so as to promote the recognition of clinicians and patients on symptom fluctuation and make rational use of its positive effects. Besides, it is hoped that more researchers will pay attention to symptom fluctuation and advance the exploration of it in academic field.
Humans ; Tinnitus/physiopathology* ; Acupuncture Therapy ; Male ; Female

OBJECTIVES: To explore the mechanism by which Pulsatilla saponin D (PSD) inhibits invasion and metastasis of triple-negative breast cancer (TNBC). METHODS: The public databases were used to identify the potential targets of PSD and the invasion and metastasis targets of TNBC to obtain the intersection targets between PSD and TNBC. The "PSD-target-disease" interaction network was constructed and protein-protein interaction (PPI) analysis was performed to obtain the core targets, which were analyzed for KEGG pathway and GO functional enrichment. Molecular docking study of the core targets and PSD was performed, and the therapeutic effect and mechanism of PSD were verified using Transwell assay and Western blotting in cultured TNBC cells. RESULTS: Network pharmacology analysis identified a total of 285 potential PSD targets and 26 drug-disease intersection core targets. GO analysis yielded 175 entries related to the binding of biomolecules (protein, DNA and RNA), enzyme activities, and regulation of gene transcription. KEGG analysis yielded 46 entries involving pathways in cancer, chemical carcinogenesis-receptor activation, microRNAs in cancer, chemical carcinogenesis-reactive oxygen species, PD-L1 expression and PD-1 checkpoint pathway in cancer. Molecular docking showed high binding affinities of PSD to MTOR, HDAC2, ABL1, CDK1, TLR4, TERT, PIK3R1, NFE2L2 and PTPN1. In cultured TNBC cells, treatment with PSD significantly inhibited cell invasion and migration and lowered the expressions of MMP2, MMP9, N-cadherin and the core proteins p-mTOR, ABL1, TERT, PTPN1, HDAC2, PIK3R1, CDK1, TLR4 as well as NFE2L2 expressionin the cell nuclei. CONCLUSIONS The inhibitory effects of PSD on TNBC invasion and metastasis are mediated by multiple targets and pathways.
Humans ; Triple Negative Breast Neoplasms/metabolism* ; Saponins/pharmacology* ; Pulsatilla/chemistry* ; Female ; Molecular Docking Simulation ; Cell Line, Tumor ; Neoplasm Invasiveness ; Protein Interaction Maps ; Neoplasm Metastasis ; Signal Transduction/drug effects* ; Cell Movement/drug effects*

This article reported a case of kaposiform lymphangiomatosis (KLA) identified in the fetal stage and diagnosed at the neonatal stage. A routine ultrasound examination at 19 weeks of gestation showed multiple masses in the whole body of the fetus (involving neck, chest wall and armpit) complicated by pleural and peritoneal effusion. Shunting was performed to drain pleural effusion from the right chest in another hospital at 26 +5 weeks of gestation. The patient was born at 34 +3 weeks of gestation by cesarean section due to "intrauterine distress" and required invasive ventilator assisted ventilation support after birth because of respiratory distress. A large amount of hemorrhagic effusion was drained out during the shunting. Coagulation dysfunction and thrombocytopenia occurred on the 3rd day after birth and KLA was suspected. Empirical treatment with sirolimus turned out to be ineffective. Biopsy was taken on postnatal day 7. However, the patient died on the 12th day after birth due to respiratory and circulatory failure. Pathological findings obtained the day after death were consistent with the features of KLA. The diagnosis of KLA was confirmed based on the clinical manifestations and pathological results.

Objective:To analyze the clinical efficacy of treatment of cement dislodgement after vertebral augmentation for osteoporotic vertebral fractures.Methods:A retrospective study was conducted to analyze the data of 13 patients who had been treated at Department of Orthopaedics, The First Affiliated Hospital of Soochow University for cement dislodgement after vertebral augmentation for osteoporotic vertebral fractures from July 2013 to July 2022. There were 4 males and 9 females, with an average age of (76.5±8.6) years and a T value of bone mineral density of -3.3±0.6. By the CT and MRI features of cement dislodgement, their conditions fell in 4 types: cement loosening in situ (4 cases), anterior cement moving (6 cases), anterior cement moving with posterior bone mass moving (2 cases), and posterior cement moving (1 case). They were treated by percutaneous vertebroplasty (3 cases), pedicle screw fixation combined with bone graft fusion and decompression (7 cases), and conservative therapy (3 cases). The curative effects for surgical patients were evaluated by comparing their visual analogue scale (VAS), Oswestry dysfunction index (ODI) and cobb angle of kyphosis at preoperation, 1 week and 1 month postoperation, and the last follow-up, and Frankel grading for nerve injury as well. The curative effects for patients undergoing conservative treatment were evaluated by observing their symptoms.Results:This cohort was followed up for 7 (5, 12) months after treatment. The VAS scores [5.0 (4.0, 5.0) points, 3.0 (2.0, 3.0) points, and 3.0 (2.0, 3.0) points] in the 10 surgical patients at 1 week and 1 month postoperation and the last follow-up were significantly improved compared with the preoperative value [8.5 (8.0, 9.0) points] ( P<0.05); the VAS scores at 1 month postoperation and the last follow-up were also significantly improved compared with that at 1 week postoperation ( P < 0.05), but there was no significant difference between the last follow-up and 1 month postoperation ( P > 0.05). The ODIs (50.6%±4.2%, 37.8%±4.5%, and 29.3%±5.6%) in the 10 surgical patients at 1 week and 1 month postoperation and the last follow-up were significantly improved compared with the preoperative value (93.2%±3.6%), showing significant differences in pairwise comparisons ( P<0.05). The cobb angles [10.0 (9.0, 11.0)°, 9.0 (9.0, 11.0)°, and 10.0 (9.0, 12.0)°] in the 10 surgical patients at 1 week and 1 month postoperation and the last follow-up were significantly improved compared with the preoperative value [12.5 (11.0, 14.0)°] ( P<0.05) , but there was no statistically significant difference between the time points after operation ( P>0.05). The Frankel grading was significantly improved in the 6 patients with nerve injury after operation. Of the 3 patients undergoing conservative treatment, the symptoms were cured in one, showed no change during follow-up in one, and aggravated in one. Conclusion:Surgical treatment can significantly relieve pain, improve spinal dysfunction and repair nerve injury in patients with bone cement dislodgement after vertebral augmentation.

Objective:A rat model of excessive gestational weight gain (EGWG) was constructed to investigate the impact of EGWG on fetal hepatic lipid metabolism and the relevant regulatory mechanism.Methods:Healthy Sprague-Dawley rats were caged together and tested for pregnancy.Rats with the sperm observed under microscope were considered pregnant for 0.5 days.Pregnant rats were divided into the normal diet (ND) group and high-fat diet (HFD) group by the random number table method, with 8 rats in each group.The body weight during pregnancy of the pregnant rats was recorded.Cesarean section was performed at day 21.5 of gestation and the birth weight of the fetal rats was recorded.Hepatic lipid deposition of the pregnant and fetal rats was examined by hematoxylin-eosin (HE) staining and oil red O staining.Triglyceride (TG) and cholesterol (TC) levels in livers and serum of the pregnant and fetal rats were detected by glycerol phosphate oxidase-peroxidase(GPO-PAP) method.The mRNA and protein expression levels of key genes FASN and SREBP1c in hepatic lipid metabolism of fetal rats were measured by real-time polyme-rase chain reaction (RT-PCR) and Western blot.Differences between the two groups were compared by independent sample t test. Results:There was no difference in pre-pregnancy body weight between the HFD group and the ND group, but the differences in the weight and the weight gain during pregnancy gradually enlarged between the two groups.At day 21.5 of gestation, the weight of the pregnant rats[(467.75±22.05) g vs.(430.88±18.80) g, t=-3.600, P=0.003], the weight gain of the pregnant rats during pregnancy[(181.50±9.68) g vs.(148.50±10.86) g, t=-6.415, P<0.001] and the birth weight of the fetal rats[(5.51±0.17) g vs.(4.85±0.35) g, t=-4.779, P<0.001] of the HFD group were significantly higher than those of the ND group.Both HE staining and oil red O staining presented increased hepatic lipid deposition in the pregnant and fetal rats of the HFD group.The hepatic and serum TG and TC levels of the pregnant and fetal rats of the HFD group were significantly higher than those of the ND group (all P<0.05). RT-PCR and Western blot showed that the mRNA and protein levels of key genes FASN and SREBP1c in hepatic lipid metabolism of fetal rats of the HFD group were significantly higher than those of the ND group (all P<0.05). Conclusions:An EGWG model can be successfully constructed by a 21-day HFD during pregnancy.EGWG can lead to hepatic lipid deposition in the fetal rats.The mechanism may be related to the expression changes of key genes FASN and SREBP1c in hepatic lipid metabolism of fetal rats.

OBJECTIVE To investigate the protective effect and potential mechanism of Arisaema Cum Bile on acute liver injury induced by carbon tetrachloride （CCl4） in mice. METHODS Fifty mice were randomly divided into normal group， model group， positive control group （Biphenyl diester dropping pills， 150 mg/kg）， Arisaema Cum Bile low-dose and high-dose groups （0.78， 2.34 g/kg）， with 10 mice in each group. The mice in each group were given relevant medicine intragastrically， once a day， for 7 consecutive days. Two hours after the last administration， those groups were given intraperitoneal injection of 0.2% CCl4-olive oil solution to induce acute liver injury model except for normal group. Seventeen hours after intraperitoneal injection， the serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， interleukin-6 （IL-6）， tumor necrosis factor-α（TNF- α）， and malondialdehyde （MDA）， superoxide dismutase （SOD） in liver tissue were measured with kit method. The hepatic index was detected. The pathological changes of liver tissue were observed by HE staining， and the degree of liver injury was scored quantitatively. The mRNA expressions of TNF-α and IL-6 in liver tissue were detected by real-time fluorescence quantitative PCR； the protein expressions of Janus kinase 2 （JAK2）， signal transducer and activator of transcription protein 3 （STAT3） and nuclear factor-κB p65 （NF-κB p65） in liver tissue were detected by Western blot assay. RESULTS Compared with normal group，the levels of ALT， AST， IL-6， TNF-α and MDA， the hepatic index were increased significantly （P＜0.05）， while the level of SOD was decreased significantly （P＜0.05）； the mRNA E-mail：qhwang668@sina.com expressions of IL-6 and TNF-α， and the protein expressions of JAK2， STAT3 and NF-κB p65 were up-regulated significantly （P＜0.05）； the pathological observation of liver tissue showed that the structure of hepatic cord was seriously disordered， there were many inflammatory cells infiltration of liver cells， and the liver injury score was significantly increased （P＜0.05）. Compared with model group， pathological changes and above indexes in mice were improved significantly in Arisaema Cum Bile low-dose and high-dose groups （P＜0.05）. CONCLUSIONS Arisaema Cum Bile has a protective effect on CCl4-induced acute liver injury in mice， which may be related to the inhibition of inflammatory response mediated by JAK2/STAT3/NF-κB signal pathway and antioxidant stress.

Objective:To investigate the clinicopathological features of gonadal neoplastic related lesions in children with disorders of sexual development (DsD).Methods:The clinical manifestations, chromosomal karyotype, histology and immunophenotype of 12 cases of neoplastic related lesions from Guangzhou Women and Children′s Medical Center, Guangzhou were analyzed during Jan 2015 to May 2020.Results:Twelve cases of neoplastic related lesions were screened in 205 cases of DsD, and 6 patients with gonadal germ cell neoplasia aged 3-13 years with an average age of 8.3 years. There were 2 males and 4 females. Clinical features showed malformation of external genitalia in 2 cases, short stature in 2 cases, clitoral enlargement in 1 case, lower abdominal pain and a huge pelvic mass in 1 case. Chromosomal karyotyping of peripheral blood showed 2 cases of 46XY and 4 cases of 45X/46XY. Fourteen gonadal specimens were examined. Microscopically, 1 case showed dysgerminoma in left ovary, and malignant mixed germ cell tumors in right ovary, as well as gonadoblastoma (GB) and undifferentiated gonadal tissue (UGT). The remaining 5 cases were all precursor lesions of germ cell tumor. Six specimens showed GB, 3 of UGT, and 3 specimens showed germ cell neoplasia in situ (GCNIS), one of which was accompanied by intratubular seminoma and 1 was GB with GCNIS. The other 6 patients with DsD were aged from 8 months to 2 years and 5 months, including 5 males and 1 females. Clinical manifestations showed 5 cases of hypospadias and 1 case of bilateral indirect inguinal hernia. Microscopically, 6 cases showed maturation delay of gonocytes in seminiferous tubules. Immunohistochemically, the primordial germ cells/gonocytes expressed OCT3/4, PLAP and c-KIT in the 12 cases.Conclusion:Gonadal neoplasia in children with DsD is mainly precursor lesions of germ cell tumor and improved understanding of these lesions is of great significance.

Objective To explore the application value of chromosomal microarray analysis(CMA)technolo-gy in children with abnormal development at the endocrine clinic,and to summarize the data of diagnosis and treatment. Methods A retrospective analysis of 15 children with abnormal development was performed at the endocrinology clinic of Guangzhou Women and Childrenˊs Medical Center from January 2015 to December 2017. The whole genome CMA was applied according to the standard operation procedure of CytoScan 750 arrays of Affymetrix,USA. The results were analyzed by chromosome analysis suite( CHAS)software and related bioinformatics methods. Results The report on CMA showed that the genomes of 15 children had the pathogenic copy number variation(CNVs)or variants of uncer-tain significance. The chromosomal abnormalities were consistent with the clinical manifestations of all children. There were deletions in 14 cases and duplications in 3 cases. Among the 15 cases,loss of heterozygosity was found in 2 cases, uniparental disomy in 1 case,trisomy in 2 cases,Turner syndrome in 2 cases,Smith-Magenis syndrome in 1 case,and wolf Hirschhorn syndrome in 1 case. Only 2 of 15 children were diagnosed as chromosomal abnormalities by routine kar-yotype analysis. Conclusions The whole genome high resolution CMA can significantly improve the rate of diagnosis in children with abnormal development at endocrinology clinic,and is worthy of recommendation.

Objective: To investigate the pathologic features of gonadal tissues of disorders of sexual development (DSD) in children. Methods: Fifty-three cases of gonadal developmental disorders were collected from July 2015 to August 2017 at Guangzhou Women and Children′s Medical Center. Clinical manifestations, karyotypes, sex hormone levels, ultrasound imaging, histology and immunophenotype of gonadal tissues were analyzed. Results: The age of patients ranged from 7 months to 17 years with an average of (50.7 ± 47.1) months. Social genders of the patients included 32 males and 21 females. Forty-eight patients had abnormal sex hormone levels. Clinical presentations included: toward female genitalia in 25 cases, male genitalia tendency in 17 cases and ambiguous external genitalia in 11 cases. Hypospadias was seen in 31 cases and short stature was seen in 8 cases. Chromosomal karyotyping of peripheral blood revealed 23 cases of sex chromosome disorders, 22 cases of 46 XY disorders, of which 3 cases were 5α-reductase deficiency and 8 cases of 46 XX disorders. Ultrasound examination showed cryptorchidism in 30 cases, including 16 cases of unilateral, 14 cases of bilateral and 1 case presenting a huge pelvic tumor. A total of 97 gonadal tissues from 53 cases of DSD were examined, including 9 cases of unilateral and 44 cases of bilateral gonads. Microscopically, 55 gonads (56.7%) showed dysplastic testes including 17 unilateral and 19 bilateral gonads. Fourteen were streak gonads (14.4%) including 8 unilateral and 3 bilateral gonadal tissues. Nine streak gonad with epithelial cord-like structures (9.3%) were found, of which 5 were unilateral and 2 were bilateral lesions. Seven gonads were ovotestis (7.2%), unilateral in 5 cases (the other side of the gonads of ovary in 4 cases, 1 case of dysplastic testes) and bilateral in 1 case. Seven gonads showed follicular-rich ovarian tissue (7.2%). One case showed bilateral dysplastic testes with gonadoblastoma and ectopic adrenal cortex. One case of streak gonad showed epithelial cord-like structures and undifferentiated glandular tissue embedded in malignant mixed germ cell tumors (mixed gonadoblastoma, dysgerminoma, mature teratoma and yolk sac tumor). One case had testicular microlithiasis. Uterus and fallopian tube structures were found in 11 cases. Immunohistochemical stains were performed in 15 cases. D2-40, PLAP and CKIT were expressed in germ cells and Calretinin, WT1 and inhibin were positive in Setoli cells. SALL4 and OCT3/4 were positive in 3 cases. Inhibin highlighted interstitial Leydig cells in 2 cases. GPC3 was positive in yolk sac tumor component. Conclusions Gonadal dysgenesis presents a broad spectrum of gonadal phenotypes with variable degrees of differentiation. The development of bilateral gonadal tissues has certain variability. Chromosomal karyotypes have no correlation with gonadal phenotypes. Accurate histopathologic diagnosis of gonadal dysgenesis plays an important role in the treatment and prognosis of the patient.

Objective To observe the clinical efficacy of HE’s needling method (three ways for unblocking) in treating mild simple obesity due to dampness from spleen deficiency.Method Forty eligible subjects with mild simple obesity due to dampness from spleen deficiency were randomized into group A and group B, 20 cases in each group. Group A was intervened by mild unblocking method plus intensive unblocking method from HE’s needling method, and group B was by mild unblocking method plus warm unblocking method. The obesity-related indexes were observed before and after treatment, and the clinical efficacies were compared.Result The body weight and Body Mass Index (BMI) were significantly changed after intervention in the treatment group (P<0.05). The body weight was significantly changed after treatment in the control group (P<0.05). After treatment, there were no significant differences in comparing the obesity-related indexes (body weight, BMI, waist circumference, hip circumference, and waist-hip ratio) between the two groups (P>0.05). The total effective rate was 55.0% in the treatment group versus 10.0% in the control group, and the difference was statistically significant (P<0.01).Conclusion HE’s needling method is effective in treating mild simple obesity due to dampness from spleen deficiency, and mild unblocking method plus intensive unblocking method can produce a more significant efficacy compared to mild unblocking method plus warm unblocking method.