Effect of the area under the curve of carboplatin dosage on therapeutic efficacy and safety in Chinese patients with epithelial ovarian cancer / 西安交通大学学报(医学版)

【Objective】 To retrospectively analyze the average carboplatin dosage and calculate the area under the curve (AUC) using the Calvert formula in first-line chemotherapy in patients with epithelial ovarian cancer in The First Affiliated Hospital of Xi’an Jiaotong University so as to evaluate the effect of the AUC difference in the Chinese population on therapeutic efficacy and safety. 【Methods】 We enrolled patients who underwent first-line chemotherapy with paclitaxel and carboplatin 3-week regimen in our hospital from January 1, 2012 to January 1, 2022. According to the median of AUC, the patients were divided into high-dose group and low-dose group. The overall response rate (ORR), disease control rate (DCR), progression free survival (PFS), overall survival (OS), and the incidence of adverse events (AEs) were compared. 【Results】 A total of 153 patients were enrolled in this study and the median AUC of carboplatin was 3.981 (range 2.314-5.446). Only 10.46% patients (16/153) had an AUC above 5. There were 77 patients with the AUC0.05). The ORR in the low-dose group and the high-dose group was 59.74% and 57.89%, respectively, and the DCR was 87.01% and 85.53%, respectively. The median PFS of the two groups was 14 and 15.5 months, respectively, and the median OS was 50 and 55 months, respectively. None of the above outcomes were statistically different between the two groups (P>0.05). The two groups showed significant differences in the incidence of anemia, neutropenia, and thrombocytopenia (P<0.05). The incidence of nausea and vomiting, grade 1-2 diarrhea or constipation, and grade 1-2 fever showed significant differences (P<0.05). In addition, the incidence of dose limiting toxicity (DLT), including grade 4 thrombocytopenia and febrile neutropenia (FN), was significantly increased in the high-dose group (P<0.05). 【Conclusion】 Compared with the recommended AUC 5-6 of carboplatin abroad, the actual carboplatin dosage in the first-line chemotherapy for patients with epithelial ovarian cancer was generally insufficient in our hospital. There was no difference in therapeutic efficacy between the patients with AUC<4 and AUC≥4. However, considering the increased risk of some AEs and DLT in the high-dose group, it is not recommended to increase the carboplatin AUC blindly.

Binder jet 3D printing composite bilayer tablet of extended-release printing technology in the study / 药学学报

Based on the dual needs of analgesia and anti-inflammation in trauma treatment, this study uses acetaminophen and moxifloxacin hydrochloride as active pharmaceutical ingredients and develops a composite bilayer tablet with a dual-phase drug release system by using binder jet 3D printing technology. Due to the complexity of the 3D printing process, there is an interaction between the various parameters. Through the optimization of the process, the relationship between the key process parameters can be determined more intuitively. In this study, the process of extended-release tablets was optimized to maintain the mechanical properties of the tablets while realizing the regulation of release. The full-factor experimental design of three central points 23 was used to analyze the factors that significantly affect the quality attributes of extended-release tablets and the interaction between factors. The optimal extended-release process parameters were obtained by the response optimizer: the inkjet quantity of the printing ink was 10 (about 13.8 pL), the powder thickness was 180 μm, and the running speed was 360 mm·s-1. The in vitro of release of 3D printed composite bilayer tablets showed that the in vitro of release of 3D printed tablets and commercially available tablets conformed to the Ritger-Peppas release model. The results of porosity showed that the immediate-release layer of the preparation has many pores and large pore size, and the dissolution of the immediate release layer within 15 min was greater than 85%. The internal pore size of the extended release layer is large, but it can still release slowly for up to 8 h, the mechanism may be related to the extended release of HPMC gelation. On the basis of verifying the rationality of the design goal of 3D printed composite bilayer tablets, this study also provides a theoretical basis for the preparation of 3D printing complex preparations.

Preparation of 3D printed metoprolol tartrate chewable tablets and optimization of printing process / 药学学报

With the growing demand of personalized medicine for children, it is especially important to develop medicines for children. In this study, using metoprolol tartrate as model drug, we developed 3D printed chewable tablets suitable for children with automated dosage distribution using semi-solid extruded (SSE) 3D printing technology. Based on the quality by design concept, this study prepared a semi-solid material with good printability using gelatin as the substrate, constructed 3D models and printed tablets with the aid of computer-aided design. The printing parameters were optimized and determined as follows: print temperature of 35-37 ℃, print speed of 25 mm·s-1, fill rate of 15%, and number of outer profile layers of 2. Subsequently, the printing process and the quality uniformity of the tablets were verified, and a linear relationship between the dose and the number of model layers was obtained. Finally, 3D printed chewable tablets were superior in terms of appearance, dose accuracy and compliance compared with traditional split-dose commercially available tablets. In this study, 3D printed metoprolol tartrate chewable tablets with good performance were successfully prepared to address the personalized medication needs of pediatric patients.

Association of serum complement C3, C4 with renal pathological lesion degree in IgA nephropathy patients / 中华肾脏病杂志

Objective:To explore the relationship between the levels of serum complement C3 and C4 and the degree of renal pathological injury in patients with IgA nephropathy (IgAN).Methods:It was a retrospective study. The clinical and pathological data of patients with primary IgAN diagnosed by renal biopsy in the Department of Nephrology of the Second People's Hospital of Qujing City, Yunnan Province from December 1, 2019 to December 31, 2022 were collected. According to the IgAN Oxford classification criteria, the patients were divided into mild renal pathological injury group (mild group, <3 pathologic types) and severe renal pathological injury group (severe group, ≥3 pathological types). The levels of serum C3 and C4 and other clinical data were compared between the two groups. Spearman correlation method was used to analyze the correlation between serum C3, C4 levels and estimated glomerular filtration rate (eGFR) during renal biopsy.Multivariate logistic regression model was used to analyze the influencing factors of the pathological injury degree in IgAN patients and the forest map depicted the effect of risk factors.Results:A total of 164 IgAN patients were included in the study, including 77 males (47.0%), aged (35.5±12.9) years old. There were 60 patients in the mild group and 104 patients in the severe group. Compared with the mild group, the patients in the severe group were older, had higher levels of serum C4, serum uric acid, low density lipoprotein cholesterol and 24 h urinary protein, higher proportions of hypertension, glucocorticoids/immunosuppressant therapy, C3 deposition in renal tissues and microscopic hematuria, and had lower hemoglobin and serum C3 level (all P<0.05). The results of Spearman correlation analysis showed that the level of serum C3 was positively correlated with eGFR ( r=0.303, P<0.001), and the level of serum C4 was negatively correlated with eGFR ( r=-0.238, P=0.002). Multivariate logistic regression analysis results showed that serum C3 (every 0.01 g/L increase, OR=0.976, 95% CI 0.957-0.996, P=0.018), serum C4 (every 0.01 g/L increase, OR=1.091, 95% CI 1.020-1.166, P=0.011), hemoglobin ( OR=0.969, 95% CI 0.950-0.988, P=0.002), and serum uric acid ( OR=1.005, 95% CI 1.001-1.009, P=0.012) were independent related factors of renal pathological damage (severe injury /mild injury) in IgAN patients. Conclusions:Serum C3 and C4 are independent related factors of the severity of renal pathological injury in IgAN patients.

Research progress of artificial intelligence in 3D printed drugs / 药学学报

In 2015, the United States put forward the concept of precision medicine, which changed medical treatment from "one size fits all" to personalization, and paid more attention to personalization and drug customization. In the same year, Spritam®, the world's first 3D printed tablet, was in the market, marking the emerging pharmaceutical 3D printing technology was recognized by regulatory authorities, and it also provided a new way for drug customization. 3D printing technology has strong interdisciplinary and high flexibility, which puts forward higher requirements for pharmaceutical staffs. With the development of artificial intelligence (AI), modern society can perform various tasks, such as disease diagnosis and robotic surgery, with superhuman speed and intelligence. As a major AI technology, machine learning (ML) has been widely used in many aspects of 3D printing drug, accelerating the research and development, production, and clinical application, and promoting the new process of global personalized medicine and industry 4.0. This paper introduces the basic concepts and main classifications of 3D printing drug, non-AI drug optimization technology and ML. It focuses on the analysis of the research progress of ML in 3D printing drug, and elucidates how AI can empower the intelligent level of 3D printing drug in pre-processing, printing, and post-processing process. It provides a new idea for accelerating the development of 3D printed drug.

Effects and mechanism of astilbin on myocardial ischemia-reperfusion injury in rats / 中国药房

OBJECTIVE To investigate the effects of astilbin （AST） on myocardial ischemia-reperfusion injury （MIRI） in rats and its potential mechanism. METHODS SD male rats were randomly divided into sham operation group， model group， positive control group （Compound Salvia miltiorrhiza tablets， 240 mg/kg）， AST low-dose and high-dose groups （30， 90 mg/kg）， and high- dose of AST+hypoxia-inducible factor-1α（HIF-1α） inhibitor group （AST 90 mg/kg+2ME2 15 mg/kg）， with 25 rats in each group. Except for sham operation group， MIRI model was induced in other groups， and then given relevant drug or normal saline intragastrically or intraperitoneally， for consecutive 28 d. Serum contents of cardiac troponin I （cTnI） and creatine kinase isoenzyme （CK-MB） were detected； volume ratio of myocardial infarction was measured； the pathological changes of myocardium， the apoptotic rate of myocardial cells and ultrastructure of mitochondria in myocardial tissue were all observed. The contents of tumor necrosis factor α （TNF-α）， interleukin 6 （IL-6） and malondialdehyde （MDA）， the activity of superoxide dismutase （SOD）， the expressions of HIF-1α， adenovirus E1B interacting protein 3 （BNIP3） and myosin-like Bcl-2 interacting protein （Beclin1） were determined in myocardium. The ratio of microtubule-associated protein light chain 3 （LC3） Ⅱ to Ⅰ （LC3 Ⅱ/Ⅰ） in rat myocardium was calculated. RESULTS Compared with model group， no obvious swelling was found in the myocardial tissue of rats in positive control group， AST low-dose and high-dose groups， and the myocardial fibers were arranged regularly； the volume ratio of myocardial infarction， the contents of cTnI， CK-MB， TNF-α， IL-6 and MDA， the apoptotic rate were decreased significantly （P＜0.05）， while SOD activity， protein expressions of HIF-1α， BNIP3 and Beclin1， LC3Ⅱ/Ⅰ were increased significantly （P＜0.05）. HIF-1α inhibitor could significantly weaken the improvement effect of AST on the above indicators in MIRI model rats （P＜0.05）. CONCLUSIONS AST enhances mitochondrial autophagy by activating HIF-1α/BNIP3 signaling pathway， thereby reducing MIRI in rats.

Research progress on autologous vascularized graft bone implant repair for maxillofacial bone defect / 中华口腔医学杂志

Maxillofacial bone defect can seriously affect the patient's appearance, mastication, deglutition and speech function. At present, autologous bone grafting combined with implant repair is an effective method for reconstruction of maxillofacial bone defects. Due to the differences in density, nutrition, immunity and other aspects of bone graft at different donor sites, there may be a potential impact on implant repair. In this paper, the biological characteristics of vascularized autologous bone used in maxillofacial bone defect repair were reviewed, and the risk factors of implantation on the bone graft were discussed. It provides support for clinicians in the selection of bone graft donor site and the design of prosthesis.

Advances in the study of new BCR-ABL kinase inhibitors / 药学学报

The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

Evaluation of inhibitory effect of tumor vaccine in colon carcinoma model mice / 中国生物制品学杂志

Objective@#To evaluate the inhibitory effect of tumor vaccines in colon carcinoma model mice.@*Methods@# Mouse bone marrow⁃derived dendritic cells（BMDCs）were stimulated by using CpG β⁃glucan nanoparticles（CNP）in vitro. The BMDCs were divided into PBS group，NP group（without CpG nanoparticles），Lysate group（MC38 cell lysate）and CpG group（CpG1826），which were determined for the expression of marker molecules on the surface by flow cytometry and for the contents of interleukin⁃6（IL⁃6）and IL⁃12p40 in the culture supernatant by ELISA. The tumor lysate nano⁃vaccine was pre⁃ pared by mixing 50 mg／mL tumor lysate（MC38 cell lysate）with 200 mg／mL CNP in a volume ratio of 1∶1，with which mice were subcutaneously immunized as Vaccine group. Vaccine group，PBS group，CNP group and Lysate group were im⁃ munized once a week，for three times in total. Mice were subcutaneously inoculated with MC38 cells，2 × 105 cells for each， in the right lower limb 1 h after the last immunization，and measured for tumor volume once every three days to plot the tumor growth curve. The ratios of CD3+ CD4+ T and CD3+ CD8+ T cells in the blood were analyzed by flow cytometry and the levels of tumor necrosis factor⁃α（TNF⁃α）and interferon γ（IFNγ）in the blood and spleen of mice were determined by ELISA.@*Results@# CNP effectively increased the expression of CD11c+ CD80+，CD11c+ CD86+，CD11c+ MHC⁃Ⅱ+ and the secretion of IL⁃6 and IL⁃12p40 in BMDCs in vitro，which were significantly higher than those in other 4 groups（t = 4. 3 ~ 46. 2，each P < 0. 05）. Compared with that of the other three groups，the tumor volume of mice in Vaccine group decreased significantly（t =2.6~3.4，eachP <0. 05）；TherewasnosignificantdifferenceinCD3+ CD8+ TandCD3+ CD8+ Tcellratios（t = 0.5~ 1. 9，each P > 0. 05）；The content of IFNγ in blood increased significantly（t = 3. 8 ~ 4. 6，P < 0. 05），while thatof TNF⁃α showed no significant difference（t = 0. 4 ~ 2. 0，each P > 0. 05）；However，the contents of IFN γ and TNF⁃α in spleen increased significantly（t = 6. 3 ~ 13. 0，each P < 0. 001）.@*Conclusion@#The prepared nano⁃vaccine of tumor lysate improvedtheimmune level in mice and effectively inhibited the growth of colon carcinoma.

Preparation of nanocapsules of active ingredients of Garcinia hanburyi and evaluation of their antidiabetic activity / 中国药房

OBJECTIVE To prepare Gambogic acid （GA） nanocapsules （GA-LNCs） and Neogambogic acid （NGA） nanocapsules（NGA-LNCs），and to evaluate their antidiabetic activities. METHODS Using water as the aqueous phase ，medium- chain triglyceride as the oil phase and polyethylene glycol monostearate as the surfactant ，GA-LNCs and NGA-LNCs were prepared by phase inversion method. Using entrapment efficiency and drug-loading amount as index ，the formulation technologies of above 2 nanocapsules were optimized by simplex lattice design. Its physical and chemical properties were investigated. The diabetic mice model was established. GA-LNCs and NGA-LNCs （1.92 and 2.42 mg/kg respectively ）were given intragastrically ，once a day ，for consecutive 6 weeks. The fasting blood glucose of mice ，the activities of superoxide dismutase （SOD）and glutathione peroxidase （GSH-Px），the contents of malondialdehyde （MDA），total cholesterol （TC），triglyceride （TG），high-density lipoprotein cholesterol（HDL-C）and low-density lipoprotein cholesterol （LDL-C）were all detected. RESULTS The optimal formulation of 2 kinds of nanocapsules included 60％ water，10％ medium-chain triglyceride ，30％ polyethylene glycol monostearate （total amount of the three was 2 g）and 35 mg GA or NGA . The encapsulation efficiencies of GA-LNCs and NGA-LNC obtained by the optimal formulation were （92.01±0.68）％ and（93.12±2.11）％；the drug-loading amount were （0.99±0.21）％ and（1.21±0.22）％， respectively. GA-LNCs and NGA-LNCs were yellow ，homogeneous and transparent liquid without precipitation. They were spherical in microscopic shape ， and had obvious shell- Δ 基金项目：吉林省科技发展计划项目（No.20200404090YY）；吉 membrane structure. The particle sizes were （28.11 ± 9.76） 林省教育厅科学技术研究项目（No.JJKH20210372KJ） ＊硕士研究生 。研究方向 ：植物药 。E-mail：zhanhe0108@163. and（22.06±6.84）nm；Zeta potential were （－4.09±1.00） com and（－17.40±1.32）mV，and polydispersity were 0.93±0.06 # 通信作者：讲师，博士。研究方向：中药有效成分治疗疾病的作 and 0.74±0.12. The results of animal experiments showed that 用机制。E-mail：chenweijia_jlau@163.com both GA-LNCs and NGA-LNCs could sig nificantly increase 中国药房 2022年第33卷第9期 China Pharmacy 2022Vol. 33 No. 9 ·1075· the activities of SOD and GSH-Px and the seru m content of HDL-C （P＜0.05 or P＜0.01）in model mice ，and significantly decreased the fasting blood glucose and the serum contents of MDA ， TC， TG and LDL-C （P＜0.05 or P＜0.01）. CONCLUSIONS GA-LNCs，NGA-LNCs prepared in this study are good in physical and chemical properties and have good anti-diabetes activity.

Meta-analysis of efficacy and safety of Suhuang Zhike Capsules in treatment of chronic obstructive pulmonary disease / 中国中药杂志

This study aims to evaluate the effectiveness and safety of Suhuang Zhike Capsules in treating chronic obstructive pulmonary disease. The Chinese and English databases were searched(from the establishment to July 2021) for randomized controlled trials(RCTs) on the treatment of chronic obstructive pulmonary disease with Suhuang Zhike Capsules, yielding 130 articles and finally 12 eligible RCTs. The 12 RCTs enrolled a total of 1 159 patients(579 in experimental group, 580 in control group), with 728 males(62.8%) and 431 females(37.2%). Meta-analysis showed that the conventional western medicine combined with Suhuang Zhike Capsules increased clinical efficacy(OR=4.31, 95%CI[2.88, 6.46], Z=7.08, P<0.000 01), forced expiratory volume in one second(FEV1)(SMD=0.88, 95%CI[0.60, 1.16], Z=6.24, P<0.000 01), forced vital capacity(FVC)(SMD=0.96, 95%CI[0.38, 1.55], Z=3.22, P=0.001), forced vital capacity rate of one second(FEV1/FVC%)(SMD=0.85, 95%CI[0.51, 1.19], Z=4.92, P<0.000 01), and maximum voluntary ventilation(MVV)(SMD=0.61, 95%CI[0.39, 0.83], Z=5.40, P<0.000 01) compared with the conventional western medicine alone. The differences in residual volume/total lung capacity(RV/TLC)(SMD=-0.93, 95%CI[-3.38, 1.53], Z=0.74, P=0.46) and adverse reactions(OR=1.39, 95%CI[0.76, 2.56], Z=1.07, P=0.28) are insignificant. The study showed that the conventional western medicine combined with Suhuang Zhike Capsules could improve clinical efficacy and lung functions in the treatment of chronic obstructive pulmonary disease. In addition, the combination had been verified to be safe. However, in view of the uneven method quality, small sample size, and inconsistent outcome indicators of the included studies, higher-quality, multi-center, and large-sample RCTs are needed for further verification.

Prenatal ultrasound diagnosis of fetal right aortic arch / 中国医师进修杂志

Objective:To explore the prenatal ultrasound manifestations of fetal congenital right aortic arch and its diagnostic significance.Methods:The characteristics of prenatal ultrasound images (focusing on the three vessel trachea section) and clinical data of 128 cases of fetal congenital right aortic arch diagnosed in Dalian Women and Children′s Medical Center(Group) from January 2014 to January 2019 were analyzed retrospectively.Results:Among 128 cases of fetal congenital right aortic arch, 111 cases were right aortic arch and leftductus arteriosus with aberrant left subclavian artery (RAA-LDA-ALSA), 1 case was diagnosed as left aortic arch atresia of double aortic arch by operation after birth; 9 cases were right aortic arch and right ductus arteriosus (RAA-RDA); 6 cases were mirror-image right active aortic arch and left ductus arteriosus connected to descending aorta (RAA-BAMB-LDA-DAO); 2 cases were mirror-image right aortic arch and left ductus arteriosus connected to the left innominate artery (RAA-BAMB-LDA-LINA). The three vessels and trachea view (3VT) had characteristic sonographic features.If necessary, coronary section of the upper thoracic aorta and / or stic were added - HD live flow technology assisted the diagnosis of 3vt section.Conclusions:Three vessel trachea view is a sensitive and effective view for prenatal detection and diagnosis of congenital right aortic arch. Upper thoracic aorta coronal section and combined stic - HD live flow technology can make up for its shortcomings. Prenatal ultrasound diagnosis of right aortic arch hasguiding significance for prenatal prognosis consultation.

Role of dexamethasone/captopril co-loaded immunoliposome-nanoparticle hybrids on the regulation of macrophage polarization in mice with glomerulonephritis / 药学学报

In this study, dexamethasone (DXMS) and captopril (CAP) were co-loaded into poly(lactic-co-glycolic acid) (PLGA) nanoparticles with a surface coating of a phospholipid bilayer, and then the core-shell nanoparticles were modified with polyethylene glycol and integrin α8 antibody to obtain immunoliposome-nanoparticle hybrids (DXMS/CAP@PLGA-ILs). The role of nanoparticles on the renal targeting, anti-inflammatory effects, and macrophage differentiation were investigated. The results showed that the particle size of the nanoparticles was 115.9 ± 2.89 nm, and the core-shell structure could be observed under an electron microscope. The drug loading capacity of DXMS and CAP was 5.72% ± 0.37% and 7.51% ± 0.07%, respectively. The results of in vitro experiments showed that DXMS/CAP@PLGA-ILs could reduce the secretion of specific cytokines and the mRNA expression of markers in M2-type macrophages, thus promoting the differentiation of M2-type macrophages in the direction of unpolarized macrophages. In vivo experiments in mice showed that DXMS/CAP@PLGA-ILs had a significant renal targeting effect, which could restore the renal index, serum creatinine, and urea nitrogen levels of mesangial proliferative glomerulonephritis in mice. Moreover, DXMS/CAP@PLGA-ILs could reduce both the secretion of inflammatory cytokines and the mRNA expression levels of M1 and M2 macrophage markers in the kidney. All the animal experiments were in accordance with the regulations of Animal Ethics Committee of Sichuan Agricultural University. In conclusion, renal-targeting DXMS/CAP@PLGA-ILs could effectively regulate the polarization of macrophages and had an "anti-inflammatory/anti-fibrosis" therapeutic effect, providing a new strategy and basis for the targeted therapy of glomerulonephritis.

Development and research of compound caffeine waterless swallowed granules based on reverse engineering / 药学学报

In this study, the reverse engineering technology was used to analyze the prescription and process of Doppelherz® Energy DIRECT, based on the composition of the prescription on the official website of the product, the detection method of composition is established according to the pharmacopoeia and literature information, combined with gravimetric analysis to complete prescription analysis. The prescription composition of the reference listed drug was determined to be composed of caffeine, taurine, vitamin B, anhydrous glucose, citric acid, sorbitol, sucralose, magnesium salts of fatty acids, in which the glucose content was 71.4%, the citric acid content was 7.0% and the magnesium salts of fatty acids content was < 5.8%. According to patent inquiry, Raman imaging and other technologies, the preparation process of the marketed preparation has been basically obtained, and the development of the self-made preparation has been completed on this basis. The study was approved by the Ethics Committee of the Academy of Military Medical Sciences. Combined with the results of the taste evaluation experiment and the caffeine dissolution test of the preparation in 1 min, the hot-melt extrusion technology was screened out as the taste-masking technology of the self-made preparation, the parameters of the hot-melt extrusion process were screened by differential scanning calorimetry analysis, and finally a product with good taste and qualified quality was obtained, which provided a reference method for the research and development of related preparations.

Clinical analysis of 10 patients of pregnancy with cervical cancer / 中国医师进修杂志

Objective:To analyze the clinical features, diagnosis and treatment plan, clinical outcomes of pregnancy with cervical cancer.Methods:The clinical data of 10 pregnant women with cervical cancer from January 2008 to October 2018 in Dalian Obstetrics and Gynecology Hospital Affiliated to Dalian Medical University, the First Hospital of Dalian Medical University, Dalian Central Hospital, Dalian Women and Children′s Medical Center and Wafangdian Central Hospital of Liaoning Province were retrospectively analyzed.Results:The incidence of pregnancy with cervical cancer was 0.004% (10/238 128). Among the 10 cases of pregnancy with cervical cancer, the gestational weeks ≤ 20 weeks at the time of diagnosis was in 6 cases, and they all chose to terminate the pregnancy; the gestational weeks 20 +1 to 30 weeks at the time of diagnosis was in 1 case, and the patient chose to terminate the pregnancy; the gestational weeks >30 weeks at the time of diagnosis was in 2 cases, and they all chose to continue the pregnancy; 1 case was diagnosed after delivery. There were 3 newborns, including 1 premature infants, and they all survived. Conclusions:It is helpful to the diagnose of the disease to strengthen cervical cancer screening before pregnancy and improve the examination of patients with abnormal symptoms during pregnancy. The treatment plan should be individualized according to the pregnancy status, stage of the disease, and wishes of the patient and family.

Effect of Danggui Shaoyaosan on TLR4/MyD88/JNK Signaling Pathway on Rats with Nonalcoholic Fatty Liver Disease / 中国实验方剂学杂志

Objective:To explore<italic> </italic>the efficacy and mechanism of Danggui Shaoyaosan on rats of nonalcoholic fatty liver disease （NAFLD）. Method:Sixrty SPF SD male rats were randomly divided into normal group， model group，essentiale （0.144 g·kg^-1） and low， middle and high-dose of Danggui Shaoyaosan groups （2.44， 4.88， 9.76 g·kg^-1）. High fat diet were fed to bulid the NAFLD model， and each treatment group was given corresponding drugs at the same time. After 8 weeks， the serum and liver tissue were collected to detect the contents or activities of total cholesterol （TC）， triglyceride （TG）， alanine aminotransferase （ALT）， aspartic acid aminotransferase （AST）， tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） and interleukin-10 （IL-10） in serum， the contents of TC， TG and free fatty acid （FFA） in liver tissue， Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） and Western blot were used to observe the gene and protein expressions of Toll-like receptor 4 （TLR4）， myeloid different factory 88 （MyD88） and c-Jun n-terminal kinase （JNK） and the protein expression of phosphorylation JNK（p-JNK） in liver tissue. Hematoxylin-eosin （HE） staining and Oil red staining to observe the pathological morphological changes of liver. Result:Compared with control group， the contents or activities of TC， TG， ALT， AST and TNF-<italic>α</italic> in serum， the contents of TC， TG and FFA in liver and the gene and protein expressions of TLR4， MyD88， JNK， and the protein expression of p-JNK in liver tissue of model group were distinctly increased （<italic>P</italic><0.01）， the content of IL-10 was significantly decreased （<italic>P</italic><0.01）. Compared with model group， the contents or activities of TC， TG， ALT， AST and TNF-<italic>α</italic> in serum， the contents of TC， TG and FFA in liver and the mRNA and protein expressions of TLR4， MyD88 and JNK， and the protein expression of p-JNK in liver tissue of Danggui Shaoyaosan groups were significantly reduced （<italic>P</italic><0.05，<italic>P</italic><0.01）， the content of IL-10 in serum of Danggui Shaoyaosan groups was distinctly increased（<italic>P</italic><0.05，<italic>P</italic><0.01）， HE staining and Oil red staining show that the degree of liver steatosis was alleviated obviously by Danggui Shaoyaosan. Conclusion:Danggui Shaoyaosan has a better treatment on NAFLD by inhibiting TLR4/MyD88/JNK pathway and alleviating the inflammation response.

Full-factor design of experiment application in the development of printing ink for binder jetting 3D printed preparation / 药学学报

The development of printing ink is a challenge for binder jetting 3D printed preparations, which directly determines the quality of the printed product. This study adopted a 23 full-factor Design of Experiment (DoE) with three central points to optimize the printing ink composition of levetiracetam 3D printed dispersible tablet based on the concept of Quality by Design. Firstly, using polyvinyl pyrrolidone K30, glycerin and polysorbate 20 as independent variables based on 40% (v/v) isopropanol aqueous solution, and weight variation, hardness, friability and dispersion uniformity of the printed tablets were used as dependent variables. Then obtained the design space of the printing ink prescription by DoE model analysis, and the response optimizer was used to obtain the optimal printing ink prescription: isopropanol aqueous solution containing 0.1% (w/w) polyvinyl pyrrolidone K30 and 4.0% (w/w) glycerin. The jetting mechanism and wettability of the printing ink were analyzed, and different strengths of personalized 3D printed tablets were prepared and characterized, which verified the rationality of the printing ink formulation. This study provided a reference for the development of printing ink for binder jetting 3D printed preparations.

Optimization of process parameters of 3D printed clozapine dispersive tablets and establishment of personalized dose model / 药学学报

This study aims to establish the design space of the key processes for drop-on-powder 3D printing based on design of experiment (DoE). By utilizing Minitab, an experimental scheme with three factors, two levels and three center points was designed to analyze the factors that significantly affected the tablet quality attributes. Furthermore, the factor interactions were analyzed using Minitab. subsequently, the computer aided drafting (CAD) software was used to adjust the model volume with fixed radius/height ratio (r/h = 1.25) and establish a linear regression equation between model volume and dose. As a result, the drug dose could be controlled in a flexible manner. The finally determined process parameters were: ink-jet level is 12, layer thickness is 150 μm, and the X-axis printing head speed of 635 mm·s-1. Regression equation between drug content (y) and model volume (x) was y = 0.062 x - 0.582 7 (R2 = 0.999 9) showing good linear relationship. This indicated that robust and feasible process parameters were obtained through DoE, and the preparation of personalized-dose tablets was realized with good reproducibility.

Circadian rhythm abnormality and time therapy of bipolar disorder / 中华行为医学与脑科学杂志

Bipolar disorder is a common, highly disabling psychiatric disorder characterized by early onset, frequent episodes, high suicide risk, and chronic outcomes, and is associated with severe social dysfunction. The pathogenesis of bipolar disorder is still unclear, and current studies mainly focus on circadian rhythm abnormalities, including rhythm gene mutation, polymorphism, abnormal kinase expression, and rhythm abnormalities in neurotransmitter secretion and transport. It has been found that at any stage of bipolar disorder, whether prodrome, episode, or remission, patients exhibit circadian rhythm disruptions, including disrupted sleep-wake cycles, hormonal phase abnormalities, and irregular social rhythms. Based on this mechanism, the time therapy, such as light therapy, dark therapy, sleep deprivation and behavioral intervention, can rapidly improve the circadian rhythm of patients with bipolar disorder, achieve the goal of rapid relief of symptoms, with fewer side effects, low risk of switching to manic. In this paper, circadian rhythm mechanism, clinical manifestations and chronotherapy of bipolar disorder are reviewed to provide a basis for clinical diagnosis and treatment.

Predictive performance of Smart Dose, PharmVan and JPKD on Vancomycin plasma concentration / 中华危重病急救医学

Objective:To evaluate the predictive performance of the individualized drug delivery decision-making system including Smart Dose, PharmVan and JPKD on predicting the Vancomycin plasma concentration and to analyze the related factors affecting the predictive performance.Methods:The clinical data of patients who were treated with Vancomycin and received therapeutic drug monitoring (TDM) admitted to the First Affiliated Hospital of Wenzhou Medical University from January 2018 to July 2020 were retrospectively collected. Smart Dose and PharmVan were used to predict the plasma concentration of Vancomycin of the initial regimen. Smart Dose, PharmVan and JPKD were used to predict the plasma concentration of Vancomycin of the adjustment regimen for patients whose initial steady-state trough concentration were not qualified. The relative predictive error (PE) between the measured plasma concentration and predicted plasma concentration was calculated and box plotted. Mann-Whitney U test was used to evaluate the difference of the absolute value of PE (APE) predicted by each software for Vancomycin plasma concentration. The TDM results were divided into accurate prediction group (APE < 30%) and the inaccurate prediction group (APE≥30%) according to the APE value. Patients and disease characteristics including gender, age, body weight complication, Vancomycin medication and TDM results were collected from electronic medical records. Univariate analysis and multivariate Logistic regression analysis were used to screen the related factors that influence the predictive performance of Smart Dose, PharmVan and JPKD; and receiver operating characteristic curve (ROC curve) was drawn to evaluate its predictive value. Results:A total of 185 patients were enrolled, and 258 plasma concentration of Vancomycin were collected, including 185 concentrations of initial regimen and 73 concentration of adjustment regimen. There was no significant difference in the APE of the initial regimen of plasma concentration between Smart Dose and PharmVan. No significant difference in the APE of the adjustment regimen of plasma concentration was found among Smart Dose, PharmVan and JPKD. The accuracy of Smart Dose in predicting the plasma concentration of the adjustment regimen was better than that of the initial regimen [22.94% (10.50%, 36.24%) vs. 29.33% (13.07%, 47.99%), P < 0.05]. The univariate analysis of factors affecting the performance of Smart Dose in predicting the concentration of initial regimen showed that the proportion of patients with hypertension in the accurate prediction group was significantly higher than that in the inaccurate prediction group [43.3% (42/97) vs. 27.3% (24/88), P < 0.05]. The univariate analysis of factors affecting the performance of Smart Dose in predicting the concentration of adjustment regimen showed that the proportion of patients with valvular heart disease in the accurate prediction group was significantly lower than that in the inaccurate prediction group [23.4% (11/47) vs. 46.2% (12/26), P < 0.05]. The univariate analysis of factors affecting the performance of JPKD in predicting the concentration of adjustment regimen showed that the body weight of patients in the accurate prediction group was significantly higher than that in the inaccurate prediction group (kg: 62.8±14.9 vs. 54.8±12.8, P < 0.05). Multivariate Logistic regression analysis indicated that hypertension was a beneficial factor for Smart Dose to predict the initial plasma concentration of Vancomycin [odds ratio ( OR) = 0.526, 95% confidence interval (95% CI) was 0.281-0.983, P = 0.044], and low body weight was an independent risk factor for the inaccurate prediction of JPKD for adjustment regimen ( OR = 1.042, 95% CI was 1.001-1.085 , P = 0.043). ROC curve analysis indicated that the area underROC curve (AUC) of the body weight for evaluating the accuracy of JPKD in predicting Vancomycin plasma concentration was 0.663, and 95% CI was 0.529-0.796 ( P = 0.023). When the body weight was less than 55.95 kg, the risk of inaccurate prediction of JPKD in predicting Vancomycin plasma concentration was increased, and the predictive sensitivityand specificity were 75% and 60% respectively. Conclusions:There is no significant difference in the predictive performance of Smart Dose, PharmVan or JPKD on Vancomycin plasma concentration. Smart Dose had a better predictive performance for the Vancomycin plasma concentration of adjustment regimen than initial regimen. Smart Dose had a better predictive performance when the patient was concomitant with hypertension. JPKD had a poor predictive performance for low-body weight patients. The predictive performance of JPKD was decreased when the body weight was lower than 55.95 kg.