A case of action myoclonus-renal failure syndrome caused by SCARB2 gene mutation / 中华神经科杂志

The article reported the clinical, electrophysiological, renal pathology and gene mutation characteristics of a patient with action myoclonus-renal failure syndrome (AMRF). The patient was a young male who developed epilepsy at the age of 16 and gradually developed tremor, ataxia, and myoclonic seizures. Brain magnetic resonance imaging was normal. The electrophysiological manifestations of the nerve were symmetrical multiple sensory and motor nerve conduction velocity deceleration, especially the easily embedded site of the nerve. Renal pathology showed focal segmental glomerulosclerosis. A new complex heterozygous mutation of SCARB2 gene c.534_537delinsCT (chr4:7710074) and c.358G>T (chr4:7710217) was detected in the patient and verified by his family. The 2 heterozygous mutations were respectively from the patient′s parents. AMRF is a rare type of epilepsy in adolescents. The early manifestations were myoclonus or abnormal renal function, with great clinical heterogeneity and easy to be misdiagnosed and missed diagnosis. The final diagnosis depends on genetic testing.

Analysis of pathogenic bacteria and influencing factors of death in patients with severe neurological pulmonary infection / 中国医师杂志

Objective:To investigate the distribution of respiratory pathogens and risk factors of death in patients with pulmonary infection in neurosurgical intensive care unit (NICU).Methods:A total of 87 patients with pulmonary infection in the NICU of the First Affiliated Hospital of Hunan University of Traditional Chinese Medicine from January 2018 to December 2019 were collected, and the pathogens of their respiratory tract were analyzed to understand the types and distribution of bacteria in the lung infection. Univariate statistical analysis was used to analyze the relationship between the patient′s clinical outcome with age, diabetes, hypertension, renal insufficiency, hypoproteinemia, anemia, chronic respiratory disease, surgery, tracheotomy, and bacterial multi-resistance. Binary logistic regression analysis was used to analyze the influencing factors of death in NICU patients with pulmonary infection.Results:A total of 112 pathogenic bacteria were isolated in this research group, including 83 Gram-negative bacteria (74.11%), 22 Gram-positive bacteria (19.64%), and 7 Fungi (5.25%). Imipenem was highly sensitive to Gram-negative bacteria, vancomycin was highly sensitive to Gram-positive bacteria, and other drugs were highly resistant. 41 patients died (47.13%). Age≥60 ( OR=3.501, 95% CI: 1.152-10.638), renal insufficiency ( OR=3.872, 95% CI: 1.336-11.224), tracheotomy ( OR=0.317, 95% CI: 0.114-0.882), bacteria multi-drug resistance ( OR=3.480, 95% CI: 1.162-10.422) were independent risk factors for death in NICU patients with pulmonary infection. Conclusions:Patients with severe neurological diseases are in critical condition, and there are many patients with pulmonary infection, with poor prognosis and high mortality. Gram-negative bacteria are the most common respiratory pathogens. Carbapenems account for the highest proportion of antibiotics in clinic. Advanced age, renal insufficiency and bacterial multidrug resistance increase the mortality of patients, while early tracheotomy can reduce the mortality of patients.

Clinical study of posterior capsular opacification after cataract surgery in diabetic patients / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To study the incidence and risk factors of posterior capsular opacification(PCO)after cataract surgery in diabetic patients.<p>METHODS: Clinical data of 182 cases(203 eyes)who underwent cataract phacoemulsification combined with intracellular lens implantation in our hospital from April 2016 to August were collected. The patients were divided into diabetic group(DM group, 98 eyes)and non-diabetic group(non-DM group, 105 eyes)according to whether they had diabetes before operation. DM group were divided into groups according to whether PCO occurred 30mo after cataract surgery, 26 eyes in the PCO group, and 72 eyes in non-PCO group. The incidence and grading of PCO in the DM group and the non-DM group were compared. The effects of preoperative diabetic course, HbA1c level and the presence of diabetic retinopathy on PCO in DM group were tested.<p>RESULTS: The incidence of PCO was 10.2%, 14.3%, 22.4%, 26.5% at 12, 18, 24 and 30mo in the DM group and 2.8%, 4.8%, 10.5%, and 14.3% in the non-DM group. Two groups of patients with the degree of PCO are gradually increasing, and the degree of each point in time the PCO patients with DM group were heavier than patients without DM group(all P<0.05). There were differences in the preoperative course of diabetes and the presence of DR between PCO and non-PCO groups(P<0.05), but there was no difference in the preoperative level of HbA1c(P>0.05).<p>CONCLUSION: The incidence of PCO in diabetic patients after cataract surgery was higher than that in non-diabetic patients, and the degree of opacity was more severe. Preoperative course of diabetes and the presence of DR were risk factors for PCO.

Antiviral effect of Fufang yinhua jiedu (FFYH) granules against coronavirus and its potential mechanism / 药学学报

To investigate the effect of Fufang yinhua jiedu (FFYH) granules against coronavirus and its potential mechanism, we used Huh7, Huh7.5, H460, and C3A cell lines as in vitro models to evaluate the cytotoxicity and antiviral activity of FFYH by observation of cell pathogenic effect (CPE); and then the inhibitory effect of FFYH on the transcription expression of coronavirus RNA and inflammatory factor mRNA were evaluated by quantitive reverse transcription PCR (qRT-PCR); finally, the inhibitory effect of FFYH on the expression of coronavirus protein and its underlying mechanism against coronavirus were investigated by Western blot and immunofluorescence. Our results indicated that 50% toxic concentration (TC50) FFYH on Huh7, Huh7.5, H460, and C3A cells were 2 035.21, 5 245.69, 2 935.28 and 520 µg·mL-1, respectively; 50% inhibitory concentration (IC50) of FFYH on HCoV-229E in Huh7 and Huh7.5 cells were 438.16 and 238.54 µg·mL-1 with safety index (SI) of 4.64 and 21.99, respectively; IC50 of FFYH on HCoV-OC43 in H460 cells was 165.13 µg·mL-1 with SI of 17.78. Moreover, FFYH not only could inhibit the replication of coronaviruses (HCoV-OC43 and HCoV-229E) through inhibiting the transcription of viral RNA and the expression of viral protein, but also effectively suppress the expression of inflammatory factors interleukin-6 (IL-6), tumor necrosis factor α (TNF-α) and interleukin-8 (IL-8) at mRNA level caused by coronaviruses, which might be associated with the inhibitory effect of FFYH on mitogen-activated protein kinase (MAPK) pathway and the nuclear translocation of nuclear transcription factor-κB (NF-κB). In summary, our results demonstrated that FFYH exhibited a good in vitro anti-coronavirus effect, which provides a theoretical basis for its clinical use in the treatment of anti-coronavirus pneumonia.

Identification of pathogenic variant and preimplantation genetic testing for a Chinese family affected with osteogenesis imperfecta / 中华医学遗传学杂志

OBJECTIVE@#To identify the pathogenic variant for a husband with osteogenesis imperfecta and provide preimplantation genetic testing (PGT) for the couple.@*METHODS@#High-throughput sequencing and Sanger sequencing were carried out to identify the pathologic variant in the husband patients. PGT of embryos was performed through direct detection of the mutation site. Meanwhile, chromosome aneuploidy of the blastocysts was screened. Following transplantation, cytogenetic and genetic testing of fetal amniotic fluid sample was carried out during mid-pregnancy. Chromosome copy number variant (CNV) was detected at multiple sites of the placenta after delivery.@*RESULTS@#The husband was found to harbor heterozygous c.544-2A>G variant of the COL1A1 gene. The same variant was not detected in either of his parents. PGT revealed that out of three embryos of the couple, one was wild-type for the c.544-2A site but mosaicism for duplication of 16p13.3.11.2. The other two embryos were both heterozygous for the c.544-2A>G variant. Following adequate genetic counseling, the wild-type embryo was transplanted. Amniotic fluid testing confirmed that the fetus had normal chromosomes and did not carry the c.544-2A>G variant. The copy number of chromosomes at different parts of placenta was normal after birth.@*CONCLUSION@#For couples affected with monogenic disorders, e.g., osteogenesis imperfecta, direct detection of the mutation site may be used for PGT after identifying the pathogenic variant. After adequate genetic counseling, prenatal diagnosis must be carried out to ensure the result.

Characteristic chromatogram and index components content of substance benchmark of Xuanfu Daizhe Decoction / 中国中药杂志

The methods for determining the characteristic chromatogram and index components content of Xuanfu Daizhe Decoction were established to provide a scientific basis for the quality evaluation of substance benchmarks and preparations. Eighteen batches of Xuanfu Daizhe Decoction were prepared with the decoction pieces of different batches and of the same batch were prepared respectively, and the HPLC characteristic chromatograms of these samples were established. The similarities of the chromatographic fingerprints were analyzed. With liquiritin, glycyrrhizic acid, 6-gingerol, ginsenoside Rg_1, and ginsenoside Re as index components, the high performance liquid chromatography was established for content determination with no more than 70%-130% of the mass average as the limit. The results showed that there were 19 characteristic peaks corresponding to the characteristic chromatograms of 18 batches of Xuanfu Daizhe Decoction, including 8 peaks representing liquiritin, 1,5-O-dicaffeoylqunic acid, ginsenoside Rg_1, ginsenoside Re, 1-O-acetyl britannilactone, ginsenoside Rb_1, glycyrrhizic acid, and 6-gingerol, and the fingerprint similarity was greater than 0.97. The contents of liquiritin, glycyrrhizic acid, 6-gingerol, and ginsenosides Rg_1 + Re in the prepared Xuanfu Daizhe Decoction samples were 0.53%-0.86%, 0.61%-1.2%, 0.023%-0.068%, and 0.33%-0.66%, respectively. Except for several batches, most batches of Xuanfu Daizhe Decoction showed stable contents of index components, with no discrete values. The characteristic chromatograms and index components content characterized the information of Inulae Flos, Ginseng Radix et Rhizoma, Glycyrrhizae Radix et Rhizoma, and Zingiberis Rhizoma Recens in Xuanfu Daizhe Decoction. This study provides a scientific basis for the further research on the key chemical properties of substance benchmark and preparations of Xuanfu Daizhe Decoction.

Association between Maternal Drug Use and Cytochrome P450 Genetic Polymorphisms and the Risk of Congenital Heart Defects in Offspring / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to assess the associations between maternal drug use, cytochrome P450 ( CYP450) genetic polymorphisms, and their interactions with the risk of congenital heart defects (CHDs) in offspring.@*METHODS@#A case-control study involving 569 mothers of CHD cases and 652 controls was conducted from November 2017 to January 2020.@*RESULTS@#After adjusting for potential confounding factors, the results show that mothers who used ovulatory drugs (adjusted odds ratio [a OR] = 2.12; 95% confidence interval [ CI]: 1.08-4.16), antidepressants (a OR = 2.56; 95% CI: 1.36-4.82), antiabortifacients (a OR = 1.55; 95% CI: 1.00-2.40), or traditional Chinese drugs (a OR = 1.97; 95% CI: 1.26-3.09) during pregnancy were at a significantly higher risk of CHDs in offspring. Maternal CYP450 genetic polymorphisms at rs1065852 (A/T vs. A/A: OR = 1.53, 95% CI: 1.10-2.14; T/T vs. A/A: OR = 1.57, 95% CI: 1.07-2.31) and rs16947 (G/G vs. C/C: OR = 3.41, 95% CI: 1.82-6.39) were also significantly associated with the risk of CHDs in offspring. Additionally, significant interactions were observed between the CYP450genetic variants and drug use on the development of CHDs.@*CONCLUSIONS@#In those of Chinese descent, ovulatory drugs, antidepressants, antiabortifacients, and traditional Chinese medicines may be associated with the risk of CHDs in offspring. Maternal CYP450 genes may regulate the effects of maternal drug exposure on fetal heart development.

Application value of the modified blood smear technique for platelet counting / 中国基层医药

Objective:Four methods were used to count platelets to recommend suitable retest methods for abnormal blood platelet count.Methods:A total of 300 patients who received treatment in the Second People's Hospital of Lianyungang during August-September 2020 were included in this study. They were divided into low-value, median-value, and high-value groups ( n = 100/group) according to blood platelet counts determined by the electrical impedance method. The consistency in blood platelet counting was analyzed between flow cytometry and electrical impedance method, Neubauer chamber method, and modified blood smear method. Results:There was no significant difference in blood platelet count between the electrical impedance method [low-value group: (86.1 ± 10.3) × 10 9/L, median-value group: (221.8 ± 41.8) × 10 9/L, high-value group: (441.3 ± 51.4) × 10 9/L, Neubauer chamber method [low-value group: (85.2 ± 10.1) × 10 9/L, median-value group: (219.3 ± 37.7) × 10 9/L, high-value group: (443.1 ± 54.5) × 10 9/L, modified blood smear technique [low-value group: (86.1 ± 10.1) × 10 9/L, median-value group: (218.1 ± 37.7) × 10 9/L, high-value group: (442.6 ± 53.3) × 10 9/L], and flow cytometry [low-value group: (85.4 ± 10.1) × 10 9/L, median-value group: (220.7 ± 42.0) × 10 9/L, high-value group: (440.9 ± 50.0) × 10 9/L] (all P > 0.05). The Bland-Altman analysis revealed that the electrical impedance method, Neubauer chamber method and modified blood smear method, and flow cytometry showed consistency in blood platelet count. Conclusion:The modified blood smear method showed consistency with the electrical impedance method, Neubauer chamber method, and flow cytometry in blood platelet counting. It does not require a special instrument and can help observe cell morphology for blood platelet counting. In addition, the blood smears are easy to be preserved. The modified blood smear technique should be the first choice for re-checking blood platelet counts.

Application of humanistic care combined with experiential teaching in practice nursing students teaching in the department of respiratory and critical care medicine / 中华医学教育探索杂志

Objective:To explore the application of humanistic care combined with experiential teaching in the teaching of nursing students in the department of respiratory and critical care medicine.Methods:A total of 100 full-time undergraduate nursing interns in the Department of Respiratory and Critical Care Medicine of Beijing Chaoyang Hospital, Capital Medical University from July 2019 to December 2020 were selected as the research objects. The nursing students were divided into a control group and a research group according to the order of admission, with 50 students in each group. The control group adopted traditional teaching, while the research group adopted humanistic care combined with experiential teaching. After the internship, the self-assessment scale of humanistic care literacy ability was used to measure the humanistic care behavior of the practice nursing students, and the teaching effect was evaluated by the self-designed teaching effect evaluation table. SPSS 22.0 was used for t test and chi-square test. Results:The scores of humanistic care literacy ability of practice nursing students in the research group were higher than those in the control group in the five aspects of skill, communication, respect, understanding and dedication, and the difference was statistically significant ( P<0.05). The teaching effect evaluation of interns in the research group were significantly better than those in the control group in 8 aspects, including humanistic care literacy ability, nurse-patient communication ability, independent learning ability, problem analysis and solving ability, keen observation ability, emergency response ability, critical thinking ability and teamwork ability ( P<0.05). Conclusion:Humanistic care combined with experiential teaching can help practice nursing students in department of respiratory and critical care medicine improve their humanistic care literacy ability, their comprehensive clinical practice ability and the quality of clinical teaching.

Association between maternal reduced folate carrier gene polymorphisms and congenital heart disease in offspring: a case-control study / 中国当代儿科杂志

OBJECTIVE@#To study the association between maternal reduced folate carrier (@*METHODS@#A hospital-based case-control study was conducted. The mothers of 683 infants with CHD who attended the Department of Cardiothoracic Surgery, Hunan Children's Hospital, from November 2017 to March 2020 were enrolled as the case group. The mothers of 740 healthy infants without any deformity who attended the hospital during the same period of time were enrolled as the control group. A questionnaire survey was performed to collect the exposure data of subjects. Venous blood samples of 5 mL were collected from the mothers for genetic polymorphism detection. A multivariate logistic regression analysis was used to evaluate the association of @*RESULTS@#After control for confounding factors, the multivariate logistic regression analysis showed that maternal @*CONCLUSIONS@#Maternal

The development of auditory speech perception and spatial hearing abilities within one year after cochlear implantation in preschool prelingual deaf children / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the development of auditory speech perception and spatial hearing abilities within one year after cochlear implantation in preschool prelingual deaf children and the relationship between the two abilities. Methods: This retrospective study analyzed 31 preschool children with an average age of (2.3±1.2) years. All cases were assessed at pre-implant, 6 months and 12 months post-implant using the Infant-toddler Meaningful Auditory Integration Scale (IT-MAIS), the Meaningful Auditory Integration Scale (MAIS) and the Mandarin Early Speech Perception test (MESP) to evaluate their listening and speech perception abilities, and using the Speech,Spatial,and Other Qualities of Hearing Scale for Parents (SSQ-P) questionnaires to evaluate their speech perception and spatial hearing abilities. SPSS 23.0 was used for the statistical analysis. Results: All children performed better at 6 months and 12 months post-implant with IT-MAIS/MAIS, MESP than pre-implant, and the scoring rate continued to improve, with a significant difference (P<0.01). For the SSQ-P (Speech) and SSQ-P (Spatial) scores, the mean scores of pre-implant were (0.9±0.2) points and (0.8±0.3) points, those of 6 months post-implant were (4.6±0.2) and (2.6±0.3), and 12 months post-implant were (6.2±0.2) and (6.3±0.3), the scores of the two groups were significantly different at pre-implant, 6 months and 12 months post-implant (P<0.01). The growth rate of SSQ-P (Spatial) from pre-implant to 12 months post-implant was 675.3%, and the growth rate from 6 months post-implant to 12 months post-implant was 140.6%, the growth rate showed an significant increase compared with IT-MAIS/MAIS, MESP and SSQ-P (Speech).SSQ-P (Speech) and SSQ-P (Spatial) scores were moderate correlation at 12 months post-implant(r=0.465, P=0.008). Conclusions: Within one year after cochlear implantation, listening, speech perception and spatial hearing abilities of preschool prelingual deaf children could show a comprehensive, continuous and significant progress as the implantation time increasing. The growth rate of spatial hearing is greater than that of speech perception at 12 months post-implant, and the spatial hearing could still show rapid development characteristics after 6 months post-implant.

Qualitative and quantitative analysis of Arnebiae Radix and Dictamni Cortex and efficacy study of herbal extracts on allergic contact dermatitis using 3D human reconstructed epidermis / 中草药·英文版

Objective: To evaluate the quality of Arnebiae Radix (AR) and Dictamni Cortex (DC) and study the efficacy of herbal extracts of these two herbs on the treatment of allergic contact dermatitis (ACD). Methods: Qualitative and quantitative analysis of effective components was performed using High Performance Thin Layer Chromatography (HPTLC), High Performance Liquid Chromatography (HPLC), and HPLC-Quadrupole Time of Flight-Mass Spectrometry (HPLC-QTOF-MS). In vitro allergic ACD 3D model was established by incubating 3D reconstructed human epidermis (RHE) with skin sensitizer, potassium dichromate. A total of 65 gene expression that were associated with ACD, which included 24 antioxidant responsive element (ARE) and 41 SENS-IS genes were quantified by qRT-PCR. More than or equal to 10 ARE genes and 18 SENN-IS genes were induced by 1.3-fold, demonstrating the successful establishment of in vitro ACD model. Oil extracts of AR and DC were applied on the in vitro ACD model to study the efficacy. Results: Batch 3 of AR and batch 2 of DC showed presence of all active ingredients with the highest concentrations. Active ingredients of the herbs were extracted using a special oil and formulated into herbal oil extracts. The herbal oil extracts were able to down regulate the induced genes in the in-vitro ACD skin model, bringing the tissue back to homeostatic status. Conclusion: The oil extracts showed the potent efficacy of using AR and DC in ACD treatment. The combination study will be done to optimize the formulation ratio which will be developed into a topical cream.

Quality evaluation of Aralia taibaiensis based on spectrum-activity relationship / 中国中药杂志

A spectrum-activity relationship is established with high performance liquid chromatography(HPLC) fingerprints and the in vitro antioxidant activity to improve the quality evaluation system of Aralia taibaiensis. The HPLC profiles of 12 batches of samples were collected, and the similarity evaluation, heat map analysis and principal component analysis were conducted for the chemometric study of the fingerprint data. Combined with grey correlation analysis, the contributions of the common peaks in the fingerprints to the antioxidant activity were clarified, and the important peaks reflecting the efficacy were identified. The results showed that 17 common peaks were found in 12 batches of A. taibaiensis samples, and 6 of them were identified as saponins. Similarity evaluation, heat map analysis and principal component analysis roughly classified the A. taibaiensis herbs into two categories, i.e.,(1) S1-S10, S12 and(2) S11. Twelve batches of samples showed different antioxidant activities in a dose-dependent manner. In particular, S9 had the strongest antioxidant activity, while S11 was the weakest in antioxidant capacity, which was basically consistent with the overall score results. The results of grey correlation analysis demonstrated that the 17 common peaks scavenged DPPH radicals in the following order: X_3>X_(17)>X_4>X_8>X_7>X_(13)>X_2>X_6>X_(11)>X_(10)>X_(16)>X_(12)>X_9>X_5>X_(14)>X_1>X_(15), and scavenged ABTS radicals in the order of X_4>X_3>X_7>X_8>X_2>X_(17)>X_(13)>X_6>X_(16)>X_(11)>X_5>X_(12)>X_(10)>X_9>X_(14)>X_1>X_(15). Among them, X_3, X_4, X_7(araloside C), X_8 and X_(17) were the important peaks reflecting the efficacy of A. taibaiensis, which were basically consistent with those contained in the principal component 1. In this study, the correlation between the HPLC fingerprints of 12 batches of A. taibaiensis and its antioxidant activity provides a reference for the Q-marker screening and quality control of A. taibaiensis.

Effects and mechanisms of Supplemented Gegen Qinlian Decoction Formula against podocyte pyroptosis and insulin resistance in model rats with diabetic kidney disease / 中国中药杂志

This study explored the in vivo effects and mechanisms of the modern classical prescription Supplemented Gegen Qinlian Decoction Formula(SGDF) against diabetic kidney disease(DKD). Sixty rats were randomly divided into the normal group, model group, SGDF group, and rosiglitazone(ROS) group. The modified DKD rat model was established by employing the following three methods: exposure to high-fat diet, unilateral nephrectomy, and intraperitoneal injection of streptozotocin(STZ). After modeling, rats in the four groups were treated with double distilled water, SGDF suspension, and ROS suspension, respectively, by gavage every day. At the end of the 6 th week of drug administration, all the rats were sacrificed for collecting urine, blood, and kidney tissue, followed by the examination of rat general conditions, urine and blood biochemical indicators, glomerulosclerosis-related indicators, podocyte pyroptosis markers, insulin resistance(IR)-related indicators, and key molecules in the insulin receptor substrate(IRS) 1/phosphatidylinositol-3-kinase(PI3 K)/serine threonine kinase(Akt) signaling pathway. The results showed that SGDF and ROS improved the general conditions, some renal function indicators and glomerulosclerosis of DKD model rats without affecting the blood glucose(BG). Besides, they ameliorated the expression characteristics and levels of podocyte pyroptosis markers, alleviated IR, and up-regulated the protein expression levels of the key molecules in IRS1/PI3 K/Akt pathway to varying degrees. In conclusion, similar to ROS, SGDF relieves DKD by targeting multiple targets in vivo. Specifically, it exerts the therapeutic effects by alleviating podocyte pyroptosis and IR. This study has preliminarily provided the pharmacological evidence for the research and development of new drugs for the treatment of DKD based on SGDF.

Analysis of the diagnostic and prognostic value of growth differentiation factor 15 and procalcitonin in sepsis / 中华检验医学杂志

Objective:To investigate the diagnostic and prognostic value of the growth differentiation factor 15 (GDF15) and the procalcitonin (PCT) in sepsis.Methods:A total number of 137 patients with sepsis (considered as the sepsis group) and 59 patients with inflammatory infection but not diagnosed as sepsis (the non-sepsis group) received treatment in intensive care unit of Renming Hospital of Wuhan University were collected from July 2020 to January 2021, and 62 cases of healthy physical examination (control group) were simultaneously chosen as control. Sepsis patients were divided into two groups (death group [ n=48] and survival group [ n=89]) according to their 28-day′s survival. The serum levels of GDF15, PCT, C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-10 (IL-10) were examined, and the levels of each index, was dynamically monitored on the 1st, 3rd and 7th day after admission. The differences of the two indicators between different groups were compared by non-parametric test. The correlation between GDF15 and PCT was analyzed by Spearman correlation test. The receiver operating characteristic (ROC) curve was drawn to evaluate the diagnostic and prognostic value of the two indicators for sepsis. Results:The levels of GDF15 in the sepsis group, non-sepsis group and control group were 3.22 (1.39, 6.31) μg/L, 0.84 (0.21, 1.66) μg/L and 0.11 (0.09, 0.13) μg/L, respectively. The levels of PCT were 13.10 (1.99, 50.25) μg/L, 0.24 (0.13, 0.68) μg/L and 0.05 (0.03, 0.10) μg/L, respectively. The levels of CRP were 115.80 (26.40, 184.07) mg/L, 24.20 (11.30, 53.20) mg/L and 0.50 (0.50, 2.76) mg/L, respectively. The levels of IL-6 were 68.26 (21.59, 255.46) ng/L, 33.20 (10.81, 89.27) ng/L and 8.82 (7.33, 11.23) ng/L, respectively. The levels of IL-10 were 11.30 (5.88, 25.50) ng/L, 9.34 (5.65, 16.90) ng/L and 4.94 (4.31, 5.31) ng/L, respectively. The GDF15, PCT, CRP and IL-6 of the sepsis group were significantly higher than those of the non-sepsis group (The U values were 67.681, 86.034, 44.164 and 38.934, respectively, with P values less than 0.05) and the control group (The U values were 136.475, 138.667, 120.701 and 100.886, respectively, with P values less than 0.001). There was no significant difference in IL-10 between sepsis group and nonsepsis group, but it was higher than that of control group ( U=80.221, P<0.001). There was a positive correlation between GDF15 and PCT in patients with sepsis, and the spearman correlation coefficient was 0.234 ( P=0.006). The GDF15 of the death group and the survival group were 5.49 (3.60, 8.25) μg/L and 2.03 (1.06, 3.69) μg/L, and the PCT levels were 26.45 (11.23, 94.25) μg/L and 9.08 (1.33, 22.75) μg/L, respectively. GDF15 and PCT in the death group were significantly higher than those in the survival group ( U values were 3 305.500 and 3 060.000, respectively, and P values were both less than 0.001). The GDF15 and PCT levels in the death group were higher than those in the survival group on the 1st, 3rd and 7th day of dynamic monitoring ( P<0.05), however, the level of CRP and IL-10 were not significantly different ( P>0.05). The level of IL-6 in the death group was not significantly different from that of the death group on 1st day, but was higher than that of the survival group on the 3rd and 7th day ( P<0.05). The area under the curve (AUC) of GDF15, PCT, CRP, IL-6 and IL-10 alone and in the combined diagnosis of sepsis were 0.899, 0.938, 0.874, 0.789, 0.698 and 0.962, respectively. The combined detection of AUC was better than a single index; the GDF15, PCT, CRP, IL-6 and IL-10 alone and combined detection of sepsis prognosis AUC were 0.774, 0.716, 0.522, 0.623, 0.520 and 0.839, respectively, the combined detection of AUC is also better than single index. Conclusions:GDF15 and PCT have good clinical reference value in the differential diagnosis and prognosis of sepsis. The combination of indicators has a higher clinical value. GDF15 may become a biomarker for the diagnosis and prognosis of sepsis.

Current state and progress of rapamycin in the treatment of non-infectious uveitis / 中华眼底病杂志

Glucocorticoids (GCS) are the main treatment for non-infectious uveitis (NIU). However, long-term GCS treatment may induce systemic side effects including hypertension, hyperlipidemia and diabetes. Patients may develop cataract, ocular hypertension or glaucoma because of topical application of GCS. Rapamycin (RAPA) exhibits immunosuppressive, antiangiogenic and antiproliferative effects. Animal experiments and clinical trials have shown that RAPA has therapeutic potential for NIU, especially the treatment of intravitreal injection. In particular, intravitreal injection of RAPA can result in minimal systemic exposure and reduce adverse events. Meanwhile, systemic unwanted effects should be concerned about. In recent years, some studies have attempted to employ nanostructured carriers to improve penetrating abilities of RAPA and efficacy of treatment for ocular posterior segment diseases. These carriers include micelles, liposomes, nanocrystals, polymeric nanoparticles, magnetic nanoparticles and so on. Whether they can load RAPA for treating NIU deserves further study and exploration.

Prognostic analysis of early stage extranodal natural-killer/T cell lymphoma treated with induced chemotherapy combined with radiotherapy / 中华放射肿瘤学杂志

Objective:To analyze the efficacy and prognostic factors of induced chemotherapy combined with radiotherapy in the treatment of early stage extranodal natural-killer/T cell lymphoma (ENKTCL).Methods:Two hundred and eighty-seven early stage NKTCL patients were treated in Affiliated Cancer Hospital of Guizhou Medical University from October 2003 to October 2021. All patients were aD ministrated with short courses of induced chemotherapy combined with radiotherapy. Clinical prognostic factors of early stage NKTCL were analyzed. The overall survival (OS) and progression-free survival (PFS) were calculated by Kaplan- Meier method, log-rank test was conducted for univariate analysis and Cox models were performed for multivariate analysis. Results:The 5-year OS and PFS were 72.8% and 68.9% in all patients. According to Nomogram risk index (NRI) prognostic model, 286 patients were divided into the low risk (NRI=0), intermediate low risk (NRI=1), intermediate high risk (NRI=2), high risk (NRI=3) and very high risk (NRI≥4) groups. In these 5 groups, the 5-year OS were 95.6%, 76.3%, 69.5%, 61.0% and 23.3%(all P<0.001), and the 5-year PFS were 93, 2%, 69.8%, 64.6%, 60.2% and 23.3%(all P<0.001), respectively. In the radiotherapy with a dose of ≥50 Gy and<50 Gy groups, the 5-year OS were 73.8% and 65.9%( P=0.123) and the 5-year PFS were 72.8% and 45.3%( P=0.001). According to the response to induced chemotherapy of complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD), the 5-year OS were 85.4%, 74.0%, 61.8% and 28.5%(all P<0.001), and the 5-year PFS were 83.7%, 66.8%, 65.7% and 27.4%(all P<0.001), respectively. Univariate analyses showed that stage Ⅱ, ECOG≥2, primary tumor invasion, radiotherapy dose<50 Gy and short-term efficacy of induced chemotherapy were poor prognostic factors for the 5-year OS and PFS (all P<0.05). Multivariate analyses demonstrated that primary tumor invasion, ECOG≥2 and stage Ⅱ were poor prognostic factors for OS (all P<0.05), and primary tumor invasion and ECOG≥2 were poor prognostic factors for PFS (all P<0.05). Conclusions:Early stage NKTCL patients can obtain high efficacy after induced chemotherapy combined with radiotherapy. Complete response to induced chemotherapy is associated with favorable prognosis.

Expression of glypican1 protein in pancreatic ductal adenocarcinoma and its clinical significance / 中华胰腺病杂志

Objective:To investigate the expression of glypican1 (GPC1) in pancreatic ductal adenocarcinoma (PDAC) and its relationship with the prognosis of patients with PDAC.Methods:From January 2015 to December 2018, 125 PDAC tumor specimens and corresponding para-carcinoma normal pancreatic tissue were collected from the Department of Pathology of Peking University Third Hospital. The expression of GPC1 protein was detected by the immunohistochemical Envision two-step method in all specimens. The specimens were divided into high and low GPC1 expression groups according to immunohistochemical scores, and the correlation between GPC1 protein expression and clinicopathological features and overall survival time was analyzed.Results:The positive expression rate of GPC1 protein was 0 score in 30.4% of PDAC tissues, 1 score in 15.2%, 2 score in 18.4% and 3 score in 36.0%, respectively, and high expression rate (2+ 3) was 54.4%. GPC1 protein was negatively expressed in para-carcinoma pancreatic tissues. The positive expression rate of GPC1 protein in PDAC tissue was significantly higher than that in para-carcinoma pancreatic tissue, and the difference was statistically significant ( P=0.000). The high expression of GPC1 protein was significantly correlated with tumor location and T stage ( P<0.05), but not with gender, age, history of diabetes and pancreatitis, preoperative blood CA19-9 level, postoperative surgical margin, tumor differentiation, lymph node metastasis, nerve invasion and vascular invasion (all P values >0.05). Univariate Cox proportional hazards analysis showed that GPC1 expression was associated with postoperative overall survival time in PDAC patients ( P<0.001). Multivariate Cox proportional hazards analysis showed that GPC1 protein expression level was an independent prognostic factor affecting overall survival time in PDAC patients ( P<0.001). The median survival time of PDAC patients with high GPC1 expression was significantly lower than that of PDAC patients with low GPC1 expression (11.00 months vs 18.00 months), and the difference was statistically significant ( P<0.01). Conclusions:GPC1 protein was abnormally high expressed in PDAC tumor tissue, and the high expression of GPC1 protein was positively correlated with tumor stage and negatively correlated with the overall survival time of patients. High expression of GPC1 was an independent risk factor for poor prognosis in PDAC patients.

Effects of intravenous injection of human umbilical cord mesenchymal stem cells-derived small extracellular vesicles on experimental autoimmune uveitis in mice / 中华实验眼科杂志

Objective:To explore the therapeutic effects of intravenous injection of small extracellular vesicles (sEVs) derived from human umbilical cord mesenchymal stem cells (MSCs) on experimental autoimmune uveitis (EAU) in mice.Methods:MSCs from human umbilical cord were cultured and the supernatant was collected.The sEVs were isolated by ultracentrifugation method and a NanoSight instrument was used to analyze the particle size.The expression of surface markers sEVs, CD9, CD81 and CD63 was determined via Western blot.The morphology of sEVs was observed with a transmission electron microscope.Forty-eight 7-week-old female C57BL/6 mice were seclected to establish the EAU model through immunization with interphotoreceptor retinoid-binding protein peptide 651-670 (IRBP 651-670). The mice were divided into sEVs treatment group and phosphate buffer solution (PBS) control group using a random number table, with 24 mice in each group.The mice in the sEVs treatment group were injected with 50 μg of MSCs-derived sEVs via tail vein on the 11th day after modeling.In the PBS control group, the mice were injected with the same volume of PBS.Six mice in each group were randomly selected to observe the inflammation of the retina after mydriasis with an ophthalmoscope every other day from 8th day following modeling and the inflammation scores were evaluated.Six mice were randomly selected and sacrificed on the 14th day and 6 on the 18th day following modeling in each group, and both eyeballs of the mice were enucleated.Retinal tissue sections of the 6 mice sacrificed on the 18th day were stained with hematoxylin-eosin and the pathological scores were evaluated.The infiltration of helper T 1 (Th1) cells and Th17 cells in the eyeballs of the 6 mice sacrificed on the 18th day following modeling was detected by flow cytometry.T cells were isolated from spleen and lymph nodes of the 6 mice sacrificed on the 14th day, and the proliferation of T cells under different concentrations of IRBP 651-670 (0, 1, 10 and 20 μg/ml) was detected using a 5-bromodeoxyuridine (BrdU) method.To further study the effects of MSCs-derived sEVs on Th1/Th17 cells differentiation, naive T cells of spleen from another 3 normal mice were isolated by magnetic bead negative sorting and incubated with 10 μg/ml MSCs-derived sEVs or 10 μg/ml PBS, and then were cultured under Th1/Th17 cell differentiation conditions, respectively.Flow cytometry was used to measure the differentiation of naive T cells into Th1/Th17 cells.This study protocol complied with the regulations of the care and use of laboratory animals in China and was approved by an Ethics Committee of Tianjin Medical University (No.TJYY2019103022). Results:The isolated human MSCs-derived sEVs was with an average diameter of (102.4±33.6) nm and showed a double-layer membrane vesicle structure under the transmission electron microscope.The CD9, CD63 and CD81 proteins were highly expressed in sEVs.The inflammation scores of the sEVs treatment group were significantly lower than those in the control group on day 14, 16, 18, 20 and 22 after modeling (all at P<0.05). The pathological score of mice in the sEVs treatment group was significantly lower than that of PBS control group on the 18th day following modeling ( P<0.05). The flow cytometry results showed that on day 18 after modeling, the proportions of Th1 and Th17 cells in eyeballs in the sEVs treatment group were (15.55±2.03)% and (15.67±2.15)%, respectively, which were significantly lower than (21.35±0.72)% and (20.90±1.10)% in the PBS control group ( t=6.58, 5.31; both at P<0.01). BrdU results showed that when the IRBP 651-670 concentration was 20 μg/ml, the T cell proliferation ability in the sEVs treatment group was inhibited obviously compared with the control group ( P<0.05). The proportions of naive T cells differentiated into Th1 cells and Th17 cells in the sEVs treatment group were (28.15±1.32)% and (11.60±2.23)% respectively, which were significantly lower than (31.58±1.75)% and (23.52±1.76)% of the PBS control group, and the differences were statistically significant ( t=3.93, 10.26; both at P<0.05). Conclusions:Intravenous injection of human umbilical cord MSCs-derived sEVs can reduce the inflammation in EAU mice.The mechanism may be related to inhibiting the differentiation of naive T cells to Th1 and Th17 cells, and reducing the infiltration of Th1 and Th17 cells in the eyeballs.

Effect of Shenwei Ningyu Pills on Immunoinflammatory Response Mediated by TLR4/MyD88 Signaling Pathway in Hippocampus of Rats Exposed to Chronic Restraint Stress / 中国实验方剂学杂志

Objective:To explore the effects of Shenwei Ningyu pills （SNP）， a new Chinese medicine for depression， on the immunoinflammatory response mediated by Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88） signaling pathway in the hippocampus of rats exposed to chronic restraint stress （CRS）. Method:Forty-four male Sprague Dawley rats were randomly enrolled into a normal group， a model group， an escitalopram group， and an SNP group. Except for the rats in the normal group， all rats were exposed to CRS and isolated rearing for 21 days continuously. Rats in the escitalopram group and the SNP group were administered with escitalopram （30 mg·kg^-1） and SNP （18 mg·kg^-1） one hour prior to CRS， respectively. The changes in body weight， sucrose preference index， horizontal movement scores， and vertical movement scores were observed by body weight assessment， sucrose preference test， and open field test. The expression of hippocampal TLR4 and MyD88 was detected by Western blot. The content of serum interleukin-1<italic>β</italic> （IL-1<italic>β</italic>）， IL-10， and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） was detected by enzyme-linked immunosorbent assay （ELISA）. Result:The results of the behavioral assessment showed that there was no significant difference in the changes of behavioral baselines among the groups before intervention. However， significant differences were found among the groups following different interventions. The body weight， sugar preference index， horizontal movement score， and vertical movement score of rats in the model group decreased after CRS for 21 days as compared with those in the normal group （<italic>P</italic><0.01）. The above indicators in the SNP<italic> </italic>group and the escitalopram group were higher than those in the model group （<italic>P</italic><0.01）， which indicated that SNP<italic> </italic>exerted an obvious antidepressant effect. The results of Western blot and ELISA showed that compared with the normal group， the model group showed elevated levels of hippocampal TLR4 and MyD88 and serum IL-1<italic>β</italic> and TNF-<italic>α </italic>（<italic>P</italic>˂0.01） and dwindled serum IL-10 （<italic>P</italic>˂0.01）， while SNP<italic> </italic>and escitalopram reversed the conditions in the model group （<italic>P</italic>˂0.01） except for TNF-<italic>α</italic>. Conclusion:The present study indicated that the antidepressant effect of SNP was presumedly achieved by inhibiting the immunoinflammatory response mediated by the TLR4/Myd88 signaling pathway in CRS rats.