Objective To examine the occupational stability,training needs and capacity building requirements of the general practitioners purposely trained to work in rural communities,for improvement of policies regarding their training and issues related. Methods There counties were selected by stratified random sampling, where general practitioners graduated from such training completed an anonymous questionnaire. Focus group interviews were made to officials of the local Health and Family Planning Commission,those of primary healthcare institutions,and general practitioners themselves. Results The of the 190 valid questionnaires recovered, male accounted for 34. 2% and female 65. 8%. These general practitioners were mostly satisfied with their working environment, social status, work stress and job achievement,yet with lower satisfaction with their salary and availability of medical devices. Consideration of resignation was reported by only 5. 3% of them,with more males than females. As high as 63. 2% of them prefer to work in hospitals of county level. 91. 1% of them held it as necessary to participate in standard resident training,and 98. 4% held it as necessary to have on-job training. 94. 7% of them have participated in further education to gain a bachelor degree in medicine. Conclusions These doctors were found with high stability to work in rural communities and low turnover intention. Further studies are required to encourage these general practitioners to serve rural communities in a long term, and to improve the standard resident training mechanism,and their career development.

Objective To construct erythromycin-overproducing mutants by tandemly expressing S-adenosylmethionine synthetase gene metK, Vitreoscilla hemoglobin gene vhbS and pleiotropic regulatory gene adpA in Saccharopolyspora eryth-raea.Methods Through PEG-mediated protoplast transformation , the integrative plasmid carrying metK, vhbS and adpA was respectively introduced into erythromycin-producing wild-type strain S.erythraea A226 and industrial strain WB .The engineered strains were generated by apramycin resistance screening and PCR identification .The erythromycin production was compared in original strains and their mutants by the inhibition test of Bacillus subtilis and HPLC analysis .Results and Conclusion Four A226-derived mutants A226-P1-P4 and three WB-derived mutants WB-P1-P3 were independently obtained.Compared with wild-type strain A226, the relative erythromycin titer of the four engineered strains A 226-P1-P4 was increased from 8%to 25%by scoring the growth-inhibition zones .Further HPLC analysis showed that the four mutants had increased erythromycin A yield by 64%-94%.Likewise, the relative erythromycin titer and erythromycin A yield of the three engineered strains WB-P1-P3 were enhanced by 6%-10%and 31%-62%, respectively, in comparison with the original strain WB.The results show the universality of enhancing erythromycin productionvia tandem expression of metK, vhbS and adpA in S.erythraea.

Objective To investigate the expression of miR-6768-5p in lung cancer tissue and its effect on the proliferation and invasion of lung cancer cells through targeted regulation of carboxypeptidase A4(CPA4).Methods The expression of miR-6768-5p in lung cancer tissues and adjacent tissues was analyzed u-sing the TCGA database.Quantitative real-time PCR(qPCR)was used to detect the expression of miR-6768-5p in human lung cancer cell lines(HCC1588,H1650,H1299,A549,HCC827)and normal alveolar epithelial cells(HPAEpiC cells).Lung cancer cells were transfected with NC mimics and miR-6768-5p mimics,respec-tively,and divided into NC group and miR-6768-5p group.The MTS assay and Matrigel invasion assay were used to detect the cell proliferation and invasion ability of each group,respectively.The putative binding sites of miR-6768-5p and CPA4 were verified using RNAhybrid software and dual-luciferase reporter gene experi-ment.The expression of CPA4 mRNA in each group of cells was detected by qPCR.The expression of AKT/c-MYC signaling pathway proteins in the cells of each group was analyzed by Western blot.Results Com-pared with the adjacent tissues,the relative expression level of miR-6768-5p in lung cancer tissues was signifi-cantly decreased,and the difference was statistically significant(P＜0.05).Compared with HPAEpiC cells,the relative expression level of miR-6768-5p was significantly decreased in lung cancer cell lines,and the differ-ence was statistically significant(P＜0.05).Compared with the NC group,the cell proliferation rate of miR-6768-5p group was significantly decreased(P＜0.05).The number of invasive cells in NC group and miR-6768-5p group was(131.30±12.55)and(37.45±7.77),respectively,and the number of invasive cells in miR-6768-5p group was significantly lower than that in NC group(P＜0.05).The relative expression level of CPA4 mRNA in H1299 cells of miR-6768-5p group was significantly lower than that in NC group(t=4.93,P＜0.05).Compared with the NC group,the expressions of AKT/c-myC signaling pathway proteins p-AKT,p-mTORC1,XIAP,MDM2 and C-myC proteins in miR-6768-5p group were significantly decreased.Conclusion The expression of miR-6768-5p is decreased in lung cancer tissues,and miR-6768-5p may inhibit the activation of AKT/c-MYC signaling pathway by targeting CPA4,and reduce the proliferation and invasion ability of lung cancer H1299 cells.

Objective:To investigate the effect of lncRNA AC132217.4 on the proliferation and invasion of liver cancer MHCC97-H cells and its molecular mechanism.Methods:The TCGA database was used to analyze the differential expression of AC132217.4 in liver cancer tissue and adjacent tissue, and to analyze the relationship between the expression level of AC132217.4 and the overall survival of liver cancer patients. Transfection of pcDNA-AC132217.4 plasmid into MHCC97-H cells was defined as AC132217.4 group, transfection of pcDNA plasmid into MHCC97-H cells was defined as negative control (NC) group, respectively. The proliferation and invasion ability of MHCC97-H cells were detected by MTT method and Matrigel invasion assay. The binding site between AC132217.4 and miR-18a-5p was analyzed by starBase v2.0 software and dual luciferase reporter gene assay. Real-time quantitative PCR (RT-qPCR) detected the differential expression of miR-18a-5p in the two groups of MHCC97-H cells. The expression of epithelial-mesenchymal transition protein was detected by Western-blotting. Measurement data with normal distribution were expressed as mean±standard deviation ( ± s), and t-test was used for comparison between the two groups. Results:Compared with adjacent tissues, the expression of AC132217.4 was down-regulated in liver cancer tissues ( P<0.01). Compared with liver cancer patients with low expression of AC132217.4, the overall survival of liver cancer patients with high AC132217.4 expression was longer ( P<0.05). The pcDNA-AC132217.4 plasmid significantly inhibited the proliferation of MHCC97-H cells ( P<0.05). The number of invasive cells in the NC group and AC132217.4 group were (131.30±12.55) and (37.45±7.77), respectively. The pcDNA-AC132217.4 plasmid significantly inhibited the invasive ability of MHCC97-H cells ( t=6.36, P<0.01). AC132217.4 directly complemented miR-18a-5p ( P<0.01). The expression of miR-18a-5p in MHCC97-H cells in AC132217.4 group (1.04±0.30) was significantly lower than that in NC group (6.13±0.75) ( t=6.27, P<0.01). Compared with the NC group, the expressions of epithelial phenotype proteins Cytokeratin and Claudin-1 in MHCC97-H cells in AC132217.4 group were up-regulated, while the expressions of mesenchymal phenotype proteins Vimentin, Slug and Snail were down-regulated. Conclusions:The expression of AC132217.4 is low in liver cancer tissue, and it is related to the overall survival of liver cancer patients. AC132217.4 might inhibit the proliferation and invasion of liver cancer MHCC97-H cells by sponge miR-18a-5p.

Objective:To investigate the application of three-dimensional digital technique in customized ear framework fabrication for auricular reconstruction.Methods:From July 2018 to October 2019, the patients with microtia who underwent ear reconstruction in the Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University were enrolled. Each patient with unilateral microtia underwent auricular CT scan and preoperative analysis and ear framework design were carried out with Mimics software 18.0. The two-dimension(2D) ear films and three-dimension(3D) silicon models were produced by 1∶1 2D printing and 3D printing, respectively. Microtia reconstruction was performed according to the guide of the models, patients were followed up over a six-month period to evaluate the size, outline, height and auriculocephalic angle of the reconstructed ear. The satisfactory outcomes of the patients were scored according to a 5-point Likert scale.Results:A total of 15 patients were included in this study, including 11 males and 4 females, aged 8-27 years, with an average of 15.5 years old. All the 15 patients completed the surgical planning and ear reconstruction successfully, without major complications, such as hematomas, inflammation, skin necrosis and framework exposure. The costal cartilage frameworks were very similar to the printed 3D models in size and contour. Comparison between the two sides was made at six months postoperatively. The reconstructed ear was much the same as that of contralateral side, and all patients were satisfied with their reconstructed ear outcomes with average score of 4.4.Conclusions:With the application of digital technique for pre-surgical planning in microtia reconstruction patients, ear templates were produced from 2D to 3D, and the correction of microtia was changed from standard auricular reconstruction to personalized auricular reconstruction, with a great improvement of the precision in ear framework fabrication.

Objective:To investigate the application of three-dimensional digital technique in customized ear framework fabrication for auricular reconstruction.Methods:From July 2018 to October 2019, the patients with microtia who underwent ear reconstruction in the Department of Plastic and Aesthetic Surgery, Nanfang Hospital, Southern Medical University were enrolled. Each patient with unilateral microtia underwent auricular CT scan and preoperative analysis and ear framework design were carried out with Mimics software 18.0. The two-dimension(2D) ear films and three-dimension(3D) silicon models were produced by 1∶1 2D printing and 3D printing, respectively. Microtia reconstruction was performed according to the guide of the models, patients were followed up over a six-month period to evaluate the size, outline, height and auriculocephalic angle of the reconstructed ear. The satisfactory outcomes of the patients were scored according to a 5-point Likert scale.Results:A total of 15 patients were included in this study, including 11 males and 4 females, aged 8-27 years, with an average of 15.5 years old. All the 15 patients completed the surgical planning and ear reconstruction successfully, without major complications, such as hematomas, inflammation, skin necrosis and framework exposure. The costal cartilage frameworks were very similar to the printed 3D models in size and contour. Comparison between the two sides was made at six months postoperatively. The reconstructed ear was much the same as that of contralateral side, and all patients were satisfied with their reconstructed ear outcomes with average score of 4.4.Conclusions:With the application of digital technique for pre-surgical planning in microtia reconstruction patients, ear templates were produced from 2D to 3D, and the correction of microtia was changed from standard auricular reconstruction to personalized auricular reconstruction, with a great improvement of the precision in ear framework fabrication.

Objective:To explore the differences of immune reconstitution between peripheral blood stem cell transplantation and umbilical cord blood transplantation.Methods:A total of 300 patients (aged 18 (8, 33), 163 males and 137 females) with malignant hematological diseases who received allogeneic hematopoietic stem cell transplantation in the First Affiliated Hospital of University of Science and Technology of China from January 2018 to March 2020 were enrolled in this study, including 255 cases of umbilical cord blood transplantation and 45 cases of peripheral blood stem cell transplantation. Multicolor flow cytometry was applied to analyze lymphocyte subsets of the percentages and absolute counts in the two donor types and peripheral blood of patients after receiving hematopoietic stem cell transplantation. The differences between the two grafts were compared, and the lymphocyte subsets results were evaluated at 1, 2, 3, 4, 6, 9, 12, and 18 months after transplantation. 18-month disease-free survival (DFS) within the 300 patients under the two transplantation types were retrospectively analyzed.Results:1. The proportion of NKT cells in peripheral blood group was significantly higher than that in cord blood group (2.79% vs 0.24%, P<0.001). 2. The proportion of helper T cells in the UCBT group was higher than that in the PBSCT group, as well as the counts 6 months after transplantation ( P<0.05). 3. The proportion of NK1 cells (3 rd to 9 th month) and count (4 th to 12 th month) in UCBT group were significantly higher than those in PBSCT group ( P<0.05). 4. NKT cells in the UCBT group were lower than those in the PBSCT group (proportion and count) throughout the monitoring process ( P≤0.001). 5. The proportion of DNT cells (within 1 year) and count (within 6 months) in the UCBT group were significantly lower than those in the PBSCT group ( P<0.05). Conclusions:Compared with the peripheral blood stem cell transplantation group, the umbilical cord blood transplantation patients had a faster rate of lymphocyte reconstitution, and patients received umbilical cord blood transplantation had a stronger ability of immune reconstitution and could achieve long-term hematopoiesis.

OBJECTIVE To explore the correlation between SLCO1B3 gene polymorphisms and early postoperative tacrolimus concentrations in renal transplant recipients. METHODS A total of 68 patients who underwent kidney transplantation in the First Hospital of Kunming were selected, tacrolimus plasma concentrations were monitored by chemoluminescence, CYP3A5*3, SLCO1B3 T334G and G699A gene polymorphisms were detected by polymerase chain reaction, and genotyping was performed to analyze the correlation between each genotype and tacrolimus plasma concentrations. RESULTS Different genotypes of CYP3A5*3 had significant effects on postoperative tacrolimus plasma concentration and standardized plasma concentration(P＜0.05), and different genotypes of SLCO1B3 T334G and G699A gene loci had no significant effect on postoperative tacrolimus plasma concentration and standardized plasma concentration. CONCLUSION Compared with CYP3A5*3/*3 genotype, CYP3A5*1 allele carriers need to reach the same tacrolimus concentration to increase tacrolimus dose. SLCO1B3 T334G and G699A gene polymorphisms has no effect on tacrolimus plasma concentration in the early stage after renal transplantation.

OBJECTIVE To evaluate the influence of gene polymorphism on plasma minimum concentration （cmin） of voriconazole （VRZ） in patients with invasive fungal infection. METHODS The Cochrane Library， Embase， PubMed， Web of Science， China Biomedical Literature Database， CNKI， VIP and Wanfang Data were searched for literature on the correlation between gene polymorphisms and cmin of VRZ from inception to April 2024. After screening the literature， extracting data， and evaluating the quality of the literature， meta-analysis was performed using R 4.3.2 software. RESULTS A total of 21 studies with 2 454 patients were included. The results of meta-analysis showed that the VRZ cmin of CYP2C19 IM and PM types was significantly higher than EM type， and the VRZ cmin of IM type was significantly lower than PM type （P＜0.01）. The VRZ cmin of CYP2C9 rs1057910 AA type was significantly higher than AC/CC type， and that of CYP3A5 rs776746 CC type was significantly higher than TT type （P＜0.01）. The VRZ cmin of POR rs10954732 GG type was significantly higher than GA and AA types， and that of POR rs1057868 CT type was significantly lower than TT type （P＜0.01）. The VRZ cmin of ABCB1 rs1045642 CC type was significantly higher than TT type （P＜0.05）. The VRZ cmin of NR1I2 rs2472677 CT type was significantly higher than TT type， and rs7643645 AA type was significantly higher than AG type （P＜0.05）. The VRZ cmin of ABCC2 rs717620 CC type was significantly lower than CT type and TT type， and the CT type was significantly lower than TT type （P＜0.01）. CONCLUSIONS Mutant alleles in CYP2C19， CYP2C9 rs1057910， CYP3A5 rs776746， POR rs10954732， ABCB1 rs1045642 and NR1I2 rs7643645 can lead to a decrease in VRZ plasma concentration， and mutant allele in ABCC2 rs717620 can lead to an increase in VRZ plasma concentration.

OBJECTIVE To evaluate the influence of gene polymorphism on plasma minimum concentration （cmin） of voriconazole （VRZ） in patients with invasive fungal infection. METHODS The Cochrane Library， Embase， PubMed， Web of Science， China Biomedical Literature Database， CNKI， VIP and Wanfang Data were searched for literature on the correlation between gene polymorphisms and cmin of VRZ from inception to April 2024. After screening the literature， extracting data， and evaluating the quality of the literature， meta-analysis was performed using R 4.3.2 software. RESULTS A total of 21 studies with 2 454 patients were included. The results of meta-analysis showed that the VRZ cmin of CYP2C19 IM and PM types was significantly higher than EM type， and the VRZ cmin of IM type was significantly lower than PM type （P＜0.01）. The VRZ cmin of CYP2C9 rs1057910 AA type was significantly higher than AC/CC type， and that of CYP3A5 rs776746 CC type was significantly higher than TT type （P＜0.01）. The VRZ cmin of POR rs10954732 GG type was significantly higher than GA and AA types， and that of POR rs1057868 CT type was significantly lower than TT type （P＜0.01）. The VRZ cmin of ABCB1 rs1045642 CC type was significantly higher than TT type （P＜0.05）. The VRZ cmin of NR1I2 rs2472677 CT type was significantly higher than TT type， and rs7643645 AA type was significantly higher than AG type （P＜0.05）. The VRZ cmin of ABCC2 rs717620 CC type was significantly lower than CT type and TT type， and the CT type was significantly lower than TT type （P＜0.01）. CONCLUSIONS Mutant alleles in CYP2C19， CYP2C9 rs1057910， CYP3A5 rs776746， POR rs10954732， ABCB1 rs1045642 and NR1I2 rs7643645 can lead to a decrease in VRZ plasma concentration， and mutant allele in ABCC2 rs717620 can lead to an increase in VRZ plasma concentration.