Objective To observe the clinical efficacy and safety of Shuxuetong in treatment of paroxysmal atrial fibril-lation in patients with chronic pulmonary heart disease. Methods A randomized single-blinded study was performed. A to-tal of 91 patients with paroxysmal atrial fibrillation and chronic pulmonary heart disease were randomly divided into treat-ment group (n=45) and control group (n=46). The treatment group was received Shuxuetong and clopidogrel treatment for 14 days. The control group was given routine treatment plus clopidogrel 75 mg orally. The average time of cardioversion of parox-ysmal atrial fibrillation was detected within 48 hours. The cardioversion rate of paroxysmal atrial fibrillation and the total effi-ciency were detected after14 days. The serum D-Dimer was detected before and 14 days after treatment . Liver and kidney function and adverse drug reactions were also detected. Results There was no significant difference in average time of car-dioversion of paroxysmal atrial fibrillation in 48 h between two groups (h:12.62±2.32 vs 13.32±2.25,t=1.461). The cardiover-sion rates were 86.67%(39/45) and 82.22%(37/45) at 48 h and 14 d in treatment group, which were significantly higher than those of control group [69.56%(32/46) and 60.87(28/46)]. The D-Dimer at 14 d after treatment was significantly lower in treatment group [(2.05±0.34)mg/L] than before treatment[(2.61±0.27)mg/L], also than that of control group[(2.53±0.31)mg/L]. There were no abnormal liver and kidney function and no adverse reactions between two groups. Conclusion Shuxuetong can significantly prevent the recurrence of paroxysmal atrial fibrillation in patients with chronic pulmonary heart disease, and help to reduce the risk of thromboembolism. It is safe and effective.

OBJECTIVETo investigate the mechanism underlying the inhibitory effect of STOML-2 overexpression on apoptosis of human cervical squamous carcinoma Siha cells.

METHODSSiha cells were transfected with an adenoviral vector carrying STOML-2, and 72 h later STOML-2 expression and the proliferation of the cells were detected by Western blotting and MTT assay. The transfected cells were treated with IC50 Cisplatin for 24 h, and the morphological changes of cells were observed using fluorescence, and the cell apoptosis was analyzed using flow cytomerty; the expression levels of proteins related with mitochondrial apoptosis pathway, including caspase-3, cleaved caspase-3, Bcl-2, Bax and cytochrome C (Cyt C), were detected by Western blotting.

RESULTSWestern blotting showed a significantly increased STOML-2 expression in the transfected cells. Overexpression of STOML-2 obviously promoted the proliferation of Siha cells. The STOML-2-overexpressing cells exhibited an obvious resistance to IC50 Cisplatin-induced apoptosis as shown by both fluorescence microscopy and flow cytometry and presented with decreased expressions of cleaved caspase-3, Bax, and cytosol Cyt C and increased expressions of caspase-3, Bcl-2, and mitochondrial Cyt C.

CONCLUSIONSOverexpression of STOML-2 can enhance the proliferation of Siha cells by inhibiting cell apoptosis possibly through the mitochondrial apoptosis pathway.

Apoptosis ; Apoptosis Regulatory Proteins ; Blood Proteins ; genetics ; Carcinoma, Squamous Cell ; metabolism ; Caspase 3 ; metabolism ; Cell Line, Tumor ; Cisplatin ; pharmacology ; Cytochromes c ; metabolism ; Female ; Flow Cytometry ; Humans ; Membrane Proteins ; genetics ; Mitochondria ; metabolism ; Uterine Cervical Neoplasms ; metabolism ; bcl-2-Associated X Protein ; metabolism

Objective To investigate the mechanism underlying the inhibitory effect of STOML-2 overexpression on apoptosis of human cervical squamous carcinoma Siha cells. Methods Siha cells were transfected with an adenoviral vector carrying STOML-2, and 72 h later STOML-2 expression and the proliferation of the cells were detected by Western blotting and MTT assay. The transfected cells were treated with IC50 Cisplatin for 24 h, and the morphological changes of cells were observed using fluorescence, and the cell apoptosis was analyzed using flow cytomerty; the expression levels of proteins related with mitochondrial apoptosis pathway, including caspase-3, cleaved caspase-3, Bcl-2, Bax and cytochrome C (Cyt C), were detected by Western blotting. Results Western blotting showed a significantly increased STOML-2 expression in the transfected cells. Overexpression of STOML-2 obviously promoted the proliferation of Siha cells. The STOML-2-overexpressing cells exhibited an obvious resistance to IC50 Cisplatin-induced apoptosis as shown by both fluorescence microscopy and flow cytometry and presented with decreased expressions of cleaved caspase-3, Bax, and cytosol Cyt C and increased expressions of caspase-3, Bcl-2, and mitochondrial Cyt C. Conclusion Overexpression of STOML-2 can enhance the proliferation of Siha cells by inhibiting cell apoptosis possibly through the mitochondrial apoptosis pathway.

Objective To investigate the mechanism underlying the inhibitory effect of STOML-2 overexpression on apoptosis of human cervical squamous carcinoma Siha cells. Methods Siha cells were transfected with an adenoviral vector carrying STOML-2, and 72 h later STOML-2 expression and the proliferation of the cells were detected by Western blotting and MTT assay. The transfected cells were treated with IC50 Cisplatin for 24 h, and the morphological changes of cells were observed using fluorescence, and the cell apoptosis was analyzed using flow cytomerty; the expression levels of proteins related with mitochondrial apoptosis pathway, including caspase-3, cleaved caspase-3, Bcl-2, Bax and cytochrome C (Cyt C), were detected by Western blotting. Results Western blotting showed a significantly increased STOML-2 expression in the transfected cells. Overexpression of STOML-2 obviously promoted the proliferation of Siha cells. The STOML-2-overexpressing cells exhibited an obvious resistance to IC50 Cisplatin-induced apoptosis as shown by both fluorescence microscopy and flow cytometry and presented with decreased expressions of cleaved caspase-3, Bax, and cytosol Cyt C and increased expressions of caspase-3, Bcl-2, and mitochondrial Cyt C. Conclusion Overexpression of STOML-2 can enhance the proliferation of Siha cells by inhibiting cell apoptosis possibly through the mitochondrial apoptosis pathway.

Objective:To explore the clinical application of autologous freezing fat granule injection grafting in facial rejuvenation.Methods:A total of 64 cases of facial skin soft tissues ageing atrophy were treated by transplantation of autologous purification freezing lipochondria. Autologous fat was obtained from patient＇s abdomen or thighs, centrifugated at low velocity and low pressure to remove the oil and fluid, then stored the lipochondria in -20℃. Rewarming the fat under 37 ℃ for 1 hour, we observed the integrity of the adipocyte and detected the vitality of the fat. Then the purified autologous fat was injected into the recipient site of the face.Results:The fat cell membrane and cell nucleus were clear and integrity after stored in -20℃ for 24 weeks, and the vitality of the fat was (88.89±1.23)%. 21 cases gained satisfactory clinical results by injecting once and 35 cases with 2 times injections, 8 cases with 3 times injections, the effects were satisfactory and there was no complication by follow-up from 6 to 24 months. 82.81% patients and doctors were satisfactory with the curative effect, and 1.56% patients and doctors were unsatisfactory.Conclusions:The effects are satisfactory of autologous purified freezing microparticle fat injected transplant. It has low absorptivity, can duplicate injection, and accept easily by people. It is a good method for facial rejuvenation and worth to spread in the clinical practice.

Objective:To investigate the effects of osimertinib on proliferation, migration and invasion of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) overexpressing HCC827 cells and explore the potential mechanism of PLOD2 induced osimertinib resistance.Methods:We transfected HCC827 cells with LV-vector and LV-over/PLOD2. The expression of PLOD2 was detected by quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. The effects of osimertinib on the proliferation of HCC827-vector and HCC827-PLOD2 cells were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. The effects of osimertinib on the migration and invasion of HCC827-vector and HCC827-PLOD2 cells were determined by Transwell assays. The expressions of E-cadherin and vimentin in cells were detected by immunofluorescence (IF). The expressions of epithelial-mesenchymal transition (EMT), FAK-PI3K/AKT and MAPK signal pathway related proteins were detected by western blotting.Results:The MTT assay showed that HCC827-PLOD2 cells were hyposensitive to osimertinib. The 50% inhibitory concentration (IC 50) and resistance index of osimertinib for HCC827-PLOD2 cells was over 1 000 nmol/L and over 100, respectively. The result of wound healing assay showed that the migration distance of HCC827-PLOD2 was about (2.13±0.21) fold changes as that of HCC827-vector cells. The result of Transwell assay showed that the numbers of HCC827-PLOD2 passing through the matrix membrane were (212.78±10.43), significantly higher than (101.32±12.52) of HCC827-vector cells ( P<0.01). The result of IF showed that compared with HCC827-vector cells, the expression of E-cadherin was down-regulated while vimentin was up-regulated in HCC827-PLOD2 cells. Osimertinb downregulated E-cadherin and upregulated vimentin expression in HCC827-vector cells but had limited effect in HCC827-PLOD2 cells. The result of western blotting showed that PLOD2 significantly increased vimentin expression level while decreased E-cadherin expression level. Osimertinib inhibited the expression of p-EGFR, but did not affect the expressions of PLOD2, p-FAK, p-AKT, p-ERK, vimentin and E-cadherin in HCC827-PLOD2 cells. Conclusion:PLOD2 confers resistance to osimertinib in HCC827 cells by regulating EMT, FAK-PI3K/AKT and MAPK signal pathways.

Objective:To investigate the effects of osimertinib on proliferation, migration and invasion of procollagen-lysine 2-oxoglutarate 5-dioxygenase 2 (PLOD2) overexpressing HCC827 cells and explore the potential mechanism of PLOD2 induced osimertinib resistance.Methods:We transfected HCC827 cells with LV-vector and LV-over/PLOD2. The expression of PLOD2 was detected by quantitative real time polymerase chain reaction (qRT-PCR) and western blotting. The effects of osimertinib on the proliferation of HCC827-vector and HCC827-PLOD2 cells were evaluated by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay. The effects of osimertinib on the migration and invasion of HCC827-vector and HCC827-PLOD2 cells were determined by Transwell assays. The expressions of E-cadherin and vimentin in cells were detected by immunofluorescence (IF). The expressions of epithelial-mesenchymal transition (EMT), FAK-PI3K/AKT and MAPK signal pathway related proteins were detected by western blotting.Results:The MTT assay showed that HCC827-PLOD2 cells were hyposensitive to osimertinib. The 50% inhibitory concentration (IC 50) and resistance index of osimertinib for HCC827-PLOD2 cells was over 1 000 nmol/L and over 100, respectively. The result of wound healing assay showed that the migration distance of HCC827-PLOD2 was about (2.13±0.21) fold changes as that of HCC827-vector cells. The result of Transwell assay showed that the numbers of HCC827-PLOD2 passing through the matrix membrane were (212.78±10.43), significantly higher than (101.32±12.52) of HCC827-vector cells ( P<0.01). The result of IF showed that compared with HCC827-vector cells, the expression of E-cadherin was down-regulated while vimentin was up-regulated in HCC827-PLOD2 cells. Osimertinb downregulated E-cadherin and upregulated vimentin expression in HCC827-vector cells but had limited effect in HCC827-PLOD2 cells. The result of western blotting showed that PLOD2 significantly increased vimentin expression level while decreased E-cadherin expression level. Osimertinib inhibited the expression of p-EGFR, but did not affect the expressions of PLOD2, p-FAK, p-AKT, p-ERK, vimentin and E-cadherin in HCC827-PLOD2 cells. Conclusion:PLOD2 confers resistance to osimertinib in HCC827 cells by regulating EMT, FAK-PI3K/AKT and MAPK signal pathways.

Objective:To analyze the curative effect of sandwich cheiloplasty for the treatment of macrocheilia secondary to port-wine stain (PWS).Methods:A total of 43 patients, including 20 males and 23 females, aged 37.0 years (ranged from 4 to 69 years), who underwent sandwich cheiloplasty for the treatment of macrocheilia secondary to PWS from March 2008 to March 2022 were retrospectively enrolled. According to the location of the lesions, they were divided into two groups: upper lip group (21 cases) and lower lip group (22 cases). Pathological examinations were performed in all excised specimens. Postoperative attentions should be paid to keeping incisions locally clean, observing the blood supplying, and taking care of fluid accumulation or incision split. After discharge, the lip appearance and function were evaluated every six months in the outpatient department, and the long-term efficacy was further divided into three levels: grade Ⅰ (poor), grade Ⅱ (moderate), and grade Ⅲ (good). The comparison of grade data named long-term efficacy between the two groups was conducted by Mann-Whitney U test.Results:All 43 patients underwent sandwich cheiloplasty, of which 40 patients received one operation, whereas the other 3 received two due to recurrences. One-stage incision healing was achieved in 43 cases, whereas partial mucosal necrosis appeared in 2 cases, and slight incision dehiscence occurred in 1 case, which healed well after local dressing change. The pathological examination results of 43 excised tissue specimens all showed capillary malformations. After follow-up for 1 to 10 years, long-term efficacy evaluation was made up as follows: 36 cases were evaluated as grade Ⅲ, 7 cases as grade Ⅱ, and 0 case as grade Ⅰ. There were 18 cases of grade Ⅲ, and 3 cases of grade Ⅱ in group A, compared to 18 cases of grade Ⅲ, and 4 cases of grade Ⅱ in group B. By rank sum test, there was no significant difference in overal efficacy between the two groups ( Z=0.342, P>0.05). Conclusions:Sandwich cheiloplasty for the treatment of macrocheilia secondary to PWS effectively removes malformed vascular lesions, and consequently, it can achieve a good long-term therapeutic effect.

The stability of vaccines has a major impact on the success of immunization programmes worldwide. Stability evaluation is a vital part of the assessment of the vaccine quality and safety. It should be regarded as a continuous process from the development of the vaccine through licensing to post-licensure monitoring. To ensure the quality of the vaccine, related guidelines were issued by both World Health Organization and Chinese regulatory authority. This paper reviews the progress of relevant guidelines and studies for providing the stability considerations of vaccine.

Background The benchmark dose (BMD) method calculates the dose associated with a specific change in response based on a specific dose-response relationship. Compared with the traditional no observed adverse effect level (NOAEL) method, the BMD method has many advantages, and the 95% lower confidence limit of benchmark dose lower limit (BMDL) is recommended to replace NOAEL in deriving biological exposure limits. No authority has yet published any health-based guideline for rare earth elements. Objective To evaluate genotoxicity threshold induced by acute exposure to neodymium nitrate in mice using BMD modeling through micronucleus test and comet assay. Methods SPF grade mice (n=90) were randomly divided into nine groups, including seven neodymium nitrate exposure groups, one control group (distilled water), and one positive control group (200 mg·kg⁻¹ ethyl methanesulfonate), 10 mice in each group, half male and half female. The seven dose groups were fed by gavage with different concentrations of neodymium nitrate solution (male: 14, 27, 39, 55, 77, 109, and 219 mg·kg⁻¹; female: 24, 49, 69, 97, 138, 195, and 389 mg·kg⁻¹) twice at an interval of 21 h. Three hours after the last exposure, the animals were neutralized by cervical dislocation. The bone marrow of mice femur was taken to calculate the micronucleus rate of bone marrow cells, and the liver and stomach were taken for comet test. Results The best fitting models for the increase of polychromatophil micronucleus rate in bone marrow of female and male mice induced by neodymium nitrate were the exponential 4 model and the hill model, respectively. The BMD and the BMDL of female mice were calculated to be 31.37 mg·kg⁻¹ and 21.90 mg·kg⁻¹, and those of male mice were calculated to be 58.62 mg·kg⁻¹ and 54.31 mg·kg⁻¹, respectively. The best fitting models for DNA damage induced by neodymium nitrate in female and male mouse hepatocytes were the exponential 5 model and the exponential 4 model, respectively, and the calculated BMD and BMDL were 27.15 mg·kg⁻¹ and 11.99 mg·kg⁻¹ for female mice, and 16.28 mg·kg⁻¹ and 10.47 mg·kg⁻¹ for male mice, respectively. The hill model was the best fitting model for DNA damage of gastric adenocytes in both female and male mice, and the calculated BMD and BMDL were 36.73 mg·kg⁻¹ and 19.92 mg·kg⁻¹ for female mice, and 24.74 mg·kg⁻¹ and 14.08 mg·kg⁻¹ for male mice, respectively. Conclusion Taken the micronucleus rate of bone marrow cells, DNA damage of liver cells and gastric gland cells as the end points of genotoxicity, the BMDL of neodymium nitrate is 10.47 mg·kg⁻¹, which can be used as the threshold of genotoxic effects induced by acute exposure to neodymium nitrate in mice.