Development and prospects of predicting drug polymorphs technology / 药学学报

Most chemical medicines have polymorphs. The difference of medicine polymorphs in physicochemical properties directly affects the stability, efficacy, and safety of solid medicine products. Polymorphs is incomparably important to pharmaceutical chemistry, manufacturing, and control. Meantime polymorphs is a key factor for the quality of high-end drug and formulations. Polymorph prediction technology can effectively guide screening of trial experiments, and reduce the risk of missing stable crystal form in the traditional experiment. Polymorph prediction technology was firstly based on theoretical calculations such as quantum mechanics and computational chemistry, and then was developed by the key technology of machine learning using the artificial intelligence. Nowadays, the popular trend is to combine the advantages of theoretical calculation and machine learning to jointly predict crystal structure. Recently, predicting medicine polymorphs has still been a challenging problem. It is expected to learn from and integrate existing technologies to predict medicine polymorphs more accurately and efficiently.

Efficacy comparison of Jensen and augmented Hummelsheim procedure in the treatment of complete paralytic esotropia / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the efficacy of Jensen and augmented Hummelsheim procedures in the treatment of complete paralytic esotropia.METHOD: A total of 35 patients(44 eyes)who were diagnosed with complete paralytic esotropia from October 2016 to October 2020 were retrospectively analyzed, of which 15 cases(21 eyes)underwent Jensen procedure combined with recession of antagonist muscle(Jensen procedure group), and 20 cases(23 eyes)received augmented Hummelsheim procedure combined with recession of antagonist muscle(Hummelsheim procedure group). The operation time, preoperative and postoperative esotropia deviation, degree of abduction paralysis, recession of medial rectus muscle and cure rate were observed.RESULTS: Clinical data and operation time of the patients in two groups were not statistically significant(P >0.05). During the last follow-up, the esotropia deviation of Jensen procedure group decreased from 102.33±41.70PD to 3.93±4.82PD(P<0.001), and it decreased from 94.75±33.03PD to 2.85±5.96PD in Hummelsheim procedure group(P<0.001), while the degree of abduction paralysis were significantly improved from -4.81±0.40 to -1.57±0.51 in the Jensen procedure group(P<0.001)and from -4.91±0.29 to -1.22±0.42 in Hummelsheim procedure group(P<0.001). Besides, there was no statistical difference in postoperative esotropia deviation between the two groups(P>0.05), but the degree of postoperative abduction paralysis in the Hummelsheim procedure group was significantly better than that of Jensen procedure group(P<0.05). The recession of medial rectus muscle of the two groups were 7.16±2.07 and 6.37±2.34 mm, respectively(P>0.05). During the last follow-up, in the Jensen procedure group, 2 patients were undercorrection(+10PD and +12PD respectively)and 13 cases(87%)were cured. In the Hummelsheim procedure group, 1 patient was undercorrection(+25PD)and 19 patients were cured(95%), and there was no statistical significance in cure rates of the two groups(P=0.565).CONCLUSIONS: Both Jensen procedure and augmented Hummelsheim procedure can effectively treat complete paralytic esotropia, and the latter is more effective in improving the abduction paralysis.

Mismatched donor cell infusion-related syndrome following microtransplant in patients with acute myeloid leukemia / 中华医学杂志(英文版)

BACKGROUND@#Immunotherapies such as adoptive immune cell infusion and immune-modulating agents are widely used for cancer treatment, and the concomitant symptoms, including cytokine release syndrome (CRS) or immune-related adverse events (irAEs), are frequently reported. However, clinical manifestations induced by mismatched donor granulocyte colony-stimulating factor mobilized peripheral blood mononuclear cell (GPBMC) infusion in patients receiving microtransplant (MST) have not yet been well depicted.@*METHODS@#We analyzed 88 cycles of mismatched GPBMC infusion in patients with acute myeloid leukemia receiving MST and 54 cycles of chemotherapy without GPBMC infusion as a comparison. Clinical symptoms and their correlation with clinical features, laboratory findings, and clinical response were explored.@*RESULTS@#Fever (58.0% [51/88]) and chills (43.2% [38/88]) were the significant early-onset symptoms after GPBMC infusion. Patients possessing less human leukocyte antigen-matching loci with the donor or those with unrelated donors experienced more chills (3 [2-5] loci vs. 5 [3-5] loci, P  = 0.043 and 66.7% [12/18] vs. 37.1% [26/70], P  = 0.024). On the other hand, those with decreased CD4 + /CD8 + T-cell ratio developed more fever (0.8 [0.7-1.2] vs. 1.4 [1.1-2.2], P  = 0.007). Multivariable analysis demonstrated that younger patients experienced more fever (odds ratio [OR] = 0.963, 95% confidence interval [CI]: 0.932-0.995, P  = 0.022), while patients with younger donors experienced more chills (OR = 0.915, 95% CI: 0.859-0.975, P  = 0.006). Elevated ultra-sensitive C-reactive protein levels in the absence of cytokine storm were observed following GPBMC infusion, which indicated mild and transient inflammatory response. Although no predictive value of infusion-related syndrome to leukemia burden change was found, the proportion of host pre-treatment activated T cells was positively correlated with leukemia control.@*CONCLUSIONS@#Mismatched GPBMC infusion in MST induced unique infusion-related symptoms and laboratory changes, which were associated with donor- or recipient-derived risk factors, with less safety and tolerance concerns than reported CRS or irAEs.

Clinical characteristics and treatment of patients with acute acquired concomitant esotropia in different refractive status / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the clinical characteristics and treatment of patients with acute acquired concomitant esotropia(AACE)in different refractive status.METHODS: A retrospective analysis was conducted on 110 patients with non-type I AACE treated from January 2020 to January 2022. The non-myopic group(30 cases, spherical equivalent>-0.5D)and the myopic group(80 cases, spherical equivalent≤-0.5D)were divided according to the refractive status. The degree of deviation, accommodative convergence and accommodation ratio(AC/A), visual function, and surgical methods were observed. RESULTS: The non-myopic group had no difference in the degree of near deviation [(47.13±23.54)△] and the degree of distant deviation [(48.90±22.59)△](P>0.05); near deviation [(40.49±26.09)△] of myopic group was less than distant deviation [(50.09±25.41)△](P<0.001); and there was no difference in the same distance between the two groups(P>0.05). AC/A in the non-myopic group(5.40±2.23)was higher than that in the myopic group(3.14±3.10; P<0.05). Patients in the myopic group had better near stereopsis than the non-myopic group(P<0.05). The non-myopic group had a variety of surgical methods, while the myopic group mostly used lateral rectus resection or/and medial rectus recession.CONCLUSION: AACE can occur in different refractive status. Non-myopic patients have the same degree of distant and near strabismus, high AC/A, and varied surgical methods. However, myopic patients have less degree of near deviation than distant deviation and have normal AC/A and better near stereopsis, and lateral rectus resection or/and medial rectus recession are commonly used.

The effect of Endocrine disrupting chemicals on myocardial fibrosis and related mechanism / 中华劳动卫生职业病杂志

Endocrine-disrupting chemicals (EDCs) an exogenous agent that interferes with the synthesis, secretion, transport, binding, action, or can mimic the occurrence of natural hormones that damage for the balance of homeostasis. Exposure to EDCs results in damage to human health that may persist in the long term. In recent years, accumulative evidence has demonstrated that EDCs also play a pivotal role in the onset and development of myocardial fibrosis, including heart failure, hypertension and vascular stiffening. Studies indicate that EDCs plays the negative effects of the cardiovascular system, however, EDCs-induced toxicity on heart remains unclear. This review summarized EDCs-induced myocardial fibrosis, and discuss the possible mechanisms of myocardial fibrosis induced by EDCs. This paper could provide further understandings for prevention, diagnosis and treatment of myocardial fibrosis.

Effect and influence factors of cardiopulmonary resuscitation in children with congenital heart disease in pediatric intensive care unit / 中华儿科杂志

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ2=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ2=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.

Comparison of the objective ocular torsion measured with GMPE module-based OCT and fundus color photography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To compare the consistency and feasibility of objective ocular torsion measured with GMPE module-based optical coherence tomography(OCT)and fundus color photography(FCP).METHODS: Patients were enrolled in our strabismus clinic from December 2020 to March 2021, and the objective ocular torsion of the eyes was measured by both GMPE module-based OCT and FCP on the same day. FCP was used to measure the fovea-disc angle(FDA)manually by using the Adobe Photoshop software, while the GMPE module-based OCT software positioned automatically the macula and the center of the optic disc to measure the FDA.RESULTS: Fifty-five patients were included, the FDA measured by OCT was -6.6°±4.5° in the right eye and -8.8°±4.7° in the left eye, respectively; The FDA measured by FCP was -6.6°±4.7° in the right eye and -8.4°±4.1° in the left eye, respectively, with no statistically significant difference between the results of the two methods(Pright eye=0.90, Pleft eye=0.08). In patients with exotropia, the FDA measured by OCT was -5.8°±4.9° in the right eye and -9.1°±4.5° in the left eye, respectively, the FDA measured by FCP was -5.7°±5.0° in the right eye and -8.6°±4.3° in the left eye, respectively,(Pright eye=0.75, Pleft eye=0.15). Similarly, the patients with esotropia, the FDA measured by OCT was -9.0°±7.3° in the right eye and -11.3°±3.5° in the left eye, respectively, while the FDA measured by FCP was -10.0°±7.0° in the right and -10.1°±2.8° in the left eye(Pright eye=0.21, Pleft eye=0.10), respectively. There were no significant differences between the two methods in patients with esotropia or exotropia(P>0.05). The results of both Pearson test and Bland-Altman analysis were highly correlated(rright eye=0.93, rleft eye=0.94, P<0.01). CONCLUSION: GMPE module-based OCT can be used for objective ocular torsion measurement with high reliability and reproducibility, and is a promising clinical alternative to the fundus color photographic method.

Herbal Textual Research on Schizonepetae Herba in Famous Classical Formulas / 中国实验方剂学杂志

In this paper， the name， classification， origin and other aspects of Schizonepetae Herba in the famous classical formulas were researched by referring to the related herbal literature， medical books and prescription books in the past dynasties. The results showed that Schizonepetae Herba first appeared in Shennong Bencaojing （《神农本草经》） as Jiasu， while Jingjie first appeared in Wupu Bencao （《吴普本草》）， and the name of Jingjie was mainly used as the rectification of name in later generations. The name of Jiasu is mostly derived from its smell， and the name of Jingjie is mostly derived from its pronunciation. Schizonepeta tenuifolia has been highly praised in the past as a original material， and its genuine producing area is Jiangsu， Hebei and other places， medicinal part is whole herb with spike. In modern times， the quality of Schizonepetae Herba is best described as having thin stems， green spike， and aroma. In clinical application， the raw products of Schizonepetae Herba is mainly used， and the carbonisata is mainly used for hemostasis. Famous classical formulas of Huaihuasan and Danggui Yinzi are all made of Schizonepetae Spica， so it is recommended to use the dried panicle of S. tenuifolia. In Liangxue Dihuangtang， Schizonepetae Herba Carbonisata is used， therefore， it is suggested to adopt the processing method of Schizonepetae Herba Carbonisata in the 2020 edition of Chinese Pharmacopoeia.

Inferior oblique belly transposition in the treatment of mild inferior oblique overaction with small angle vertical strabismus / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM:To observe the effect of inferior oblique belly transposition(IOBT)in unilateral mild inferior oblique overaction with small angle vertical stabismus.<p>METHODS: The data of patients who underwent IOBT in our hospital from September 2019 to August 2021 were analyzed retrospectively. Inclusion criteria targeted patients with mild inferior oblique overaction(2+ and below)and small angle incomitant vertical strabismus(4-9PD). The horizontal deviation and vertical deviation in both primary and lateral gazes were measured, and the degree of inferior oblique overaction and fovea-disc angle(FDA)were also evaluated preoperatively and postoperatively.<p>RESULTS: A total of 16 cases(16 eyes)were included, aged 4-39 years. One case was 5a postoperative congenital esotropia with secondary unilateral inferior oblique overaction by mild superior oblique palsy, whereas 15 patients had monocular primary inferior oblique overaction with horizontal strabismus. The follow-up was 3-6mo. The mean improvement of inferior oblique overaction was 2.00(1.25, 2.00)grade from +2.00(2.00, 2.00)preoperatively to 0.00(0.00, 0.00)postoperatively, the difference was statistically significant(<i>Z</i>=-3.70, <i>P</i><0.001). The horizontal strabismus decreased from 69.13±25.86PD preoperatively to 2.75±2.59PD postoperatively(<i>t</i>= 9.929, <i>P</i><0.001). The vertical strabismus in the primary position decreased from preoperative 7.44±1.32PD to 1.00±1.21PD postoperatively(<i>t</i>=22.335, <i>P</i><0.001), mean corrected hypertropia 6.44±1.15PD, and vertical strabismus in lateral gazes decreased from preoperative 12.44±2.73PD to 3.00±2.13PD postoperatively, mean corrected hypertropia 9.44±2.73PD, these differences were statistically significant(<i>t</i>=13.819, <i>P</i><0.001). The FDA decreased from -8.85°±6.53° preoperatively to -6.49°±7.01° postoperatively, the difference was statistically significant(<i>t</i>=-2.384, <i>P</i><0.001), with a mean reduction of 2.36°. No postoperative complications such as postoperative overcorrection or inferior oblique underaction were observed.<p>CONCLUSION:IOBT is safe and effective in correcting unilateral mild inferior oblique overaction with small angle vertical strabismus.

Research on the role of miR-125b-1-3p in rotavirus replication / 中华微生物学和免疫学杂志

Objective:To investigate the role and regulatory mechanism of miR-125b-1-3p in rotavirus replication.Methods:MA104 cells were infected with rotavirus after upregulation and down-regulation of miR-125b-1-3p, respectively. The expression of miR-125b-1-3p and the copy number of rotavirus were analyzed by RT-PCR. The effect of miR-125b-1-3p on the protein expression of rotavirus was analyzed by immunofluorescence. The expression of related proteins involved in the regulation of miR-125b-1-3p was analyzed by Western blot analysis.Results:After rotavirus infection, the expression level of miR-125b-1-3p was significantly up-regulated, the copy number of VP7 and NSP3 gene of rotavirus decreased after up-regulation of miR-125b-1-3p, and the copy number of VP7 and NSP3 gene of rotavirus was significantly increased after down-regulation of miR-125b-1-3p.The fluorescence number of rotavirus protein decreased after upregulation of miR-125b-1-3p expression level, and increased after down-regulation of miR-125b-1-3p expression level. The activity of PI3K/Akt pathway was inhibited 16 h after rotavirus infection, and the up-regulation of miR-125b-1-3p could inhibit the activation of PI3K/Akt pathway.Conclusions:MiR-125b-1-3p inhibits rotavirus replication by regulating the PI3K/Akt pathway. These results provide an experimental basis for exploring the specific regulatory mechanism between miR-125b-1-3p and PI3K/Akt pathway, and provide a target for anti-infection therapy of rotavirus.

Effect of D-dimer abnormality on the prognosis of patients with frontal lobe injury / 中华急诊医学杂志

Objective:To investigate the effect of abnormal D-dimer level on the prognosis of patients with frontal lobe injury, and to provide a new idea for clinical diagnosis, treatment and prognosis evaluation of frontal lobe injury.Methods:A retrospective analysis was performed on 71 patients with traumatic brain injury (TBI) who were admitted to the Surgical Care Unit of the First Affiliated Hospital of Zhejiang University School of Medicine from November 1, 2020 to February 1, 2021. According to whether TBI involved in the frontal lobe, the patients were divided into the experimental group ( n = 44) and the control group ( n = 27). Clinical data including sex, age, body mass index (BMI), length of hospital stay, ISS trauma score, GCS coma score, qSOFA score, GOS prognostic score and coagulation index test results within 24 h of admission of the two groups were recorded, and the difference of each index between the two groups was compared. Results:① D-dimer levels were significantly higher in the experimental group than in the control group ( P<0.01); ② The incidence of complications in the experimental group was 40.9%, of which the incidence of lower limb vein thrombosis was 18.2%, and the incidence of complications in the control group was 18.5%, of which the incidence of lower limb vein thrombosis was 3.7%; there were statistical differences between the two groups ( P<0.05); ③ The average hospital stay of patients was 10.96 days in the control group, and 15.50 days in the experimental group with a statistically significant difference between the two groups ( P<0.05); ④ The 28-day mortality rate of patients in the experimental group was 18.2% and 7.4% in the control group. There was no significant difference in 28-day mortality between the two groups ( P>0.05); ⑤ The level of D-dimer was negatively correlated with GOS prognostic score in patients with frontal lobe injury ( r=-0.501, P<0.01). Conclusions:Patients with frontal lobe injury have increased D-dimer levels, increased incidence of complications, and longer hospital stay. There is a significant negative correlation between D-dimer level and prognosis in patients with frontal lobe injury. D-dimer can be used as a sensitive indicator to evaluate the prognosis of patients with frontal lobe injury. The higher the D-dimer level, the worse the prognosis of patients.

Chinese Medicine Involving Triple Rehabilitation Therapy for Knee Osteoarthritis in 696 Outpatients: A Multi-Center, Randomized Controlled Trial / 中国结合医学杂志

OBJECTIVE@#To determine the effects of Chinese medicine (CM) involving triple rehabilitation therapy on the progression of knee osteoarthritis (KOA).@*METHODS@#A total of 722 patients recruited from 38 community health service centers located in China from March 2013 to March 2017 were randomly divided into treatment and control groups equally, using a cluster randomization design. Health education combined with CM involving triple rehabilitation therapy for KOA (electro-acupuncture, Chinese medicinal herb fumigating-washing, and traditional exercises) was administered in the treatment group while conventional rehabilitation therapy (physical factor therapy, joint movement training, and muscle strength training) was administered in the control group. Patients with a visual analog scale (VAS) scores ≽4 were treated with dispersible meloxicam tablets (7.5 mg, once daily). The Lequesne index scores, VAS scores, range of motion (ROM), lower limb muscle strength, knee joint circumference, quantitative scores of KOA symptoms, and the short-form 36 item health survey questionnaire (SF-36) scores were measured for each patient at 5 checkpoints (before treatment, at the 2nd week and the 4th week during the 4-week treatment period, at 1 month and 3 months after end of treatment), and adverse reactions were observed also.@*RESULTS@#A total of 696 patients completed the entire process, with 351 in the treatment group and 345 in the control group. At all treatment checkpoints, the treatment group demonstrated better outcomes than the control group with regard to the total Lequesne index scores, effective rate and improvement rate of the total Lequesne index scores, VAS scores, lower limb muscle strength, knee circumference, quantitative scores of KOA symptoms, and SF-36 scores as well (P<0.05 or P<0.01). No adverse reactions were encountered in this study.@*CONCLUSIONS@#CM involving triple rehabilitation therapy can alleviate KOA-related pain and swelling, improve lower limb muscle strength, promote flexion and activity of the knee and improve the quality of life in patients undergoing KOA. It is suitable for patients with early or mid-stage KOA. (Registration No. ChiCTR-TRC-12002538).

The Effect of γ-secretase Inhibitor Combined with BMSC on the aGVHD in Mice Model / 中国实验血液学杂志

OBJECTIVE@#To establish the aGVHD mouse model，and investigate the regulatory effect and its mechanism of low-dose GSI combined with BMSC on aGVHD mice.@*METHODS@#C57BL/6 (H-2b) and BALB/c (H-2d) were selected as donor and recipient of allogeneic transplantation to establish the aGVHD mouse model. BALB/c mice were randomly divided into 6 groups, which were the bone marrow cell infusion after irradiation (BM) group; the bone marrow cells + spleen cells after irradiation (BM+SC) group; the bone marrow cells + spleen cells + DMSO (BM+SC+DMSO) (transplant control) group; bone marrow cells + splenocytes +GSI after irradiation (BM+SC+GSI) group; bone marrow cells + spleen cells + bone marrow mesenchymal stromal infusion after irradiation cell (BM+SC+BMSC) group; bone marrow cells + spleen cells + bone marrow mesenchymal stromal cells +GSI infused after irradiation (BM+SC+BMSC+GSI) group. The mice in the two groups containing GSI were intraperitoneally injected with GSI at 5 μmol/kg on day 1, 2, and 3 after transplantation with DMSO as a control. The general conditions, survival time and hematopoietic recovery of mice were observed, cytokines were detected by ELISA, and histopathological changes were detected by immunohistochemistry. The effects of low-dose GSI combined with BMSC on hematopoietic reconstruction and aGVHD development after allo-BMT were investigated.@*RESULTS@#The survival rate of the mice in BM+SC+BMSC+GSI combination group was 80% during the observation period, which was significantly higher than that in the other groups; the incidence of aGVHD was reduced in the BMSC GSI or their combination groups after 21 days of transplantation. GSI could partly promote the recovery of leukocytes, and show no significant delayed effect on the recovery platelets. Moreover, the level of Th1 cytokines (IFN-γ) in BM+SC+BMSC+GSI combined group was lower than that in BM+SC+GSI group (P<0.01), the level of Th2 cytokines (IL-4) in the combination group was higher than that in BM+SC+GSI group (P<0.01), also the level of IL-17 was significantly lower than that in the corresponding control group (P<0.001).@*CONCLUSION@#Low dose GSI combined with BMSC can promote hematopoietic reconstruction and regulate cytokines secretion including IFN-γ, IL-4 and IL-17. GSI combined with BMSC achieve the goal of synergistically inhibiting the occurrence and progression of aGVHD.

Quality evaluation of Saposhnikoviae Radix based on QAMS combined with information entropy-response surface method / 中国中药杂志

This research was used with high performance liquid chromatography(HPLC), combined with information entropy-response surface method(RSM) to investigate the ethanol concentration, extraction time, liquid-to-material ratio. Taking the content of four chromogens as evaluation indexes, the weight coefficients of each index were given, and the comprehensive score was calculated to optimize the extraction process. Then, prim-O-glucosylcimifugin was used as the reference, the relative calibration factors(RCFs) of cimifugin, 4'-O-β-D-glucosyl-5-O-methylvisamminol and sec-O-glucosylhamaudo to prim-O-glucosylcimifugin were calculated respectively. The contents of four components in Saposhnikoviae Radix were determined by both external standard method(ESM)and quantitative analysis of multi-components by single marker(QAMS) method, and the results were compared. At last, combined with principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) to evaluate the quality of the Saposhnikoviae Radix in different production areas. The optimal extraction process parameter of the Saposhnikoviae Radix was as follows: liquid-to-material ratio is 60∶1(mL·g~(-1)), extraction time is 35 min, and ethanol concentration is 70%. The repeatability of the RCFs was perfect, and the results calculated by the QAMS were consistent with the results from the ESM. The stoichiometric results indicate that there are obvious differences in the distribution of Saposhnikoviae Radix in different production areas, and cimifugin and prim-O-glucosylcimifugin are the characteristic compounds that cause this difference. In this study, the optimal extraction process is stable and feasible, and the method of QAMS is accurate and reliable. From the perspective of four chromogens, there are differences in the quality of the Saposhnikoviae Radix in different production areas. Therefore, the established extraction process combined with the method of QAMS can be used to evaluate the quality of Saposhnikoviae Radix and provide a scientific basis for the quality control of Saposhnikoviae Radix.

Analysis of Quality Markers Related to Expelling Phlegm and Arresting Coughing of Trichosanthis Fructus Based Pharmacokinetics and Multivariate Statistical Methods / 中国实验方剂学杂志

Objective:Based on pharmacokinetics， the antitussive and expectorant related quality markers （Q-marker） of Trichosanthis Fructus were screened from diosmetin-7-<italic>O</italic>-glucopyranoside， diosmetin， apigenin， vanillic acid and cinnamic acid， and the candidate Q-marker was evaluated by multivariate statistical method. Method:Six healthy rats were randomly selected and the 70% ethanol extract of Trichosanthis Fructus （dose of 20 g·kg^-1） was given by intragastric administration. Blood was collected from the orbital vein at different time points， and the plasma concentrations of 5 components （diosmetin-7-<italic>O</italic>-glucopyranoside， diosmetin， apigenin， vanillic acid and cinnamic acid） from Trichosanthis Fructus were detected simultaneously by high performance liquid chromatography-triple quadrupole tandem mass spectrometry （HPLC-QqQ-MS/MS）. The main detection conditions were as following：mobile phase of 0.2% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-4 min， 6%-23%B； 4-5 min， 23%-59.5%B； 5-10 min， 59.5%-60%B）， flow rate of 0.5 mL·min^-1， the detection wavelength at 254 nm， electrospray ionization （ESI）， positive ion mode detection， multiple reaction monitoring （MRM） mode scanning， scanning range of <italic>m</italic>/<italic>z</italic> 50-1 500. Diosmetin-7-<italic>O</italic>-glucopyranoside， diosmetin， apigenin and vanillic acid with clear pharmacokinetic behaviors were selected as candidate Q-marker about antitussive and expectorant of Trichosanthis Fructus. The contents of these components in 9 batches of medicinal materials were determined and the main detection conditions were the same as the pharmacokinetic study. SPSS 21.0 was used for cluster analysis and principal component analysis （PAC） based on the results of determination. Result:The pharmacokinetic results showed that the area under concentration-time curve （AUC_0-<italic>_t</italic>） of 4 components （diosmetin-7-<italic>O</italic>-glucopyranoside， diosmetin， apigenin and vanillic acid） were （111.28±9.94）， （27.08±2.76）， （1 376.12±101.86）， （631.32±64.72） μg·h·L^-1， respectively. The 9 batches of Trichosanthis Fructus samples were clustered into 3 groups by systematic cluster analysis. The clustering results were related to the variety of Trichosanthis Fructus and also affected by the origin. The PCA results showed that the comprehensive scores of Gaotang Trichosanthis Fructus， Shanxi Trichosanthis Fructus， Hebei Ben Trichosanthis Fructus were 1.919， 1.356 and 0.299， respectively， ranking in the top 3 among all samples. The comprehensive scores of Nongkeyuan No. 1， Hebei Trichosanthis Fructus and Nongkeyuan No. 2 were -0.804， -1.085， -1.120， respectively， which were in the last 3 positions among all samples. Conclusion:The pharmacokinetic characteristics and quality evaluation of diosmetin-7-<italic>O</italic>-glucopyranoside， diosmetin， apigenin and vanillic acid meet the requirements about antitussive and expectorant related Q-marker of Trichosanthis Fructus.

Dynamic changes of volatile components of Qiai from different harvest time based on GC-MS and chemometrics analysis / 中国中药杂志

Artemisiae Argyi Folium, the dried leaves of Artemisia argyi, has been widely used in traditional Chinese and folk medicines for a long time. Qiai is one of the top-geoherb of Artemisiae Argyi Folium. Qiai contains various bioactive constituents, such as volatile oils, phenolic acids, flavonoids and terpenoids. Phytochemical studies demonstrated that volatile compounds are the main bioactive constituents in Qiai. Try to investigate dynamic changes of volatile components of Qiai from different harvest time and explore the optimum harvest time of Qiai, in this study, the contents of total volatile oils in Qiai collected from five different harvest time were analyzed by steam distillation method. The results showed that the contents of volatile oils of Qiai were higher in the third harvest time(around the Dragon Boat Festival), which is basically consistent with the traditional harvest time. Furthermore, a sensitive method based on gas chromatography-mass spectrometry(GC-MS) was established for qualitative analysis of volatile compounds in Qiai, and a total of thirty volatile compounds were identified. Chemometrics methods including principal component analysis(PCA) and orthogonal partial least-squares discriminate analysis(OPLS-DA) were applied to explore chemical markers and dynamic changes of volatile components in Qiai from different harvest time, and the results indicated that there were obvious differences in the relative contents of volatile compounds of Qiai samples from different harvest time. Eight volatile compounds, including α-terpinene, γ-terpinene, D-camphor, trans-carveol, α-copaene, isobornylisobutyrate, humulene, and caryophyllene oxide were selected as potential chemical markers. Among the eight chemical markers, the relative contents of α-terpinene, γ-terpinene, α-copaene and caryophyllene oxide were higher in the third harvest period(around the Dragon Boat Festival), which is consistent with the contents of total volatile oils. The present study could provide the basis for investigating the optimum harvest time of Qiai, and might be useful for the quality control of this herbal medicine.

Effect of Tongfengning on Expression of Renal Urate Transporter in Hyperuricemia Rats / 中国实验方剂学杂志

Objective:Study on the mechanism of Tongfengning in promoting uric acid excretion from the perspective of urate transporter and mRNA in renal of hyperuricemia （HUA） model rats. Method:The 80 sprague-dawley rats were randomly divided into two groups， the blank group with 20 rats and the model group with 60 rats. Rats in model group were established as hyperuricemia （HUA） models by intraperitoneal injection of oxonic acid potassium salt （OAPS） and intragastric administration ethambutol hydrochloride （EMB） once a day for 21 days. After successful modeling， rats in the model group were divided into the model group， Tongfengning group and benzbromarone group， with 20 rats per group. Tongfengning solution （15.3 g·kg-1·d-1） was administered to the Tongfengning group by gavage feeding. Rats in benzbromarone group were administered 5.2 mg·kg-1·d-1 benzbromarone suspension， whereas those in the blank group and the model group were administered the equivalent amount of normal saline for 21 days. On days 14th and 21st following intervention， urine， blood， and kidney were collected from rats， serum uric acid （SUA） and urinary uric acid （UUA） levels， blood urea nitrogenand（BUN） and creatinine（CRE） levels and the expression of urate transporter proteins and their mRNAs of all rats were detected by enzyme-colorimetric method， urease method， sarcosine oxidase method， Western blot and Real-time quantitative PCR（Real-time PCR）， respectively. Result:On days 14th and 21th following intervention， compared with blank group， SUA， CRE and BUN levels， and urate transporter 1（URAT1），glucose transporter 9（GLUT9） expression increased（P<0.05，P<0.01）， whereas UUA level， and adenosine triphosphate-binding cassette transporter protein G2（ABCG2）， organic anion 1（OAT1）， organic anion 3（OAT3） expression decreased in the model group（P<0.05，P<0.01）. Compared with model group， SUA， CRE and BUN levels， and URAT1， GLUT9 expression decreased in Tongfengning group and the benzbromarone group（P<0.05）， whereas UUA level， and ABCG2， OAT1， OAT3 expression increased（P<0.05）. Creatinine and BUN levels decreased in the Tongfengning group（P<0.05，P<0.01）， with the trend much better than the benzbromarone group（P<0.05）. On day 21st， except for the BUN level did not change much compared with day 14th， all the rest indicators got improved obviously. Conclusion:Intraperitoneal injection of OAPS and intragastric administration of EMB can cause HUA models with renal dysfunction. Tongfengning reduced URAT1， GLUT9 mRNA and protein expression， and upregulated ABCG2， OAT1， OAT3 mRNA and protein expression in the rat kidney， which may be one of the mechanisms of promoting uric acid excretion. Tongfengning has a certain protective effect on renal function.

Effect of Chaenomelis Fructus Alcohol Extract on Arthritis Inflammation and Apoptosis of Synovial Cells in Rheumatoid Arthritis Model / 中国实验方剂学杂志

Objective:To study the protective effect and mechanism of Chaenomelis Fructus alcohol extract (CFE) on the synovium of rheumatoid arthritis (RA). Method:Sixty male SD rats were randomly divided into normal group and model group. RA model was made by injection of complete Freund's adjuvant， and then was randomly divided into model group， CFE low， medium and high dose group and Tripterygium glycoside group according to the inflammatory score. The CFE groups (0.15，0.30，0.60 g·kg-1·d-1) had intragastric administration once a day for 30 d after the model establishment. The blank control group and the model group were given the same volume saline water by gavage. After all the drugs were given， the blood， joint tissues and synovium tissue of rats were collected. The levels of interleukin-1β (IL-1β)， interleukin-6 (IL-6)， interleukin-10 (IL-10) and tumor necrosis factor (TNF)-α in serum were detected by enzyme linked immunosorbent assay (ELISA)， the pathological changes of synovium were observed by hematoxylin eosin (HE) staining， and the expressions of B-cell lymphoma-2 (Bcl-2)，Bcl-2 associated X protein (Bax) and death factor (Fas) in joints were detected by Western blot. Result:Compared with normal group， the swelling degree and inflammation index of rats' feet in model group increased significantly， the levels of inflammatory factors IL-1β， IL-6， TNF-α in serum increased (P<0.01)， anti-inflammatory factor IL-10 decreased (P<0.01)， the protein expression of Bax， Fas and Bcl-2 increased， and the statistical results of Bcl-2 showed significant difference (P<0.05). Compared with model group， the swelling degree and inflammatory index of the plantar of RA rats were improved in the middle and high dose groups of CFE (P<0.01)， the pathological changes such as synovial tissue hyperplasia and inflammatory cell infiltration were reduced in each dose group， and the levels of IL-1β， IL-6 and TNF-α in serum were reduced (P<0.05)， anti inflammatory factor IL-10 increased (P<0.05)， the disorder of inflammatory cytokine in the model was corrected， Bax， Fas expression increased， Bcl-2 protein expression decreased (P<0.01). Conclusion:CFE can reduce the degree of inflammation in RA joint and has obvious anti RA effects， which may be related to the apoptosis of synoviocytes induced by CFE.

Inhibition of invasion and metastasis of human tonguesquamous cell carcinoma Tca8113 cells by Src kinase inhibitor PP2 / 西安交通大学学报(医学版)

Objective: To investigate the inhibitory effects of Src kinase inhibitor PP2 on migration and invasion of Tca8113 cells. Methods: Tca8113 cells were cultured for 24 h with 5 mol/L, 10 mol/L and 20 micron mol/L of Src kinase inhibitor PP2. The effects of PP2 on the invasion and migration of Tca8113 cells were measured with Transwell chamber and scratch method, respectively. Results: After the treatment with PP2 for 24 h, the expression of p-Src in 5, 10, 20 μmol/L of Src kinase inhibitor PP2 treatment groups was significantly lower than that of the non-drug treatment group (all P<0.05). The number of Tca8113 cells in the non-drug treatment group and the 5, 10, and 20 μmol/L of Src kinase inhibitor PP2 treatment groups was (232.76±28.65), (186.53±21.34), (129.18±17.96), and (37.82±12.41), respectively; the number of migratory cells was (259.38±25.27), (193.45±20.18), (143.24±18.04), and (32.94±14.39), respectively, the cell migration rate was (11.51±0.84)%, (8.06±0.51)%, (5.13±0.57)%, and (3.18±0.12)%, respectively; the overall difference was statistically significant (F=73.852, 85.687, 48.157, all P=0.000). It had a negative correlation with PP2 dose. Conclusion: Src kinase inhibitor PP2 can effectively inhibit the invasion and migration of Tca8113 cells in the concentration-dependent manner, and it may have certain clinical value in the treatment of human tongue squamous cell carcinoma.

Venovenous extra-corporeal membrane oxygenation for severe acute respiratory distress syndrome: a matched cohort study / 中华医学杂志(英文版)

Background@#Although the use of extra-corporeal membrane oxygenation (ECMO) has been rapidly increasing, the benefit of ECMO in patients with acute respiratory distress syndrome (ARDS) remains unclear. Our objective was to investigate the effect of venovenous ECMO (VV-ECMO) on adult patients with severe ARDS.@*Methods@#We conducted a multi-center, retrospective, cohort study in the intensive care units (ICUs) of six teaching hospitals between January 2013 and December 2018. Patients with severe ARDS who received VV-ECMO support were included. The detailed demographic data and physiologic data were used to match ARDS patients without ECMO. The primary endpoint was the 28-day mortality.@*Results@#Ninety-nine patients with severe ARDS supported by VV-ECMO and 72 patients without ECMO were included in this study. The acute physiology and chronic health evaluation II score was 23.1 ± 6.3 in the ECMO group and 24.8 ± 8.5 in the control group (P = 0.1195). The sequential organ failure assessment score was 12.8 ± 3.4 in the ECMO group and 13.7 ± 3.5 in the control group (P = 0.0848). The 28-day mortality of patients with ECMO support was 39.4%, and that of the control group was 55.6%. The survival analysis curve showed that the 28-day mortality in the ECMO group was significantly lower than that in the control group (P = 0.0097). Multivariate Cox regression analysis showed that the independent predictors of the 28-day mortality were the requirement of vasopressors before ECMO (hazard ratio [HR]: 1.006; 95% confidence interval [CI]: 1.001–1.013; P = 0.030) and duration of mechanical ventilation before ECMO (HR: 3.299; 95% CI: 1.264–8.609; P = 0.034).@*Conclusions@#This study showed that ECMO improved the survival of patients with severe ARDS. The duration of mechanical ventilation and the requirement of vasopressors before ECMO might be associated with an increased risk of death.