PiT2 is an inorganic phosphate (Pi) transporter whose mutations are linked to primary familial brain calcification (PFBC). PiT2 mainly consists of two ProDom (PD) domains and a large intracellular loop region (loop7). The PD domains are crucial for the Pi transport, but the role of PiT2-loop7 remains unclear. In PFBC patients, mutations in PiT2-loop7 are mainly nonsense or frameshift mutations that probably cause PFBC due to C-PD1131 deletion. To date, six missense mutations have been identified in PiT2-loop7; however, the mechanisms by which these mutations cause PFBC are poorly understood. Here, we found that the p.T390A and p.S434W mutations in PiT2-loop7 decreased the Pi transport activity and cell surface levels of PiT2. Furthermore, we showed that these two mutations attenuated its membrane localization by affecting adenosine monophosphate-activated protein kinase (AMPK)- or protein kinase B (AKT)-mediated PiT2 phosphorylation. In contrast, the p.S121C and p.S601W mutations in the PD domains did not affect PiT2 phosphorylation but rather impaired its substrate-binding abilities. These results suggested that missense mutations in PiT2-loop7 can cause Pi dyshomeostasis by affecting the phosphorylation-regulated cell-surface localization of PiT2. This study helps understand the pathogenesis of PFBC caused by PiT2-loop7 missense mutations and indicates that increasing the phosphorylation levels of PiT2-loop7 could be a promising strategy for developing PFBC therapies.
Humans ; Cell Membrane ; Mutation, Missense ; Phosphates/metabolism* ; Sodium-Phosphate Cotransporter Proteins, Type III/genetics*

This article reported the clinical features of a rare patient with anti-metabotropic glutamate receptor 5 （mGluR5） encephalitis with mental disorders as the initial symptom， so as to provide references for clinical diagnosis and treatment. The patient was a 38-year-old male， developed pharyngeal pain as prodromal symptoms， and the main clinical manifestations included rapidly progressive memory loss， anxiety and depression， and psychomotor excitement symptoms including irritability and impulsive behaviors. The disease had a progressive deterioration. In the most severe state， the patient became unconscious in a shallow coma， with further cognitive decline， hallucinations and delusions， and lack of self-awareness. Both cerebrospinal fluid and serum anti-mGluR5 antibody were strongly positive （1∶100）. After two sessions of hormone shock therapy， the patient showed significantly improvement in consciousness， cognitive， emotional and psychiatric dimensions.

Objective:To investigate the effect of Chaishao-Shugan-Lidan-Paishi Decoction assisted with laparoscopic cholecystectomy in the treatment of chronic cholecystitis with gallstones. Methods:According to the random number table method, 198 cases of chronic cholecystitis combined with cholecystolithiasis were admitted to our hospital from January 2016 to January 2019 and were divided into two groups, 99 cases in each group. Laparoscopic cholecystectomy was performed in both group. Then the control group was treated with Ursodeoxycholic Acid, and the observation group was treated with Chaishao-Shugan-Lidan-Paishi Decoction on the basis of the control group. Both groups were treated for 8 weeks. The clinical efficacy was evaluated after the treatment TCM symptoms and signs were scored before and after the treatment; the levels of TNF-α, IL-6, hs-CRP, gastrin (GAS), motilin (MOT) and somatostatin (SST) were detected by double antibody sandwich ELISA, and the adverse reactions during the treatment were recorded. Results:The total effective rate of the observation group was 94.9% (94/99), the control group was 82.8% (82/99), the difference between the two groups was statistically significant ( χ2=7.364, P=0.007). The score of the right flank pain, the level of upset and irritable condition, the sense of fullness of epigastric cavity, greasiness, nausea and vomiting, belching score after the treatment in the observation group were significantly lower than those in the control group ( t values were 7.229, 4.773, 4.442, 2.302, 5.887, 4.235, respectively, P<0.05 or P<0.01). After the treatment, the levels of serum TNF-α, IL-6, hs-CRP in the observation group were significantly lower than those in the control group ( t values were 9.330, 18.425, 26.886, respectively, all Ps<0.05), and the levels of serum GAS (104.53 ± 2.13 ng/L vs. 96.61 ± 3.29 ng/L, t=20.106) and MOT (386.60 ± 9.42 ng/L vs. 345.50 ± 12.80 ng/L, t=25.731) in the observation group were significantly higher than those of the control group, SST (40.05 ± 4.39 ng/L vs. 48.42 ± 5.11 ng/L, t=12.362) in the observation group was significantly lower than that of the control group ( P<0.01). No serious adverse reactions occurred during the treatment period in both groups. Conclusion:Chaishao-Shugan-Lidan-Paishi Decoction assisted laparoscopic cholecystectomy in the treatment of chronic cholecystitis with gallstones can improve the clinical symptoms, inhibit inflammation, improve gastrointestinal function, improve clinical efficacy.

Objective To develop a diagnostic model based on deep neural network for intelligent discrimination of thyroid function. Methods A total of 1616 patients ( 283 males, 1333 females, average age:52 years) who underwent thyroid imaging between May 2016 and June 2018 were selected. According to the clinical diagnosis, the 1616 cases included 299 normal thyroid cases, 876 hyperthyroidism cases and 441 hypothyroidism cases. Feature extraction and learning training were performed on 1000 training set sam-ples by two deep neural network models ( AlexNet;deep convolution generative adversarial networks ( DCGAN) ) using deep learning algorithm. Performance verifications were implemented on 616 test set samples. The con-sistency between the verification results of the two models and the clinical diagnosis was analyzed by Kappa test. Meanwhile, the time advantage of the intelligent diagnosis models was analyzed. Results The average diagnostic time of AlexNet model was 1 s/case, and the classification accuracy for normal thyroid, hyperthy-roidism, hypothyroidism were 82.29％(79/96), 94.62％(369/390), 100％(130/130), respectively. The Kappa value between results of AlexNet model and clinical diagnosis was 0.886 ( P<0.05) . The average di-agnostic time of DCGAN model was 1 s/case, and the classification accuracy for normal thyroid, hyperthy-roidism, hypothyroidism were 85.42％(82/96), 95.64％(373/390), 99.23％(129/130), respectively. The Kappa value between results of DCGAN model and clinical diagnosis was 0.904 ( P<0.05) . Conclusion The deep neural network intelligent diagnosis model can quickly determine the functional status of thyroid gland in thyroid imaging, and it has a high recognition accuracy, thus providing a new method for thyroid image review.

Objective To understand the cognitive level of chronic obstructive pulmonary disease (COPD) disease management and pulmonary rehabilitation among medical staff in the respiratory departments and community of public health institutions in Panyu of Guangzhou, in order to assess the status of prevention and treatment of COPD in this area. Methods From March to October 2017, a questionnaire survey was conducted among 339 medical staff in Panyu, including respiratory doctors, nurses and therapists of four tertiary hospitals, five secondary hospitals, and three first-level hospitals, GPs, nurses and therapists at 16 community health service centres, among them, there are 147 respiratory and general practitioners (hereinafter referred to as doctors), 171 respiratory and general nurses (hereinafter collectively referred to as nurses), and 22 rehabilitation therapists (hereinafter collectively referred to as therapists). Using Epidata software to create questionnaire database entry data. Results The awareness rate of COPD airflow limitation severity of nurses was only 19.9％, which was lower than that of doctors (39.7％) and therapists (22.7％). Doctors, nurses, and therapists are familiar with the low percentage of the GOLD guidelines, which are respectively only 12.3％, 7.6％, and 4.5％. Nurses were diagnosed with pulmonary function as a basis for COPD, and the awareness rate was only 60.2％ lower than that of doctors (82.9％) and therapists (81.8％). In alleviating COPD patients′shortness of breath, only 31.8％therapists chose short-acting beta-agonists, lower than doctors (61％) and nurses (45％). There is disagreement about the long-term use of inhaled corticosteroids in COPD. Medical staff have the highest awareness of lip-reducing and abdominal breathing, followed by Taiji and Ba Duan Jin exercises, and low awareness of modern rehabilitation programs such as elastic bands, upper and lower limb exercises. The effective pulmonary rehabilitation program should last at least 8 weeks, and the awareness rate of this therapy practice was 40.9％, higher than doctors (13.7％) and nurses (18.1％). Medical staff believe that the main factors affecting patient compliance are the cost of the drug and the patient′s lack of understanding of the benefits of the treatment. Additionally, 40.4％ of doctors, 51.5％ of nurses, and 54.5％of therapists believe that community health services cannot manage COPD. The reasons that affect community management of COPD, doctors believe that patient compliance and lack of man power, nurses believe that the main shortage of manpower and equipment, the therapist believes that the lack of medical awareness and poor patient compliance. Conclusion Doctors, nurses, and therapists have inconsistent understandings of COPD disease management and pulmonary rehabilitation, and each has its own focus. It is necessary to strengthen learning exchanges for each weak knowledge point. The awareness rate of modern rehabilitation exercise for pulmonary rehabilitation is not as high as that of traditional Chinese medicine. It is necessary to pay attention to the promotion of the benefits and significance of COPD pulmonary rehabilitation treatment and improve compliance.

Objective To compare the effect and safety of rituximab plus CHOP (R-CHOP) and CHOP regimens for the treatment of newly diagnosed patients with early-stage primary gastric diffuse large B-cell lymphoma (PG-DLBCL). Methods A total of 65 patients with PG-DLBCL were retrospectively divided into two groups: 35 patients were treated with R-CHOP regimen, the others with CHOP regimen. NHL international efficacy assessment and WHO criteria were used to assess the therapeutic and the adverse reactions respectively. Results The complete remission (CR) rate of R-CHOP group was 74.3 % (26/35), which was significantly higher than that of CHOP group [50.0 % (15/30), P< 0.05], but the adverse reactions rates of two groups had no significant difference (P>0.05). The Kaplan-Meier survival analysis showed that the five-year survival rates of two groups had no significant difference (88.6%vs 75.0%, P>0.05). The PFS of R-CHOP group was better than that of CHOP group (94.4 months vs 74.9 months, P< 0.05). Conclusion Compared with CHOP regimen , R-CHOP regimen increases the therapeutic efficacy in patients with PG-DLBCL, and dose not increase the adverse reactions.

Fifty outpatients of newly diagnosed hypertension (NDH,with course of disease ≤ 3 months) and 50 patients with routinely revisit hypertension (RRH,with course of disease ≥ 1 year) were consecutively enrolled respectively from February 2010 to July 2010.They were asked to complete the Beck Depression Inventory (BDI),Spielberger State-Trait Anxiety Inventory (STAI) and the SF-36 questionnaire.The results showed that compared with the RRH group,the NDH group were more worried about being diagnosed as hypertension,dependence and side effects of antihypertensive drugs and complications of hypertension (all P ＜ 0.05).The NDH group displayed significantly higher level of anxiety compared with that of the RRH group (P ＜ 0.001).No significant differences were found in depression and 8 dimensions of SF-36 forms between two groups (P ＞ 0.05).The results indicated that patients of NDH have significant higher level of anxiety than that of RRH,they should be given more psychological intervention and appropriate health education.

Objective To detect the strain features of regional wall abnormalities in patients with coronary artery disease during each diastolic period, and its possibility to evaluate regional left ventricular cardiocyte viability and diastolic function.Methods 54 patients with anterior myocardial infarction (MI group) and 78 normal subjects (NOR group) underwent Doppler tissue imaging, which were performed in 2-chamber-view by strain curves synchronously.Results In the NOR group, strain value of 66 cases (84.62%) showed an gradually increasing negative value from the apex to base to middle of left ventricle, while in the MI group, there were 9 cases (16.67%) with such a trend. IR phase: in the NOR group, 564 segments (90.38%) were upward wave bands, but in the MI group, there were 123 segments (28.47%) having such waves ( P<0.05). RF phase: in the NOR group, 576 segments (92.31%) were upward and steep wave bands, but in the MI group, the number of upward waves were obviously less (102 segments,23.61%) ( P<0.01). SF period: compared with the NOR group, which was horizontal, the MI group had upward wave bands ( P<0.05).Conclusion Regional myocardial ischemia and infarction can cause significant regional diastolic wall abnormalities of strain value in active diastolic phase. Regional diastolic wall motion abnormalities can be evaluated quantitatively and synchronously with high sensitivity by strain curve which has the potential value in cardiocyte viability and diastolic function.

BACKGROUND:After acute myocardial infarction(AMI),there is still surviving myocardium in and around the infarcted area,which plays an important role in the occurrence of arrhythmia. OBJECTIVE:To study the alterations of the activities of Na+ channel current(INa),L-calcium current(ICa-L),transient outward K+ current(Ito) and inward rectifying K+ current(IK1) in the cardiomyocytes in the infarcted area after AMI. DESIGN: A randomized controlled study. SETTING:Department of Cardiology,Bethune International Peace Hospital. PARTICIPANTS:The experiment was finished in the Central Laboratory of the Department of Cardiology,Bethune International Peace Hospital from January to June 2003.Twenty New Zealand pure big-ear rabbits were randomly divided into AMI group(n=10) and control group(n=10). INTERVENTIONS:Rabbit AMI models were established by ligation of the left anterior descending coronary artery.The ventricular myocytes were separated with the method of enzymatic dissociation technique,and the changes of the ion currents were recorded with the whole cell patch-clamp techniques. MAIN OUTCOME MEASURES:The changes of INa,ICa-L,Ito and IK1 in the cardiomyocytes taken from the infarcted area of epicardium 24 hours after AMI in both the AMI and control groups. RESULTS:Twenty-four hours after AMI,the peak current densities of INa,ICa-L and IK1 in the AMI group [(28.48± 3.53) pA/pF,n=16;(3.91± 0.95) pA/pF,n=12;(26.93 ± 3.48) pA/pF,n=16]were all significantly reduced as compared with those in the control group [(45.50± 5.33) pA/pF,n=12;(5.58± 1.53) pA/pF,n=10;(34.12± 4.21) pA/pF,n=10] (t=3.026,P< 0.01;t=2.985,P< 0.01;t=2.706,P< 0.05).There was no significant difference in the Ito density between the AMI group and control group (P >0.05). CONCLUSION:The reduce of INa,ICa-L and IK1 caused by AMI can result in the decrease of myocardial conduction velocity,the shortening of action potential-time,abnormal repolarization,which is possibly the ionic mechanism for the reentrant ventricular arrhythmia after AMI.

AIM: To study the current density of transient outward potassium current (I_(to)) in cells from the epicardial zone of the 1-week and 2-month infarcted rabbit heart. METHODS: Rabbits were infarcted by ligation of the left anterior descending coronary artery, 1 week as well as 2 months later, the single ventricular myocytes were isolated enzymatically from the infracted area of 1-week infracted rabbit heart (PMI-1 week) and 2-month infracted heart (PMI-2 months), region remote from the infracted zone of 2-month infracted heart (REM-2 months) and free wall of left ventricule from noninfarcted heart (CON). I_(to) was recorded using whole cell patch-clamp techniques. (RESULTS:) Membrane capacitance of myocytes in REM-2 months group was signifitantly larger than that in CON. I_(to)current density (at +60 mV) was significantly reduced in PMI-1 week [(7.5?2.4) pA/pF, n=12] and PMI-2 months [(10.6?4.1) pA/pF, n=18] compared with CON [(17.4?5.2) pA/pF, n=16], P