The incidence of parathyroid hyperfunction is high and its clinical manifestations are diverse. Some patients develop chest tightness and palpitations as the main discomfort, which may be caused by the hypocalcemia and hypercalcemia related to negative calcium balance and parathyroid hyperfunction. We report a case of 53 years old male with parathyroid hyperfunction who was diagnosed with osteoporosis before and received conventional regular supplementation of vitamin D and calcium supplements. However, his condition worsened and he developed chest tightness and palpitation. After 1 month of sufficient supplementation of calcium, the symptoms of chest tightness and palpitation disappeared completely. Then we continued to provide the patients enough vitamin D and calcium supplementation actively. After 1 year of follow-up, the patient's condition was stable. His discomfort of chest tightness and palpitation never recurred, and all the bone metabolism indicators returned to normal.

Surgery is the important treatment for each type of thyroid cancer. Single or multiple parathyroid injuries or blood supply disorders may occur during the operation, resulting in dramatic decline of parathyroid hormone and hypocalcemia after operation, which is common in clinical practice. After discharge, chronic hypocalcemia can cause great physical and psychological pain to patients. Although the residual parathyroid glands can compensate after surgery in some cases, long-term negative calcium balance and postoperative hypocalcemia may cause excessive hyperplasia of the residual parathyroid glands, resulting in parathyroid hyperfunction or even hyperparathyroidism, which can lead to osteoporosis, urinary calculi, metastatic vascular calcification, and systemic abnormal migratory calcium deposits. It’s advisable to enhance the awareness of the cause and harm of the postoperative hypocalcemia, evaluate and diagnose it early, and actively intervene in every stage of before, during and after the operation and long-term follow-up, which can effectively reduce the occurrence and severity of hypocalcemia and improve the postoperative life quality and the prognosis.

Thyroid cancer is the common malignant tumor in the neck, and surgery is the important treatment measure for it. Some patients suffer from hypoparathyroidism and hypocalcemia after thyroidectomy, which will seriously affect the patient’s life quality and prognosis. This article reported a case of 42 years old female patient with hypocalcemia for 6 years after total thyroidectomy due to thyroid cancer, who still had frequent hypocalcemia with high dose of oral calcium and active vitamin D supplementation. Long-term and frequent facial and limb numbness, convulsions, epileptic-like seizures and sudden unconsciousness afflicted her due to hypocalcemia. After admission, her symptoms were obviously relieved after one week of adequate calcium supplementation through oral administration or intravenous infusion under close monitoring. Upon discharge she was able to maintain the normal level of blood calcium by decreased dose of oral calcium supplementation alone. Long-term limb numbness, convulsions, low back pain, shoulder pain, walking instability and other symptoms disappeared basically. The epileptic-like seizures did not recur. During six months of follow-up, her blood calcium was still well controlled in normal level.

Depression is a common mental illness in adolescents, and some patients do not respond well after medication, which may be partly related to vitamin D deficiency and insufficient calcium intake. This paper reports a 15-year-old patient with depression, whose condition was still unstable and the effect was not good despite routine use of antidepressant drugs and psychological intervention. After adequate supplementation of vitamin D and calcium, the patient's depression improved significantly, and the follow-up for 4 months, the condition was stable and did not recur.

OBJECTIVE: To explore the genetic basis for a child featuring complex cortical dysplasia and other brain malformations (CDCBM3). METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and his parents. Whole exome sequencing (WES) was carried out for the family trio. Suspected variant was verified by Sanger sequencing. RESULTS: The proband, a 1-year-and-2-month old Chinese boy, had presented with motor developmental delay, lissencephaly, severe cognitive impairments, absent speech and congenital laryngomalacia. WES revealed that he has harbored a heterozygous missense variant of the KIF2A gene, namely NM_001098511.2: c.952G>A, p.Gly318Arg (GRCh37/hg19). The highly conserved residue is located around the ATP nucleotide-binding pocket in the kinesin motor domain (PM1). The variant was not found in the Genome Aggregation Database and the 1000 Genomes Project (PM2), and was predicted to be deleterious on the gene product by multiple in silico prediction tools (PP3). This variant was unreported previously and was de novo in origin (PS2). Based on the ACMG guidelines, it was categorized as likely pathogenic (PS2+PM1+PM2+PP3). Furthermore, the congenital laryngomalacia found in our patient was absent in previously reported CDCBM3 cases. CONCLUSION The novel variant of the KIF2A gene probably underlay the disorders in the proband. Above finding has expanded the phenotypic and mutational spectrum of CDCBM3.
Asians/genetics* ; Brain ; China ; Humans ; Infant ; Kinesins/genetics* ; Male ; Malformations of Cortical Development/genetics* ; Whole Exome Sequencing

OBJECTIVE: To explore the genotype-phenotype correlation of a case with GM1-gangliosidosis caused by compound heterogenic variants in GLB1. METHODS: Genomic DNA was extracted from peripheral blood samples from the patient and her parents. Trio-based whole-exome sequencing (WES) was performed for the family and suspected mutation was verified by Sanger sequencing. RESULTS: The proband, a 2-year-3-month old Chinese girl, presented with psychomotor deterioration, absent speech, intellectual disabilities and behavior problem. Trio-based WES has identified compound heterozygosity for 2 variants in the GLB1 gene: NM_000404.2:c.1343A>T, p.Asp448Val and c.1064A>C, p.Gln355Pro (GRCh37/hg19),which was inherited from the mother and father, respectively. Homozygous or compound heterozygous pathogenic variants in GLB1, encoding β-galactosidase, are responsible for GM1-gangliosidosis,an autosomal recessive lysosomal storage disorder characterized by variable degrees of neurodegeneration and skeletal abnormalities. The p.Asp448Val variant has been classified as pathogenic for GM1 gangliosidosis in medical literatures for the reason that functional studies demonstrated that expression of the p.Asp448Val variant in COS-1 cells resulted in no detectable β-galactosidase activity compared to wild type GLB1. The p.Gln355Pro variant has not been reported in literatures or database. The variant is highly conserved residue (PM1), and was not found in either the Genome Aggregation Database or the 1000 Genomes Project (PM2) and was predicted to have a deleterious effect on the gene product by multiple in silico prediction tools (PP3). Next, the β-galactosidase activity of the patient's peripheral blood leukocytes was determined by fluorescent method. The result was 0.0 nmol/mg. It showed that the p.Gln355Pro variant also resulted in loss of β-galactosidase activity, thus the variant was classified into clinical pathogenic variant. CONCLUSION Our study expands the mutational spectrum of the GLB1 gene and provides genetic counseling for the family.
Asians/genetics* ; China ; Female ; G(M1) Ganglioside ; Gangliosidosis, GM1/genetics* ; Humans ; Mutation ; beta-Galactosidase/genetics*

BACKGROUND: Microglia plays an indispensable role in the pathological process of sleep deprivation (SD). Here, the potential role of microglial CX3C-chemokine receptor 1 (CX3CR1) in modulating the cognition decline during SD was evaluated in terms of microglial neuroinflammation and synaptic pruning. In this study, we aimed to investigat whether the interference in the microglial function by the CX3CR1 knockout affects the CNS's response to SD. METHODS: Middle-aged wild-type (WT) C57BL/6 and CX3CR1-/- mice were either subjected to SD or allowed normal sleep (S) for 8 h to mimic the pathophysiological changes of middle-aged people after staying up all night. After which, behavioral and histological tests were used to explore their different changes. RESULTS: CX3CR1 deficiency prevented SD-induced cognitive impairments, unlike WT groups. Compared with the CX3CR1-/- S group, the CX3CR1-/- SD mice reported a markedly decreased microglia and cellular oncogene fos density in the dentate gyrus (DG), decreased expression of pro-inflammatory cytokines, and decreased microglial phagocytosis-related factors, whereas increased levels of anti-inflammatory cytokines in the hippocampus and a significant increase in the density of spines of the DG were also noted. CONCLUSIONS These findings suggest that CX3CR1 deficiency leads to different cerebral behaviors and responses to SD. The inflammation-attenuating activity and the related modification of synaptic pruning are possible mechanism candidates, which indicate CX3CR1 as a candidate therapeutic target for the prevention of the sleep loss-induced cognitive impairments.
Animals ; Cognitive Dysfunction ; Mice ; Mice, Inbred C57BL ; Microglia ; Neuroinflammatory Diseases ; Sleep Deprivation

ObjectiveTo analyze the articles on endoscopic retrograde cholangiopancreatography (ERCP), an important method for minimally invasive treatment of biliary and pancreatic diseases, published worldwide, and to investigate the status, hotspots, and development trends in this field. MethodsThe web of science core collection database in Web of Science platform was selected to search by the subject words “TS = (Cholangiopancreatography, Endoscopic Retrograde)”, for the articles published from January 1, 2015 to December 31, 2019, and the literature type was selected as “article”. CiteSpace 5.6.R2 (64-bit) was used to analyze the authors, key words, institutions, countries (regions), and references and plot visualized maps. ResultsA total of 1535 articles on ERCP were included. The analysis showed that Hiroyuki Isayama had the highest number of published articles, followed by Yousuke Nakai and Takeshi Ogura, and University of Tokyo had the highest number of published articles, followed by Shanghai Jiao Tong University and University of Ulsan College of Medicine. Moreover, the US, Japan, and China were the top three countries from the aspect of the number of published articles in the recent 5 years, and ERCP, complication, and risk factor were the key words with the highest frequency in the recent 5 years. The most frequently cited articles mainly focused on the complications of ERCP and related consensus or guidelines. ConclusionThe main research hotspots and trends in the field of ERCP are related factors and clinical prevention of ERCP-related complications.

Objective: To elucidate the mechanism of melatonin combined with cisplatin in promoting cell apoptosis of rat pancreatic cancer AR42J cells. Methods: Rat pancreatic cancer AR42J cells were divided into control group, 1 mmol/L cisplatin treated group (cisplatin group), 1 mmol/L melatonin treated group (melatonin group), 1 mmol/L cisplatin combined with 1 mmol/L melatonin treated group (combined group), 1 μmol/L cisplatin combined with melatonin treated group after 1 μmol/L PBN pretreatment for an hour (PBN+ combined group) and 1 μmol/L cisplatin combined with melatonin treated group after PBN solvent pretreatment for an hour (solvent+ combined group). MTT and annexin V-FITC/PI were used to detect the cell proliferation rate and cell apoptosis rate, respectively. The protein expression of caspase-3 was detected by Western blot. DCFH-DA was used to detect the level of ROS. ROS level and caspase-3 expression in AR42J cells pretreated with ROS antagonist PBN for 24 hours were detected. Results: The cell proliferation rate of control group, cisplatin group, melatonin group and combination group after 24-hour culture was (96.29±3.49)%, (81.38±6.01)%, (80.72±3.68)% and (42.26±6.35)%, respectively. The cell apoptosis rate was (16.42±4.15)%, (56.47±9.06)%, (52.94±6.57)% and (87.36±6.48)%, respectively. The percentage of ROS positive cells was (1.33±1.53)%, (46.67±7.64)%, (45.67±5.13)% and (83.33±7.64)%, respectively. The expression of cspase-3 was 100%, (150.64±7.70)%, (147.00±7.27)% and (190.04±5.07)%, respectively. The cell proliferation rate of cisplatin group and melatonin group was significantly lower than that of the control group. The apoptotic rate, the proportion of ROS positive cells and the expression of caspase-3 were significantly higher than those in control group. The changes in the combined group were more obvious than those in the single drug treatment group, and the differences were all statistically significant (all Pvalues <0.05). The percentage of ROS positive AR42J cells [(45.24±4.64)% vs (84.90±6.13)%)] induced by melatonin combined with cisplatin could be significantly reversed by PBN pretreatment for 1 hour, and the expression of caspase-3 in AR42J cells could be down regulated (124.92±9.72 vs 184.69±7.76) with statistically significant difference (all P values<0.05). Conclusions Melatonin combined with cisplatin may promote cell apoptosis of pancreatic cancer AR42J cells through ROS/caspase-3 pathway.

Objective To summarize the characteristics of clinical manifestation of bone flare after the treatment with new endocrine therapy in patients with metastatic castration-resistant prostate cancer (mCRPC) in order to evaluate the curative effect of patients properly and determine the reasonable treatment strategy.Methods We retrospectively analyzed the clinical data of two patients with mCRPC performed "bone flare" defined as PSA decline and bone metastases progression in the initial treatment with new endocrine therapy in Urology Department of Peking University First Hospital,and analyzed the clinical characteristics and treatment methods with the relative literature.Case 1,a 79-year-old man,presented with frequent urination and prostate-specific antigen (PSA) was 115.900 ng/ml,was diagnosed as prostate cancer (cT3N0M1) with bone metastasis.After androgen deprivation therapy of 24 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of enzalutamide.Case 2,a 62-year-old man,complained about emaciation and frequent urination,was diagnosed with prostate cancer(cT4N1M1)with bone and lymph metastases.After androgen deprivation therapy of 22 months,PSA elevated and multiple bone metastases progressed.The patient was diagnosed with mCRPC and then began the treatment of abiraterone.Results Case 1 was treated with enzalutamide and 2 months later PSA decreased from 133.400 ng/ml to 5.530 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions kept stable,and part of lesions presented metabolism decrease.8 months later,the number of metastatic lesions began to decrease.1 year later,the patient started to receive chemical therapy because of the progression of the disease.After 5 cycles of chemotherapy,PSA progression occurred and chemotherapy was stopped.Liver failure and disseminated intravascular coagulation caused death in June 2016.Case 2 was treated with abiraterone and 2 months later PSA decreased from 54.820 ng/ml to 3.580 ng/ml,while bone scan showed multiple bone metastases,part of which was newly metastatic lesions.6 months later,the number of metastatic lesions began to decline.10 months later,the number of metastatic lesions kept stable.The treatment of abiraterone was continued so far and the patient was in a stable condition.Conclusions Enzalutamide and abiraterone,two new endocrine therapy,are determined as preferred methods for the treatment of mCRPC.The bone scanning is required to evaluate the possibility of "bone flare" which is defined as PSA decline and bone metastases progression in the initial treatment.These patients should be evaluated to make appropriate clinical decision.