Prescription optimization is a crucial aspect in the study of traditional Chinese medicine （TCM） compounds. In recent years， the introduction of mathematical methods， data mining techniques， and artificial neural networks has provided new tools for elucidating the compatibility rules of TCM compounds. The study of TCM compounds involves numerous variables， including the proportions of different herbs， the specific extraction parts of each ingredient， and the interactions among multiple components. These factors together create a complex nonlinear dose-effect relationship. In this context， it is essential to identify methods that suit the characteristics of TCM compounds and can leverage their advantages for effective application in new drug development. This paper provided a comprehensive review of the cutting-edge optimization experimental design methods applied in recent studies of TCM compound compatibilities. The key technical issues， such as the optimization of source material selection， dosage optimization of compatible herbs， and multi-objective optimization indicators， were discussed. Furthermore， the evaluation methods for component effects were summarized during the optimization process， so as to provide scientific and practical foundations for innovative research in TCM and the development of new drugs based on TCM compounds.

ObjectiveTo investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and to establish a predictive model. MethodsA total of 217 patients who were diagnosed with decompensated hepatitis C cirrhosis and were admitted to The Third People’s Hospital of Kunming l from January， 2019 to December， 2022 were enrolled， among whom 63 patients who were readmitted within at least 1 year and had no portal hypertension-related complications were enrolled as recompensation group， and 154 patients without recompensation were enrolled as control group. Related clinical data were collected， and univariate and multivariate analyses were performed for the factors that may affect the occurrence of recompensation. The independent-samples t test was used for comparison of normally distributed measurement data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed measurement data between two groups； the chi-square test or the Fisher’s exact test was used for comparison of categorical data between two groups. A binary Logistic regression analysis was used to investigate the influencing factors for recompensation in patients with decompensated hepatitis C cirrhosis， and the receiver operating characteristic （ROC） curve was used to assess the predictive performance of the model. ResultsAmong the 217 patients with decompensated hepatitis C cirrhosis， 63 （29.03%） had recompensation. There were significant differences between the recompensation group and the control group in HIV history （χ²=4.566， P=0.034）， history of partial splenic embolism （χ²=6.687， P=0.014）， Child-Pugh classification （χ²=11.978， P=0.003）， grade of ascites （χ²=14.229， P<0.001）， albumin （t=4.063， P<0.001）， prealbumin （Z=-3.077， P=0.002）， high-density lipoprotein （t=2.854， P=0.011）， high-sensitivity C-reactive protein （Z=-2.447， P=0.014）， prothrombin time （Z=-2.441， P=0.015）， carcinoembryonic antigen （Z=-2.113， P=0.035）， alpha-fetoprotein （AFP） （Z=-2.063， P=0.039）， CA125 （Z=-2.270， P=0.023）， TT3 （Z=-3.304， P<0.001）， TT4 （Z=-2.221， P=0.026）， CD45⁺ （Z=-2.278， P=0.023）， interleukin-5 （Z=-2.845， P=0.004）， tumor necrosis factor-α （Z=-2.176， P=0.030）， and portal vein width （Z=-5.283， P=0.005）. The multivariate analysis showed that history of partial splenic embolism （odds ratio ［OR］=3.064， P=0.049）， HIV history （OR=0.195， P=0.027）， a small amount of ascites （OR=3.390， P=0.017）， AFP （OR=1.003， P=0.004）， and portal vein width （OR=0.600， P<0.001） were independent influencing factors for the occurrence of recompensation in patients with decompensated hepatitis C cirrhosis. The ROC curve analysis showed that HIV history， grade of ascites， history of partial splenic embolism， AFP， portal vein width， and the combined predictive model of these indices had an area under the ROC curve of 0.556， 0.641， 0.560， 0.589， 0.745， and 0.817， respectively. ConclusionFor patients with decompensated hepatitis C cirrhosis， those with a history of partial splenic embolism， a small amount of ascites， and an increase in AFP level are more likely to experience recompensation， while those with a history of HIV and an increase in portal vein width are less likely to experience recompensation.

BACKGROUND:Our previous studies have found that poly(vinylidene fluoride)bionic periosteum prepared by electrospinning has good cytocompatibility,but its biocompatibility is unknown. OBJECTIVE:To evaluate the biocompatibility of poly(vinylidene fluoride)bionic periosteum doped with Zn2+and Mg2+. METHODS:Poly(vinylidene fluoride),poly(vinylidene fluoride)bionic periosteum doped with 1％Zn2+,doped with 1％Mg2+,and doped with 1％(Zn2++Mg2+)were prepared by electrospinning to make bionic periosteum extract.SD rats were selected as the experimental subjects for hemolysis test,short-term systemic toxicity test,and heat source test.Guinea pigs were selected as the experimental subjects for skin sensitization test.The biocompatibility of bionic periosteum of four groups was tested. RESULTS AND CONCLUSION:(1)The hemolysis test results showed that the hemolysis rates of 1％Zn2+poly(vinylidene fluoride),1％Mg2+poly(vinylidene fluoride),1％Zn2++1％Mg2+poly(vinylidene fluoride)bionic periosteum and poly(vinylidene fluoride)extract were(0.130±0.013)％,(0.149±0.020)％,(0.466±0.018)％,and(0.037±0.018)％,respectively,which met the hemocompatibility standard of biomaterials.(2)The results of short-term systemic toxicity test showed that the four groups of bionic periosteal extract had no toxic signs such as body mass reduction,food intake changes,and dyspnea in SD rats,and had no toxic effects on major organs of rats.(3)Heat source test results showed that after intervention with poly(vinylidene fluoride)bionic periosteum doped with 1％Zn2+,doped with 1％Mg2+,and doped with 1％(Zn2++Mg2+),and poly(vinylidene fluoride)bionic periosteum extract,the elevated body temperature values of SD rats were(0.133±0.058),(0.100±0.010),(0.300±0.010),and(0.300±0.017)℃respectively.All were less than 0.6 ℃and the total temperature increase was less than 1.4 ℃.(4)The results of skin sensitization test showed that no erythema or edema was observed under the skin of guinea pigs after the intervention of bionic periosteum extract of four groups.(5)The results showed that poly(vinylidene fluoride)and poly(vinylidene fluoride)bionic periosteum doped with Zn2+and Mg2+had good biocompatibility.

OBJECTIVE To investigate the prognostic value of pre-treatment serum lactate dehydrogenase(LDH)levels in patients with locally recurrent nasopharyngeal carcinoma(NPC)treated with salvage intensity-modulated radiotherapy(IMRT)and to determine its association with rT staging.METHODS The records of 97 patients with locally relapsed and non-metastatic NPC who received salvage IMRT treatment in our center from January 2018 to April 2022 were collected,including 51 patients who died,18 patients with distant metastases,30 patients with local failure,and 67 patients with prognostic adverse events(death,distant tumors/local metastases).Clinical data,local failure-free survival(LFFS),distant metastasis-free survival(DMFS)and overall survival(OS)were obtained from all patients,and the relationship between LDH and the prognosis of salvage IMRT therapy in NPC patients was analyzed.RESULTS The serum LDH level before salvage IMRT was significantly higher in the death[221.25(178.24,339.13)U/L vs.124.82(79.0,159.50)U/L,Z=-5.122],local failure[230.75(170.89,394.50)U/L vs.157.85(91.78,216.95)U/L,Z=-3.442],distant metastasis[261.62(153.55,465.50)U/L vs.168.98(101.75,237.75)U/L,Z=-2.478]and poor prognosis group[220.05(167.20,506.16)U/L vs.93.45(69.95,154.35)U/L,Z=-6.018],and all P<0.05.Serum LDH levels were divided into dichotomous variables according to median values(≥177.50 U/L vs.<177.50 U/L),the Cox univariate model found that the hazard ratios of LDH affecting LFFS,DMFS,OS and toxic-related death(TRD)were 3.759(1.660-8.558),4.217(1.383-12.861),3.226(1.715-6.069),3.363(1.750-6.463),P<0.05.LDH remained an independent prognostic factor for LFFS,DMFS,OS,and TRD in multivariate regression analysis(P<0.05).Compared with patients with LDH<177.50 U/L,more patients in the LDH≥177.50 U/L group had local progression-related death,and the no LFFS stage,no DMFS stage and OS were shorter in the LDH≥177.50 U/L group(log rank=11.624,7.559,14.758),P<0.05.In predicting overall survival,adding LDH to the rT stage is preferable to the rT stage alone.CONCLUSION LDH is an important factor in predicting LFFS,DMFS,OS,and TRD after saving IMRT in patients with locally relapsed,non-metastatic NPC,and the value of LDH combined with rT staging in predicting overall survival is high.

BACKGROUND:Due to the unstable drug release rate of uniaxial bone scaffolds,multi-structure composite printing methods have been sought in and outside China in recent years.Currently,coaxial drug-loaded bone scaffolds,which combine drug-loaded sustained release system with bone transplantation and repair technology,not only replace the defective bone after implantation,but also release drugs slowly,providing a microenvironment conducive to bone formation at the implant site. OBJECTIVE:To explore and assess the in vitro antibacterial properties of uniaxial and coaxial minocycline hydrochloride bone scaffolds. METHODS:Rapid prototyping technology was used to prepare uniaxial hydroxyapatite/silk fibroin-polyvinyl alcohol scaffold,uniaxial hydroxyapatite/silk fibroin-polyvinyl alcohol scaffold,coaxial hydroxyapatite/silk fibroin-polyvinyl alcohol scaffold,and coaxial hydroxyapatite/silk fibroin-polyvinyl alcohol scaffold,respectively,which were named S1,S2,T1 and T2.The morphology,porosity,degradation performance,in vitro sustained-release performance and cytotoxicity of scaffolds were characterized.Four kinds of bone scaffolds were immersed in PBS to prepare the extracts at different time points(1,3,5,7,14,21,and 28 days).The qualitative filter paper was placed into the extract for 24 hours.The filter paper was co-cultured with Porphyromonas gingivalis and Fusobacterium nucleatum for 72 hours.The bacteriostatic effect of four groups of scaffolds was detected by the agar diffusion method. RESULTS AND CONCLUSION:(1)Scaffold characterization:Four groups of scaffolds were well formed.The surface of micro-wires in the S1 and S2 groups was dense and smooth,and the surface of micro-wires in the T1 and T2 groups was rough.Porosity was between 40%-47%and met the requirements of bone scaffolds.Compared with the S2 group,sustained release time was longer in the T2 group.The sustained release concentration of the drug was between 1-10 μg/mL for a long time,which was more conducive to bacteriostasis and osteogenesis.After 10 weeks of immersion in PBS in vitro,the degradation rate of the coaxial printed bone scaffold was faster than that of the corresponding uniaxial printed bone scaffold,and the degradation rate of the coaxial loaded bone scaffold was lower than that of the coaxial non-loaded bone scaffold.The four groups of scaffold extracts were co-cultured with osteoblasts respectively.CCK-8 assay displayed that the cell proliferation rate was greater than 75%,which met the requirements of biocompatibility.(2)In vitro antibacterial effect:S1 and T1 did not have antibacterial activity.S2 and T2 had an obvious antibacterial effect.Under the extraction solution on day 28,the diameter of Porphyromonas gingivalis and Fusobacterium nucleatum inhibition zone in the S2 group was smaller than that in the T2 group(P<0.05).(3)These findings exhibit that hydroxyapatite/silk fibroin-polyvinyl alcohol scaffolds with coaxial minocycline have good physical properties and bacteriostatic properties.

BACKGROUND:Polyvinylidene fluoride(PVDF)with piezoelectric properties,good biocompatibility and nontoxicity make it a suitable candidate for periosteal repair. OBJECTIVE:To evaluate the cytotoxicity of PVDF bionic periosteum by electrospinning with zinc and magnesium ions in vitro. METHODS:Pure PVDF,zinc-doped PVDF,magnesium-doped PVDF and Zinc-magnesium ion PVDF piezoelectric bionic periosteum were prepared by electrospinning technology,respectively.They were named PVDF,PVDF-Zn,PVDF-Mg and PVDF-Zn-Mg,in which the mass fraction of zinc and magnesium ions were all 1%.Osteoblasts and vascular endothelial cells were co-cultured with four groups of bionic periosteum.Cell compatibility of bionic periosteum was determined by alkaline phosphatase staining,CD31 immunofluorescence staining,and scanning electron microscopy. RESULTS AND CONCLUSION:(1)Osteoblasts:Alkaline phosphatase staining after 7 days of culture showed that the PVDF-Zn group secreted more alkaline phosphatase than the other three groups.Under a scanning electron microscopy,after 1 day of culture,the cells had a certain spread on the surface of PVDF-Mg and PVDF-Zn-Mg bionic periosteum,and the pseudopod extended to all sides.On day 3,the cell edge of each group extended pseudopods to the material.By days 5 and 7,the cells were fully spread,well grown and firmly covered the surface of the fibers,and the cellular pseudopods extended around and into the interstitial space of the fibers.CCK-8 assay showed that the cell proliferation on the bionic periosteum of each group showed an increasing trend over time and the relative proliferation rate of cells at 1,3,5,and 7 days was≥75%,and the cytotoxicity was≤grade 1.(2)Vascular endothelial cells:CD31 immunofluorescence staining for 3 days showed that the cells adhered and spread well on the bionic periosteum of each group and connected with each other,and the number of cells in the PVDF-Zn-Mg group was more than that in the other three groups.Under scanning electron microscope,the cells began to adhere to the surface of each group of fibers after 1 and 3 days of culture.On day 5,the cells were well spread on the surface of the fibers and extended obvious pseudopods.On day 7,the cells on the PVDF-Mg and PVDF-Zn-Mg bionic periosteum grew in multiple layers and extended the pseudopod into the fibrous void.CCK-8 assay showed that the cell proliferation on the bionic periosteum of each group showed a downward trend over time,and the relative proliferation rate of cells at 1,3,5 and 7 days was≥125%,and the cytotoxicity was grade 0.(3)The results showed that Zn-Mg electrospun PVDF piezoelectric bionic periosteum had good cytocompatibility.

Objective To analyze the current status of anti-bacterial activity of carbapenem-resistant Klebsiella pneumoniae and Escherichia coli clinically isolated from hospitalized patients,detect their related resistance genes,and provide reference for the clinical treatment of carbapenem resistant Enterobacteria(CRE)infections and the rational use of antibiotics.Methods A total of 400 non-repetitive isolates of Klebsiella pneumoniae and Escherichia coli isolated from clinical specimens of Punan Branch of Renji Hospital,Shanghai Jiao Tong University School of Medicine from January 2022 to December were collected.The minimum inhibitory concentrations of these strains against commonly used antibiotics were determined by the broth microdilution method.The carbapenemase and related resistance genes of CRE were detected by drug resistance phenotype testing and PCR.Results Among the 400 strains,51 strains were identified as CRE,accounting for 12.75%.Among these,49 strains produced carbapenemases,with 41 strains(80.39%)being CR Klebsiella pneumoniae and 10 strains(19.61%)being CR Escherichia coli.Among the CRE strains,34 strains(66.67%)carried blaKPC,13 strains(25.49%)carried blaNDM,and 2 strains(3.92%)carried blaOXA-48.Conclusion Compared with other commonly used antibiotics,colistin and tigecycline exhibited good in vitro antibacterial activity against carbapenemase-producing Klebsiella pneumoniae and Escherichia coli.In addition,there was good concordance between drug resistance phenotype testing and genotyping.Clinical microbiology laboratories could continuously monitor the drug resistance phenotype and genotype of CRE and develop appropriate treatment plans based on actual conditions.

Objective:To describe the current situation of blood glucose control in 18-64 year-old people with type 2 diabetes in the Shenzhen community and analyze the influencing factors to provide a reference for enhancing the management effect of type 2 diabetes in community health service institutions.Methods:The data were from the Shenzhen Community Health Service Information System. A cross-sectional survey design was adopted to include 18-64 year-old patients with type 2 diabetes in Shenzhen community health service institutions in 2022. The blood glucose control rate was calculated through the physical examination data recorded by the information system in 2022, and the influencing factors of blood glucose control in this group of patients were analyzed using a multivariate logistic regression model.Results:A total of 120 174 patients were included in the study. The blood glucose control rate was 53.04%. The results of multivariate logistic regression analysis showed that women ( OR=1.07, 95% CI: 1.04-1.10), ages 45-54 ( OR=1.10, 95% CI: 1.01-1.19), 55-64 ( OR=1.24, 95% CI: 1.14-1.35), middle school ( OR=1.09, 95% CI: 1.05-1.13), high school and technical secondary school ( OR=1.26, 95% CI: 1.21-1.31), junior college or above ( OR=1.75, 95% CI: 1.67-1.83), basic medical insurance for urban employees ( OR=1.05, 95% CI: 1.01-1.08), weekly exercise ( OR=1.26, 95% CI: 1.22-1.31), daily exercise ( OR=1.31, 95% CI: 1.28-1.35) and combined hypertension ( OR=1.21, 95% CI: 1.18-1.24) were more likely to reach the standard of blood glucose control; while unmarried ( OR=0.85, 95% CI: 0.77-0.95), divorced ( OR=0.84, 95% CI: 0.73-0.97), insurance status was fully self-funded ( OR=0.95, 95% CI: 0.91-0.99), disease duration was 5- years ( OR=0.65, 95% CI: 0.63-0.66), ≥10 years ( OR=0.41, 95% CI: 0.39-0.42), the treatment method was diabetes drug therapy ( OR=0.74, 95% CI: 0.71-0.76), low weight ( OR=0.89, 95% CI: 0.80-1.00), obese group ( OR=0.85, 95% CI: 0.82-0.88), combined with central obesity ( OR=0.83, 95% CI: 0.81-0.86), combined with dyslipidemia ( OR=0.69, 95% CI: 0.68-0.71), current smoking ( OR=0.74, 95% CI: 0.72-0.77), and current drinking ( OR=0.97, 95% CI: 0.93-1.00) were less likely to reach the standard of blood glucose control. Conclusions:The blood glucose control rate of 18-64 year-old people with type 2 diabetes in Shenzhen still has room for improvement. More attention should be paid to 18-64 year-old patients with type 2 diabetes, especially for patients with dyslipidemia, central obesity, and diabetes with a long course, and supervision and guidance should be strengthened for patients with bad habits such as smoking, drinking alcohol, and lack of exercise.

Objective To investigate the risk factors for pulmonary embolism (PE)in patients with acute spinal cord injury (ASCI).Methods A case-control design was adopted in this study.Basic information,injury cause,injury site,imaging and laboratory examination results and other relevant data of 840 ASCI patients admitted to 3 affiliated hospitals of Army Medical University from January 2018 to August 2023 were collected.According to occurrence of PE or not,these patients were divided a PE group (n=83) and a non-PE group (n=757).Univariate analysis was performed on 37 risk factors including gender,age,length of hospital stay,length of intensive care unit (ICU)stay,cause of injury,and so on,and then multivariate logistic regression analysis was applied to analyze these selected significant variables.Results Univariate analysis showed that 24 factors such as age,length of hospital stay,lower limb fracture,pulmonary contusion and infection,shock and number of operations were related to the occurrence of PE in ASCI patients (P<0.05).Binary logistic regression analysis indicated that age (P=0.000,OR=1.957,95％CI:1.532～2.499),length of ICU stay (P=0.000,OR=2.561,95％CI:1.728～3.794),number of operations (P=0.015,OR=1.814,95％CI:1.124～2.927),spinal fixation (P=0.004,OR=0.370,95％CI:0.189～0.724),restrictive position (P=0.000,OR=21.269,95％CI:5.276～85.740),platelet count (P=0.000,OR=1.553,95％CI:1.236～1.951),D-dimer level (P=0.000,OR=1.600,95％CI:1.376～1.860)and prothrombin time (P=0.025,OR=2.756,95％CI:1.138～6.670)were independent risk factors for PE in the patients.Conclusion The mortality of the ASCI patients with PE is significantly higher than those without.Age,length of ICU stay,number of operations,spinal fixation,restrictive position,platelet count,D-dimer level and prothrombin time are closely associated with PE in ASCI patients.

OBJECTIVE To develop a magnetic resonance(MRI) imaging radiomics and clinical factor model to predict recurrence and metastasis in patients with primary stage Ⅱ-Ⅳa nasopharyngeal carcinoma(NPC) and to validate its predictive effect on adjuvant chemotherapy(AC) outcomes. METHODS A retrospective analysis was performed on 135 patients with stage Ⅱ to Ⅳa NPC diagnosed in Longgang Otolaryngology Hospital of Shenzhen City from February 2018 to October 2021. After receiving standard synchronous radiotherapy and chemotherapy at our hospital,some patients received induction chemotherapy and/or AC based on cisplatin/nedaplatin. The imaging features of enhanced MRI sequences were extracted using PyRadiomics platform. Using the least absolute shrinkage and selection operator(LASSO) algorithm to filter features associated with recurrence or metastasis,a clinical radiomics model(CRM) was constructed by Cox multivariate analysis in a training cohort and validated in a validation cohort. All patients were divided into high-risk and low-risk groups based on the model's median Rad score. Kaplan-Meier survival curves were used to compare 3-year recurrence or metastasis free survival(RMFS) in patients with AC in high-risk group and low risk-group. RESULTS A total of 960 imaging features were extracted. The CRM consists of 9 features(6 imaging features and 3 clinical factors). In the training cohort,the area under the CRM curve(AUC) of 3-year RMFS was 0.867(P<0.001),and the sensitivity and specificity were 90.32％ and 79.66％,respectively. In the validation cohort,the AUC was 0.836(P<0.001) and the sensitivity and specificity were 100.0％ and 71.43％,respectively. The 3-year RMFS in high-risk and low-risk groups was 42.86％(27/63) and 94.44％(68/72)(log rank=50.818,P<0.001),respectively. Among CRM high-risk patients,3-year RMFS was significantly better in patients who received AC than those who did not(log rank=6.204,P=0.013). CONCLUSION CRM based on 3 clinical factors and 6 MRI features provides a non-invasive method for predicting the prognosis of NPC,which may help guide treatment decisions for clinical adjuvant chemotherapy,but further external verification is needed.