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.

Immunosuppressants （including cyclosporine， tacrolimus， mycophenolate esters， glucocorticoids， etc.） are the first choice of drugs to prevent organ rejection after liver transplantation， which can effectively reduce the host immune response to the graft， improve the success rate of transplantation， and prolong the survival of patients. Liver transplantation is associated with intestinal flora， while immunosuppressive agents interact with intestinal flora. Immunosuppressive agents change the abundance， composition and metabolites of intestinal flora， while a series of enzymes and metabolites produced by intestinal flora may chemically alter the absorption and metabolism of immunosuppressants. In addition， the incidence of postoperative infection in liver transplantion patients is relatively high， while gut flora affects inflammatory factors， and immunosuppressants interact with inflammatory factors. To some extent， immunosuppressants can be thought of as acting through intestinal flora in patients after liver 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 compare the efficacy and safety of Cefazolin sodium for injection， Cefuroxime sodium for injection， and Ceftazidime for injection from nationally organized centralized drug procurement （hereinafter referred to as “centralized procurement”） and non-centralized procurement in patients with bacterial infection. METHODS The case data of hospitalized patients who had used 3 kinds of Cephalosporins for injection from centralized procurement or non-centralized procurement in the treatment of bacterial infections were retrospectively collected from 19 medical institutions in Kunming from January 2020 to September 2022. After balancing the baseline differences between the groups with the propensity score matching method， the effectiveness and safety differences of 3 kinds of Cephalosporins for injection from centralized procurement or non- centralized procurement were compared respectively. RESULTS After balancing the baseline differences among the groups， 394 cases in each group of Cefazolin sodium for injection from centralized procurement or non-centralized procurement， 472 cases in each group of Cefuroxime sodium for injection from centralized procurement or non-centralized procurement， 504 cases in group of Ceftazidime for injection from centralized procurement and 590 cases in group of non-centralized procurement were included in the analysis. In terms of effectiveness， there were no significant differences in clinical response rate， 72 h response rate， bacterial clearance rate， and the recovery rate of body temperature， white blood cell count， neutrophil count， neutrophil percentage， C-reactive protein， procalcitonin recovery between the centralized procurement group and non-centralized procurement group of Cefazolin sodium for injection and Cefuroxime sodium for injection （P＞0.05）. The proportion of patients in centralized procurement group of Ceftazidime for injection with C-reactive protein restored to normal reference range was significantly higher than that in non-centralized procurement group （46.9% vs. 27.9%， P＜0.05）， but there were no statistically significant differences in other effectiveness indicators among groups （P＞0.05）. In terms of safety， there was no statistical difference in the incidence of adverse drug reactions between centralized procurement group and non-centralized procurement group of 3 kinds of Cephalosporins for injection （P＞0.05）； the incidence of platelet count reduction in centralized procurement group of Cefazolin sodium for injection was significantly higher than non-centralized procurement group （20.7% vs. 7.1%， P＜0.05）， the incidence of eosinophilia elevation in centralized procurement group of Ceftazidime for injection was significantly higher than non-centralized procurement group （5.3% vs. 1.9%， P＜0.05）. In addition， there was no statistically significant difference in the abnormal rates of other laboratory indicators among the three types of injection Cephalosporins （P＞ 0.05）. CONCLUSIONS The efficacy of 3 kinds of Cephalosporin for injection from centralized procurement is not inferior to non- centralized procurement varieties， and the safety is equivalent to that of non-centralized procurement varieties.

Objective To prepare a nano drug(PFOB@Lip-MMC)with liposome as the carrier,liquid perfluorooc-tyl bromide(PFOB)as core and mitomycin C(MMC)loading on the liposome shell and study its inhibitory effect on the proliferation of human pterygium fibroblasts(HPFs).Methods The thin film dispersion-hydration ultrasonic method was used to prepare PFOB@Lip-MMC and detect its physical and chemical properties.Cell Counting Kit-8,Cam-PI cell viability staining and flow cytometry were employed to detect the impact of different concentrations of PFOB@Lip-MMC on the via-bility of HPFs.DiI fluorescence labeled PFOB@Lip-MMC was used to observe the permeability of the nano drug to HPFs under a laser confocal microscope.After establishing HPF inflammatory cell models,they were divided into the control group(with sterile phosphate-buffered saline solution added),PFOB@Lip group(with PFOB@Lip added),MMC group(with MMC added),PFOB@Lip-MMC group(with PFOB@Lip-MMC added)and normal group(with fresh culture medi-um added)according to the experimental requirements.After co-incubation for 24 h,flow cytometer was used to detect the apoptosis rate of inflammatory cells,and the gene expression levels of interleukin(IL)-1β,prostaglandin E2(PGE2),tumor necrosis factor(TNF)-α and vascular endothelial growth factor(VEGF)in cells were analyzed by PCR.Results The average particle size and Zeta potential of PFOB@Lip-MMC were(103.45±2.17)nm and(27.34±1.03)mV,respec-tively,and its entrapped efficiency and drug loading rate were(72.85±3.28)％and(34.27±2.04)％,respectively.The sustained-release MMC of drug-loaded nanospheres reached(78.34±2.92)％in vitro in a 24-hour ocular surface environ-ment.The biological safety of PFOB@Lip-MMC significantly improved compared to MMC.In terms of the DiI fluorescence labeled PFOB@Lip-MMC,after co-incubation with inflammatory HPFs for 2 h,DiI fluorescence labeling was diffusely dis-tributed in the cytoplasm of inflammatory HPFs.The apoptosis rate of inflammatory HPFs in the PFOB@Lip-MMC group[(77.23±4.93)％]was significantly higher than that in the MMC group[(51.62±3.28)％].The PCR examination results showed that the gene transcription levels of IL-1 β,PGE2,TNF-α and VEGF in other groups were significantly reduced com-pared to the control group and PFOB@Lip group,with the most significant decrease in the PFOB@Lip-MMC group(all P＜0.05).Conclusion In this study,a novel nano drug(PFOB@LIP-MMC)that inhibited the proliferation of HPFs was successfully synthesized,and its cytotoxicity was significantly reduced compared to the original drugs.It has good bio-compatibility and anti-inflammatory effects,providing a new treatment approach for reducing the recurrence rate after pte-rygium surgery.

Objective To evaluate the relationship between diabetic nephropathy(DN)and diabetic retinopathy(DR)in patients with type 2 diabetes mellitus(T2DM)based on imaging and clinical testing data.Methods Totally 600 T2DM patients who visited the First People's Hospital of Ziyang from March 2021 to December 2022 were included.The fundus photography and fundus fluorescein angiography were performed on all these patients and their age,gender,T2DM duration,cardiovascular diseases,cerebrovascular disease,hypertension,smoking history,drinking history,body mass in-dex,systolic blood pressure,diastolic blood pressure and other clinical data were collected.The levels of fasting blood glu-cose(FPG),triglyceride(TG),total cholesterol(TC),high-density lipoprotein cholesterol(HDL-C),low-density lipo-protein cholesterol(LDL-C),glycosylated hemoglobin(HbA1c),24 h urinary albumin(UAlb),urinary albumin to creati-nine ratio(ACR),serum creatinine(Scr)and blood urea nitrogen(BUN)were measured.Logistic regression was used to analyze the risk factors associated with DR.DR staging was performed according to fundus images,and the convolutional neural network(CNN)algorithm was used as an image analysis method to explore the correlation between DR and DN based on emission computed tomography(ECT)and clinical testing data.Results The average lesion area rates of DR and DN detected by the CNN in the non-DR,mild-non-proliferative DR(NPDR),moderate-NPDR,severe-NPDR and pro-liferative DR(PDR)groups were higher than those obtained by the traditional algorithm(TCM).As DR worsened,the Scr,BUN,24 h UAlb and ACR gradually increased.Besides,the incidence of DN in the non-DR,mild-NPDR,moderate-NPDR,severe-NPDR and PDR groups was 1.67％,8.83％,16.16％,22.16％and 30.83％,respectively.Logistic regression analysis showed that the duration of T2DM,smoking history,HbA1c,TC,TG,HDL-C,LDL-C,24 h UAlb,Scr,BUN,ACR and glomerular filtration rate(GFR)were independent risk factors for DR.Renal dynamic ECT analysis demonstrated that with the aggravation of DR,renal blood flow perfusion gradually decreased,resulting in diminished renal filtration.Conclusion The application of CCN in the early stage DR and DN image analysis of T2DM patients will improve the diag-nosis accuracy of DR and DN lesion area.The DN is worsening as the aggravation of DR.

OBJECTIVE To evaluate the accuracy of three individualized drug delivery tools， i.e. JPKD， SmartDose and NextDose， in predicting tacrolimus dose and blood concentration after kidney transplantation， and analyze the influential factors of prediction accuracy. METHODS The clinical data of adult hospitalized patients treated with tacrolimus after kidney transplantation from January 2021 to June 2023 were retrospectively collected. Three individualized dosing tools， i.e. JPKD， SmartDose and NextDose， were used to predict the dose and plasma concentration of tacrolimus. The absolute prediction error （APE） and prediction error （PE） between the measured value and the predicted value， and prediction success rate were calculated （APE＜30% indicating a good forecast）. Pearson assay or Spearman assay was used to analyze the correlation between the predicted dosage and actual dosage， as well as the predicted and measured blood concentration values using three software； univariate analysis was used to investigate the influential factors for prediction accuracy of JPKD， SmartDose and NextDose. RESULTS A total of 110 hospitalized patients were included in this study， and tacrolimus doses and plasma concentrations were monitored. The predicted doses of JPKD， SmartDose and NextDose were （2.0±0.7）， （2.7±1.9）， （1.8±0.8） mg， their measured value was （1.9±0.6） mg， and the correlation coefficients between the predicted values and the measured value were 0.841， 0.450， 0.247 （P＜0.001）； the median APEs were 6.00%， 52.07% and 30.40%， and the median PEs were 5.00%， 18.50% and －3.50%； the prediction success rates were 98.45%， 30.05% and 49.22%. The predicted values of tacrolimus concentrations using JPKD， SmartDose， NextDose were （6.74±3.36）， （6.93±5.02）， 9.00（5.80±12.60） ng/mL， the measured value was 8.64（7.11，9.77） ng/mL， and the correlation coefficients between the predicted values and the measured value were 0.997 （P＜0.001）， －0.066 （P＝0.360）， 0.920 （P＜0.001）. The median APEs were 5.54%， 45.91% and 35.56%， and PEs were －4.94% （median）， －17.050% （median） and 36.93% （average value）； the prediction success rates were 97.93%， 32.64% and 37.31%. Univariate analysis showed that the dosage， blood concentration， body weight， transplantation time and others were related to the prediction accuracy （P＜0.05）. CONCLUSIONS The good prediction rates of tacrolimus dose and blood concentration in kidney transplant patients using three personalized drug delivery tools， from high to low， are JPKD， NextDose， and SmartDose， suggesting that JPKD can be prioritized in clinical use.

AIM: To prepare a nanodrug MMC-ATS-@PLGA using polylactic acid hydroxyacetic acid copolymer(PLGA)as a carrier and mitomycin C(MMC)loaded on PLGA, and to analyse the biological safety and treatment effect of this nanodrug on inhibiting the proliferation of filtering bleb scarring after glaucoma surgery in vivo.METHODS: The thin-film dispersion hydration ultrasonic method was used to prepare the MMC-ATS-@PLGA, and its physical and chemical properties were detected. The effect of MMC-ATS@PLGA on rabbit corneas was analysed through corneal fluorescence staining and HE staining, and tear film rupture time(BUT), Schirmer test and intraocular pressure data were collected to analyse ocular surface biosafety. A slit lamp was used to observe and calculate the filtration bubble size, and the tissue morphological changes were analysed by conjunctival HE staining. In addition, immunohistochemistry and Elisa were used to compare the anti-inflammatory effects of Flumiolone Eye Drops(FML), MMC, and MMC-ATS-@PLGA nanoparticles on inhibiting the formation of filtering bleb scarring after glaucoma surgery from multiple perspectives via comparative proteomic analysis.RESULTS: The average particle size and zeta potential of MMC-ATS-@PLGA were 128.78±2.54 nm and 36.49±4.25 mV, respectively, with an encapsulation efficiency and a drug loading rate of(78.49±2.75)% and(30.86±1.84)%, respectively. At 33°C(the ocular surface temperature), the cumulative release rate of the MMC-ATS-@PLGA nanoparticles reached(76.58±2.68)% after 600 min. Moreover, corneal fluorescence staining, HE, BUT, Schirmer, and intraocular pressure results showed that MMC-ATS-@PLGA had good biocompatibility with the ocular surface of rabbits. At 3 wk after surgery, the area of filtering blebs in the MMC-ATS-@PLGA group was significantly larger than that in the FML group and MMC group, and the filtering blebs in the control group had basically disappeared. Pathological tissue analysis of the conjunctiva in the filtering blebs area of the eyes of the rabbits revealed that compared with that in the normal group, the morphology of the collagen fibres in the MMC-ATS-@PLGA group was relatively regular, the fibres were arranged neatly, and the tissue morphology was similar to that of the normal group. Immunohistochemistry and Elisa confirmed that compared with those in the normal group, the expression levels of α-SMA, CTGF, and type Ⅲ collagen fibre antibodies were significantly increased in the control group. After FML, MMC, or MMC-ATS-@PLGA treatment for 3 wk, the expression of inflammatory factors gradually decreased. Among the groups, the MMC-ATS-@PLGA group showed the most significant decrease(P<0.05).CONCLUSION: This study successfully synthesized a nanomedicine(MMC-ATS-@PLGA)that inhibits scar proliferation after glaucoma filtration surgery. The drug had stable physicochemical properties, good biocompatibility, and better anti-inflammatory effects by inhibiting the expression of α-SMA, CTGF, and type Ⅲ collagen fibres, which can prevent the formation of scarring in the filtering blebs area, thereby improving the success rate of glaucoma filtering surgery.

OBJECTIVE To screen the prescription and preparation method of Bupleurum nanoemulsion, and evaluate its quality, study the antipyretic effect. METHODS The emulsifier and co-emulsifier of the nanoemulsion were preliminarily screened, and then the prescription was screened by pseudo-ternary phase diagram. The quality evaluation of the appearance, particle size distribution, structure type, stability and content of the prepared Bupleurum nanoemulsion was performed. Wistar rats were further randomly divided into blank control group, model control group, positive control group(aspirin group), Bupleurum nanoemulsion high-dose, medium-dose and low-dose groups(18.00, 9.00, 3.00 g·kg−1). Except for the blank control group, the pathological model of fever rats was prepared in the other groups. According to the scheduled experimental requirements, rats in each group were given the corresponding drugs. And the temperature changes of rats in each group were recorded at 0.5, 1, 1.5, 2, 3 h to observe the antipyretic effect of Bupleurum nanoemulsion. RESULTS The best prescription of Bupleurum nanoemulsion: Tween-80 6 g and n-butanol 3 g, Bupleurum extract dissolved in pure water as water phase 20 mL, Bupleurum oil as oil phase 2 g. At room temperature, the Bupleurum nanoemulsion was a yellow-brown clear and transparent liquid, O/W nanoemulsion, with an average particle size of (77.21±3.66)nm, polydispersity index of 0.28±0.04, Zeta potential of (–18.81±1.42)mV, and saikosaponin content of 3.071 mg·mL−1, with good stability. In animal experiments, compared with the model control group, the rectal temperature of aspirin group and Bupleurum nanoemulsion high-dose group was significantly lower after the first administration(P<0.01), the rectal temperature of Bupleurum nanoemulsion middle-dose group was significantly lower after the first administration 2, 3 h(P<0.01). CONCLUSION The Bupleurum nanoemulsion is transparent and stable, and it has good antipyretic effect on fever rat model.

Percutaneous coronary intervention(PCI)is one of the most important therapeutic measures for coronary heart disease.It can quickly and effectively relieve coronary artery obstruction.Patients with coronary heart disease often suffer from the complication of emotional disorders like anxiety and depression.The incidence of anxiety and depression in patients having undergone PCI is significantly higher in those having not.But anxiety and depression can remarkably increase the major adverse cardiac events(MACE)in patients after PCI.This article reviews the associations,mechanisms and treatments of anxiety and depression after PCI.