Mechanism of astragaloside Ⅳ in regulating autophagy of PC12 cells under oxygen-glucose deprivation by medicating Akt/mTOR/HIF-1α pathway / 中国中药杂志

This study explored the protective effect of astragaloside Ⅳ(AS-Ⅳ) on oxygen-glucose deprivation(OGD)-induced autophagic injury in PC12 cells and its underlying mechanism. An OGD-induced autophagic injury model in vitro was established in PC12 cells. The cells were divided into a normal group, an OGD group, low-, medium-, and high-dose AS-Ⅳ groups, and a positive drug dexmedetomidine(DEX) group. Cell viability was measured using the MTT assay. Transmission electron microscopy was used to observe autophagosomes and autolysosomes, and the MDC staining method was used to assess the fluorescence intensity of autophagosomes. Western blot was conducted to determine the relative expression levels of functional proteins LC3-Ⅱ/LC3-Ⅰ, Beclin1, p-Akt/Akt, p-mTOR/mTOR, and HIF-1α. Compared with the normal group, the OGD group exhibited a significant decrease in cell viability(P<0.01), an increase in autophagosomes(P<0.01), enhanced fluorescence intensity of autophagosomes(P<0.01), up-regulated Beclin1, LC3-Ⅱ/LC3-Ⅰ, and HIF-1α(P<0.05 or P<0.01), and down-regulated p-Akt/Akt and p-mTOR/mTOR(P<0.05 or P<0.01). Compared with the OGD group, the low-and medium-dose AS-Ⅳ groups and the DEX group showed a significant increase in cell viability(P<0.01), decreased autophagosomes(P<0.01), weakened fluorescence intensity of autophagosomes(P<0.01), down-regulated Beclin1, LC3-Ⅱ/LC3-Ⅰ, and HIF-1α(P<0.05 or P<0.01), and up-regulated p-Akt/Akt and p-mTOR/mTOR(P<0.01). AS-Ⅳ at low and medium doses exerted a protective effect against OGD-induced autophagic injury in PC12 cells by activating the Akt/mTOR pathway, subsequently influencing HIF-1α. The high-dose AS-Ⅳ group did not show a statistically significant difference compared with the OGD group. This study provides a certain target reference for the prevention and treatment of OGD-induced cellular autophagic injury by AS-Ⅳ and accumulates laboratory data for the secondary development of Astragali Radix and AS-Ⅳ.

Relationships of Low Serum Levels of Interleukin-10 With Poststroke Anxiety and Cognitive Impairment in Patients With Clinical Acute Stroke

Background@#and Purpose The relationships among interleukin (IL)-10 levels, anxiety, and cognitive status after stroke remain controversial. We aimed to determine the associations of serum IL-10 levels with poststroke anxiety (PSA) and poststroke cognitive impairment (PSCI). @*Methods@#We recruited 350 patients with stroke, of whom only 151 completed a 1-month follow-up assessment. The Mini Mental State Examination (MMSE) and Hamilton Anxiety Scale (HAMA) were used to assess the cognitive status and anxiety, respectively. Serum IL-10 levels were measured within 24 hours of admission. @*Results@#IL-10 levels were significantly lower in the PSA group than in the non-PSA group, and they were negatively associated with HAMA scores (r=-0.371, p<0.001). After adjusting for all potential confounders, IL-10 levels remained an independent predictor of PSA (odds ratio=0.471, 95% confidence interval=0.237–0.936, p=0.032). IL-10 levels were strongly correlated with behavior during interviews, psychic anxiety, and somatic anxiety. Patients without PSCI had higher IL-10 levels were higher in non-PSCI patients than in PSCI patients, and they were positively associated with MMSE scores in the bivariate correlation analysis (r=0.169, p=0.038), and also with memory capacity, naming ability, and copying capacity.However, IL-10 did not predict PSCI in the univariable or multivariable logistic regression. @*Conclusions@#Low IL-10 levels were associated with increased risks of PSA and PSCI at a 1-month follow-up after stroke. Serum IL-10 levels may therefore be helpful in predicting PSA.

Research progress of reversion multi-drug resistance in tumor by berberine / 中国药理学通报

Tumor is a kind of disease with high morbidity, high mortality and poor prognosis. Chemotherapy is the main treatment of tumor, but the problem of chemotherapy resistance is becoming increasingly prominent, so finding ways to overcome chemotherapy resistance and improve the therapeutic effect has become an urgent problem to be solved. At present, with the development of research, the anti-tumor effect of some traditional Chinese medicine has attracted extensive attention. Berberine, traditionally used in the treatment of digestive system diseases, has been proved to have the effect of anti-tumor and reversing tumor multi-drug resistance. This review summarizes the recent researches on the reversion multi-drug resistance in tumor by berberine, in order to explore the means to improve the therapeutic effect and prognosis of tumor drug resistance.

Effect of processing method on chemical constituents of Rehmanniae Radix: based on UHPLC-LTQ-Orbitrap MS / 中国中药杂志

This study aims to explore the chemical composition of Rehmanniae Radix braised with mild fire and compare the effect of processing method on the chemical composition of Rehmanniae Radix. To be specific, ultra-high performance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS) was used to screen the chemical constituents of Rehmanniae Radix. The chemical constituents were identified based on the relative molecular weight and fragment ions, literature information, and Human Metabolome Database(HMDB). The ion peak area ratio of each component before and after processing was used as the index for the variation. SIMCA was employed to establish principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) models of different processed products. According to the PCA plot, OPLS-DA plot, and VIP value, the differential components before and after the processing were screened out. The changes of the content of differential components with the processing method were analyzed. A total of 66 chemical components were identified: 57 of raw Rehmanniae Radix, 55 of steamed Rehmanniae Radix, 55 of wine-stewed Rehmanniae Radix, 51 of repeatedly steamed and sundried Rehmanniae Radix Praeparata, 62 of traditional bran-braised Rehmanniae Radix, and 63 of electric pot-braised Rehmanniae Radix. Among them, the 9 flavonoids of braised Rehmanniae Radix were from Citri Reticulatae Pericarpium. PCA suggested significant differences in the chemical composition of Rehmanniae Radix Praeparata prepared with different processing methods. OPLS-DA screened out 32 chemical components with VIP value >1 as the main differential components. Among the differential components, 9 were unique to braised Rehmanniae Radix(traditional bran-braised, electric pot-braised) and the degradation rate of the rest in braised(traditional bran-braised, electric pot-braised) or repeatedly steamed and sundried Rehmanniae Radix was higher than that in the steamed or wine-stewed products. The results indicated the chemical species and component content of Rehmanniae Radix changed significantly after the processing. The 32 components, such as rehmapicrogenin, martynoside, jionoside D, aeginetic acid, hesperidin, and naringin, were the most important compounds to distinguish different processed products of Rehmanniae Radix. The flavonoids introduced by Citri Reticulatae Pericarpium as excipient may be the important material basis for the effectiveness of braised Rehmanniae Radix compared with other processed products.

Efficacy and Safety of Jianpi Jieyu Decoction for Patients with Mild-to-Moderate Depression of Xin (Heart)-Pi (Spleen) Deficiency Syndrome: A Multi-centre Randomized Controlled Study / 中国结合医学杂志

OBJECTIVE@#To evaluate the efficacy and safety of Jianpi Jieyu Decoction (JJD) for treating patients with mild-to-moderate depression of Xin (Heart)-Pi (Spleen) deficiency (XPD) syndrome.@*METHODS@#In this multi-center, randomized, controlled study, 140 patients with mild-to-moderate depression of XPD syndrome were included from Xiyuan Hospital of China Academy of Chinese Medical Sciences and Botou Hospital of Traditional Chinese Medicine from December 2017 to December 2019. They were randomly divided into JJD group and paroxetine group by using a random number table, with 70 cases in each group. The patients in the JJD group were given JJD one dose per day (twice daily at morning and evening, 100 mL each time), and the patients in the paroxetine group were given paroxetine (10 mg/d in week 1; 20 mg/d in weeks 2-6), both orally administration for a total of 6 weeks. The primary outcome was the change of 17-item Hamilton Depression Rating Scale (HAMD-17) score at week 6 from baseline. The secondary outcomes included the Hamilton Anxiety Scale (HAMA) score, Traditional Chinese Medicine Symptom Scale (TCMSS), and Clinlcal Global Impression (CGI) scores at the 2nd, 4th, and 6th weekends of treatment, HAMD-17 response (defined as a reduction in score of >50%) and HAMD-17 remission (defined as a score of ⩽7) at the end of the 6th week of treatment. Adverse events (AEs) were also recorded.@*RESULTS@#From baseline to week 6, the HAMD-17 scores decreased 10.2 ± 4.0 and 9.1 ± 4.9 points in the JJD and paroxetine groups, respectively (P=0.689). The HAMD-17 response occurred in 60% of patients in the JJD group and in 50% of those in the paroxetine group (P=0.292); HAMD-17 remission occurred in 45.7% and 30% of patients, respectively (P=0.128). The differences of CGI scores at the 6th week were not statistically significant (P>0.05). There were significant differences in HAMD-17 scores between the two groups at 2nd and 4th week (P=0.001 and P=0.014). The HAMA scores declined 8.1 ± 3.0 and 6.9 ± 4.3 points from baseline to week 6 in the JJD and paroxetine groups, respectively (P=0.905 between groups). At 4th week of treatment, there was a significant difference in HAMA between the two groups (P=0.037). TCMSS decreased 11.4 ± 5.1, and 10.1 ± 6.8 points in the JJD and paroxetine groups, respectively (P=0.080 between groups). At the 6th week, the incidence of AEs in the JJD group was significantly lower than that in the paroxetine group (7.14% vs. 22.86%, P<0.05).@*CONCLUSION@#Compared with paroxetine, JJD was associated with a significantly lower incidence of AEs in patients with mild-to-moderate depression of XPD syndrome, with no difference in efficacy at 6 weeks. (Trial registration No. ChiCTR2000040922).

Comparative Study of the Two High-Efficient Strategies for in vitro Generation of Human Umbilical Cord Blood-derived Natural Killer Cells / 中国实验血液学杂志

OBJECTIVE@#To explore the similarities and variations of biological phenotype and cytotoxicity of human umbilical cord blood natural killer cells (hUC- NK) after human umbilical cord blood-derived mononuclear cells (hUC-MNC) activated and expanded by two in vitro high-efficient strategies.@*METHODS@#Umbilical cord blood mononuclear cells (MNC) from healthy donor were enriched by Ficoll-based density gradient centrifugation. Then, the phenotype, subpopulations, cell viability and cytotoxicity of NK cells derived from Miltenyi medium (denoted as M-NK) and X-VIVO 15 (denoted as X-NK) were compared using a "3IL" strategy.@*RESULTS@#After a 14-day's culture, the contents of CD3-CD56+ NK cells were elevated from 4.25%±0.04% (d 0) to 71%±0.18% (M-NK) and 75.2%±1.1% (X-NK) respectively. Compared with X-NK group, the proportion of CD3+CD4+ T cells and CD3+CD56+ NKT cells in M-NK group decreased significantly. The percentages of CD16+, NKG2D+, NKp44+, CD25+ NK cells in X-NK group was higher than those in the M-NK group, while the total number of expanded NK cells in X-NK group was half of that in M-NK group. There were no significant differences between X-NK and M-NK groups in cell proliferation and cell cycle, except for the lower percentage of Annexin V+ apoptotic cells in M-NK group. Compared with X-NK group, the proportion of CD107a+ NK cells in M-NK group were higher under the same effector-target ratio (E∶T) (P<0.05).@*CONCLUSION@#The two strategies were adequate for high-efficient generation of NK cells with high level of activation in vitro, however, there are differences in biological phenotypes and tumor cytotoxicity.

Effect of platelet-derived growth factor-BB on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension and its mechanism / 中国当代儿科杂志

OBJECTIVES@#To study the effect of platelet-derived growth factor-BB (PDGF-BB) on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH).@*METHODS@#A total of 128 neonatal rats were randomly divided into four groups: PDGF-BB+HPH, HPH, PDGF-BB+normal oxygen, and normal oxygen (n=32 each). The rats in the PDGF-BB+HPH and PDGF-BB+normal oxygen groups were given an injection of 13 μL 6×1010 PFU/mL adenovirus with PDGF-BB genevia the caudal vein. After 24 hours of adenovirus transfection, the rats in the HPH and PDGF-BB+HPH groups were used to establish a neonatal rat model of HPH. Right ventricular systolic pressure (RVSP) was measured on days 3, 7, 14, and 21 of hypoxia. Hematoxylin-eosin staining was used to observe pulmonary vascular morphological changes under an optical microscope, and vascular remodeling parameters (MA% and MT%) were also measured. Immunohistochemistry was used to measure the expression levels of PDGF-BB and proliferating cell nuclear antigen (PCNA) in lung tissue.@*RESULTS@#The rats in the PDGF-BB+HPH and HPH groups had a significantly higher RVSP than those of the same age in the normal oxygen group at each time point (P<0.05). The rats in the PDGF-BB+HPH group showed vascular remodeling on day 3 of hypoxia, while those in the HPH showed vascular remodeling on day 7 of hypoxia. On day 3 of hypoxia, the PDGF-BB+HPH group had significantly higher MA% and MT% than the HPH, PDGF-BB+normal oxygen, and normal oxygen groups (P<0.05). On days 7, 14, and 21 of hypoxia, the PDGF-BB+HPH and HPH groups had significantly higher MA% and MT% than the PDGF-BB+normal oxygen and normal oxygen groups (P<0.05). The PDGF-BB+HPH and HPH groups had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group at all time points (P<0.05). On days 3, 7, and 14 of hypoxia, the PDGF-BB+HPH group had significantly higher expression levels of PDGF-BB and PCNA than the HPH group (P<0.05), while the PDGF-BB+normal oxygen group had significantly higher expression levels of PDGF-BB and PCNA than the normal oxygen group (P<0.05).@*CONCLUSIONS@#Exogenous administration of PDGF-BB in neonatal rats with HPH may upregulate the expression of PCNA, promote pulmonary vascular remodeling, and increase pulmonary artery pressure.

Research status of Bovis Calculus and relevant Chinese patent medicines based on bibliometric analysis / 中国中药杂志

With scarce resources, natural Bovis Calculus is expensive and hard to meet clinical demand. At the moment, four kinds of Bovis Calculus are available on the market: the natural product, in vitro cultured product, synthesized product, and the product formed in cow after manual intervention. In this study, papers on the four kinds of Bovis Calculus products and relevant Chinese patent medicines were searched from Web of Science, PubMed, and China National Knowledge Infrastructure(CNKI). CiteSpace, citexs AI, and CNKI were employed for bibliometric analysis and knowledge map analysis. On this basis, the status, trend, and focuses of research on Bovis Calculus and relevant Chinese patent medicines were summarized. The results suggested overall slow development in the research on Bovis Calculus and relevant Chinese patent medicines with three typical growth stages. It is consistent with the development of Bovis Calculus substitutes and the national policy for the development of traditional Chinese medicine. At the moment, the research on Bovis Calculus and relevant Chinese patent medicines has been on the rise. In recent years, there has been an explosion of research on them, particularly the quality control of Bovis Calculus and the Chinese patent medicines, the pharmacological efficacy of Chinese patent medicines, such as Angong Niuhuang Pills, and the comparison of the quality of various Bovis Calculus products. However, there is a paucity of research on the pharmacological efficacy and the mechanism of Bovis Calculus. This medicinal and the relevant Chinese patent medicines have been studied from diverse perspectives and China becomes outstanding in this research field. However, it is still necessary to reveal the chemical composition, pharmacological efficacy, and mechanism through multi-dimensional deep research.

Feasibility analysis of puncture robot technology for the application of acupuncture robot / 中国针灸

The difficulties such as how to accurately locate acupoints and safely insert needles are presented in acupuncture robot. The puncture robot with high technological similarity to acupuncture robot is getting mature, and a large number of human trials and animal experiments have been conducted for the development of puncture robot. Through comparing the similarities and differences between puncture robot and acupuncture robot in the aspects of through-skin puncture, needle insertion and needle removal, the valuable technology of puncture robot is analyzed for the development of acupuncture robot, and the crucial direction of technology migration is determined. ①Integrating the mechanical feedback and medical imaging technology and utilizing the multi-modal perception to achieve the safety of acupuncture operation. ②Emphasizing the integration of the existing designs of chest puncture robot to realize the acupuncture operation with inhalation and exhalation involved. ③Focusing on the development of relevant technology of automatic needle removal through conducting the actual scenario of treatment with acupuncture robot in patients under non-anaesthetic condition.

The modified Valsalva maneuver in hypopharynx CT scan / 临床耳鼻咽喉头颈外科杂志

Objective:To analyze the significance and factors influencing of CT scan under the modified Valsalva maneuver. Methods:Clinical data of 52 patients with hypopharyngeal carcinoma diagnosed from August 2021 to December 2022 were collected, all patients had calm breathing CT scan and modified Valsalva maneuver CT scan. Compare the exposure effect of the aryepiglottic fold, interarytenoid fold, postcricoid area, piriform fossa apex, posterior hypopharyngeal wall, and glottis with each CT scanning method. The effects of age, neck circumference, neck length, BMI, tumor site, and T stage on the exposure effect were analyzed. Results:In 52 patients, 50 patients（96.15%） completed CT scan at once time. The exposure effect of the CT scan under modified Valsalva maneuver in the aryepiglottic fold, interarytenoid fold, postcricoid area, piriform fossa apex, posterior hypopharyngeal wall was significantly better than CT scan under calm breathing（Z=-4.002, -8.026, -8.349, -7.781, -8.608, all P<0.01）, while CT scan under modified Valsalva maneuver was significantly worse in glottis than CT scan under calm breathing（Z=-3.625, P<0.01）. In the modified Valsalva CT scan, age had no obvious effect on the exposure effect. The exposure effect was better with long neck length, smaller neck circumference, smaller BMI and smaller T stage. The exposure of postcricoid carcinoma was better than pyriform sinus carcinoma and posterior hypopharyngeal wall carcinoma. But differences were not all statistically significant. Conclusion:The anatomical structure of the hypopharynx was clearly under CT scan with modified Valsalva maneuver, which clinical application is simple, but the effect of glottis was worse. The influence of age, neck circumference, neck length, BMI, and tumor T stage on the exposure effect still needs further investigation.

Determination of prucalopride in human plasma by LC-MS/MS analysis / 中国药理学通报

Aim To develop an LC-MS/MS method for the determination of prucalopride(PCP)in human plasma.Methods Prucalopride -13CD3(dPCP)was used as the internal standard.The analytes were extracted from human plasma through liquid-liquid extraction method using ethyl acetate, followed by being dried, and then the reconstitution was injected into LC-MS/MS systems.Agilent ZORBAX SB C18(3.0×100 mm, 3.5 μm)column and isocratic elution system composing of methanol and 1 mmol·L-1 ammonium acetate(80:20, V/V)provided chromatographic separation of PCP and dPCP.AB Sciex API4000 mass spectrometer equipped with an electrospray ionization source in positive ion mode was employed for mass detection, and data acquisition was carried out in multiple reaction monitoring(MRM)mode.The mass transition ion-pair was followed as m/z 368.4/196.0 for PCP and m/z 374.4/198.0 for dPCP.Results PCP and dPCP were eluted at 3.6 min, with no interference in human blank plasma.PCP in human plasma showed good linearity over the concentration range of 0.058 96-7.547 μg·L-1 with the correlation coefficient of 0.996 3-0.999 6.The lower limit of quantitation of this method was 0.058 96 μg·L-1.The intra-batch and inter-batch accuracy ranged from 98.29% to 108.2%, with good precision(CV<5.2%).The average matrix factors of normal, haemolysed and lipaemic matrix human samples all ranged from 96.48% to 106.3% with CV less than 8.39%.The average extraction recoveries of PCP at low, medium and high concentrations were 89.88%, 95.27% and 94.52% respectively, with CV less than 7.21%.PCP was stable in human samples after 6 h at room temperature, 60 h at -20 ℃, 56 days or three freeze-thaw cycles at -80 ℃; meanwhile, the processed plasma samples remained stable after being stored for 24 hours in autosampler at 8 ℃.Furthermore, PCP in human blood samples was proved to be stable after 4 h at room temperature.Conclusions The present LC-MS/MS method for the determination of PCP in human plasma was convenient, accurate, sensitive, stable, specific and reproducible and was proved to be suitable for the clinical pharmacokinetics and bioequivalence studies of PCP preparations.

Effect of Decitabine on Regulatory T Cells Relative Content in Peripheral Blood and Bone Marrow of Patients with Myelodysplastic Syndrome/Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate regulatory T cells (Tregs) relative content in peripheral blood and bone marrow of patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) treated with or without decitabine (DAC), analyze the immunomodulatory of Tregs in pathogenesis and remission of MDS and AML, as well as effect of DAC on Tregs.@*METHODS@#From October 2018 to February 2019, 15 patients with MDS and 49 patients with AML (newly diagnosed, treated with DAC or other chemotherapy regimens) were enrolled in this study, and 14 cases with iron deficiency or megaloblastic anemia while without malignant tumor and autoimmune disease as controls. The Tregs relative contents in bone marrow and peripheral blood were analyzed by flow cytometry, meanwhile clinical data of the objects were collected.@*RESULTS@#In peripheral blood and bone marrow of the patients with MDS and AML, the Tregs relative contents at newly diagnosed were higher than those of the control group (P=0.05, P=0.043). The Tregs relative content of AML patients in DAC regimen treatment group was significantly lower than that in the newly diagnosed group and non-DAC chemotherapy group (P<0.05). In DAC regimen treatment group, the Tregs relative contents was significantly lower in remission group than in non-remission group (P<0.05). There was no difference between DAC regimen treatment group and control group in Tregs relative content.@*CONCLUSION@#DAC may increase the body's anti-tumor immunity by consuming Tregs content, enhance the body's immune function to identify and kill tumor cells, thereby promote the patients' reliefs.

Role of DNMT3a in Hydroquinone-Induced Hematopoietic Stem Cell Toxicity / 中国实验血液学杂志

OBJECTIVE@#To investigate the regulatory effect and mechanism of DNA methyltransferase 3A (DNMT3a) in hydroquinone-induced hematopoietic stem cell toxicity.@*METHODS@#Cells (HSPC-1) were divided into 4 groups, that is A: normal HSPC-1; B: HQ-intervented HSPC-1; C: group B + pcDNA3 empty vector; D: group B + pcDNA3- DNMT3a. RT-qPCR and Western blot were used to detect the expression levels of DNMT3a and PARP-1 mRNA and protein, respectively. Cell morphology was observe; Cell viability and apoptosis rate of HSPC-1 were detected by MTT and flow cytometry, respectively.@*RESULTS@#Compared with group A, the expression levels of DNMT3a mRNA and protein in HSPC-1 of group B were decreased, while PARP-1 mRNA and protein were increased (P<0.05); there was no significant difference in the above indexes between group C and group B; compared with group B, the expression levels of DNMT3a mRNA and protein showed increased, while PARP-1 mRNA and protein were decreased significantly in cells of group D transfected with DNMT3a (P<0.05). Cells in each group were transfected with DNMT3a and cultured for 24 h, HSPC-1 in group A showed high density growth and mononuclear fusion growth, while the number of HSPC-1 in group B and C decreased and grew slowly. Compared with group B and C, the cell growth rate of group D was accelerated. The MTT analysis showed that cell viability of HSPC-1 in group B were lower than that of group A at 24 h, 48 h and 72 h (P<0.05); after transfected with DNMT3a, the cell viability of HSPC-1 in group D were higher than that of group B at 24 h, 48 h and 72 h (P<0.05). The apoptosis rate of cells in group B was significantly higher than that of group A (P<0.001), while the apoptosis rate in group D was lower than that of group B (P<0.001).@*CONCLUSION@#DNMT3a may be involved in the damage of hematopoietic stem cells induced by hydroquinone, which may be related to the regulation of PARP-1 activity by hydroquinone-inhibited DNMT3a.

Pharmacokinetics and bioequivalence study of efavirenz tablets in healthy Chinese subjects under fasting administration / 药学学报

A randomized, open, fasting, single dose, two sequence, two cycle and double cross administration trial design was adopted. Took the test or reference efavirenz tablets of 200 mg orally in a single time. The plasma concentration of efavirenz in healthy subjects was determined by LC-MS/MS. WinNonLin8.1 software was used to calculate the main pharmacokinetic parameters of efavirenz and to evaluate the bioequivalence. The main pharmacokinetic parameters within 72 h: tmax were 2.574 ± 0.871 and 2.808 ± 0.912 h; Cmax were 1 586.732 ± 424.538 and 1 549.518 ± 366.086 ng·mL-1; AUC0-72 h were 28 464.672 ± 5 682.518 and 27 828.826 ± 5 082.487 h·ng·mL-1; t1/2 were 63.524 ± 26.037 and 58.748 ± 20.950 h; λz were 0.013 ± 0.006 and 0.013 ± 0.005 h-1. The main bioequivalence indicators were as follows: The 90% confidence interval of Cmax was 95.62%-107.15%, and the geometric mean ratio was 101.22%; The 90% confidence interval of AUC0-72 h was 100.43%-104.38%, and the geometric mean ratio was 102.38%. The results showed that the main pharmacokinetic parameters of the test drug and the reference drug were similar, and the two preparations had bioequivalence. This human bioequivalence clinical study was approved by the drug clinical trials ethics committee of the Second Hospital of Anhui Medical University (ethics approval No.: YW2021-110).

Robot-assisted laparoscopic total hysterectomy in a patient with giant uterine fibroids and complex pelvic adhesions: a case report / 南方医科大学学报

We report a case of giant hysteromyoma and complex pelvic adhesion treated by robotic assisted laparoscopic total hysterectomy and bilateral salpingectomy. The patient was diagnosed with uterine fibroids after physical examination in 1998 but did not receive any treatment, and regular examinations reported progressive growth of the fibroids. Ultrasound suggested multiple uterine fibroids, and pelvic MRI indicated large uterine fibroids with bleeding. Robot-assisted laparoscopic total hysterectomy and bilateral salpingectomy were performed after relevant examinations, and the operation was completed smoothly. The patient was discharged 4 days after surgery with good appearance of the abdominal wall and good recovery during the follow-up. With its unique advantages, robot-assisted laparoscopy provides a minimally invasive surgical approach for giant hysterectomy with complex pelvic adhesions.

Comparative Analysis of Lonicera japonica Flower from Different Harvesting Periods Based on UV Fingerprint and Chemometrics / 中国实验方剂学杂志

ObjectiveTo investigate the quality variation of Lonicera japonica flower from different harvesting periods by ultraviolet visible（UV-Vis） fingerprint combined with chemometrics. MethodTwenty-five L. japonica flower samples from five harvesting periods， including young bud stage，green bud stage，white bud stage，silver and golden flower stages， were collected， with five samples for each stage. UV-Vis fingerprints of L. japonica flower from different harvesting periods were established in the context of the optimum extraction method based on the single factor experiment. The results showed that the absorption values at 209，216，226，250，280，303，318， and 350 nm were significantly different. Moreover，after data pretreatment and normalization，multivariate statistical analyses， such as principal component analysis （PCA），partial least squares discriminant analysis （PLS-DA），and orthogonal PLS-DA （OPLS-DA）were performed by SIMCA-P+ to establish the quality variation model of L. japonicas flower from harvesting periods. ResultAs revealed by PCA and PLS-DA， L. japonicas flower samples from five harvesting periods were clustered separately and closely in a harvesting time-dependent manner， suggesting that the content of components contained in samples from different harvesting periods was highly distinct and correlated with harvesting periods. The pairwise comparison of OPLS-DA indicated that triterpenoids or volatile oils were the main components causing the changes from the young bud stage to the green bud stage，and the content of them decreased. The main components from the green bud stage to the white bud stage were triterpenoids （or iridoids），volatile oils，phenolic acids， or flavonoids，and the content of them decreased， which was consistent with the HPLC result of chlorogenic acid. From the white bud stage to the silver flower stage， the main components were iridoids （increasing in content） and triterpenoids （or volatile oils） （decreasing in content）. The main altered components from the silver flower stage to the golden flower stage were triterpenoids （or volatile oils） whose content increased. ConclusionThis method is simple and feasible， which can provide references for the quality control of Chinese medicine.

Effect and Mechanism of Prunellae Spica on Metabolic Syndrome in Rats / 中国实验方剂学杂志

ObjectiveMetabolic syndrome is the inherent phenotype of many diseases， which seriously endangers the cardio-cerebrovascular system. Prunellae Spica can regulate lipid metabolism disorder in high-fat mice and inhibit the metabolic disorder of liver injury. This study analyzed the effect of Prunellae Spica on metabolic syndrome and its mechanism， and it is of great significance to find potential safe drugs from natural products. MethodIn this study， the metabolic syndrome model was induced by fructose. The metabolomics method based on gas chromatography-mass spectrometry （GC-MS） was used to explore the effect and mechanism of Prunellae Spica on rats with metabolic syndrome. ResultPharmacological results showed that Prunellae Spica significantly reduced the body weight， blood lipid level and lipid peroxidation level and inhibited the release of tumor necrosis factor-α （TNF-α） in rats with metabolic syndrome. Thus， Prunellae Spica protected the liver and maintained its normal functions. Multivariate statistical analysis revealed that metabolites in the serum of rats with metabolic syndrome changed significantly， which was improved after Prunellae Spica treatment. Compared with the metabolites in normal group， 11 differential metabolic markers were found in rats with metabolic syndrome. Compared with model group， Prunellae Spica group had 8 significantly different metabolic markers， among which phosphate， pyruvic acid and succinic acid were common markers. Pathway analysis indicated that the regulatory effect of Prunellae Spica was mainly related to citrate cycle， glycolysis and gluconeogenesis， serine/threonine and glycine metabolic pathways. ConclusionPrunellae Spica can be used as a potential natural source for the treatment of metabolic syndrome. It can regulate the metabolic disorder in metabolic syndrome via energy and amino acid metabolism.

Predictive model of curative effect of mite subcutaneous immunotherapy in 5-18 years of age patients with allergic asthma / 中华儿科杂志

Objective: To analyze the factors affecting the efficacy of mite subcutaneous immunotherapy (SCIT) in allergic asthma patients aged 5-18 years, and to find the best predictive model for the curative effect. Methods: The data of 688 patients aged 5-18 years with allergic asthma who completed more than 3 years of mite SCIT from December 2006 to November 2021 in the Department of Respiratory Medicine, Children's Hospital Affiliated to Nanjing Medical University were retrospectively analyzed. Male, results of skin prick test (SPT), age, daily medication score (DMS), visual analogue scale (VAS) score, and enrollment season were defined as independent variables. R language models, including Logistic regression model, random forest model and extreme gradient boosting (XGboost) model, were used to analyze the impact of these independent variables on the outcomes. The receiver operating characteristic curve was applied to compare the predictive ability of the models. Hypothesis testing of the area under curve (AUC) of the 3 models was performed using DeLong test. Results: There were 435 males and 253 females in the 688 patients. There were 349 patients aged 5-<8 years, 240 patients aged 8-<11 years, and 99 patients aged 11-18 years. SPT showed that 429 cases (62.4%) were only allergic to mite, and 259 cases (37.7%) were also allergic to other allergens. According to the efficacy after 3 years of SCIT, 351 cases (51.0%) discontinued the treatment and 337 cases (49.0%) required continued treatment. The DMS was 4 (3, 6) at initiation, 3 (2, 5) at 3 months, 3 (2, 5) at 4 months, 2 (1, 3) at 12 months, and 0 (0, 1) at 3 years of SCIT treatment. The VAS was 3.5 (2.5, 5.2) at initiation, 3.2 (2.2, 4.8) at 3 months, 2.6 (1.4, 4.1) at 4 months, 1.0 (0.6, 1.8) at 12 months, and 0.5 (0, 1.2) at 3 years of treatment. At 3, 4, and 12 months, the rate of decline in DMS was 0 (0, 20%), 16.7% (0, 33.3%), and 50.0% (31.0%, 75.0%), respectively; and the VAS decreased by 7.1% (3.2%,13.8%), 27.6% (16.7%,44.4%), and 70.2% (56.1%, 82.3%), respectively. Regarding the enrollment season, 99 cases were in spring, 230 cases in summer, 171 cases in autumn, and 188 cases in winter. The R language Logistic regression model found that DMS>3 points at 3 months (OR=-3.5, 95%CI:-4.3--2.7, P<0.01), male (OR=-1.7, 95%CI:-2.3--1.0), P<0.01), DMS decline rate>16.7% at 4 months (OR=-1.6, 95%CI:-2.3--0.8, P<0.01) and DMS decline rate>0 at 3 months (OR=-0.7, 95%CI:-1.3--0.2, P<0.05) had higher possibility of drug discontinuation; whereas, the decline rate of DMS at 12 months>50.0% (OR=0.7, 95%CI: 0.1-1.3, P<0.05), VAS at 12 months>1.0 points (OR=0.9, 95%CI: 0.3-1.6, P<0.05), and initial VAS<4.0 points (OR=1.0, 95%CI: 0.4-1.6, P<0.01) had lower possibility of drug discontinuation. Both the random forest model and the XGboost model showed that DMS>3 points at 3 months (mean decrease accuracy=30.9, importance=0.45) had the greatest impact on drug discontinuation. The AUC of the random forest model was the largest at 0.900, with an accuracy of 78.2% and a sensitivity of 84.5%. Logistic regression model had AUC of 0.891, accuracy of 80.0%, and sensitivity of 80.0%; XGboost model had AUC of 0.886, accuracy of 76.9%, and sensitivity of 84.5%. The AUC of the pairwise comparison model by DeLong test found that all three models could be used for the prediction of this data set (all P>0.05). Conclusions: The more drugs used to control the primary disease, and the more careful reduction of the control medicine after starting SCIT treatment, the more favorable it is to stop all drugs after 3 years. The random forest model is the best predictive model for the efficacy of mite SCIT in asthmatic children.

Effect and mechanism of vascular endothelial growth factor-A on pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension / 中国当代儿科杂志

OBJECTIVE@#To study the role of vascular endothelial growth factor-A (VEGF-A) in pulmonary vascular remodeling in neonatal rats with hypoxic pulmonary hypertension (HPH) by regulating survivin (SVV).@*METHODS@#A total of 96 neonatal rats were randomly divided into three groups: HPH+VEGF-A group, HPH group, and control group. Each group was further randomly divided into 3-, 7-, 10-, and 14-day subgroups (@*RESULTS@#The HPH group had a significantly higher mean RVSP than the control and HPH+VEGF-A groups at each time point (@*CONCLUSIONS@#Prophylactic intratracheal administration of exogenous VEGF-A in neonatal rats with HPH can inhibit pulmonary vascular remodeling and reduce pulmonary arterial pressure by upregulating the expression of SVV in the early stage of hypoxia. This provides a basis for the interventional treatment of pulmonary vascular remodeling in neonatal HPH.

Expert Consensus on Otorhinolaryngology Head and Neck Diseases Responding Specifically to Traditional Chinese Medicine / 中国实验方剂学杂志

Traditional Chinese medicine （TCM） and western medicine have their respective advantages and limitations in the diagnosis and treatment of common otorhinolaryngology head and neck diseases. Although the integrated TCM and western medicine exhibits definite curative effects， there is no consensus on the otorhinolaryngology head and neck diseases responding specifically to TCM or integrated TCM and western medicine， as well as the diagnosis and treatment schemes. The China Association of Chinese Medicine （CACM） thus organized the otorhinolaryngology head and neck specialists of both TCM and western medicine to discuss the etiology， pathogenesis， and clinical diagnosis and treatment methods of common otorhinolaryngology head and neck diseases with the results of multiple clinical trials taken into account. The acute pharyngitis， chronic pharyngolaryngitis， paraesthesia pharyngis， hysterical aphasia， allergic rhinitis， subjective tinnitus， and otogenic vertigo were confirmed to respond specifically to TCM or integrated TCM and western medicine. Then a mutually agreed diagnosis and treatment scheme and recommendation with integrated TCM and western medicine was formulated as a reference for clinical practice， thus benefiting more patients.