Correlation of anti-phosphatidylserine/prothrombin antibodies with unexplained recurrent miscarriages / 北京大学学报(医学版)

OBJECTIVE@#To investigate whether anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes were correlated with unexplained recurrent miscarriages.@*METHODS@#In our a single-center retrospective study, 283 patients with at least one unexplained miscarriage who visited the Third Hospital of Peking University between January 2021 and August 2023, aged between 18-40 years, and tested for anti-phosphatidylserine/prothrombin antibodies IgG or IgM subtypes, were included. The patients with either positive IgG or IgM anti-phosphatidylserine/prothrombin antibody were regarded as positive for anti-phosphatidylserine/prothrombin antibody. SPSS 26.0 software was used for statistical analysis. Chi-square test and Logistic regression analysis were used to study the correlation of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes with unexplained recurrent miscarriages. And the diagnostic sensitivity, specificity, the positive predictive value, the negative predictive value of anti-phosphatidylserine/prothrombin antibodies and its IgG or IgM subtypes in unexplained miscarriages was calculated with four-fold table.@*RESULTS@#Chi-square analysis showed that anti-phosphatidylserine/prothrombin antibodies and its IgM subtypes were correlated with recurrent miscarriages (both P < 0.05), while the IgG subtype was not correlated with recurrent miscarriages (P>0.05). After adjusting with anticardiolipin antibodies, anti-β2 glycoprotein antibodies, lupus anticoagulants, antinuclear antibodies, and age by Logistic regression analysis, anti-phosphatidylserine/prothrombin antibodies were correlated with unexplained recurrent miscarriages (OR=2.084, 95%CI 1.045-4.155, P < 0.05), and anti-phosphatidylserine/prothrombin antibody IgM subtypes were correlated with unexplained recurrent miscarriages (OR=2.368, 95%CI 1.187-4.722, P < 0.05).The sensitivity of anti-phosphatidylserine/prothrombin antibody in recurrent miscarriage was 65.43%, the specificity was 48.51%, the positive predictive value was 33.76%, and the negative predictive value was 77.78%. In the patients with recurrent miscarriages with negative classical antiphospholipid antibodies, the sensitivity of anti-phosphatidylserine/prothrombin antibody was 59.09%, the specificity was 63.23%, the positive predictive value was 40.63%, and the negative predictive value was 78.40%. The sensitivity of the anti-phosphatidylserine/prothrombin antibody IgM subtype for the diagnosis of recurrent miscarriage was 65.43%, the specificity was 50.99%, the positive predictive value was 34.87%, and the negative predictive value was 78.63%.@*CONCLUSION@#Anti-phosphatidylserine/prothrombin antibody and IgM subtype antibody are correlated with unexplained recurrent miscarriages in patients with at least one unexplained miscarriage. Whether positive anti-phosphatidylserine/prothrombin antibody or IgM subtype could predict future unexplained recurrent miscarriages warrants a prospective study.

Medical visit status and clinical features in patients with IgG4 related disease / 北京大学学报(医学版)

OBJECTIVE@#To understand the medical treatment and clinical characteristics of patients with IgG4-related disease (IgG4-RD) with complex clinical manifestations and easy to be misdiagnosed and missed, and to improve the recognition of this disease among doctors from relevant medical departments.@*METHODS@#A retrospective analysis was conducted on the medical records of patients diagnosed with IgG4-RD who were hospitalized and discharged from Peking University Third Hospital from January 1, 2012 to December 31, 2022. The patient' s medical visit status, clinical manifestations, laboratory examinations, diagnosis, and treatment information were summarized.@*RESULTS@#A total of 116 patients diagnosed with IgG4-RD were included in this study, with a male to female ratio of 2. 52∶ 1 and an average age of (61.83±10.80) years. The departments for initial visits were gastroenterology, general surgery, and ophthalmology. While the departments responsible for definitive diagnosis were gastroenterology, rheumatology and immunology, and respiratory medicine. Twenty-one patients (18. 10%) required consultation and treatment from three or more departments before receiving a definitive diagnosis. The median time from symptom onset to the initial clinic visit was 2 (1, 7) months, and the median time from symptom onset to diagnosis was 1 (1, 12) month. Twenty-four patients (20.69%) underwent surgical resection of the affected sites before diagnosis. According to the classification criteria of IgG4-RD, sixty-eight (58.62%) cases were diagnosed definitively, eight (6.9%) cases were likely to be diagnosed, and 40 (34.48%) cases were suspected to be diagnosed. In the 68 definitively diagnosed patients, the most commonly affected organs were submandibular gland, the pancreas, biliary tract, parotid in sequence. The median serum IgG4 (IgG4, immunoglobulin G4) level was 6.16 (3. 61, 12. 30) g/L. Fifty-seven patients (83.82%) were treated with glucocorticoids, and 14 patients (20.59%) were treated with immunosuppressants. The use of immunosuppressants was mainly in the rheumatology and immunology department (78. 57%).@*CONCLUSION@#IgG4-RD is more common in elderly males, with submandibular gland, the pancreas, biliary tract, and parotid being most commonly affected. The distribution of initial visit departments in patients is wide. The proportion of definitive diagnosis based on pathology is relatively low. In terms of treatment, the main approach is steroid treatment, while the use of immunosuppres-sants is not widespread.

Epidemiological characteristics of human adenovirus 2, 3 and 7 genetypes in hospitalized children with respiratory infection in a hospital of pediatric in Hebei Province from 2018 to 2020 / 中华预防医学杂志

Objective: To investigate the epidemiological characteristics of human adenovirus (HADV) 2, 3 and 7 in hospitalized children with respiratory infection. Methods: A total of 25 686 children with respiratory infection hospitalized at Children's Hospital of Hebei Province from January 2018 to December 2020 were retrospectively included.Deep sputum or nasopharyngeal aspirates of those children were collected. Then thirteen common respiratory pathogens were detected by multiplex PCR. 510 HADV positive specimens were randomly selected via random number and classified for type 2, 3 and 7 using a multiplex real-time quantitative PCR. SPSS 21.0 software was used to perform all of the statistical analyses. Enumeration data were expressed by frequency and percentage. χ2 test was used for comparison between groups. Results: The HADV-positive rate was 7.99% (2 052/25 686). Children at age 3-<6 years had the highest HADV-positive rate (11.44%). The HADV-positive rate in 2019 was highest (10.64%). Among the 510 HADV-positive specimens, the proportion of type 3 was the highest (31.16%), followed by type 7 (21.37%) and type 2 (11.18%). The rate of type 2 in 2019 was significantly lower than that in 2018 and 2020 (χ2=8.954 and 16.354; P=0.003 and <0.01), while the rate of type 3 was significantly higher than that in 2018 and 2020 (χ2=5.248 and 4.811; P=0.022 and 0.028). The rate of type 2, type 3 and type 7 were lowest in winter, spring and autumn, respectively. The rate of type 2 increased significantly in autumn and the rate of type 3 and type 7 increased significantly in winter.The co-detection rate of HADV with other respiratory pathogens was 43.33%(221/510). Among, the co-detection rate of type 3 was highest (47.32%), and the co-detection rate of type 2, 3 and 7 was significantly higher than the alone detection rate (χ2=20.438, P<0.01; χ2=42.105, P<0.01; χ2=27.573, P<0.01).The proportion of severe pneumonia in children with type 7 positive (15.89%) was higher than that in children with non-type 7 positive (8.23%) (χ2=5.260, P=0.022). Conclusion: HADV is one of the important pathogens of children with respiratory infection in Children's Hospital of Hebei Province. The susceptible population of HADV is preschool children aged 3 to 6 years. HADV often co-detects with other respiratory pathogens. Type 3 and 7 is likely to be the dominant genotypes in this region, and type 7 may be one of the risk factors of severe pneumonia in children.

Regulation of Endoplasmic Reticulum Stress and Its Targeting Role in Spinal Cord Injury / 中国生物化学与分子生物学报

Endoplasmic reticulum is one of the most important organelles in maintaining cellular homeo⁃ stasis, mainly involved in intracellular lipid synthesis, protein folding and calcium ion homeostasis. Trau⁃ ma, ischemia and hypoxia and other pathological changes can cause protein folding dysfunction in the en⁃ doplasmic reticulum, triggering endoplasmic reticulum stress (ERS). Spinal cord injury (SCI) is a com⁃ mon traumatic disease with anextremely high disability rate, which seriously affects the quality of life. There is no safe and effective clinical methods so far. Investigations have shown that ERS is one of the important pathological changes leading to cell death and neuronal dysfunction after SCI, and is closely as⁃ sociated with signaling pathways such as apoptosis, autophagy, and inflammation in neurons after SCI; however, the molecular mechanisms between ERS and SCI have not yet been thoroughly investigated. A deeper understanding and exploration of the potential molecular mechanisms associated with ERS and SCI may be the future SCI therapeutics. In this paper, we first summarized the relationship between the chan⁃ ges of ERS⁃related genes and the pathological process of SCI, Then the interrelationships between ERS and the apoptosis, inflammation, and autophagy signaling pathways after SCI were analyzed, starting from the three main modes of regulation, including unfolded protein response (UPR), endoplasmic reticulum⁃ associated degradation (ERAD), and endoplasmic reticulophagy (ER⁃phagy),Finally, we summarize the relevant drugs and application prospects of targeting ERS for SCI in recent years, which may provide a theoretical basis for targeting the ERS pathway for SCI and provide some ideas and insights for the de⁃ velopment of future therapeutic strategies after SCI.

Effects of preoperative diagnostic hysteroscopy on peritoneal cytology and prognosis in patients with non-endometrioid carcinoma / 中华妇产科杂志

Objective: To explore the effects of preoperative hysteroscopic guided biopsy and segmental diagnosis and curettage on the risk of abdominal dissemination and prognosis of non-endometrioid carcinoma. Methods: The clinical and pathological data of 97 patients who underwent surgical treatment and were pathologically confirmed as non-endometrioid carcinoma (including serous carcinoma, clear cell carcinoma, mixed adenocarcinoma, and undifferentiated carcinoma, etc.) from October 2008 to December 2021 in Peking University People's Hospital, were collected for retrospective analysis. According to preoperative diagnostic methods, they were divided into hysteroscopic group (n=44) and non-hysteroscopic group (n=53). The impact of hysteroscopy examination on peritoneal cytology and prognosis was analyzed. Results: (1) There were no statistical differences in age, body mass index, tumor size, pathological characteristics, and treatment methods between the hysteroscopic group and the non-hysteroscopic group (all P>0.05), but the proportion of stage Ⅰ-Ⅱ patients in the hysteroscopic group was significantly higher than that in the non-hysteroscopic group [68% (30/44) vs 47% (25/53); χ2=4.32, P=0.038]. (2) Among 97 patients, 25 (26%, 25/97) of them were cytologically positive for ascites. The hysteroscopic group had a lower positive rate of peritoneal cytology than that in the non-hysteroscopy group, which was significantly different [11% (5/44) vs 38% (20/53); χ2=8.74, P=0.003]. Stratification according to surgical and pathological stages showed that the positive rate of peritoneal cytology in the hysteroscopic group (3%, 1/30) was lower than that in the non-hysteroscopic group (12%, 3/25) in the 55 patients with stage Ⅰ-Ⅱ, and that in the hysteroscopic group (4/14) was also lower than that in the non-hysteroscopic group (61%, 17/28) in the 42 patients with stage Ⅲ-Ⅳ. There were no significant differences (all P>0.05). (3) The 5-year disease-free survival (DFS) rate of the hysteroscopic group and the non-hysteroscopic group were respectively 72.7% and 60.4%, and there was no significant difference between the two groups (P=0.186). After stratification according to staging, the 5-year DFS rate were respectively 90.0% and 72.0% (P=0.051) between the hysteroscopic and non-hysteroscopic groups of patients in stage Ⅰ-Ⅱ, and 35.7% and 50.0% (P=0.218) between the hysteroscopic and non-hysteroscopic groups of patients in stage Ⅲ-Ⅳ, in which there were not statistically significant differences. The 5-year overall survival (OS) rate were respectively 86.4% and 81.1% between the hysteroscopic group and the non-hysteroscopic group, with no significant difference between the two groups (P=0.388). The 5-year OS rate were respectively 93.3% and 96.0% in the hysteroscopic group and non-hysteroscopic group for patients with stage Ⅰ-Ⅱ(P=0.872), and 71.4% and 67.9% in the hysteroscopic group and non-hysteroscopic group in patients with stage Ⅲ-Ⅳ (P=0.999), with no statistical significance. Conclusions: Diagnostic hysteroscopy do not increase the rate of positive peritoneal cytology result at the time of surgery in this cohort, and no significant correlation between preoperative hysteroscopy examination and poor prognosis of non-endometrioid carcinoma is observed. Therefore, preoperative hysteroscopic guided biopsy and segmental diagnosis and curettage in non-endometrioid carcinoma maybe safe.

Neutralizing Antibody Responses against Five SARS-CoV-2 Variants and T Lymphocyte Change after Vaccine Breakthrough Infections from the SARS-CoV-2 Omicron BA.1 Variant in Tianjin, China: A Prospective Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate whether Omicron BA.1 breakthrough infection after receiving the SARS-CoV-2 vaccine could create a strong immunity barrier.@*METHODS@#Blood samples were collected at two different time points from 124 Omicron BA.1 breakthrough infected patients and 124 controls matched for age, gender, and vaccination profile. Live virus-neutralizing antibodies against five SARS-CoV-2 variants, including WT, Gamma, Beta, Delta, and Omicron BA.1, and T-lymphocyte lymphocyte counts in both groups were measured and statistically analyzed.@*RESULTS@#The neutralizing antibody titers against five different variants of SARS-CoV-2 were significantly increased in the vaccinated population infected with the Omicron BA.1 variant at 3 months after infection, but mainly increased the antibody level against the WT strain, and the antibody against the Omicron strain was the lowest. The neutralizing antibody level decreased rapidly 6 months after infection. The T-lymphocyte cell counts of patients with mild and moderate disease recovered at 3 months and completely returned to the normal state at 6 months.@*CONCLUSION@#Omicron BA.1 breakthrough infection mainly evoked humoral immune memory in the original strain after vaccination and hardly produced neutralizing antibodies specific to Omicron BA.1. Neutralizing antibodies against the different strains declined rapidly and showed features similar to those of influenza. Thus, T-lymphocytes may play an important role in recovery.

Prognosis analysis of radical or modified radical hysterectomy and simple hysterectomy in patients with stage Ⅱ endometrial cancer / 中华妇产科杂志

Objective: To compare the prognosis and perioperative situation of patients with stage Ⅱ endometrial cancer (EC) between radical hysterectomy/modified radical hysterectomy (RH/mRH) and simple hysterectomy (SH). Methods: A total of 47 patients diagnosed EC with stage Ⅱ [International Federation of Gynecology and Obstetrics (FIGO) 2009] by postoperative pathology, from January 2006 to January 2021 in Peking University People's Hospital, were analyzed retrospectively. The patients were (54.4±10.7) years old, and the median follow-up time was 65 months (ranged 9-138 months). They were divided into RH/mRH group (n=14) and SH group (n=33) according to the scope of operation. Then the prognosis of patients between the groups were compared, and the independent prognostic factors of stage Ⅱ EC were explored. Results: (1) The proportions of patients with hypertension in RH/mRH group and SH group were 2/14 and 45% (15/33), the amounts of intraoperative blood loss were (702±392) and (438±298) ml, and the incidence of postoperative complications were 7/14 and 15% (5/33), respectively. There were significant differences (all P<0.05). (2) The median follow-up time of RH/mRH group and SH group were 72 vs 62 months, respectively (P=0.515). According to Kaplan-Meier analysis and log-rank method, the results showed that there were no significant difference in 5-year progression-free survival (PFS) rate (94.3% vs 84.0%; P=0.501), and 5-year overall survival rate (92.3% vs 92.9%; P=0.957) between the two groups. Cox survival analysis indicated that age, pathological type, serum cancer antigen 125 (CA125), and estrogen receptor (ER) status were associated with 5-year PFS rate (all P<0.05). But the scope of hysterectomy (RH/mRH and SH) did not affect the 5-year PFS rate of stage Ⅱ EC patients (P=0.508). And level of serum CA125 and ER status were independent prognostic factors for 5-year PFS rate (all P<0.05). Conclusions: This study could not find any survival benefit from RH/mRH for stage Ⅱ EC, but increases the incidence of postoperative complications. Therefore, the necessity of extending the scope of hysterectomy is questionable.

Application of bacterial culture and nucleic acid detection in the diagnosis of pertussis in children / 中华检验医学杂志

Objective:To analyze the clinical characteristics of pertussis cases diagnosed by two pathological detection methods: bacterial culture and real-time polymerase chain reaction (RT-PCR), and to explore the applicable value of two pathological detection methods in the diagnosis of pertussis.Methods:Bilateral nasopharyngeal swabs and clinical information of 165 children suspected of pertussis were collected by Hebei Children′s Hospital from April 2019 to January 2020. The bacterial culture and RT-PCR for nasopharyngeal swab specimens were performed in all cases. Chi-square test was used to analyze the cases of pertussis diagnosed by the above two methods.Results:Based on clinical diagnosis, the sensitivity of bacterial culture and RT-PCR for the diagnosis of pertussis was 61.70% (58/94) and 86.17% (81/94), and the specificity was 92.96% (66/71) and 71.83% (51/71), respectively. The positive rate of RT-PCR in children of all ages, seasons and cough courses is higher than that of bacterial culture. Children with pertussis diagnosed by bacterial culture and RT-PCR were basically similar in age, season, and cough course distribution, with the most common cases ≤3 months old, a high incidence trend in summer and autumn, and the course of coughing in children was mostly within 15-21days. The positive rate of bacterial culture in the diagnosis of pertussis in children is affected by the age of the children, and there are statistical differences between children in different age groups (χ2= 11.929, P=0.036). The positive rate of bacterial culture was the highest in children with >3 years old (51.85% [14/27]), followed by children with ≤3 months old (48.72% [19/39]), and the lowest in children with >6-12 months old (15.00% [3/20]). Moreover, the positive rate of bacterial culture in the diagnosis of pertussis in children is also affected by the cough course of the children, and there are statistical differences between children in different cough course groups (χ2=9.841, P=0.020). The positive rate of bacterial culture was the highest in children with cough course 15-21 days (49.23% [32/65]), followed by 43.59% (17/39) in children with cough course 8-14 days, and the lowest in children with cough course of less than 7 days (22.86% [8/35]). Conclusions:Compared with RT-PCR, bacterial culture has lower sensitivity and higher specificity in the detection of pertussis. These two detection methods have their own advantages and limitations. Medical institutions at all levels should comprehensively analyze different laboratory detection methods. Only by combining the two methods can the diagnostic value and level be effectively improved.

Role of Cytokines in Osteoporosis and Intervention with Traditional Chinese Medicine： A Review / 中国实验方剂学杂志

Osteoporosis （OP） is one of the most common diseases in the aged population worldwide. Due to the rapid change in world population structure， the effective prevention and treatment of OP is increasingly becoming the health problem of global concern and also the hot spot of clinical research. OP can be affected by many factors such as heredity， endocrine dyscrasia， nutritional deficiency， and bad living habits. The breakdown of coupling of osteoclast-mediated bone resorption to osteoblast-mediated bone formation leads to stronger bone resorption than bone formation， which is currently recognized as the main pathogenesis of OP. The exploration of OP in modern medicine based on molecular immunology has revealed that related cytokines play an important role in the pathogenesis of OP，and regulating the osteoclast-mediated bone resorption and osteoblast-mediated bone formation is essential for controlling the occurrence and development of OP. Tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， and interleukin-6 （IL-6） are able to stimulate bone formation and inhibit osteoblast function， thus playing a key role in bone destruction. By contrast， such cytokines as vascular endothelial growth factor （VEGF）， transforming growth factor-β （TGF-β）， bone morphogenetic protein （BMP）， and osteoprotegerin （OPG） strengthen osteoblast differentiation and promote bone formation. At present， western medicine like calcitonin， estrogen， and bisphosphonate are mostly used for clinical treatment of OP， but a long-term use of these drugs will result in poor compliance and obvious gastrointestinal adverse reactions. Traditional Chinese medicine （TCM） occupies an important position in the treatment of OP due to its advantages of overall regulation， low price， and few side effects. In addition， with the deepening of research on network pharmacology and molecular biology， it has been found that TCM exerts the therapeutic effect against OP by interfering with the expression of various cytokines and adjusting bone homeostasis. This paper has elaborated the role of related cytokines in the pathogenesis of OP and reviewed the research results concerning the regulation of related cytokines by TCM， in order to provide reference for the prevention and treatment of OP with TCM.

Biomechanical Analysis on Locking Compression Plate for Fixing Periprosthetic Proximal Femur Fracture / 医用生物力学

Objective To evaluate biomechanical strength of locking compression plate (LCP) for fixation of periprosthetic proximal femur fractures (PPFF). Methods Eight matched pairs of Vancouver type B1 adult cadaveric PPFF specimens were fixed with the LCP and the inverted distal femoral less invasive stabilization system (LISS), respectively. Four bicortical locking screws (LCP group) and four unicortical locking screws were used to the length of prosthesis stem, and four double cortical locking screws were used to fix the distal end of the fracture in two groups, the distance from the locking screws to the fracture were also equal. The maximum bending load, maximum bending displacement, bending stiffness, maximum torque, maximum torsional angle and torsional stiffness of two groups in four-point bending test and torsion test were compared and analyzed. Results The maximum bending load, maximum bending displacement and bending stiffness of LCP group were all larger than those of LISS group, but the difference was not statistically significant (P>0.05). The maximum torque, maximum torsional angle and torsional stiffness of LCP group were obviously larger than those of LISS group，and there was a statistical difference between two groups (P<0.05). Conclusions The stiffness of anti-torsion with LCP is significantly better than that with LISS. Consequently, LCP has better biomechanical stability for PPFF.

Research progress on rutin derivatives / 中国中药杂志

Compounds derived from natural products present satisfactory efficacy in disease prevention and treatment. The use of chemical substances in plants to promote healthhas increasingly attracted people's attention. Rutin, a typical flavonoid, is mainly found in various vegetables, fruits and Chinese herbal medicines. As a natural antioxidant, it features many pharmacological activities, such as anti-inflammation, anti-virus, anti-tumor, and prevention and treatment of cardiovascular and cerebrovascular diseases. However, the low bioavailability and poor water solubility limit its clinical application. In view of this, its structure is optimized and modified to afford rutin derivatives with good solubility, high bioavailability, stable metabolism and small toxic side effects. So far, a large number of rutin ethers, esters, and complexes have been synthesized and undergone activity testing. This paper reviews the structural modification of rutin in recent years, and the obtained derivatives have excellent properties and significant biological activity.

Research progress on therapeutic potential of quercetin / 中国中药杂志

Quercetin is a naturally occurring phytochemical with good bioactivity, which mainly exists in the form of glycoside in vegetables, fruits, tea, and wine and exhibits beneficial health effects. Quercetin is a dietary polyphenol that exerts the protective effects through diet or use as a food supplement. Compared with chemical agents, quercetin is widely available and safe. Quercetin has been extensively studied for its anti-diabetic, anti-hypertensive, anti-Alzheimer's disease, anti-arthritic, anti-influenza virus, anti-microbial infection, anti-aging, autophagy-regulating, and cardiovascular protective effects. Studies on its activities against different can-cer cell lines have also been reported recently. However, the poor water solubility, rapid in vivo metabolism, and short half-life of quercetin have led to its low bioavailability, thus limiting its application in the field of medicine. Quercetin nanoparticles and nanoparticle drug delivery system have been effectively utilized for enhancing its bioavailability. This paper reviewed the therapeutic potential of quercetin from both preclinical and clinical aspects and proposed solutions to improve its bioavailability, so as to provide a reference for the therapeutic application of natural compounds in the field of medicine.

Research progress on antitumor activity of quercetin derivatives / 中国中药杂志

Quercetin is a kind of typical flavonoid, mainly found in various vegetables, fruits and Chinese herbs that are consumed daily, with the functions of anti-oxidation, anti-tumor, prevention and treatment of cardiovascular and cerebrovascular diseases. Quercetin is a natural compound with defined anti-tumor activity. Due to its low bioavailability and poor water solubility, quercetin has limitations in clinical application. The quercetin derivatives with good solubility, high bioavailability, metabolic stability, and low toxicity have been obtained through modification of quercetin structure. In recent years, a large number of quercetin ethers, esters, complexes, C-4 carbonyloxy substituted derivatives, A,B-ring modified compounds and other derivatives have been synthesized and tested for in vitro anticancer activity. The quercetin derivatives with anti-tumor activity synthesized in the last 5 years were reviewed in this paper.

Effects of dietary vitamin K on the stability of warfarin anticoagulation therapy / 中国临床药理学与治疗学

Change in dietary vitamin K intake is one of the main causes of abnormal fluctuations in international standardized ratio (INR) of patients on warfarin therapy. Advice from clinicians on how to manage vitamin K intake for patients has been vague. In the past, patients were often told to restrict or avoid vitamin K-rich foods including leafy greens during anticoagulation therapy, which could lead to lower vitamin K intake. Evidence-based studies in recent years have found that instability of warfarin therapy is associated with low intake of vitamin K. A stable and relatively higher daily intake of vitamin K (>100 μg/d) can reduce unexplained intra-individual variability in response to warfarin, and thus reduce abnormal fluctuations in INR and improve the stability of anticoagulation therapy.

Relationship between clinical phenotype and NOTCH3 genotype in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy / 第二军医大学学报

Objective To explore the relationship between exon mutations of NOTCH3 gene and clinical phenotype in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Methods We consecutively included 30 CADASIL patients with clinical symptoms in 15 pedigrees, who visited Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine from May 2015 to Dec. 2017, and collected the clinical data and genetic analysis results. Furthermore, we analyzed the relationship between the exon mutations of NOTCH3 gene and clinical phenotypes, including age at onset, first clinical symptoms and frequency of symptomatic ischemic stroke. Results Twelve mutation sites of NOTCH3 gene were detected in the 15 pedigrees. Seven of them were located in exon 4, 3 in exon 11, 1 in exon 19, and 1 in exon 20. The onset age of the patients carrying exon 11 mutations was the latest ([53.6±13.3] years, n＝7), followed by the patients carrying exon 4 mutations ([42.7±5.7] years, n＝15). The onset age of 8 patients with mutations in other exons (exon 19 and 20) was (33.5±7.5) years, which was significantly earlier compared with the patients with exon 4 and 11 mutation (P0.01 and P0.05). Most of the patients with mutations of exon 4 had motor and speech disorders (11/15, 73.3%), while ones with mutations of exon 19 and 20 had cognitive impairment (7/8, 87.5%). Most of the patients (11/15, 73.3%) carrying mutations in exon 4 had motor and speech disorders at onset, while 7 of 8 patients (87.5%) with mutations in exon 19 and exon 20 had impaired cognition at onset. The times of symptomatic ischemic stroke in patients with mutations in exon 4 was 3 (median) and in patients with mutations in exon 11 was 2 (median), and no symptomatic ischemic stroke occurred in the patients with mutations in exon 19 and 20. Conclusion Exon 4 and exon 11 of NOTCH3 gene are hotspots of mutations in the cohort of CADASIL cases, and the mutations in different exons are associated with onset age, first symptoms and symptomatic ischemic stroke.

The interventional effects of saturated hydrogen saline on lung injury in rats with cecal ligation and puncture operation / 中国应用生理学杂志

OBJECTIVE@#To investigate the hypothesis that hydrogen could ameliorate cecal ligation and puncture (CLP)-induced lung injury of rats by inhibiting cystathionine-gamma-lyase/hydrogen sulfide (CSE/HS) system.@*METHODS@#A total number of 24 healthy male SD rats weighting 250～300 g were randomly divided into four groups (n=6 in each group): sham operation group(sham group), hydrogen-rich saline control group(H group), CLP group and hydrogen-rich saline treatment group(CLP+H group). The rats were treated with hydrogen-rich saline or saline 10 min before CLP or sham operation. At 8 h of sham or CLP operation, lung samples were obtained to detect the changes of the CSE/HS system using biochemical and RT-PCR methods. In order to further confirm the role of HS during hydrogen improve the lung injury of CLP rats, we also observed the effect of hydrogen-rich saline on the lung injury induced by HS donor-sodium sodium hydrosulfide (NaHS). Thirty-two healthy male SD rats (250~300 g) were randomly divided into four groups (n=8 in each group): control group, HS group, HS+H group and H group. Saline(10 mg/kg) or NaHS(HS donor, 56 μmol/kg) was injected intraperitoneally (10 mg/kg) respectively into rats in the control rats or HS group. For rats in the HS+H and H group, hydrogen-rich saline (10 mg/kg) was injected 10 min before saline or NaHS administration. Eight hours after the LPS saline or NaHS administration, lung coefficient, MDA content, and MPO activity were detected. The contents of TNF-α, IL-6 and IL-10 in lung tissue were measured, and the morphological changes of lung tissue were also observed.@*RESULTS@#CSE/HS system up-regulating were observed in animals exposed to CLP. Hydrogen-rich saline treatment significantly inhibited CSE/HS system as indicated by significantly reduced HS production in lung, along with a decreased CSE activity and CSE mRNA expression (all P＜0.05). Importantly, the results showed that lung injury and lung tissue inflammation were observed in animals exposed to NaHS. Hydrogen-rich saline treatment significantly attenuated lung injury as indicated by significantly improved histological changes in lung, significantly reduced index of quantitative assessment (IQA), MDA content and lung coefficient (all P＜0.05). MPO activity in lung tissue was significantly reduced along with decreased productions of TNF-α and IL-6, and an increased production of IL-10 in the presence of hydrogen (all P＜0.05), demonstrating antioxidant and anti-inflammatory effect of hydrogen in NaHS-induced ALI.@*CONCLUSION@#These results indicate that hydrogen-rich saline peritoneal injection improves the lung injury induced by CLP operation. The therapeutic effects of hydrogen-rich saline may be related to suppressing the production of HS.

Effects of clinical P-glycoprotein inhibitors on oral bioavailability and brain penetration of gefitinib / 中国药科大学学报

@#To investigate the effects of clinical P-glycoprotein inhibitors on oral bioavailability and brain penetration of gefitinib, 16 inhibitors and gefitinib were co-administered orally to ICR mice. The suspension of gefitinib and CMC-Na were co-administered to the control group. The suspension of gefitinib and clinical P-glycoprotein inhibitors were co-administered to the control group. Blood samples and brain homogenate samples were extracted by protein precipitation with acetonitrile and determinated by LC-MS/MS. It was found that ritonavir can significantly increase the oral bioavailability of gefitinib, and the area under the plasma concentration-time curves(AUC)of gefitinib was increased by 2 times; while brain exposure was increased, there was no increment in brain penetration. Some other drugs can also increase the plasma AUC of gefitinib, but can not enhance the brain penetration; After we corrected brain concentration with fraction of unbound drug in brain, it was found that the brain concentration of gefitinib in both control group and ritonavir group did not achieve the in vitro IC50 of inhibiting non-small cell lung cancer(NSCLC)cell growth. Our results suggest that clinical doses of the 16 clinical P-glycoprotein inhibitors can not specifically increase brain tissue exposure, more specific and safer P-gp inhibitors are required. After we corrected brain concentrations with fraction of unbound drug in brain, our preclinical studies found that insufficient brain exposure may be one of the reasons for the unsatisfactory efficacy of gefitinib in the treatment of brain metastases.

Progressive pseudorheumatoid dysplasia misdiagnosed as ankylosing spondylitis: a case report / 北京大学学报(医学版)

In this study, we reported a case of progressive pseudorheumatoid dysplasia in Peking University Third Hospital. A 56-year-old male patient presented with hip joint pain for more than 40 years and multiple joints pain with limitation of movements of these joints for 28 years. This patient suffered from joint pain and impaired range of motion of the hip, knee, elbow and shoulder gradually, associated with difficulty in walking and inability to take care of himself. He was diagnosed with "femoral head necrosis" or "ankylosing spondylitis" in local hospitals, but the treatment of nonsteroidal antiinflammatory drugs (NSAIDs) and sulfasalazine was not effective. Up to the age of 14, the patient displayed normal physical development, with the highest height was about 158 cm, according to the patient recall. However, his height was 153 cm at present. There was no history of similar illness in any family member. Physical examinations descried limitation of movement of almost all joints. Enlargement and flexion deformity of the proximal interphalangeal (PIP) joints of the hands resulted in the claw hand appearance. Limited abduction and internal and external rotation of the shoulder and hip could be find. He had normal laboratory findings for blood routine test, biochemical indexes and acute phase reactants such as C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). Furthermore, HLA-B27 and autoimmune antibodies such as rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibody and antinuclear antibody (ANA) were all negative. X-ray of the hip showed loss of the joint space and irregularities of the femoral head, both femoral head were flattened, it could be see hyperplasia, osteophytes, bilateral femoral neck thicken, neck dry angle turned smaller. The radiological findings of the spinal vertebra indicated kyphosis deformity, narrowing of the intervertebral discs, vertebral syndesmophytes and flattening of the vertebra. However, there was no clues of bone marrow edema in the lumbar MRI. At last, genetic testing for the Wnt1-inducible signaling pathway protein 3 (WISP3) gene was done and indicated compound heterozygous mutations: 756C>G and c.866dupA. These two mutations were derived from the patient's mother and father (the patient's parents each had a heterozygous mutation). Two exons of the WISP3 gene had nucleotide changes leading to amino acid mutations. According to the patient's history, symptoms, physical examinations, radiological findings and genetic testing, the final definitive diagnosis was progressive pseudorheumatic dysplasia.

Exploration and practice on the training of critical thinking in medical education / 中华医学教育探索杂志

Critical thinking is one of the core professional competences for medical students.The ultimate goal of critical thinking is to combine the highly individualized experience and comprehension with the generally applicable scientific cognitive system.Therefore in medical education,the cultivation of critical thinking should embody the objective and the characteristics of critical thinking,such as rational restriction,dialectical thinking,empathy practice and scientific evaluation,and great attention to the principles and conditions of the application must be given.In the course of teaching design and implementation it's necessary to choose the appropriate point,to set up the teaching situation suitable for developing critical thinking,to optimize the structure of teaching content,to strengthen the practice of critical thinking methodology and to value "asking questions" and so on.

Advances in the treatment of cancer by PROTACs / 药学学报

Proteolysis-targeting chimeras (PROTACs) are small-molecule protein degraders based on the ubiquitin-proteasome system. Recently, the development of specific small-molecule ligands for several E3 ligases (CRL4CRBN, CRL2VHL and cIAP) have significantly advanced the PROTACs technology. Several PROTACs against various oncogenic proteins including bromodomain-containing protein 4 (BRD4), estrogen receptor (ER) and androgen receptor (AR) have been developed and considered a novel approach for therapy of cancers. There are advantages of the new technology over the traditional small-molecule strategies. This review article provides a summary on the recent progress in the small-molecule-based PROTACs as antitumor drugs, and the challenges of this technology.