Targeting FAPα-positive lymph node metastatic tumor cells suppresses colorectal cancer metastasis

Lymphatic metastasis is the main metastatic route for colorectal cancer, which increases the risk of cancer recurrence and distant metastasis. The properties of the lymph node metastatic colorectal cancer (LNM-CRC) cells are poorly understood, and effective therapies are still lacking. Here, we found that hypoxia-induced fibroblast activation protein alpha (FAPα) expression in LNM-CRC cells. Gain- or loss-function experiments demonstrated that FAPα enhanced tumor cell migration, invasion, epithelial-mesenchymal transition, stemness, and lymphangiogenesis via activation of the STAT3 pathway. In addition, FAPα in tumor cells induced extracellular matrix remodeling and established an immunosuppressive environment via recruiting regulatory T cells, to promote colorectal cancer lymph node metastasis (CRCLNM). Z-GP-DAVLBH, a FAPα-activated prodrug, inhibited CRCLNM by targeting FAPα-positive LNM-CRC cells. Our study highlights the role of FAPα in tumor cells in CRCLNM and provides a potential therapeutic target and promising strategy for CRCLNM.

Expert Consensus on Facial Reanimation with Masseteric-to-facial Nerve Transposition (2023) / 中华显微外科杂志

Facial paralysis causes both physical pain and psychological distress to patients. It is difficult for a patient with facial paralysis to engage with a normal social life and at work. Progresses have been made in recent years in the treatment of facial paralysis. More attentions have been caught by masseteric to facial nerve transposition, which has advantages of adjacency in location, abundancy in nerve supply and reliability in the outcome and now has deemed an important option of facial reanimation. It has not been long since the application of the technique of masseteric to facial nerve transposition in China, therefore it still lacks a universal guidance on practice. In order to achieve the aim of better quality control and popularisation of the technique, hereby a consensus with suggestions on facial reanimation with masseteric to facial nerve transposition is proposed as the reference for surgeons specialised in facial reanimation. This consensus is proposed, discussed and drafted by experts from plastic and reconstructive surgery, oral and maxillofacial surgery, head and neck surgery and neurosurgery.

BGB-A445, a novel non-ligand-blocking agonistic anti-OX40 antibody, exhibits superior immune activation and antitumor effects in preclinical models / 医学前沿

OX40 is a costimulatory receptor that is expressed primarily on activated CD4+, CD8+, and regulatory T cells. The ligation of OX40 to its sole ligand OX40L potentiates T cell expansion, differentiation, and activation and also promotes dendritic cells to mature to enhance their cytokine production. Therefore, the use of agonistic anti-OX40 antibodies for cancer immunotherapy has gained great interest. However, most of the agonistic anti-OX40 antibodies in the clinic are OX40L-competitive and show limited efficacy. Here, we discovered that BGB-A445, a non-ligand-competitive agonistic anti-OX40 antibody currently under clinical investigation, induced optimal T cell activation without impairing dendritic cell function. In addition, BGB-A445 dose-dependently and significantly depleted regulatory T cells in vitro and in vivo via antibody-dependent cellular cytotoxicity. In the MC38 syngeneic model established in humanized OX40 knock-in mice, BGB-A445 demonstrated robust and dose-dependent antitumor efficacy, whereas the ligand-competitive anti-OX40 antibody showed antitumor efficacy characterized by a hook effect. Furthermore, BGB-A445 demonstrated a strong combination antitumor effect with an anti-PD-1 antibody. Taken together, our findings show that BGB-A445, which does not block OX40-OX40L interaction in contrast to clinical-stage anti-OX40 antibodies, shows superior immune-stimulating effects and antitumor efficacy and thus warrants further clinical investigation.

Predictive value of 18F-FDG PET/CT for anti-MDA5 antibody and prognosis of dermatomyositis / 中华核医学与分子影像杂志

Objective:To assess the imaging characteristics of muscle FDG metabolism, tumor incidence, and pulmonary interstitial changes in patients with anti-melanoma differentiation-associated gene 5 (MDA5) antibody positivity in 18F-FDG PET/CT imaging, and the value of 18F-FDG PET/CT in differentiating anti-MDA5 antibody positive dermatomyositis. Methods:From June 2016 to July 2019, the PET/CT images of 75 patients with dermatomyositis (21 males, 54 females, age (52.3±14.3) years; 34 anti-MDA5 antibody positive and 41 anti-MDA5 antibody negative) and 30 healthy controls (10 males, 20 females; age (53.5±11.8) years) were retrospectively analyzed in Renji Hospital, School of Medicine, Shanghai Jiao Tong University. The SUV max of muscle was measured and the mean of SUV max (mSUV max) was calculated. Statistics of patients with dermatomyositis complicated with neoplastic lesions and the SUV max of pneumonia lesions in patients with dermatomyositis complicated with interstitial pneumonia was determined. Independent sample t test, one-way analysis of variance, Student-Newman-Keuls (SNK) test and χ2 test were used to analyze data. The ROC curve analysis was used to analyze the diagnostic efficacy of mSUV max for the differential diagnosis of anti-MDA5 antibody positive dermatomyositis. Results:The muscle mSUV max of the control group, anti-MDA5 antibody positive and negative groups were 0.39±0.05, 0.66±0.21 and 0.87±0.29 ( F=39.93, P<0.001), respectively. The muscle mSUV max of dermatomyositis patients was increased compared with healthy controls ( q values: 6.76, 12.63, both P<0.001), and the muscle mSUV max of anti-MDA5 antibody negative was higher than positive ( q=5.79, P<0.001). The AUC was 0.74, and the cut-off value of muscle mSUV max was 0.75 with the accuracy of 74.7%(56/75). Of 41 patients with negative anti-MDA5 antibody, there were 6 (14.6%) had malignant tumor, while there was no malignant tumor in patients with positive anti-MDA5 antibody (0/34; χ2=5.41, P=0.020). There were 11 patients (26.8%, 11/41) with anti-MDA5 antibody negative dermatomyositis complicated with interstitial pneumonia and 33 patients (97.1%, 33/34) with anti-MDA5 antibody positive dermatomyositis complicated with interstitial pneumonia ( χ2=37.81, P<0.001). FDG metabolism in anti-MDA5 antibody positive patients was higher than that in anti-MDA5 antibody negative patients (lesion SUV max: 3.65±1.83 and 2.38±1.27; t=2.13, P=0.039). Conclusions:The muscle FDG metabolism of anti-MDA5 antibody positive dermatomyositis patients is higher than that of healthy controls, but lower than that of anti-MDA5 antibody negative patients. The incidence of neoplastic lesions in patients with positive anti-MDA5 antibody is lower than that in patients with negative anti-MDA5 antibody. The proportion and severity of interstitial pneumonia are higher in patients with positive anti-MDA5 antibody than in those with negative anti-MDA5 antibody. 18F-FDG PET/CT has certain value on identifying anti-MDA5 antibody positive dermatomyositis.

A multicenter prospective cohort study of Xuebijing injection in the treatment of severe coronavirus disease 2019 / 中华危重病急救医学

Objective:To evaluate the effect of Xuebijing injection on the improvement of pneumonia severity index (PSI) and prognosis in patients with severe coronavirus disease 2019 (COVID-19).Methods:A multicenter prospective cohort study was designed. Adult patients with COVID-19 admitted to the intensive care unit (ICU) of 28 designated COVID-19 hospitals in 15 provinces and cities of China from January to March 2020 were enrolled. All patients were treated according to the standard treatment plan of COVID-19 issued by the National Health Commission of the People's Republic of China. They were divided into Xuebijing group and standard treatment group according to whether they received Xuebijing injection or not. In the standard treatment group, routine medical care measures such as antiviral, respiratory support, circulatory support and symptomatic treatment were taken. In the Xuebijing group, on the basis of standard treatment, Xuebijing was used within 12 hours of admission to the ICU, 100 mL each time, twice daily. The minimum duration of Xuebijing administration was 1 day. The improvement rate of PSI risk rating on the 8th day and clinical outcome on the 28th day were recorded.Results:A total of 276 COVID-19 patients were screened continuously, and the data of 144 severe patients who met PSI risk rating Ⅲ-Ⅴ were analyzed. Seventy-two cases were involved each in standard treatment group and Xuebijing group. The average age of the standard treatment group and Xuebijing group were (65.7±7.9) years old and (63.5±10.9) years old, and male accounted for 75.0% (54/72) and 70.8% (51/72), respectively. There were no significant differences in general conditions, comorbidities, PSI risk rating and score, sequential organ failure assessment (SOFA) score, oxygenation index (PaO 2/FiO 2), respiratory support mode and other baseline indicators between the two groups. Compared with the standard treatment group, the improvement rate of PSI risk rating in Xuebijing group on the 8th day after admission was significantly improved [56.9% (41/72) vs. 20.8% (15/72), between-group difference and 95% confidence interval (95% CI) was 36.1% (21.3% to 50.9%), P < 0.01], PSI score, SOFA score and PaO 2/FiO 2 were significantly improved [PSI score: 83.7±34.8 vs. 108.2±25.6, between-group difference (95% CI) was -24.5 (-34.9 to -14.1); SOFA score: 2.0 (1.0, 4.0) vs. 7.0 (4.0, 10.0), between-group difference (95% CI) was -3.5 (-5.0 to -2.0); PaO 2/FiO 2 (mmHg, 1 mmHg = 0.133 kPa): 289.4±111.6 vs. 188.5±98.1, between-group difference (95% CI) was 100.9 (65.3 to 136.5); all P < 0.01]. The 28-day discharge rate of Xuebijing group was 44.5% higher than that of standard treatment group [66.7% (48/72) vs. 22.2% (16/72), P < 0.01], and the 28-day survival rate was 9.8% [91.7% (66/72) vs. 81.9% (59/72), P < 0.01]. There was no significant difference in the combination of antiviral drugs, antibiotics, anticoagulants and vasopressor drugs between the two groups. There was no significant difference in the incidence of adverse events between the Xuebijing group and standard treatment group [41.7% (30/72) vs. 43.1% (31/72), P > 0.05], and no serious adverse events and adverse reactions of Xuebijing were reported. Conclusion:Standard treatment combined with Xuebijing injection can significantly improve the PSI risk score and clinical prognosis of patients with severe COVID-19 without increasing drug safety risk.

Incidence and prognoses of human cytomegalovirus reactivation in immunocompetent severe pneumonia patients with mechanical ventilation / 中华危重病急救医学

Objective:To investigate the incidence and risk factors of human cytomegalovirus (HCMV) reactivation in immunocompetent severe pneumonia patients with mechanical ventilation and their effects on clinical outcomes.Methods:A prospective observational study was conducted. Forty-eight immunocompetent patients requiring invasive mechanical ventilation due to severe pneumonia in the department of critical care medicine of the First Affiliated Hospital of Guangzhou Medical University from June 30th, 2017 to July 1st, 2018 were enrolled. Meanwhile, all cases were followed up until 90 days after inclusion and were required to quantitatively detect HCMV DNA in serum at regular weekly intervals until 28 days after transferring to intensive care unit (ICU). Patients were divided into HCMV reactivation group (≥5×10 5 copies/L) and non-reactivation group (<5×10 5 copies/L) based on HCMV DNA at any time point within 28 days. Demographic data, basic indicators, respiratory indicators, disease severity scores, laboratory indicators, complication and clinical outcomes of the two groups were collected and analyzed. Multivariate Logistic regression analysis was performed to screen independent risk factors for HCMV reactivation. Results:All 48 subjects were tested positive for HCMV immunoglobulin G (IgG), so HCMV seropositive rate was 100%. HCMV reactivation occurred in 10 patients within 28 days after admission to ICU, and the reactivation incidence of HCMV was 20.83%. There was no significant difference in gender, age, body mass index (BMI), underling disease reasons for ICU transfer (except sepsis), basic vital signs, disease severity scores, or laboratory findings including infection, immune, blood routine, liver, kidney and circulatory indicators except neutrophils count (NEU), hypersensitivity C-reactive protein(hs-CRP), hemoglobin (Hb), blood urea nitrogen (BUN), N-terminal pro-brain natriuretic peptide (NT-proBNP) between the two groups. The height (cm: 160±6 vs. 166±8), body weight (kg: 49.4±11.2 vs. 57.6±10.5), Hb (g/L: 87±18 vs. 104±24) in HCMV reactivation group were significantly lower than non-reactivation group, as well as NEU [×10 9/L:12.7 (9.9, 22.5) vs. 8.9 (6.2, 13.8)], hs-CRP [mg/L: 115.5 (85.2, 136.6) vs. 39.9 (17.5, 130.2)], BUN [mmol/L:13.7 (8.9, 21.5) vs. 7.1 (4.9, 10.5)] and NT-proBNP [ng/L: 6 751 (2 222, 25 449) vs. 1 469 (419, 4 571)] within 24 hours of admission to ICU. The prevalence of sepsis [60.0% (6/10) vs. 15.8% (6/38)], blood transfusion [100.0% (10/10) vs. 60.5% (23/38)], hospitalization expense [ten thousand yuan: 35.7 (25.3, 67.1) vs. 15.2 (10.4, 22.0)], 90-day all-cause mortality [70.0% (7/10) vs. 21.1% (8/38)], length of ICU stay [days: 26 (16, 66) vs. 14 (9, 19)], the duration of mechanical ventilation [days: 26 (19, 66) vs. 13 (8, 18)] in HCMV reactivation group were significantly higher than non-reactivation group, and there were significant statistical differences between the two groups (all P < 0.05). Logistic regression analysis showed that sepsis was an independent risk factor for HCMV reactivation in immunocompetent mechanical ventilation severe pneumonia patients with mechanical ventilation [odds ratio ( OR) = 9.35, 95% confidence interval (95% CI) was 1.72-50.86, P = 0.010]. Conclusions:HCMV infection is very common in immunocompetent severe pneumonia patients on mechanical ventilation and incidence of HCMV reactivation is high. Moreover, HCMV reactivation could adversely affect clinical prognoses, and sepsis may be a risk factor for HCMV reactivation.

Applications of Compression Therapy in Vascular Diseases and its Research Progress / 医用生物力学

Vascular diseases including cardiovascular and cerebrovascular diseases and peripheral vascular diseases of the lower extremities are serious threats to human health. The emergence of compression therapy is of great significance for the effective prevention and treatment of these vascular diseases and the therapeutic value of compression therapy has been confirmed by many research results at present. Compression therapy is a non-invasive physical therapy implemented through a series of compression therapy devices, including external counterpulsation for the treatment of various ischemic diseases, intermittent pneumatic compression for the treatment of some peripheral vascular diseases in the lower extremities, graduated compression stockings for the treatment of deep vein thrombosis, and so on. This review summarizes clinical applications of these typical compression therapies in cardiovascular and cerebrovascular diseases and peripheral vascular diseases of the lower extremities, analyzes their advantages and limitations, and discusses the necessity and significance of biomechanical research on compression therapies.

China’s contribution to scientific publications in four leading general medical journals between 2009 and 2018 / 中华医学科研管理杂志

Objective:To explore the frequencies, citations and distribution characteristics of publications published by Chinese scholars in four leading general medical journals in last decade.Methods:The Thomson-Reuter’s Web of Science (WoS) database was searched to retrieve publications published by Chinese scholars in NEJM, Lancet, JAMA and BMJ, and document type was set to Article, Editorial Material, Review and Letter between 2009 and 2018. The frequencies and characteristics of total and first author publications were analyzed. Results:A total number of 1 357 publications were identified, among which first author publications accounted for 62.64% (850/1 357). Overall trends presented fluctuating growth from 72 publications in 2009 to 97 in 2018. Among these 850 publications, there were 131 Articles (15.4%), 210 Editorial Materials (24.7%), 22 Reviews (2.6%) and 487 Letters (57.3%). The three most productive regions included Beijing (224), Hong Kong (133) and Shanghai (101). The three most productive institutions were the Chinese University of Hong Kong (64), Peking Union Medical College/Chinese Academy of Medical Sciences (54) and Peking University (50). In terms of publications supported by funds, the most common fund was National Natural Science Foundation of China, which accounted for 24.7% (44/178). China had a close cooperation with the USA, UK, Australia, Canada and Japan.Conclusions:Currently available study demonstrated that publications published by Chinese scholars in four leading general medical journals had a stable growth during last decade. However, the total amount of publications and Articles were still low. For future work, the frequency and strength should be potentiated on the research fund and cooperation.

Discovery of a highly selective VEGFR2 kinase inhibitor CHMFL-VEGFR2-002 as a novel anti-angiogenesis agent

Angiogenesis is an essential process in tumor growth, invasion and metastasis. VEGF receptor 2 (VEGFR2) inhibitors targeting tumor angiogenic pathway have been widely used in the clinical cancer treatment. However, most of currently used VEGFR2 kinase inhibitors are multi-target inhibitors which might result in target-associated side effects and therefore limited clinical toleration. Highly selective VEGFR inhibitors are still highly demanded from both basic research and clinical application point of view. Here we report the discovery and characterization of a novel VEGFR2 inhibitor (CHMFL-VEGFR2-002), which exhibited high selectivity among structurally closed kinases including PDGFRs, FGFRs, CSF1R, etc. CHMFL-VEGFR2-002 displayed potent inhibitory activity against VEGFR2 kinase in the biochemical assay (IC = 66 nmol/L) and VEGFR2 autophosphorylation in cells (ECs ∼100 nmol/L) as well as potent anti-proliferation effect against VEGFR2 transformed BaF3 cells (GI = 150 nmol/L). In addition, CHMFL-VEGFR2-002 also displayed good anti-angiogenesis efficacy and exhibited good PK (pharmacokinetics) profile with bioavailability over 49% and anti-angiogenesis efficacy in both zebrafish and mouse models without apparent toxicity. These results suggest that CHMFL-VEGFR2-002 might be a useful research tool for dissecting new functions of VEGFR2 kinase as well as a potential anti-angiogenetic agent for the cancer therapy.

Separation and Purification of Alhagi sparsifolia n -butanol Extract Monomeric Compounds and Study on Their Effects on Human Cervical Cancer HeLa Cells / 中国药房

OBJECTIVE： To separate and purify Alhagi sparsifolia n-butanol extract monomeric compounds， and to investigate its effects on the proliferation and metastasis of human cervical cancer HeLa cells. METHODS： The n-butanol extract was separated and purified by silica gel column， Sephadex LH-20 gel column and prep-HPLC. The structures of compounds were analyzed and identified according to physicochemical properties and spectrum （mass spectrum， hydrogen spectrum， carbon spectrum） data. Using human cervical cancer HeLa cells as objects， 5-FU as positive control， MTT assay was used to detect the inhibitory rate of HeLa cells pretreated with different doses of compounds （6.25， 12.5， 25， 50， 100， 200 μg/mL）； IC50 was calculated to screen active monomers. Scratch test was used to investigate the effects of above active monomers （all 50 μg/mL） on the migration ability of HeLa cells. Kim’s formula was used to evaluate the effects of 5-FU separately combined with above active monomers [（3.125+6.25），（6.25+12.5），（12.5+25），（25+50）μg/mL]. RESULTS： Six compounds were isolated from the n-butanol extract part of A. sparsifolia and identified as butin （Ⅰ）， 3′，4′，7-trihydroxyisoflavone （Ⅱ）， p-methoxyphenylacetic acid （Ⅲ）， 4-hydroxyacetophenone （Ⅳ）， aurantiamide acetate （Ⅴ）， protocatechualdehydea （Ⅵ）. Compared with blank control group， 5-FU and each compound （5-FU：6.25-200 μg/mL， compound Ⅰ： 12.5-200 μg/mL； compound Ⅱ： 25， 50， 200  μg/mL； compound Ⅲ： 6.25， 100， 200 μg/mL； compound Ⅳ： 50， 100， 200 μg/mL； compound Ⅴ： 12.5， 25， 200 μg/mL； compound Ⅵ： 6.25-200 μg/mL） could significantly increase the cell inhibition rate. IC50 of compound Ⅰ， Ⅴ， Ⅵ were decreased significantly （P＜0.05 or P＜0.01）， and those of compound Ⅰ and Ⅵ were lower relatively. The migration distance of cells in 5-FU and compound Ⅰ and Ⅵgroups were decreased significantly， compared with blank control group （P＜0.05 or P＜0.01）. 5-FU separately combined with compound Ⅰ and Ⅵ showed additive and enhanced inhibitory effects on the proliferation of HeLa cells （synergistic index＞0.9）. CONCLUSIONS： Compounds Ⅰ-Ⅵ are isolated from Alhagi for the first time. Butin and protocatechualdehydea are active monomers of its n-butanol extract part. Above two monomers can inhibit the proliferation and migration of human cervical cancer Hela cells， with strong inhibitory effect in vitro， and stronger inhibitory effect combined with 5-FU than any compound alone.

Effects of L-TH4 in pregnancy subclinical hypothyroidism on TPO and glycometabolism / 中国生化药物杂志

Objective To investigate the effects of levothyroxine (Levo-thyroid hormone,L-TH4) in pregnancy subclinical hypothyroidism (SCHT), and study the relationship between L-TH4 with thyroid peroxidase (TPO) and glucose metabolism. The research could provide theoretical basis for the treatment of SCHT. Methods Sixty pregnant women were selected and signed the medical informed consent. The pregnancy were divided into three groups, 20 cases in each group.Normal control group: pregnancy underwent routine thyroid function normal; SCHT group: SCHT pregnancy patients who did not use drugs to treat SCHT; L-TH4 group: SCHT pregnancy patients given L-TH4 treatment. The blood was taken to test the contents of glucose level and HbA1c were observed; the activity of TSH and TPO were tested by ELISA method; HE staining method was used to observe the changing of placenta tissue. Results Compared with normal control group, the glucose and HbA1c were significantly increased in SCHT group (P<0.05). However, L-TH4 could decrease these index, compare with the SCHT group, and reduce the level of TSH and the activity of TPO, the difference was statistically significantly (P<0.05). Moreover, L-TH4 could improve the changing of placenta tissue. Conclusion L-TH4 could reduce blood glucose and HbA1c levels, also reduced the level of TSH and the activity of TPO in SCHT. L-TH4 could improve the changing of placenta tissue.

Effects ofXiangsha LiujunziDecoction on Gastric Emptying Function, Pepsin Activity and Expression of HIF-1α in Chronic Atrophic Gastritis of Rats with Deficiency Spleen and Stomach / 中国中医药信息杂志

Objective To study effects ofXiangsha Liujunzi Decoction (XSLJZ) on gastric emptying function, pepsin activity and expression of HIF-1α gene and protein of gastric mucosa in chronic atrophic gastritis (CAG) of rats with deficiency of spleen and stomach.Methods Rats were randomly divided into normal group and model group. The models of CAG rats with deficiency of spleen and stomach type were induced by synthetic methods. After the modeling, models rats were divided into model group, positive control group and XSLJZ high-, medium-, and low-dose groups. Normal group and model group were given 10 mL/kg distilled water every day for gavage; XSLJZ high-, medium-, and low-dose groups were given 24, 12, and 6 g/kg XSLJZ Decoction for gavage; positive control group was given 0.30 g/kg Vatacoenayme for gavage, for successive 120 d. Gastric emptying function and pepsin activity were detected, and HIF-1α gene and protein expression in gastric mucosa were detected by RT-qPCR and IHC. Results Compared with the normal group, the gastric emptying function and pepsin activity in the model group were much lower (P<0.01); expressions of HIF-1α gene and protein in gastric tissues was much higher (P<0.01). Compared with model group, XSLJZ could increase the gastric emptying function and pepsin activity significantly (P<0.05), and decrease expressions of HIF-1α gene and protein (P<0.05).Conclusion XSLJZ has functions of improving the gastric emptying function, promoting pepsin activity, and reducing expressions of HIF-1α gene and protein.

Study on Molecular Mechanism of Reactive Changes in Kidney, Skeleton and Brain of Mice Models in High Altitude Hypoxia Environment / 中国中医药信息杂志

Objective To observe the molecular mechanism of adaptive response of the kidney and skeleton and brain issues in the high altitude hypoxia; To discuss the unity of yin and yang oscillation relationship of kidney and brain marrow.Methods SPF KM mice were randomly divided into control group and model group according to random number table method. Mice in the model group were exposed to high altitude hypoxia cabin for successive 21 d. On the 22nd day, mice got out of the cabin and their body weight was measured, and then they were put to death through eyeball blood sampling. The activities of lactic LDH and Na+-K+-ATPase in brain tissue were detected by spectrophotometric colorimetry. The PFK activities of brain and skeletal muscle were detected by ELISA. Meanwhile the contents of EPO and EPOR in the kidney were measured by ELISA. The mRNA expressions of HIF-1α and AQP-4 in brain were assessed by RT-PCR. At the same time, the protein expressions of HIF-1α and AQP-1 in brain and the protein expression of Mb in skeletal muscle were detected by Western blot.Results Compared with the normal group, the LDH and PFK in brain tissue and the content of EPO in kidney tissue were all raised in the model group(P<0.05). Meanwhile the mRNA expressions of HIF-1α and AQP-4 and the protein expressions of HIF-1α and AQP-1 in brain were all increased in the mice from the model group; the activities of PFK and the protein expression of Mb in skeletal muscle were also raised in the model group. But the activity of Na+-K+-ATPase in brain tissue and the content of EPOR in kidney tissue both decreased in the model group (P<0.05,P<0.01).Conclusion Adaptive response and the unity of yin and yang oscillation relationship between kidney, skeleton and brain tissue happen in high altitude hypoxia.

Effects of Xiangsha Liujunzi Decoction on Levels and mRNA of IL-6, IL-10 and Protein Expression of HSP70 of Gastric Mucosa in Chronic Atrophic Gastritis Rats with Spleen-Stomach Deficiency / 中国中医药信息杂志

Objective To observe the effects ofXiangsha Liujunzi Decoction (XSLJZ) on levels and mRNA of IL-6, IL-10 and protein expression of HSP70 of gastric mucosa in chronic atrophic gastritis (CAG) rats with spleen-stomach deficiency; To discuss its mechanism.Methods Rats were divided into 2 groups through random number table: normal group and model group. The model of CAG rat with spleen-stomach deficiency type was induced by synthetic methods. After successful modeling, rats were divided into model group, positive control group, XSLJZ high-, medium-, low-dose group. Rats in normal and model group received distilled water 10 mL/(kg?d) for gavage; XSLJZ high-, medium-, low-dose group received XSLJZ 24, 12, 6 g/(kg?d), respectively; positive control group received mycin 0.30 g/(kg?d) for gavage for 120 consecutive days. Generally living conditions, levels and mRNA of IL-6, IL-10 and protein expression of HSP70 in gastric mucosa tissue were detected by protein immunoblotting.Results Compared with the normal group, generally living conditions of rats in the model group were poor; mRNA and the content of IL-6 increased significantly, and mRNA and the content of IL-10 decreased significantly (P<0.05,P<0.01); mRNA and protein expression of HSP70 in gastric tissues was much lower than that of normal group (P<0.05,P<0.01). Compared with model group, generally living conditions of rats in the XSLJZ high-dose groups were improved significantly; mRNA and the content of IL-6 decreased significantly, and mRNA and the content of IL-10 increased significantly (P<0.05); XSLJZ high-, medium-dose groups mRNA and protein expression of HSP70 in gastric tissues increased significantly(P<0.05).Conclusion XSLJZ has protective effects on gastric mucosa of CAG rats with spleen-stomach deficiency.

Determination of 10 mycotoxin contaminants in Panax notoginseng by ultra performance liquid chromatography-tandem mass spectrometry / 药学学报

To ensure the quality and safety of Panax notoginseng, a method for the simultaneous determination of 10 mycotoxins in Panax notoginseng was developed using ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). The sample was extracted with acetonitrile and purified by HLB multifunction cleanup column. The separation was performed on a Phenomenex Kinetex XB-C18 column by gradient elution using methanol and 5 mmol·L(-1) ammonium acetate as mobile phase. The targeted compounds were detected in MRM mode by mass spectrometry with electrospray ionization (ESI) source operated in both positive and negative ionization modes. The linear relationships of the 10 mycotoxins were good in their respective linear ranges. The correlation coefficients (r) ranged from 0.9981 to 1.0000. The LOQs of the 10 mycotoxins were between 0.15 and 8.6 μg·kg(-1). The average recoveries ranged from 73.8% to 107.0% with relative standard deviations (RSDs) of 0.10%-10.9%. The results demonstrated that the proposed method was sensitive and accurate, and suitable for the mycotoxins quantification in Panax notoginseng.

Application of near infrared spectroscopy combined with particle swarm optimization based least square support vactor machine to rapid quantitative analysis of Corni Fructus / 药学学报

A novel method was developed for the rapid determination of multi-indicators in corni fructus by means of near infrared (NIR) spectroscopy. Particle swarm optimization (PSO) based least squares support vector machine was investigated to increase the levels of quality control. The calibration models of moisture, extractum, morroniside and loganin were established using the PSO-LS-SVM algorithm. The performance of PSO-LS-SVM models was compared with partial least squares regression (PLSR) and back propagation artificial neural network (BP-ANN). The calibration and validation results of PSO-LS-SVM were superior to both PLS and BP-ANN. For PSO-LS-SVM models, the correlation coefficients (r) of calibrations were all above 0.942. The optimal prediction results were also achieved by PSO-LS-SVM models with the RMSEP (root mean square error of prediction) and RSEP (relative standard errors of prediction) less than 1.176 and 15.5% respectively. The results suggest that PSO-LS-SVM algorithm has a good model performance and high prediction accuracy. NIR has a potential value for rapid determination of multi-indicators in Corni Fructus.

Effects of Active Fraction of Angelica Sinensis Radix on Immunological Function in Mice under High Altitude Hypoxia Condition / 中国中医药信息杂志

Objective To explore the intervention effect of active fraction of Angelica Sinensis Radix in mice under high altitude hypoxia condition. Methods Totally 72 healthy SPF mice were randomly divided into control group (K), model group (M), Rhodiola rosea group, and active fraction of Angelica Sinensis Radix groups (B, C, X). The mice were administerted corresponding treatment by gavage for 21 days. Control mice were given normal saline in same volume. From the 8th day, all mice excepted control mice were exposed to high altitude hypoxia cabin after 0.5 hour gavage treament. On the 22nd day, after got out of the cabin and their body weight were measured, mice were put to death through eyeball blood sampling to prepare splenic lymphocyte suspension. The proliferation and transformation capacities of lymphocyte cell and killing activity of NK cells were detected by MTT. The content of IL-2 in the serum of mice in each group were detected by ELISA. Results Compared with the control group, the body weight of mice, the proliferation and transformation capacities of lymphocyte cell, the killing activity of NK cells, and the content of IL-2 were all significantly decreased (P<0.05, P<0.01). Experiment tests showed that the proliferation and transformation abilities of lymphocyte cell and the killing activity of NK cells were all increased in the mice of group B, C, and X compared with those of the model group (P<0.05, P<0.01). The stimulate index of lymphocyte cell was raised after X intervention compared with those of the model group (P<0.05). The content of IL-2 in the serum was enhanced after intervention of active fraction C and X of Angelica Sinensis Radix compared with those of the model group (P<0.05, P<0.01). Conclusion Active fraction of Angelica Sinensis Radix shows increasing immunological function of mice exposed to hypoxia.

Effect of prone position ventilation on respiratory mechanics and prognosis in patients with acute respiratory distress syndrome concurrent with interstitial lung disease / 中华危重病急救医学

ObjectiveTo explore the effect of prone position ventilation (PPV) on respiratory mechanics and prognosis in patients with acute respiratory distress syndrome (ARDS) concurrent with interstitial lung disease (ILD). Methods The data of 36 severe ARDS patients admitted to Department of Critical Care Medicine of the First Affiliated Hospital of Guangzhou Medical University from February 2013 to January 2015, were retrospectively analyzed. They were then divided into two groups according to the presence of ILD or not. The changes in respiratory mechanics and oxygenation indexes were compared before and after PPV treatment in all the patients. Kaplan-Meier method was applied to draw the 60-day survival curves of both groups.Results There were 17 cases with ILD among these 36 severe ARDS patients.① No significant difference was found in baseline data between ILD group and non-ILD group.② Respiratory mechanics and oxygenation pre-PPV and post-PPV: compared with pre-PPV, oxygenation index (PaO2/FiO2, mmHg, 1 mmHg = 0.133 kPa) post-PPV was significantly increased in both groups [ILD group : 132.0 (93.5, 172.0) vs. 118.7 (92.0, 147.8); non-ILD group: 126.1 (100.9, 170.0) vs. 109.2 (89.0, 135.0), bothP 0.05], and Crs was lower after PPV treatment in both groups, but without significant difference [non-ILD group: 22.7 (15.2, 27.1) vs. 24.3 (15.9, 48.9); ILD group: 16.2 (12.8, 25.6) vs. 18.9 (12.7, 27.3), bothP> 0.05].④ The 60-day mortality in ILD group was significantly higher than that in non-ILD group [88.2% (15/17) vs. 57.9% (11/19),P = 0.047). It was shown by Kaplan-Meier curves that 60-day survival patients in ILD group was significantly lower than those in non-ILD group (χ2 = 5.658,P = 0.017). Conclusions PPV can improve oxygenation in severe ARDS. Compared with non-ILD group, though the compliance of respiratory system in ILD group is increased during PPV, long-term effect is better in non-ILD group.

Fast analytical method on content and transfer rate of marker component in ethanol precipitation of cinobufacini by near infrared spectroscopy / 中国中药杂志

The method of near infrared spectroscopy was established to analyze the content and transfer rate of the marker component, indole alkaloids, of cinobufacini in the process of ethanol precipitation. The samples of cinobufacini were collected, and the concentration of indole alkaloids was determined by the reference method, UV-vis spectroscopy. After the rejection of abnormal samples, the pretreatment of spectra and the choice of the corresponding wave band, the multivariate calibration models were established using PLS algorithm between spectra and the UV values. The samples in ethanol precipitation, which did not participate in modeling, were used to examine the performance of the models. The correlation coefficient of the calibration model was 0.9613. Root mean square error of calibration (RMSEC) and root mean square error of prediction (RMSEP) were 0.172 and 0.169, respectively. Furthermore, residual predictive deviation (RPD) of the model was 4.13, which meant quantity analysis was feasible. It is concluded that near infrared spectroscopy can be considered as a fast, effective and non-destructive analysis method applied in the process of ethanol precipitation for traditional Chinese medicine.

In-line monitoring of blending process of Zhongsheng pill powder using miniature near-infrared analyzer / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a simple and rapid method based on diffuse reflectance NIR spectra to in-line monitor the blending process of Zhongsheng pill powder.</p><p><b>METHOD</b>Zhongsheng pill powder consisted of Zhongsheng spray powder, artificial cowbezoar powder and bile arisaema powder. By means of a revolutionary miniature near-infrared analyzer mounted onto the blender, the powder homogeneity was determined in real time with noninterference. The moving block standard deviation (MBSD) method was used to identify the end point of blending process, providing real-time data and instant feedback about the blending course. Evaluation of blend uniformity was carried out by stratified in-process sampling, and the content of baicalin in samples was determined by high performance liquid chromatography (HPLC).</p><p><b>RESULT</b>The results calculated through MBSD method were generally coincided with HPLC analysis. Blend homogeneity was assumed to be reached when the standard deviations between spectra approached 0.002, and RSD values of baicalin content in samples from six positions were lower than 5%. Moreover, stratified in-process sampling has significant influence on blending process when the powder loading volume was small.</p><p><b>CONCLUSION</b>Based on this study, NIR spectroscopy can be possibly extended to be applied in blending process of Zhongsheng pill powder, ensuring a remarkable saving of time and manpower employed and creating a reliable and efficient process measurement technology.</p>