Objective To study the effect of surfactants on the dissolution profiles of poorly water-soluble acidic drug nimesulide from sustained-release tablets.Methods The anionic surfactant sodium dodecyl sulfate (SDS), cationic sur-factant cetyltrimethyl ammonium bromide (CTAB) and nonionic surfactant polysorbate 80 (Tween 80) were used to prepare nimesulide micelles .The effect of the buffer , surfactant and ionic strength on the equilibrium solubility of the drug and the in vitro release of sustained-release tablets was studied .Results and Conclusion In pH 1.2 HCl solution, water and pH 6.8 phosphate buffer, the solubilization capacity of CTAB was the highest.However, in pH 9.0 Tris buffer, when CTAB concen-tration was at about 1%, the equilibrium solubility of nimesulide was at the trough value .The in vitro release results were similar to those of equilibrium solubility and the kinetic pattern conformed to the first order equation according to the coefficient R .

Objective To test the hypothesis that p53 gene therapy combined with endostatin can enhance tumor response to radiation therapy of RM-1 mouse xenograft prostate cancer and to investigate its mechanism. Methods A mouse prostate cancer model was established. Then mice with xenograft tumor were randomly divided into group A (control), B (radiation), C (radiation and rAdp53), D (radiation and rh-endostatin) and E (radiation and rAdp53 and rh-endostatin). On day 1, rAdp53 was injected intra-tumorously with 1 × 1010 vp per animal to group C and E. From day 1 to 14, rh-endostatin was given 15 mg/kg intraperitoneally daily to group D and E. On day 4 single fraction of 15 Gy was given to tumors in groups B, C, D and E. Normal saline was injected intra-tumorously or intraperitoneaUy accordingly as control. No treatment was done to group A. Tumor volume was measured daily. Samples were collected on Days 5, 10 and 15. Ki67, CD31, p53 and VEGF were detected by means of immunohistochemistry. Results (1) Radiation alone, radiation combined with intra-tumorous injection of Adp53 and/or intraperitoneal injection of rh-endostatin resulted in tumor growth arrest of RM-1 cells in vivo (P = 0.000). Radiation combined with both rAdp53 and rh-endostatin was the most effective treatment (P < 0.05). (2) All the four treatment groups had a decreased expression of mutant type P53 (P = 0.000). The expression of Ki67 in groups B and C were equal (P 0.05) and increasing (P = 0.000), respectively. Group D had a up-down-up curve (P < 0.05), but group E had a up-down one. On day 5 the expresion of VEGF in group E was the lowest (P < 0.05). An increased expression of MVD compared with the control was shown, and MVD in groups C, D and E were always higher than that in the control (P < 0.05). Conclusions The limitation of radiotherapy could be overcome by combination with beth p53 gene therapy and endostatin on the growth of mouse prostate cancer cell. Radiation, rAdp53 and endostatin have their own role but they can be interacted with each other.

Objective:To explore the characteristics of gene mutations in patients with myelodysplastic syndromes (MDS) and the values of these mutations in prognosis assessment and curative effect prediction.Methods:The clinical data of 110 patients with newly diagnosed MDS who were admitted to Shanxi Bethune Hospital from January 2017 to December 2019 were retrospectively analyzed. The next-generation sequencing technology was used to detect mutations of 45 MDS-related genes. The patients' clinical features, results of laboratory tests, revised International Prognostic Points System (IPSS-R) scores and therapeutic responses to decitabine were analyzed and compared between the gene mutation and non-mutation groups.Results:Among 110 patients with MDS, 83.6% (92/110) of patients harbored at least one mutation. Thirty-eight gene mutations were detected, and the mutation rates of the most common mutations of ASXL1, TET2, TP53, and SF3B1 were 19.1% (21/110), 17.3% (19/110), 15.5% (17/110), and 12.7% (14/110). The IPSS-R scores of MDS patients with more mutations were higher ( F = 44.493, P < 0.01). The IPSS-R score of the SF3B1 mutation group was lower than that of the SF3B1 non-mutation group [(3.50±1.52) points vs. (4.76±1.58) points, t = -2.802, P = 0.006], and the IPSS-R score of the U2AF1 mutation group was higher than that of the U2AF1 non-mutation group [(5.78±1.39) points vs. (4.50±1.60) points, t = 2.320, P = 0.022], and the IPSS-R score of the TP53 mutation group was higher than that of the TP53 non-mutation group [(5.71± 2.24) points vs. (4.40±1.41) points, t = 2.329, P = 0.031]. There was no significant difference in IPSS-R scores between patients with and without other mutations (all P > 0.05). The overall response rate to decitabine in the TP53 mutation group was higher than that in the TP53 non-mutation group [83.3% (10/12) vs. 43.1% (22/51), χ2 = 6.280, P = 0.012], and the TP53 mutation group had a higher complete remission rate [50.0% (6/12) vs. 19.6% (10/51), χ2 = 4.736, P = 0.030]. Conclusions:Genetic mutations are common in MDS patients. Patients with SF3B1 mutation have a good prognosis, while those with U2AF1 and TP53 mutations have a poor prognosis, and patients with TP53 mutation have a high response rate to decitabine.

Objective To observe the clinical effects and safety of sodium valproate combined with decitabine for treatment of myelodysplastic syndrome (MDS). Methods Forty-two patients with MDS were enrolled in department of hematology in Shanxi Dayi Hospital from February 2012 to February 2017. According to random number table, the patients were divided into the control group (21 cases) and the experimental group (21 cases). The patients in the control group received decitabine at the dose of 20 mg·m-2·d-1, and intravenous infusion was completed in 2 hours, continuous therapy up to 5 days, 4 weeks as a course; the patients in the experimental group received combined medication, orally given sodium valproate 0.2 g once, 3 times per day. One week later, the dosage was added to 0.4 g once, 3 times per day. Both groups received at least 4 courses of treatment. The treatment was stopped when serious adverse reactions or obvious disease progression occurred. The bone marrow smear was rechecked every 4 weeks after treatment to evaluate the efficacy. The expressions of ASXL1, DNMT3A and TET2 in bone marrow cells were detected by fluorescence quantitative PCR before and after treatment. Results The total treatment response rate of the experimental group and the control group were 76.2 % (16/21) and 57.1 % (12/21) respectively, and there was statistically significant difference (P< 0.05); the total remission rate of the two groups was 47.6 % (10/21) and 38.1 %(8/21) respectively, and there was no significant difference (P> 0.05). All patients had slight adverse reactions, and the adverse reaction rate was 42.9 % (9/21) and 38.1 % (8/21), and there was no significant difference (P>0.05). The content of TET2 mRNA and DNMT3A mRNA after treatment in both groups were decreased compared with the expressions before treatment, and there were significant differences (P<0.05). However, there was no significant difference between the two groups after treatment (P> 0.05); the content of ASXL1 mRNA had no obvious change in the control group and a dramatic decrease in the experimental group compared with that before treatment (P<0.05). Conclusion Sodium valproate combined with decitabine has favorable effects and mild adverse reactions for treatment of MDS, besides, it can influence the expressions of TET2, DNMT3A and ASXL1.

Objective: To compare the clinical efficacy and safety of bortezomib, cyclophosphamide, dexamethasone (VCD) regimen and bortezomib dexamethasone (VD) regimen in the treatment of the patients with newly diagnosed multiple myeloma (NDMM). Methods: The clinical data of 73 patients with NDMM in Shanxi Dayi Hospital from January 2013 to January 2016 were retrospectively analyzed. According to the chemotherapy regimen, the patients were divided into VCD group (41 cases) and VD group (32 cases). The efficacy and adverse reactions of the two groups were evaluated. Results: The overall response rate of VCD group and VD group was 80.5% (33/41) and 78.1% (25/32) respectively, and the difference was not statistically significant (χ ²= 0.061, P= 0.804); and complete remission (CR) rate was 36.6% (15/41) and 15.6% (5/32) respectively, and the difference was statistically significant (χ ²= 3.970, P= 0.046); the median progression-free survival (PFS) was 27 months and 24 months respectively, and the median overall survival (OS) was 35 months and 33 months respectively, and the differences were not statistically significant (all P > 0.05). Most adverse reactions occurred in grade 1-2, in which peripheral polyneuropathy and thrombocytopenia were the most common. Peripheral neuritis was the most common finding among the adverse reactions of grade 3. The incidence of adverse reactions in both groups was not statistically significant (P > 0.05). Conclusions VCD and VD regimen could be recommended as a better induction therapy for NDMM patients. Compared with VD scheme, VCD scheme has a higher CR rate.

Objective:To explore the early clinical efficacy of ultrasound visualized platelet-rich plasma (PRP) in the treatment of lower back myofascial pain syndrome (MPS) after sports injury.Methods:A prospective cohort study was conducted to analyze the clinical data of 32 patients with lower back MPS after sports injury, who were admitted to West China Hospital of Sichuan University from January 2023 to March 2023. Ultrasound-guided PRP injection into the erector spinalis or quadratus psoas muscles was used for treatment. Before treatment, at 24 hours, 2 weeks, and 4 weeks after treatment, pain and function were evaluated using visual analogue scale (VAS), McGill pain questionnaire (McGill), Roland Morris dysfunction questionnaire (RMDQ), and Oswestry dysfunction index (ODI). Before treatment and 4 weeks after treatment, the quality of life was evaluated using the short-form 36 item health survey questionnaire (SF-36). The adverse reactions were observed during treatment and follow-up.Results:A total of 32 patients with lower back MPS after sports injury were enrolled, including 10 males and 22 females; aged 12-68 years [(47.3±16.3)years]. All the patients were followed up for 4 weeks. Before and at 24 hours, 2 weeks, and 4 weeks after treatment, the VAS was 5.0(4.0, 6.0)points, 3.5(3.0, 4.8)points, 2.0(2.0, 3.0)points, and 2.0(1.3, 3.0)points, respectively; the McGill score was 9.0(7.0, 11.0)points, 7.0(5.0, 9.0)points, 4.0(3.0, 5.0)points, and 3.0(3.0, 5.0)points, respectively; the RMDQ score was 8.0(5.3, 10.8)points, 5.5(3.0, 8.0)points, 4.0(3.0, 5.8)points, and 3.0(2.0, 4.8)points, respectively; the ODI was 22.0(14.5, 30.0), 20.0(14.5, 25.5), 9.0(6.0, 16.0), and 8.0(4.5, 14.0), respectively. Compared with the values before treatment, the VAS, McGill score, and RMDQ score were significantly decreased at 24 hours, 2 weeks, and 4 weeks after treatment (all P<0.05); the ODI had no significant difference at 24 hours after treatment ( P>0.05), but it was significantly decreased at 2 and 4 weeks after treatment (all P<0.05). Compared with the values at 24 hours after treatment, the VAS, McGill score, RMDQ score and ODI further decreased at 2 weeks after treatment (all P<0.05). Compared with the values at 2 weeks after treatment, there was no significant difference in the VAS, McGill score, RMDQ score, or ODI at 4 weeks after treatment (all P>0.05). In the SF-36, the scores of physiological function [77.5(60.0, 93.8)points], physiological role [50.0(0.0, 100.0)points], body pain [64.0(44.5, 74.0)points], vitality [75.0(65.0, 78.8)points], social function [87.5(75.0, 100.0)points], emotional role [66.7(33.3, 100.0)points] and mental health [72.0(68.0, 83.0)points] before treatment were increased to 90.0(80.0, 98.8)points, 100.0(56.3, 100.0)points, 84.0(74.0, 84.0)points, 75.0(70.0, 80.0)points, 100.0(87.5, 112.5)points, 100.0(66.7, 100.0)points, and 76.0(68.0, 84.0)points after 4 weeks of treatment, respectively ( P<0.05 or 0.01). However, there was no significant difference in the general health status or health changes before and after treatment (all P>0.05). During treatment and follow-up, no adverse reactions such as redness, swelling, pain, or subcutaneous bleeding were observed. Conclusion:Ultrasound-guided PRP treatment can improve the early pain, lumbar mobility and quality of life of patients with lower back MPS after sports injury, with no presence of adverse reactions.

Objective To explore esomeprazole(EMZ)on acetaminophen(APAP)pharmacokinetics and intestinal microbial balance.Methods A total of 14 rats were randomly allocated into two groups,with 7 rats in each group:acetaminophen group(APAP group),and acetaminophen+esomeprazole combination group(APAP+EMZ group),respectively.Rats in the combination group were fed in the metabolic cage.Equivalent 3.6 mg·kg-1·d-1 esomeprazole was administered intragastrically to the combination group for 14 days;Similarly,an equal volume of 0.9％sodium chloride soution(NaCl)was fed to the APAP group for 14 days.During this period,fecal samples were collected from the rats before and after 14 days of EMZ administration for microbial 16S rRNA sequencing.On the 15th day,both the APAP group and APAP+EMZ groups were administratered an equivalent of 44.82 mg·kg-1 APAP by the same method after the regular EMZ administration.The concentrations of APAP in rat plasma were determined by the UPLC-MS/MS method.Main pharmacokinetic parameters were processed and compared using the software DAS 3.0.1 and SPSS 24.0.Results The pharmacokinetic parameter Cmax of APAP was significantly different between APAP group and APAP+EMZ group(P＜0.05).Compared with APAP group,Cmax increased by 120.38％in the APAP+EMZ group.The pharmacokinetic parameters(AUC(0-∞)、CL、t 1/2、tmax)of APAP showed no statistical differences between APAP group and APAP+EMZ group(P＞0.05).The results of 16SrRNA of intestinal flora showed that the abundance of Lactobacillus,Bacteroides,Clostridium,and Escherichia decreased compared with that before drug administration,while the abundance of Bifidobacterium increased.However,the relative abundance of the above flora showed no prominent differences before and after the EMZ intervention(P＞0.05).Conclusions This study showed that when combining EMZ with APAP,the relative abundance of those related flora,which may influence the β-Glucuronidase,all changed to some extent,but made no difference in statistics.The effect of EMZ on the Cmax of APAP was statistically significant.However,the use of EMZ for two weeks did not alter the other pharmacokinetics of APAP by affecting the gut microbiota.

Mandibular defects caused by injuries, tumors, and infections are common and can severely affect mandibular function and the patient's appearance. However, mandible reconstruction with a mandibular bionic structure remains challenging. Inspired by the process of intramembranous ossification in mandibular development, a hierarchical vascularized engineered bone consisting of angiogenesis and osteogenesis modules has been produced. Moreover, the hierarchical vascular network and bone structure generated by these hierarchical vascularized engineered bone modules match the particular anatomical structure of the mandible. The ultra-tough polyion complex has been used as the basic scaffold for hierarchical vascularized engineered bone for ensuring better reconstruction of mandible function. According to the results of in vivo experiments, the bone regenerated using hierarchical vascularized engineered bone is similar to the natural mandibular bone in terms of morphology and genomics. The sonic hedgehog signaling pathway is specifically activated in hierarchical vascularized engineered bone, indicating that the new bone in hierarchical vascularized engineered bone underwent a process of intramembranous ossification identical to that of mandible development. Thus, hierarchical vascularized engineered bone has a high potential for clinical application in mandibular defect reconstruction. Moreover, the concept based on developmental processes and bionic structures provides an effective strategy for tissue regeneration.
Bone Regeneration ; Bone Transplantation/methods* ; Hedgehog Proteins ; Humans ; Mandible/surgery* ; Osteogenesis