N-type voltage-gated calcium (Ca²⁺) channels (N-type VGCC, Ca_V2.2) mediate Ca²⁺ influx in response to action potential at the presynaptic terminal, and play an important role in synaptogenesis, neurotransmitter release and nociceptive signal transduction. It is a new target for the development of drugs for the treatment of neuralgia (chronic pain) and other major diseases. Due to the difficulty of calcium channel expression in vitro and the detection of channel current, there is a great lack of new drug screening models. In this study, we established and optimized the electrophysiological drug screening model using Xenopus laevis oocytes for the recombinant expression of Ca_V2.2 in vitro (this study were reviewed and approved by the Ethics Committee of Guangxi University, approval number: GXU-2023-0249). Firstly, the linear plasmids encoding cDNA of major subunit α1B and auxiliary subunits α2δ1 and β3 of rat Ca_V2.2 were used as templates for in vitro transcription to generate their related mRNA (cRNA), after which three kinds of cRNA were injected into Xenopus laevis oocytes at the mass ratio of 2∶1∶1 for expression. The two-electrode voltage clamp (TEVC) technique was used to detect the inward current produced by Ca_V2.2. At the same time, the expression conditions of Ca_V2.2 were optimized, and its gating function was characterized from the aspects of channel activation and inactivation. The results showed that 3-5 days after cRNA microinjection, stable Ca_V2.2-mediated barium ion (Ba²⁺) currents were successfully detected. The interference of endogenous potassium channels and Ca²⁺-activated chloride channels can be eliminated by tetraethylammonium hydroxide (TEAOH) and 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetrakis (BAPTA-AM) treatment. The maximum potential for Ca_V2.2 activation is 0 mV, and the current reverses to be outward when the membrane potential is greater than +50 mV. By fitting the steady-state activation and inactivation curves, the half-maximal activation potential and half-maximal inactivation potential of Ca_V2.2 are identified as -15.9 and -60.2 mV. In this study, a stable Ca_V2.2 expression system was established based on Xenopus laevis oocytes. The in vitro expression system can provide a new way for the screening of Ca_V2.2 active compounds or lead drugs.

Objective To investigate the current situation and influencing factors of latent tuberculosis infection(LTBI)among close contacts of positive etiology pulmonary tuberculosis(PTB)patients,provide basis for formula-ting intervention measures for LTBI.Methods A multi-stage stratified cluster random sampling method was used to select close contacts of positive etiology PTB patients from 39 districts and counties in Chongqing City as the study objects.Demographic information was collected by questionnaire survey and the infection of Mycobacterium tuberculosis was detected by interferon gamma release assay(IGRA).The influencing factors of LTBI were analyzed by x2 test and binary logistic regression model.Results A total of 2 591 close contacts were included,the male to female ratio was 0.69∶1,with the mean age of(35.72±16.64)years.1 058 cases of LTBI were detected,Myco-bacterium tuberculosis latent infection rate was 40.83％.Univariate analysis showed that the infection rate was dif-ferent among peoples of different age,body mass index(BMI),occupation,education level,marital status,wheth-er they had chronic disease or major surgery history,whether they lived together with the indicator case,and whether the cumulative contact time with the indicator case ≥250 hours,difference were all statistically significant(all P＜0.05);infection rate presented increased trend with the increase of age and BMI(both P＜0.001),and decreased trend with the increase of education(P＜0.05).Logistic regression analysis showed that age 45-54 years old(OR=1.951,95％CI:1.031-3.693),age 55-64 years old(OR=2.473,95％CI:1.279-4.781),other occupations(OR=0.530,95％CI:0.292-0.964),teachers(OR=0.439,95％CI:0.242-0.794),students(OR=0.445,95％CI:0.233-0.851),junior high school education or below(OR=1.412,95％CI:1.025-1.944),BMI＜18.5 kg/m2(OR=0.762,95％CI:0.586-0.991),co-living with indicator cases(OR=1.621,95％CI1.316-1.997)and cumu-lative contact time with indicator cases ≥250 hours(OR=1.292,95％CI:1.083-1.540)were the influential fac-tors for LTBI(all P＜0.05).Conclusion The close contacts with positive etiology PTB have a high latent infection rate of Mycobacterium tuberculosis,and it is necessary to pay attention to close contacts of high age,farmers,and frequent contact with patients,and take timely targeted interventions to reduce the risk of occurrence of disease.

【Objective】 To explore the clinical features, treatment and prognosis of paraganglioma of the urinary bladder (PUB). 【Methods】 The clinical data of 41 PUB patients treated at our hospital during Sep.2012 and Sep.2022 were collected. The clinical features, surgical records, pathological reports and follow-up records were retrospectively analyzed. Patients’ survival was estimated with Kaplan-Meier estimator. The differences among groups were compared with Log-rank test. 【Results】 Among the 41 patients, 20 were male and 21 were female, with a median age of 52 years. All patients were treated with surgery, including transurethral resection of bladder tumor (TURBT) in 16 cases, partial cystectomy (PC) in 23 cases, and radical cystectomy (RC) in 2 cases. All patients were followed up for 4.0 to 125.0 months, with a median of 59.0 months. Local recurrence occurred in 5 patients, and distant metastasis occurred in 5 patients. Survival analysis showed that the 5-year overall survival (OS) rate and 5-year relapse-free survival (RFS) rate were 95.7% and 84.8%, respectively. Further analysis showed statistically significant differences in OS and RFS among groups with different maximum tumor diameters, growth patterns, and Ki-67 expressions (P<0.05). For patients with a maximum tumor diameter ≤2.8 cm, there was no significant difference in OS and RFS among different surgical groups. 【Conclusion】 PUB is rare, and a definitive diagnosis is based on pathology. In addition, the main treatment is surgery and the prognosis is good.

Objective:The investigation and research on the application status of Hepatic Venous Pressure Gradient (HVPG) is very important to understand the real situation and future development of this technology in China.Methods:This study comprehensively investigated the basic situation of HVPG technology in China, including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications and existing problems.Results:According to the survey, there were 70 hospitals in China carrying out HVPG technology in 2021, distributed in 28 provinces (autonomous regions and municipalities directly under the central Government). A total of 4 398 cases of HVPG were performed in all the surveyed hospitals in 2021, of which 2 291 cases (52.1%) were tested by HVPG alone. The average cost of HVPG detection was (5 617.2±2 079.4) yuan. 96.3% of the teams completed HVPG detection with balloon method, and most of the teams used thrombectomy balloon catheter (80.3%).Conclusion:Through this investigation, the status of domestic clinical application of HVPG has been clarified, and it has been confirmed that many domestic medical institutions have mastered this technology, but it still needs to continue to promote and popularize HVPG technology in the future.

Objective: To explore the clinical characteristics, treatment methods and outcomes of extramedullary plasmacytoma of the head and neck. Methods: A retrospective analysis was conducted on 10 cases with extramedullary plasmacytoma of the head and neck who were admitted to Henan Tumor Hospital from January 2005 to January 2020. Among the 10 patients, 6 were male and 4 were female. The average age at diagnosis was 56.3 years old (34-74 years old). Among them, 3 cases were located in the nasal cavity, 2 cases in the nasopharynx, 1 case in the sinuses, 2 cases in the larynx, 1 case in the oropharynx, and 1 case in the cervical lymph nodes. Treatments were administered according to tumor size and resection extent. Complete surgical excision (negative margins) was preferred, followed by adjuvant radiotherapy or radiotherapy alone. The clinical characteristics, diagnosis, treatment and prognosis of EMP were analyzed. Results: The patients' symptoms were not specific, frequently with local obstruction symptom and localized masses. All patients were confirmed pathologically as suffering from monoclonal plasmacytoma, with negative bone marrow biopsy and negative skeletal survey. Five patients received surgery, 3 received radiotherapy, and 2 received surgery with additional radiation. The follow-up time was 16-125 months, with a median of 92 months. Two patients developed into multiple myeloma. One patient who received radiotherapy after surgery relapsed after 7 years of follow-up and again received surgical treatment, with no evidence of second recurrence. The remaining patients had no recurrence or progression. Conclusion: Extramedullary plasmacytoma of the head and neck has a good prognosis. Surgical treatment can be considered for completely resectable lesions.
Adult ; Aged ; Female ; Head and Neck Neoplasms/therapy* ; Humans ; Male ; Middle Aged ; Multiple Myeloma/pathology* ; Plasmacytoma/surgery* ; Prognosis ; Retrospective Studies

Acute leukemia (AL) is a kind of malignant clonal disease of hematopoietic stem cells. Rearrangement of mixed lineage leukemia (MLL) gene can be observed in about 5%-10% of AL patients. Currently, AL patients with MLL-rearrangements (MLL-r) lack effective treatment and are usually associated with poor prognoses. Recent studies have shown that many epigenetic regulators are directly or indirectly involved in the occurrence and development of AL carrying MLL-r (MLL), which provides a biological basis for the use of epigenetic regulation strategies to treat MLL. In this review, we start from the epigenetic regulation mechanism of MLL, and select representative drug targets to briefly analyze the relationship between each target and MLL and summarize the development progress of their inhibitors, hoping to provide reference for the subsequent research and development of drugs for the treatment of MLL.

Elabela is a newly discovered peptide in recent years.It is the endogenous ligand of Apelin receptor(APJ)and plays an important role in embryonic development and adult organs.Elabela-APJ axis is closely related to organ fibrosis.Elabela can protect the functions of heart and kidney by antagonizing renin-angiotensin system and regulating blood pressure.In addition,it can prevent kidney and heart fibrosis by down-regulating the expression of fibrosis and inflammatory factors.However,there is a positive correlation between the level of Elabela and the degree of liver fibrosis,suggesting that Elabela may play a role in promoting liver fibrosis.This review aims to explore the role of Elabela-APJ axis in renal fibrosis,cardiac fibrosis,and liver fibrosis,and to provide a new therapeutic target for organ fibrosis.
Apelin ; Apelin Receptors ; Blood Pressure ; Female ; Fibrosis ; Humans ; Peptide Hormones ; Pregnancy

The present study investigated the effects of chikusetsu saponin Ⅳa(CHS Ⅳa) on isoproterenol(ISO)-induced myocardial hypertrophy in rats and explored the underlying molecular mechanism. ISO was applied to establish a rat model of myocardial hypertrophy, and CHS Ⅳa(5 and 15 mg·kg~(-1)·d~(-1)) was used for intervention. The tail artery blood pressure was measured. Cardiac ultrasound examination was performed. The ratio of heart weight to body weight(HW/BW) was calculated. Morphological changes in the myocardial tissue were observed by HE staining. Collagen deposition in the myocardial tissue was observed by Masson staining. The mRNA expression of myocardial hypertrophy indicators(ANP and BNP), autophagy-related genes(Atg5, P62 and beclin1), and miR199 a-5 p was detected by qRT-PCR. Atg5 protein expression was detected by Western blot. The results showed that the model group exhibited increased tail artery blood pressure and HW/BW ratio, thickened left ventricular myocardium, enlarged myocardial cells, disordered myocardial fibers with widened interstitium, and a large amount of collagen aggregating around the extracellular matrix and blood vessels. ANP and BNP were largely expressed. Moreover, P62 expression was up-regulated, while beclin1 expression was down-regulated. After intervention by CHS Ⅳa at different doses, myocardial hypertrophy was ameliorated and autophagy activity in the myocardial tissue was enhanced. Meanwhile, miR199 a-5 p expression declined and Atg5 expression increased. As predicted by bioinformatics, Atg5 was a target gene of miR199 a-5 p. CHS Ⅳa was capable of preventing myocardial hypertrophy by regulating autophagy of myocardial cells through the miR-199 a-5 p/Atg5 signaling pathway.
Animals ; Cardiomegaly/genetics* ; Isoproterenol ; Myocardium ; Myocytes, Cardiac ; Oleanolic Acid/analogs & derivatives* ; Rats ; Saponins/pharmacology*

Objective: To observe the OCT characteristics of lamellar hole-associated epiretinal proliferation (LHEP). Methods: A retrospective case analysis. A total of 128 patients (133 eyes) with lamellar macular hole (LMH) and 202 patients (212 eyes) with full-thickness macular hole (FTMH) diagnosed by the examinations of spectral-domain OCT (SD-OCT) in Department of Ophthalmology, The Third People's Hospital of Chengdu from January 2013 to December 2016 were included in this study. Among 133 eyes with LMH, there were 53 eyes (39.8%) with LHEP and 80 eyes (60.2%) without LHEP. Among 212 eyes with FTMH, there were 12 eyes (5.7%) with LHEP and 200 eyes (94.3%) without LHEP. The mean age of LMH with or without LHEP patients were 70.88±10.98, 64.76±13.60 years old, respectively. The difference of mean age between LMH with or without LHEP patients was statistically significant (U=1521.5, P=0.006). The inner diameter, median diameter and base thickness of the LMH, the height, base diameter and minimum diameter of FTMH were measured by SD-OCT. The traction index (THI) and the macular hole index (MHI) were calculated. An independent sample t-test or rank-sum test was used to compare the inner diameter, median diameter, and base thickness of the LMH in patients with or without LHEP, and χ² test was used to compare the injury rate of ellipsoid zone. Results: Of the LMH patients with or without LHEP, the inner diameter were 611.15±209.83 and 521.70±198.05 μm, the median diameter were 961.22±571.09 and 497.01±172.30 μm, the base thickness were 99.83±38.69 and 154.12±43.17 μm. The differences of the inner diameter, median diameter and the base thickness between LMH patients with or without LHEP were statistically significant (t=2.490, 5.747, -7.395; P=0.014, 0.000, 0.000). Among the 53 eyes with LHEP, There were 50 eyes (94.34%) were injured in ellipsoid zone among 53 eyes with LHEP, while 17 eyes (21.25%) were injured in ellipsoid zone among 80 eyes without LHEP. The injury rate of ellipsoid zone between LMH patients with or without LHEP was statistically significant (χ²=68.126, P=0.000). In 12 eyes of FTMH with LHEP, there were 10 eyes with THI <1.0 and MHI<0.5. Conclusion Compared with the LMH without LHEP, the LMH with LHEP has larger inner diameter and median diameter, thinner base and higher injury rate of ellipsoid zone.

Objective To observe the effects of Shenqi Xingnao Prescription on learning and memory ability, contents of choline acetyltransferase (ChAT) and acetylcholine esterase (AChE) in brain tissue in mice models with scopolamine-induced Alzheimer disease (AD); To investigate its mechanism for prevention and treatment for AD. Methods Totally 110 ICR mice were randomly divided into control group, control+Shenqi Xingnao Prescription high-dose group,model group,donepezil group,model+Shenqi Xingnao Prescription high-,medium-,and low-dose groups. The control and model group were given distilled water for gavage, and the other groups were given the corresponding medicine for gavage, once a day, for 14 days. On the 15th day, Morris water maze test and object recognition test were used to evaluate the learning and memory ability of each group. The model mice of memory impairment induced by intraperitoneal injection of scopolamine was established 20 minutes before the behavioral test. The expressions of ChAT and AChE in cortex and hippocampus were detected by Western blot. Results The results of Morris water maze test showed that compared with the control group, the model group had significant longer escape latency(P<0.05);Compared with the model group,Shenqi Xingnao Prescription medium-and high-dose groups could shorten the escape latency (P<0.05). The results of the object recognition test showed that compared with the control group, the ability of the model group to explore new things decreased and the discrimination index (DI) decreased (P<0.001);Compared with the model group,Shenqi Xingnao Prescription groups could increase the DI of model mice (P<0.05, P<0.01, P<0.001). The results of Western blot showed that the expression of AChE protein in the cortex and hippocampus of the model group was significantly higher than the control group (P<0.01); Compared with the model group, Shenqi Xingnao Prescription low- and medium-dose groups could decrease the expression of AChE in the cortex in different degrees(P<0.01);Shenqi Xingnao Prescription groups could decreaed the expression of AChE in the hippocampus (P<0.001); There was no significant statistical significance in the expression of ChAT in the cortex and hippocampus in each group.Conclusion Shenqi Xingnao Prescription can significantly improve the learning and memory ability of AD model mice induced by scopolamine, which may be related to the descent expression of AChE protein in the cortex and hippocampus of the model mice.