Application of bio-inks for 3D printing in tissue repair and regenerative medicine / 中国组织工程研究

BACKGROUND:With the right bio-inks,3D printing can be used to create replacements for human tissues and organs that work inside the body.In recent years,3D printing technology has developed rapidly and has great application potential in regenerative medicine. OBJECTIVE:To introduce the types of bio-inks for 3D printing,and review the classification,application,advantages and disadvantages of bio-inks,as well as the future vision. METHODS:With"3D printing,biological ink,tissue engineering,hydrogel,synthetic material,cytoactive factor"as search terms,relevant articles published on PubMed and CNKI databases from 2000 to 2022 were searched by computer and finally 83 articles were included for review. RESULTS AND CONCLUSION:3D bioprinting technology has developed rapidly over the past few decades and has received great attention in various fields,including tissue engineering and biomedicine.Compared with the limitations of traditional biological scaffold manufacturing methods in terms of function and structure,3D printing can better simulate the complex structure of biological tissues and has appropriate mechanical,rheological and biological characteristics.Bio-ink is an essential part of 3D printing.Bioscaffolds produced by printing bio-ink prepared by biological materials have great scientific potential and clinical significance in tissue repair and regenerative medicine.The research of the materials itself is also getting more and more attention from experts.Bio-inks for 3D printing come in a variety of materials,from natural to synthetic,to aggregations of cells that do not require any additional biomaterials,and their usefulness in practical use varies.In the future,more and more bio-inks will be developed for tissue engineering.It is necessary to analyze the printability of bio-inks through sufficient experimental simulation and equipment testing to meet the actual medical needs.

Development of porcine induced pluripotent stem cells with a CD163 reporter system / 生物工程学报

As main recipient cells for porcine reproductive and respiratory syndrome virus (PRRSV), porcine alveolar macrophage (PAM) are involved in the progress of several highly pathogenic virus infections. However, due to the fact that the PAM cells can only be obtained from primary tissues, research on PAM-based virus-host interactions remains challenging. The improvement of induced pluripotent stem cells (iPSCs) technology provides a new strategy to develop IPSCs-derived PAM cells. Since the CD163 is a macrophage-specific marker and a validated receptor essential for PRRSV infection, generation of stable porcine induced pluripotent stem cells lines containing CD163 reporter system play important roles in the investigation of IPSCs-PAM transition and PAM-based virus-host interaction. Based on the CRISPR/Cas9- mediated gene editing system, we designed a sgRNA targeting CD163 locus and constructed the corresponding donor vectors. To test whether this reporter system has the expected function, the reporter system was introduced into primary PAM cells to detect the expression of RFP. To validate the low effect on stem cell pluripotency, we generated porcine iPSC lines containing CD163 reporter and assessed the pluripotency through multiple assays such as alkaline phosphatase staining, immunofluorescent staining, and EdU staining. The red-fluorescent protein (RFP) expression was detected in CD163-edited PAM cells, suggesting that our reporter system indeed has the ability to reflect the expression of gene CD163. Compared with wild-type (WT) iPSCs, the CD163 reporter-iPSCs display similar pluripotency-associated transcription factors expression. Besides, cells with the reporter system showed consistent cell morphology and proliferation ability as compared to WT iPSCs, indicating that the edited-cells have no effect on stem cell pluripotency. In conclusion, we generated porcine iPSCs that contain a CD163 reporter system. Our results demonstrated that this reporter system was functional and safe. This study provides a platform to investigate the iPS-PAM development and virus-host interaction in PAM cells.

Adult-onset X-linked adrenoleukodystrophy characterized by brainstem symptoms: a case report / 中华神经科杂志

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. Adult-onset X-ALD characterized by brainstem symptoms is a rare phenotype of the disease. A male youth of adult-onset X-ALD characterized by brainstem symptoms in Tianjin Huanhu Hospital at April 12, 2021 is reported. The patient mainly presented with progressively gait disturbance, dysarthria and ataxia, which were consistent with the clinical diagnosis of X-ALD in combination with other ancillary tests. Genetic testing suggested the presence of a hemizygous mutation site in the ABCD1 gene. The clinical, imaging and genetic characteristics of X-ALD patients in the literature with brain stem lesion are also summarized, thereby improving the understanding of the rare clinical phenotype of X-ALD.

Clinical analysis of different parts of medullary infarction / 中华神经科杂志

Objective:To investigate the clinical, imaging, etiological and prognostic features of patients with infarctions in different locations of the medulla oblongata.Methods:Patients with acute medullary infarction hospitalized at Tianjin Huanhu Hospital from July 2017 to July 2022 were included. The risk factors, clinical manifestation, stroke mechanism and 90-day prognosis of these patients were analyzed retrospectively.Results:Among the 256 patients enrolled, 150 (58.6%) had lateral medullary infarction (LMI), 106 (41.4%) had medial medullary infarction (MMI). The most frequent clinical manifestation of patients with LMI was dizziness (84.7%,127/150). And motor disorders (83.0%,88/106) was the most frequent clinical manifestation of patients with MMI. LMI lesions were mostly located in the middle (42.7%,64/150) and MMI lesions were mostly located in the upper (60.4%,64/106) medulla oblongata, with statistically significant difference (χ 2=47.53, P<0.001). Large artery atherosclerosis (LAA) was the main stroke mechanism in LMI and MMI [57.3%(86/150) vs 56.6%(60/106)]. Early neurological deterioration was more common in MMI (25.5%,27/106) and less common in LMI (7.3%,11/150), with statistically significant difference (χ 2=16.17, P<0.001). At discharge, more patients with MMI showed poor prognosis in short term [45.3% (48/106) vs 24.0% (36/150), with statistically significant difference (χ 2=12.76, P<0.001)] and even long term at 90-day follow-up [33.0% (35/106) vs 12.7% (19/150), also with statistically significant difference (χ 2=15.48, P<0.001)] than those with LMI. A total of 10 patients (4.0%, 10/256) developed respiratory failure during hospitalization, including 7 patients with LMI (4.7%, 7/150) and 3 patients with bilateral MMI (2.8%,3/106). Early neurological deterioration ( OR=3.38, 95% CI 1.25-9.10, P=0.016) and LAA (compared with small artery occlusion) ( OR=3.08, 95% CI 1.13-8.37, P=0.028) were independent risk factors for poor prognosis in MMI. Age ( OR=1.01, 95% CI 1.01-1.17, P=0.026) and early neurological deterioration ( OR=20.19, 95% CI=2.63-155.06, P=0.004) were independently correlated with poor outcome in LMI. Conclusions:LMI and MMI had similar etiology and significant differences in clinical manifestations, early neurological deterioration and prognosis. Further classification of medullary infarction was of great significance for diagnosis, treatment and prognosis evaluation.

Treatment duration of wrist-ankle acupuncture for relieving post-thyroidectomy pain: A randomized controlled trial / 中西医结合学报

BACKGROUND@#Treatment duration of wrist-ankle acupuncture (WAA) is uncertain for post-thyroidectomy pain relief.@*OBJECTIVE@#This study evaluated the effect of different WAA treatment duration on post-operative pain relief and other discomforts associated with thyroidectomy.@*DESIGN, SETTING, PARTICIPANTS AND INTERVENTION@#This randomized controlled trial was conducted at a single research site in Guangzhou, China. A total of 132 patients receiving thyroidectomy were randomly divided into the control group (sham WAA, 30 min) and three intervention groups (group 1: WAA, 30 min; group 2: WAA, 45 min; group 3: WAA, 60 min), with group allocation ratio of 1:1:1:1. Acupuncture was administered within 1 hour of leaving the operating room.@*OUTCOMES AND MEASURES@#Primary outcome was patients' pain at the surgical site assessed by visual analogue scale (VAS) at the moment after acupuncture treatment (post-intervention). Secondary outcomes included the patients' pain VAS scores at 6, 12, 24, 48 and 72 h after the thyroidectomy, the 40-item Quality of Recovery (QoR-40) score, the grade of post-operative nausea and vomiting (PONV), and the use of additional analgesic therapy.@*RESULTS@#The adjusted mean difference (AMD) in VAS scores from baseline to post-intervention in group 1 was -0.89 (95% confidence interval [CI], -1.02 to -0.76). The decrease in VAS score at post-intervention was statistically significant in group 1 compared to the control group (AMD, -0.43; 95% CI, -0.58 to -0.28; P < 0.001), and in groups 2 and 3 compared to group 1 (group 2 vs group 1: AMD, -0.65; 95% CI, -0.81 to -0.48; P < 0.001; group 3 vs group 1: AMD, -0.66; 95% CI, -0.86 to -0.47; P < 0.001). The VAS scores in the four groups converged beyond 24 h after the operation. Fewer patients in group 2 and group 3 experienced PONV in the first 24 h after operation. No statistical differences were measured in QoR-40 score and the number of patients with additional analgesic therapy.@*CONCLUSION@#Compared with the 30 min intervention, WAA treatment with longer needle retention time (45 or 60 min) had an advantage in pain relief within 6 h after surgery. WAA's analgesic effect lasted for 6-12 h post-operatively. Please cite this article as: Han XR, Yue W, Chen HC, He W, Luo JH, Chen SX, Liu N, Yang M. Treatment duration of wrist-ankle acupuncture for relieving post-thyroidectomy pain: A randomized controlled trial. J Integr Med. 2023; 21(2): 168-175.

CT perfusion combined with energy spectrum imaging to evaluate the short-term efficacy of bronchial arterial chemoembolization for lung cancer / 中华内科杂志

Objective: To evaluate the clinical value of dynamic volumetric CT perfusion combined with energy spectrum imaging in bronchial arterial chemoembolization (BACE) in patients with lung cancer. Methods: The data of 31 patients with lung cancer confirmed by pathology and treated with BACE in Lishui Central Hospital from January 2018 to February 2022 were retrospectively collected, including 23 men and 8 women, aged 31-84 (67) years. All patients received perfusion scans of lesion sites within 1 week before surgery and 1 month after surgery. We collected and compared the changes in preoperative and postoperative perfusion parameters such as blood flow (BF), blood volume (BV), mean through time (MTT), permeability surface (PS) and energy spectrum parameters including arterial phase CT value (CTA), venous phase CT value (CTV), arterial phase iodine concentration (ICA), venous phase of iodine concentration (ICV), arterial standardization iodine concentration (NICA), and intravenous standardized iodine concentration (NICV) to confirm the significance of these parameters in evaluating the short-term efficacy of BACE in the treatment of advanced lung cancer. Data normality was tested using the Kolmogorov-Smirnov test and normally distributed measurement data are expressed here as mean ± standard deviation; the independent-samples t-test was used for comparisons between two groups. The measurement data that were not normally distributed are expressed as median (interquartile interval) [M (Q1, Q3)], and the comparison between the two groups used the Kruskal-Wallis test. Count data are expressed as cases (%), and comparisons between groups used the χ2 test. Results: The objective response rate (ORR) and disease control rate (DCR) at 1 month after BACE were 54.8% (17/31) and 96.8% (30/31), respectively. CT perfusion parameters and energy spectrum parameters of patients before and after BACE treatment were compared. The results showed that BF, BV, MTT, ICA, ICV and NICV were significantly decreased after BACE treatment compared with before treatment, and the differences were statistically significant[58.06 (40.47,87.22) vs.23.57(10.92, 36.24) ml·min-1·100g-1,3.33(2.86,6.09) vs.2.12(1.96,3.61)ml/100g,2.70(2.19,3.88) vs.1.53 (1.12,2.25)s, 3.51 (3.11,4.14)vs.1.74 (1.26,2.50)mg/ml,2.00 (1.30,2.45) vs.1.32(0.92,1.76)mg/ml,0.51(0.42,0.57) vs.0.33(0.23,0.39)](all P<0.05). At the same time, compared with the non-remission group, the study results showed that the difference of parameters in remission group before and after BACE was more obvious, including ΔBF, ΔBV, ΔMTT, ΔPS, ΔCTA, ΔCTV, ΔICA, ΔICV, ΔNICA, ΔNICV were significantly increased, and the difference was statistically significant [36.82(32.38, 45.34) vs.9.50(-1.43, 12.34) ml·min-1·100g-1,4.46(2.52, 5.79) vs.0.22(-0.76, 4.09) ml/100g,4.22(2.25, 6.77) vs.0.43(-2.53, 1.88) s,10.07 (2.89, 13.13) vs.-2.01(-6.77, 4.28) ml·min-1·100g-1,14.22(11.88, 20.57) vs.4.18(-5.25, 6.37) HU, 34.6(14.88, 43.15) vs.11.60(0.26, 25.05) HU,0.95(0.54, 1.47) vs.0.11(0.20, 0.59) mg/ml,1.57(1.10, 2.38) vs. 0.26(-0.21, 0.63) mg/ml,0.05(0.03, 0.08) vs.-0.02(-0.04, 0.01),0.18(0.13, 0.21)vs. 0.11(-0.06, 0.16)](all P<0.05). Conclusions: CT perfusion combined with spectral imaging could effectively evaluate the changes in tumor vascular perfusion in patients with advanced lung cancer before and after BACE treatment, which has important value in judging the short-term efficacy after treatment.

Analysis of factors influencing the frequency of health check-up and health check-up behavior in healthy population / 中华行为医学与脑科学杂志

Objective:To analyze the relevant factors affecting the frequency and behavior of health check-up among the population of medical examinees.Methods:From January to June 2022, 491 health examinees who had health check-ups at the Second Affiliated Hospital of Shandong First Medical University were included.Basic information of the check-up population and their needs for check-up services (form of check-up, content of check-up, cost of check-up, form of feedback on check-up results, and needs for check-up providers) were obtained based on a questionnaire survey.According to the frequency of previous medical check-up, the examinees were divided into never-check-up group (frequency of check-up was 0, n=45), the irregular check-up group (the interval between two physical examinations >1 year, n=49) and the regular check-up group (frequency of check-up=1 year, n=347). The frequency of previous medical check-up was used as the dependent variable, and the age, gender, education level, income, form of medical check-up and cost of medical check-up were used as independent variables to analyse the relevant factors affecting the frequency of their medical check-ups.The above count data were analyzed by one-way analysis using chi-square test, and the count data with statistically significant differences in one-way analysis were analyzed by binary logistic regression.The statistical software was SPSS 21.0. Results:The study included 491 medical examinees, of which 9.16%(45/491) were in the never-check-up group, 20.16%(99/491) in the irregular check-up group and 70.68%(347/491) in the regular check-up group. The impact of demography characteristics of physical examinees on the frequency of health check-up, and there were statistically significant differences in the frequency of health check-up in terms of gender, job, education, and income ( χ2=21.826, 157.113, 104.764, 45.486, all P<0.05). The understanding of health check-up and the attention paid to one's own health were influencing factors that affected the frequency of health check-up. There were statistically significant differences in the frequency of health check-up in necessity of health check-up, attention to one's own health, health check-up forms, health check-up institutions, health check-up price and health check-up contents ( χ2=9.277, 25.863188.239, 59.115, 39.250, 28.314, all P<0.05). Logistic regression analysis showed gender, job type, monthly income, necessity of health check-up, concerns for items of check-up, forms and institutions of check-up were influencing factor of health check-up frequency(all P<0.05). Conclusion:The health check-up behavior of the population and the frequency of regular medical check-ups are influenced by the factors such as gender, education, occupation, income, form of medical check-up, price of medical check-up, choice of medical check-up institution and the degree of concern for one’s own health. The popularisation of health check-ups for special groups such as men, low-income people, low literacy and insufficient awareness of the importance of one’s own health will help improve the overall health awareness of the population.

Erratum: Author correction to 'Amino-functionalized poloxamer 407 with both mucoadhesive and thermosensitive properties: Preparation, characterization and application in vaginal drug delivery system' Acta Pharm Sin B 7 (2017) 593-602

[This corrects the article DOI: 10.1016/j.apsb.2017.03.002.].

Research progress of methodological techniques of generation of platelets from induced pluripotent stem cells in vitro / 中国输血杂志

Platelets play a role in hemostasis in vivo, and platelet transfusion is the main means to treat bleeding diseases caused by thrombocytopenia or platelet dysfunction. However, platelets are in short supply due to the increasing demand for platelet products in clinical, the limited number of blood donors and the disadvantages of platelet products such as short shelf life and bacteria contamination. Currently, induced pluripotent stem cells are considered an ideal source for producing platelets in vitro. They have the potential for self-renewal and differentiation into any cell type, and can be obtained and manipulated easily. Given the recent advances in megakaryocytic series, bioreactors, feeder-free cell production and large-scale propagation research, platelet preparations derived from induced pluripotent stem cells have gradually shown great potential for clinical applications. Considering the minimal risk of alloimmunization and tumorigenesis with these blood products, they are promising to become the standard source of future blood transfusions. This paper reviews the research progress of the methodological techniques of in vitro generation of platelets from induced pluripotent stem cells.

Epidemiological and clinical features of 62 patients with visceral leishmaniasis / 中华传染病杂志

Objective:To analyze the epidemiological and clinical features of patients with visceral leishmaniasis (VL), and to improve the understanding of the disease and standardize the diagnosis and treatment.Methods:The clinical data and diagnosis and treatment process of 62 patients with VL admitted to The First Hospital of Lanzhou University from January 2010 to December 2020 were retrospectively analyzed. The clinical symptoms and laboratory data, including aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and procalcitonin (PCT) were compared between children and adults. Chi-square test was used for statistical analysis.Results:Of the 62 patients, 31(50.0%) patients were males, 38(61.3%) patients were children and 24(38.7%) were adults. There were 32 cases (51.6%) living in Longnan City, and 11 cases (17.7%) living in Gannan Tibetan Autonomous Prefecture. Forty-seven cases (75.8%) had a delay over 30 days from onset to diagnosis. All patients had fever and chills, 34 cases (54.8%) had fatigue and poor appetite, 30(48.4%) had cough and expectoration, 10 cases (16.1%) had headache and dizziness, 45 cases (72.6%) had splenomegaly, 40 cases (64.5%) had anemia, and 29 cases (46.8%) had hepatomegaly. There were 32 cases (51.6%) accompanied with respiratory infection, 11 cases (17.7%) accompanied with hemophagocytic lymphohistiocytosis and 10 cases (16.1%) accompanied with abnormal liver function. Of the 60 patients who received treatment, 14 were recurrent cases who had received at least one course of pentavalent antimony monotherapy before admission. Forty-six patients received standard antimony monotherapy, 14 patients received standard antimony combined with amphotericin B therapy. Thirteen patients discontinued amphotericin B due to impaired renal function, and 50 patients were followed up for half a year without recurrence. The proportions of splenomegaly and hepatomegaly in children were 86.8%(33/38) and 65.8%(25/38), respectively, and the corresponding numbers in adults were 50.0%(12/24) and 16.7%(4/24), respectively. The differences were statistically significant ( χ2=10.03 and 14.26, respectively, both P<0.050). Thirty-three cases (86.8%) in children and 14 cases (58.3%) in adults had a delay over 30 days from onset to diagnosis. The difference was statistically significant ( χ2=6.52, P=0.011). The proportions of patients who had elevated AST, LDH and PCT were 76.3%(29/38), 94.3%(33/35) and 73.9%(17/23) in children, respectively, while 45.8%(11/24), 71.4%(15/21) and 5/17 in adults, respectively, and the differences were all statistically significant ( χ2=5.97, 3.89 and 7.82, respectively, all P<0.050). Conclusions:Patients with VL are tend to have complications and be severe. Early diagnosis and standardized treatment are important measures to improve the prognosis. Patients who have failed antimony treatment can be treated with amphotericin B or combination therapy, but kidney injury and other adverse reactions should be closely monitored.

Effect of Echinococcus granulosus hydatid cyst fluid protein on allergic rhinitis induced by ovalbumin in mice / 中国血吸虫病防治杂志

Objective To investigate the protective effect of Echinococcus granulosus hydatid cyst fluid protein (HCFP) on ovalbumin (OVA)-induced allergic rhinitis (AR) in mice. Methods Twenty-four BALB/c mice at ages of 8 to 10 weeks, each weighing approximately 20 g, were randomly divided into four groups, including groups A (blank control group), B (blank intervention group), C (AR model group) and D (AR+HCFP intervention group), with 6 mice in each group. On days 0, 2, 4, 6, 8, 10 and 12, mice in groups A, B, C and D were injected with 200 μL sterile phosphate buffered saline (PBS), 200 μL sterile PBS containing 20 μg HCFP, 200 μL sterile PBS containing 50 μg OVA and 5 mg Al(OH)3 gel, and 200 μL sterile PBS containing 50 μg OVA, 5 mg Al(OH)3 gel and 20 μg HCFP, respectively. On days 14 to 20, mice in groups A, B, C and D were administered with 40 μL sterile PBS, 40 μL sterile PBS containing 20 μg HCFP, 40 μL sterile PBS containing 2 mg OVA and 40 μL sterile PBS containing 2 mg OVA and 20 μL HCFP by nasal drop, respectively. Mouse behavioral changes were observed and behavioral scores were estimated. The serum levels of interferon-γ (IFN-γ), interleukin-4 (IL-4), IL-5, IL-10, transforming growth factor-β (TGF-β) and OVA-specific IgE antibody (OVA-sIgE) were measured using enzyme-linked immunosorbent assay (ELISA), and the pathological changes of mouse nasal mucosa were observed by hematoxylin and eosin (HE) staining. Results The mean behavioral score was significantly greater in Group C (6.83 ± 0.50) than in groups A (1.17 ± 0.52) and B (1.33 ± 0.52) (P < 0.05), while a lower mean behavioral score was estimated in Group D (3.50 ± 0.50) than in Group C (P < 0.05). There were significant differences among the groups in terms of serum IFN-γ (F = 4.08, P < 0.05), IL-4 (F = 275.90, P < 0.05), IL-5 (F = 96.82, P < 0.05), IL-10 (F = 77.67, P < 0.05), TGF-β (F = 9.98, P < 0.05) and OVA-sIgE levels (F = 44.69, P < 0.05). The serum IFN-γ level was significantly lower in Group C than in groups A, B and C (P < 0.05), and the serum levels of IL-4, IL-5 and OVA-sIgE were significantly higher in Group C than in groups A, B and C (P < 0.05), while the serum IL-10 and TGF-β levels were significantly greater in Group D than in Group C (P < 0.05). Microscopy showed apparent loss of nasal mucosa cilia, increased number and enlargement of goblet cells, interstitial edema and submucous vascular dilation in Group C, while the pathological changes of nasal mucosa were alleviated in Group D relative to Group C. Conclusions E. granulosus HCFP has a protective activity against OVA-induced allergic rhinitis in mice.

Effects of different doses of dexmedetomidine on intracranial pressure in patients undergoing gynecological laparoscopic surgery / 中国药房

OBJECTIVE To investigate the effects of different doses of dexmedetomidine on intracranial pressure in patients undergoing gynecological laparoscopic surgery. METHODS Ninety patients undergoing selective gynecological laparoscopic surgery in trendelenburg position were divided into low-dose experimental group （group D 1），high-dose experimental group （group D 2） and control group （group C ）according to random number table ，with 30 cases in each group. Group D 1 and group D 2 received continuous intravenous infusion of dexmedetomidine 1.0 μ g/kg for 10 min for induction of anesthesia ，and then continued intravenous infusion at the rate of 0.4 μg（/ kg·h）and 0.6 μg（/ kg·h）respectively. Group C was continuously pumped with the constant volume of Sodium chloride injection. Three groups stopped pumping 30 minutes before the end of the operation. The heart rate（HR）and mean arterial pressure （MAP）were recorded when entering the room （T0），10 min after intravenous pump of dexmedetomidine（T1），10 min（T2），30 min（T3），60 min（T4）after pneumoperitoneum ，10 min after pneumoperitoneum was closed to restore the supine position （T5）. At the same time ，optic nerve sheath diameter （ONSD）in both eyes was measured by ultrasound，and the occurrence of intraoperative bradycardia and the use of atropine were recorded. RESULTS There was no statistical significance in ONSD ，HR or MAP among 3 groups at T 0（P＞0.05）. Compared with T 0，ONSD of 3 groups were decreased significantly at T 1（except for group C ）；ONSD of 3 groups were increased significantly at T 2-T5，while MAP and HR were all decreased significantly （P＜0.05）. HR of group D 2 was decreased significantly at T 1（P＜0.05）. Compared with group C ， ONSD and HR of group D 1 and D 2 were all decreased significantly at T 1-T5（P＜0.05）. Compared with group C ，the number of patients with bradycardia and those who used atropine in group D 1 and D 2 were increased significantly （P＜0.05）. CONCLUSIONS Continuous pumping of dexmedetomidine during gynecologic laparoscopic surgery can reduce the increase of intracranial pressure in patients ；compared with pumping rate of 0.6 μg（/ kg·h），the change of patient ’s HR tends to be more stable with a pumping rate of 0.4 μg（/ kg·h）.

Folic acid-modified phospholipid-encapsulated paclitaxel nanocrystals for preoperative chemotherapy of gastric cancer / 药学学报

This paper aims to develop folic acid-modified paclitaxel nanocrystals (PTX NC@FA) with good stability, high drug loading and tumor cell targeting for endoscopic injection for preoperative local chemotherapy of gastric cancer. PTX NC@FA was prepared by the "bottom-up" followed by ultrasonic to study its morphology, particle size, ζ-potential, drug loading, folic acid-modified phospholipid (FA-DSPE-PEG2000) content, crystalline characteristics, stability, in vitro release, cytotoxicity against human gastric cancer cell line SGC-7901, and anti-tumor effect in two different tumor sizes (tumor volume 100 mm3 or 300 mm3) after single peri-tumor injection in a murine subcutaneous SGC-7901 tumor model. Animal experiments were approved by the Experimental Animal Ethics Committee of the School of Pharmacy, Fudan University. The resulting PTX NC@FA was of short rod-like shape, average particle size 175.3 ± 2.5 nm (PDI 0.17 ± 0.02), ζ- potential -2.5 ± 0.2 mV, PTX loading (28.23 ± 0.74) % (w/w) and FA-DSPE-PEG2000 content (4.40 ± 0.60) % (w/w). The size of the PTX NC@FA remained unchanged for 4 days in phosphate buffer with or without serum. Cellular growth inhibition effect on SGC-7901 showed the superiority of PTX NC@FA over nanocrystals without FA modification. PTX NC@FA inhibited tumor growth more efficiently than both nanocrystals without FA modification and commercially available paclitaxel injection (Taxol) 12 days after peri-tumor injection. For model tumor with the volume of 100 mm3, tumors of all animals in the PTX NC@FA group disappeared completely. For model tumor with the volume of 300 mm3, tumors of 3 animals in the PTX NC@FA group completely disappeared and tumors of the rest 4 animals also became significantly smaller with a tumor volume inhibition rate of 90%. PTX NC@FA showed good potential for preoperative chemotherapy of increase the chances of function preserving gastrectomy and improve the quality of life of patients.

Centennial history of prion diseases / 中华神经医学杂志

Prion diseases, also known as transmissible spongiform encephalopathies (TSEs), are a rare group of transmissible and fatal neurodegenerative diseases. Since Creutzfeldt-Jakob disease was first officially named in 1992, prion diseases in humans have been studied for 100 years. From the confusion of clinical symptoms to the description of typical histopathological changes, the "prion hypothesis", and the discovery of prion diseases-related genes, the recognition and researches of prion diseases have been penetrating deeply, and prion diseases have gradually received more and more attention in neurology as a group of fatal neurodegenerative diseases, including Creutzfeldt-Jakob disease and its variants, Kuru's disease, Gerstmann-Straussler-Scheinker syndrome, and fatal familial insomnia. Based on the discovery of Creutzfeldt-Jakob disease, this article elaborates the discovery of characteristic pathological changes of prion diseases, verification of infectiability, discovery of prion protein and PRNP gene, and the clinical manifestations, pathological changes and gene mutation types of various subtypes of prion diseases. It is intended to review the research history of prion diseases to help clinical colleagues understanding the progress and dilemma of diagnosis and treatment of the diseases.

Analysis of components of proteins from Echinococcus granulosus cyst fluid / 中国血吸虫病防治杂志

Objective To analyze the components of proteins from Echinococcus granulosus cyst fluid using the shotgun method, and to identify the active components with potential regulatory effects for immune dysregulation diseases. Methods The E. granulosus cyst fluid was collected aseptically from the hepatic cysts of patients with cystic echinococcosis, and characterized by liquid chromatography (LC) tandem mass spectrometry (MS/MS) following digestion with trypsin. The protein data were searched using the software MaxQuant version 1.6.1.0 and the cellular components, molecular functions, and biological processes of the identified proteins were analyzed using the Gene Ontology (GO) method. Results The E. granulosus cyst fluid separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) had a relative molecular mass of 25 to 70 kDa. LS-MS/MS analysis identified 37 proteins, including 32 known proteins and 5 unknown proteins. At least 4 proteins were preliminarily found to exhibit potential regulatory effects for immune dysregulation diseases, including antigen B, glutathione-S-transferase (GST), thioredoxin peroxidase (TPX) and malate dehydrogenase (MDH). GO enrichment analysis showed that the identified proteins had 149 molecular functions and were involved in 341 biological processes. Conclusions E. granulosus cyst fluid has a variety of protein components, and four known proteins are preliminarily identified to be associated with immune dysregulation diseases.

Amphotericin B or its liposome combined with antimony sodium gluconate in the treatment of refractory Kala-azar: a report of 4 cases / 中华地方病学杂志

Objective:To investigate the effect of amphotericin B or its liposomes combined with antimony sodium gluconate (antimonial) in the treatment of refractory Kala-azar.Methods:Four patients with Kala-azar who relapsed or were resistant to antimony after treatment were admitted to the First Hospital of Lanzhou University. The clinical medical records were retrospectively analyzed, including the general information (gender, age, etc), diagnosis and treatment process, clinical manifestations, treatment methods and treatment effect.Results:The clinical symptoms of four patients were relieved after treatment with amphotericin B or its liposomes combined with antimonial. Reexamination of bone marrow smear showed no Leishman-Donovan body. There was no recurrence after six months of follow-up.Conclusion:Amphotericin B or its liposomes combined with antimonial can be used in the treatment of refractory Kala-azar.

Epilepsy in Alzheimer's disease: a retrospective study / 中华老年医学杂志

Objective:To analyze the prevalence of epilepsy and its clinical features in patients with Alzheimer's disease(AD).Methods:Clinical data of patients with AD from a separate database of Tianjin Huanhu Hospital for dementia and degenerative diseases from January 2010 to January 2019 were retrospectively examined.The prevalence of AD combined with epilepsy was analyzed.The characteristics from neuropsychological assessment, clinical manifestations of epileptic attacks, electroencephalogic patterns and other features were analyzed and compared with those of AD patients without epilepsy.Results:Of 376 AD patients, 11.4% had epilepsy, with 4.0% showing non-induced seizures before AD diagnosis and 7.5% after AD diagnosis.The average age of AD patients at first onset of epilepsy was 59.8±19.9 years, and the average age of patients at initial diagnosis with AD was 62.8±6.6 years.The most common type was focal seizures(65.1%), and EEG showed mostly focal slow waves(69.8%)and focal epileptiform discharges(23.3%). The AD diagnosis for patients with epilepsy was 8 years earlier than those without epilepsy.Conclusions:Epilepsy has a high prevalence in AD patients, and seizures may be a risk factor for progression from cognitive impairment to AD.Early identification of seizures and cognitive impairment may have a positive effect on delaying the progression of dementia.

Effects of propofol on GRP78-ATF4-CHOP signaling pathway during apoptosis in gastric cancer cells / 中华麻醉学杂志

Objective:To evaluate the effects of propofol on glucose-regulated protein 78 (GRP78)-activating transcription factor-4 (ATF4)-CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) signaling pathway during apoptosis in gastric cancer cells.Methods:MGC-803 cells were cultured to the logarithmic phase and divided into 2 groups ( n=15 each) using the random number table method: control group (group C) and propofol group (group P). The cells in group C were cultured under normal conditions of 37 ℃ and 5% CO 2. In group P, propofol (final concentration 5 μg/ml) was added when the cells were attached to the wall and grown to 70%-90% confluence.At 24 h after propofol was added, the apoptosis rate of cells was determined by flow cytometry, the expression of GRP78, ATF4 and CHOP mRNA was detected by quantitative polymerase chain reaction, and the expression of GRP78, ATF4 and CHOP was determined by Wester blot, respectively. Results:Compared with group C, the apoptosis rate was significantly increased, and expression of GRP78, ATF4, CHOP and its mRNA was up-regulated in group P ( P<0.05). Conclusion:The mechanism by which propofol accelerates apoptosis is related to activating GRP78-ATF4-CHOP signaling pathway in gastric cancer cells.

The dilemma and breakthrough of oral administration of insulin / 药学学报

Diabetes is characterized by hyperglycemia, resulting from insulin deficiency or resistance, or both. Insulin plays an irreplaceable role in the treatment of diabetes. Subcutaneous injection is the main route of insulin administration, but usually leads to poor compliance and many side effects. Oral insulin is safer and more convenient, which has always been the Holy Grail for people to explore. After oral administration, insulin is absorbed into the hepatic portal vein and transported to the liver, which can activate the normal physiological functions and reduce the risk of hypoglycemia, insulin resistance, and improve patient compliance. However, the gastrointestinal tract has multiple absorption barriers such as chemical barrier, enzyme barrier, and permeation barrier. Due to the physical and chemical properties of insulin, it is difficult to achieve desired oral bioavailability. This article reviews the recent attempts and progress in the field of oral administration of insulin driven by innovative drug delivery technologies and biomaterials, including structural modification, enzyme inhibitors, absorption enhancers, various nanoparticles, liposomes, microspheres, and even microorganisms. Some clinical researches on oral insulin are also introduced.

Recent advance in treatment of persistent posture-perceived dizziness / 中华神经医学杂志

Persistent posture-perceived dizziness is a chronic functional vestibular disorder,which is characterized with persistent non-vertigo dizziness and unsteady for more than 3 months.Its possible pathogeneses include overlapping mechanism of vestibular pathways and anxiety-related neural networks,classical and operant conditioning,failure of re-adaptation,changes in brain activity areas,and molecular pathological mechanisms.Current treatments include psychotherapy,medication,vestibular and balance rehabilitation therapy,cognitive behavioral therapy,and non-invasive vagus nerve stimulation for refractory persistent posture-perceived dizziness.This paper mainly focuses on the above contents and summarizes as follows.