AIM: To evaluate the bioequivalence of cinacalcet hydrochloride tablets in healthy Chinese volunteers. METHODS: A randomized, open, double-period and crossover trial was conducted, 48 healthy volunteers were administered a single dose of cinacalcet test tablets or reference tablets orally under each fasting and fed condition. The concentration of cinacalcet was determined by validated LC-MS/MS method. Pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 to study its bioequivalence. RESULTS: The main pharmacokinetic parameters of test tablets and reference tablets under fasting condition were as follows: C

Ulcerative colitis （UC）， a chronic inflammatory bowel disease with the accumulation of colorectal mucosa and submucosa， has a risk of developing into cancer. In recent years， the incidence of UC has been on the rise worldwide. However， its pathogenesis has not been fully elucidated by modern medicine， and even the remission rate of the latest drugs is lower than 50%， which seriously affects the patients' work and quality of life. Mitochondria， as the "power station" of eukaryotic cells， are involved in a variety of physiological processes such as the production of reactive oxygen species and the production of adenosine triphosphate by oxidative phosphorylation， and their dysfunction can lead to a series of diseases. Mitochondrial quality control （MQC） is an important way to maintain the stability of mitochondrial form， quantity， and quality. Studies have shown that MQC disorders characterized by low mitochondrial biogenesis， excessive mitochondrial oxidative stress， mitochondrial autophagy defects， mitochondrial dynamics disorders， and calcium regulation abnormalities are closely related to the occurrence and development of UC. Although progress has been achieved in the treatment of UC by traditional Chinese medicine （TCM） which can regulated MQC in a multi-pathway and multi-target manner in recent years， a review on the treatment of UC by TCM via the intervention in MQC remains to be carried out. Therefore， this paper summarized the TCM treatment of UC by regulating MQC， aiming to provide new ideas for the clinical treatment of UC by TCM.

【Objective】 To investigate the expressions of P53 and Ki-67 in prostate cancer (PCa)and to explore their correlation with the clinicopathological characteristics. 【Methods】 The expressions of P53 and Ki-67 in 90 PCa patients were detected with immunohistochemistry. Patients’ age, preoperative prostate-specific antigen (PSA) level, postoperative Gleason score, pathological stage, and invasion of neurovascular cancer embolus of all patients were recorded. The relationship of P53 expression with the above indexes was evaluated. 【Results】 The positive rates of P53 and Ki-67 were 27.8% (25/90) and 46.7% (42/90), respectively. The positive rate of P53 in pT2 and pT3-T4 stage groups were 19.7% (13/66) and 50.0% (12/24) (P=0.005), and the positive rate of Ki-67 were 36.4% (24/66) and 75.0% (18/24) (P=0.001), respectively. The positive rate of Ki-67 in Gleason score ≤6, ≤7 and ≥8 groups were 30.4%, 53.8% and 66.7%, respectively, with statistical difference. Positive expression of P53 was related to Ki-67 expression, but not to patients’ age, preoperative PSA level, postoperative Gleason score and nerve and invasion of neurovascular cancer embolus. 【Conclusion】 P53 expression is related to tumor stage and Ki-67, while Ki-67 expression is associated with tumor stage ang grade.

Objective:To compare outcomes between standardized and misdiagnosis and mistreatment of osteosarcoma.Methods:A retrospective analysis of patients with high-grade osteosarcoma who received appropriate surgical treatment and chemotherapy (299 cases, control group) and those who were misdiagnosed (benign or infective) and received mistreatment (23 cases, study group) between January 2009 and December 2021. Gender, age, first operation mode, recurrence time, recurrence interval, metastasis time, metastasis interval, total survival time (months), survival status in the two group and tumor site reoperation mode in the study group were statistically analyzed. Further, chi-square test was performed for comparison of the clinical between two groups. The survival analysis was performed using Kaplan-Meier test and Log-rank test.Results:All the 322 patients were followed up. In the control group, the average follow-up time was 42 months (1-137 months), the average age was 24 years (3-80 years), male 184 cases, female 115 cases, and limb salvage rate was 85.3% (255/299). Seven patients underwent amputation, and the amputation rate was 17.7% (44/299). The recurrence rate was 8.4% (25/299), the average recurrence interval was 22.8 months (7-36 months), and the metastasis rate was 28.1% (85/299), the average metastasis time was 32.7 months (0-58 months). In the study group, the average of follow-up time was 30 months (9-117 months), the average age was 36 years (5-67 years), 17 males and 6 females. Among them, eleven patients were treated with limb salvage in the second stage, and the limb salvage rate was 47.8% (11/23). Seven patients underwent amputation, and the amputation rate was 30.4% (7/23). The recurrence rate was 26.1% (6/23), the average recurrence interval was 11 months (1-42 months), and the metastasis rate was 43.4% (10/23), the average metastasis time was 20.3 months (1-44 months). The 5-year survival rate was 50.7% in the study group and 56.1% in the control group. There was no significant difference between the two groups (χ 2=0.09, P=0.760). Conclusion:The overall prognosis of patients with high-grade osteosarcoma who receive active treatment after mistreatment is similar to that of patients with standardized treatment, but the recurrence and metastasis rate is higher, the recurrence time is earlier, and the amputation rate is higher.

OBJECTIVE: To explore the mechanisms of large-conductance calcium-activated potassium channel (BKCa) involved in inflammatory response in sepsis. METHODS: The serum levels of BKCa were measured by enzyme-linked immunosorbent assay (ELISA) in patients with sepsis (28 cases), patients with common infection (25 cases) and healthy people (25 cases). The relationship between levels of BKCa and acute physiology and chronic health evaluation II (APACHE II) were analyzed. Cultured RAW 264.7 cells were stimulated by lipopolysaccharide (LPS). In some experiments, a cell model of sepsis was constructed using Nigericin as the second stimulus signal. The mRNA and protein expressions of BKCa in RAW 264.7 cells stimulated with LPS (0, 50, 100, 1 000 μg/L) were measured by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR) and Western blotting. RAW 264.7 cells were transfected with small interfering RNA of BKCa (siRNA-BKCa), and the levels of caspase-1 precursor (pro-caspase-1), interleukin-1β precursor (pro-IL-1β) in cell, and the levels of caspase-1 p20, IL-1β p17 of cell culture medium, and NOD-like receptor protein 3 (NLRP3), nuclear factor-κB (NF-κB) were measured by Western blotting. The apoptosis were detected by staining with propidium iodide (PI), the release rate of lactate dehydrogenase (LDH) were measured, and the expression of apoptotic protein Gasdermin D (GSDMD) was measured by Western blotting to evaluate the effect of silencing BKCa on cell pyrosis. RESULTS: The level of serum BKCa in patients with sepsis was significantly higher than that in patients with common infection and health peoples (ng/L: 165.2±25.9 vs. 102.5±25.9, 98.8±20.0, both P < 0.05). In addition, the level of serum BKCa in patients with sepsis was significantly positively correlated with APACHE II score (r = 0.453, P = 0.013). LPS could construct a sepsis cell model by which LPS could promote BKCa expression in mRNA and protein with a concentration-dependent manner. The mRNA and protein expressions of BKCa in the cells stimulated by 1 000 μg/L LPS were significantly higher than that in the blank group (0 μg/L) [BKCa mRNA (2^-ΔΔCt): 3.00±0.36 vs. 1.00±0.16, BKCa/β-actin: 1.30±0.16 vs. 0.37±0.09, both P < 0.05]. Compared with the control group, the ratios of caspase-1 p20/pro-caspase-1 and IL-1β p17/pro-IL-1β in the model group were significantly increased (caspase-1 p20/pro-caspase-1: 0.83±0.12 vs. 0.27±0.05, IL-1β p17/pro-IL-1β: 0.77±0.12 vs. 0.23±0.12, both P < 0.05), however, transfection of siRNA-BKCa induced the decrease both of them (caspase-1 p20/pro-capase-1: 0.23±0.12 vs. 0.83±0.12, IL-1β p17/pro-IL-1β: 0.13±0.05 vs. 0.77±0.12, both P < 0.05). Compared with the control group, the number of apoptotic cells, LDH release rate and GSDMD expression in the model group were significantly increased [LDH release rate: (30.60±8.40)% vs. (15.20±7.10)%, GSDMD-N/GSDMD-FL: 2.10±0.16 vs. 1.00±0.16, both P < 0.05], however, transfection of siRNA-BKCa induced the decrease both of them [LDH release rate: (15.60±7.30)% vs. (30.60±8.40)%, GSDMD-N/GSDMD-FL: 1.13±0.17 vs. 2.10±0.16, both P < 0.05]. The mRNA and protein expressions of NLRP3 in sepsis cells were significantly higher than those in the control group [NLRP3 mRNA (2^-ΔΔCt): 2.06±0.17 vs. 1.00±0.24, NLRP3/GAPDH: 0.46±0.05 vs. 0.15±0.04, both P < 0.05]. However, the expression of NLRP3 after siRNA-BKCa transfection was significantly lower than that in model group [NLRP3 mRNA (2^-ΔΔCt): 1.57±0.09 vs. 2.06±0.17, NLRP3/GAPDH: 0.19±0.02 vs. 0.46±0.05, both P < 0.05]. Compared with the control group, the NF-κB p65 nuclear transfer of sepsis cell were significantly increased (NF-κB p65/Histone: 0.73±0.12 vs. 0.23±0.09, P < 0.05). However, the NF-κB p65 expression in the nucleus were decreased after siRNA-BKCa transfection (NF-κB p65/Histone: 0.20±0.03 vs. 0.73±0.12, P < 0.05). CONCLUSIONS BKCa is involved in the pathogenesis of sepsis, and its possible mechanism is to activate NF-κB/NLRP3/caspase-1 signaling pathway to induce inflammatory factor production and cell death.
Humans ; Histones ; Caspase 1 ; Large-Conductance Calcium-Activated Potassium Channels ; Lipopolysaccharides ; NF-kappa B ; NLR Family, Pyrin Domain-Containing 3 Protein ; L-Lactate Dehydrogenase ; Sepsis ; RNA, Small Interfering ; Caspases

Objective To study the effect of morphological characteristics of modular inner branched stent graft (MIBSG) on hemodynamic performance of postoperative aortic arch based on parameterized MIBSG model. Methods The fluid-structure interaction model of blood-MIBSG coupling performance was solved, and the effects of stent branch angles, stent diameters on hemodynamic characteristics were analyzed. Results With the increase of angles between branch stent and aortic arch stent, blood flow within the branch decreased, but the stress and displacement increased. With the decrease of stent diameters, blood flow perfusion decreased significantly, but the stress and displacement increased first, and then decreased. Conclusions The morphological changes of MIBSG not only have an impact on blood perfusion rate of branch stent, but also affect the stress exerted on stent and the corresponding displacement. Before application in clinic treatment of aortic arch diseases, the movement and torsion of MIBSG should been taken into full account in operation plan according to the actual situation.

Objective:To study the improvement of medical service quality in a public hospital by integrating Kano and quality function deployment(QFD)technology, so as to provide reference for the improvement of service quality in hospitals.Methods:The Kano questionnaire of patients′ needs was designed, the attributes of patients′ needs were identified, and the importance of patients′ needs was calculated and determined. Then, using the house of quality technology in QFD, the patient needs were transformed into corresponding medical service quality assurance elements, and the improvement priority of each assurance element was determined through calculation.Results:The six quality assurance elements most expected to be improved by patients in the hospital were to improve medical level, strengthen service management, improve supervision and review mechanism, standardize complaint process, ensure drug safety and guidance, and track treatment effect.Conclusions:The integrated Kano-QFD technology can provide an effective methodological reference for improving the quality of medical service.

A lean management practice had been in place in Taizhou Enze Medical Center during the COVID-19 epidemic period, featuring the " principle-system-tool" theory of the Shingo model, in an effort to build a new model of COVID-19 prevention and control. The center upheld such five principles of lean management as overall planning, total involvement, system collaboration, concern with process and continuous improvement, and people-oriented practice. Under such principles, the center set up five supportive systems of lean management tools, namely risk identification, rapid screening, homogeneous treatment, customized follow-up and employee care. Integrated use of multiple tools of lean management, had improved the hospital′s crisis response ability, achieving desirable outcomes in stages in combating COVID-19 epidemic.

This study prospectively collected the clinical data of patients who received sacral neuromodulation(SNM)variable-frequency stimulation (VFS) mode from June 2020 to December 2020, in order to explore the efficacy and safety of VFS mode in the treatment of refractory lower urinary tract dysfunction. The inclusion criteria were as follows: ①SNM was implanted; ②age ≥18 years old; ③The traditional constant-frequency stimulation (CFS) mode has poor therapeutic effect, and can not be improved after repeated adjustment of stimulation parameters; ④Patients with overactive bladder (OAB) symptoms, who fail to respond to conservative treatment or are intolerant to conservative treatment; ⑤The drugs that affect the lower urinary tract symptoms and pelvic function should not be increased or decreased during the trial; ⑥provision of informed consent. A total of six patients meeting the criteria were included in the study, with three males and three females. The age ranged from 47 to 74 years, with an average age of 55 years. Among those patients, three cases were diagnosed of OAB, two cases were diagnosed of interstitial cystitis, and one case was diagnosed of neurogenic bladder. All patients had received CFS-SNM for an average of 20.6 months before upgrading to VFS mode, and suffered from severe frequency of urination at the same time. Compared with the severity of symptoms during the baseline period and the CFS period, a trend of improvement was found among four patients during the VFS period. The severity of symptoms was mainly based on the average daily urination frequency and OAB-Q score. For the two patients with interstitial cystitis, OAB symptoms worsened during the VFS period, while the VAS score did not change significantly. In general, VFS-SNM is not inferior to CFS-SNM in improving the symptoms of frequent micturition. For patients with interstitial cystitis, multiple sets of VFS parameters can be tried under the premise of satisfactory pain management.

Objective:To investigate the effect of alogliptin on bone loss in ovariectomized(OVX)mice.Methods:For animal experiments, thirty 8-week-old C57BL/6J female mice were divided into Sham group, OVX group, and OVX+ alogliptin group. OVX+ alogliptin group were administered with alogliptin in a dosage of 20 mg·kg -1·d -1 by gavage, Sham and OVX groups with equivalent saline. After 12 weeks intervention, serum bone anabolism indicators were detected, and Micro CT and HE staining were used to observe and analyze the bone trabecular structure of femur and tibia in mice. For in vitro experiments, bone marrow mesenchymal stem cells(BMSCs)were incubated with 100 μmol/L alogliptin for osteoblast differentiation. Alkaline phosphatase(ALP)and alizarin red S staining were used to determine the ALP activity and mineralization after osteogenic induction and culture. Real-time fluorescence quantitative PCR and Western blot were used to detect mRNA and protein expressions of osteoblast related genes. Results:Alogliptin intervention improved the biochemical indexes of bone anabolism and protected against bone microstructure deterioration to alleviate bone loss in OVX mice. Alogliptin stimulated osteoblast differentiation and elevated expression levels of Runt-related transcription factor 2(Runx2), ALP, osteocalcin, and osterix in in vitro experiments. Conclusion:Alogliptin can alleviate bone loss in OVX mice.