Preparation,characterization,and in vitro biological performance evaluation of PLGA electrospinning membranes doped with metformin-loaded hollow mesoporous silica nanoparticles / 实用口腔医学杂志

Objective:To prepare PLGA electrospinning membranes doped with hollow mesoporous silica nanoparticles loaded with metformin and investigate their biological properties.Methods:PLGA(Control group)and PLGA/HMSN/Met electrospun membranes(Experimental group)were prepared by electrospinning technology.The microscopic morphology of the 2 groups of electrospun mem-branes was observed by SEM.The hydrophilicity,elemental composition and in vitro drug release were detected by contact angle meas-urement,EDS,and drug release test,respectively.SEM and laser scanning confocal microscope(LSCM)were used to observe the growth of periodontal ligament stem cells(PDLSCs)on the 2 groups of electrospun membranes,and CCK-8 assay was used to detect the cell proliferation.Results:Both electrospun membranes had extracellular matrix(ECM)-like fiber structures.The PLGA/HMSN/Met electrospun membranes could slowly release Met for up to 35 days,and the hydrophilicity of PLGA membranes was improved by HMSN-Met doped.The composite electrospun membranes had good cell biocompatibility in vitro,and could promote cell proliferation.Conclu-sion:Modification of PLGA with HMSN-Met can improve the hydrophilicity of PLGA electrospun membranes,continuously release Met,and have good cell biocompatibility.

Clinical features of primary sclerosing cholangitis and inflammatory bowel disease / 中华内科杂志

Objective: To explore disease characteristics of primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) and compare the differences between PSC with and without IBD. Methods: Study design was cross sectional. Forty-two patients with PSC who were admitted from January 2000 to January 2021 were included. We analyzed their demographic characteristics, clinical manifestations, concomitant diseases, auxiliary examination, and treatment. Results: The 42 patients were 11-74(43±18) years of age at diagnosis. The concordance rate of PSC with IBD was 33.3%, and the age at PSC with IBD diagnosis was 12-63(42±17) years. PSC patients with IBD had higher incidences of diarrhea and lower incidences of jaundice and fatigue than in those without IBD (all P<0.05). Alanine aminotransferase, total bilirubin, direct bilirubin, total bile acid and carbohydrate antigen 19-9 levels were higher in PSC patients without IBD than in those with IBD (all P<0.05). The positive rates for antinuclear antibodies and fecal occult blood were higher in PSC patients with IBD than in those without IBD (all P<0.05). Patients with PSC complicated with ulcerative colitis mainly experienced extensive colonic involvement. The proportion of 5-aminosalicylic acid and glucocorticoid application in PSC patients with IBD was significantly increased compared with that of PSC patients without IBD (P=0.025). Conclusions: The concordance rate of PSC with IBD is lower at Peking Union Medical College Hospital than in Western countries. Colonoscopy screening may benefit PSC patients with diarrhea or fecal occult blood-positive for early detection and diagnosis of IBD.

Association between time-weighted individual exposure to ambient pollutants and carotid intima-media thickness / 环境与职业医学

Background Evidence about the association between air pollution and carotid intima-media thickness (CIMT) is inconsistent, and limited studies have explored the relationship between gaseous pollutants and CIMT. Additionally, personal activity patterns and infiltrated ambient pollution are not comprehensively considered to estimate individual exposure to air pollutants. Objective To investigate the relationship between long-term time-weighted individual exposure to ambient pollutants [fine particulate matter (PM2.5), inhalable particulate matter (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), ozone (O3), and carbon monoxide (CO)] and the progression of CIMT. Methods This study was performed among 554 participants in the Beijing Health Management Cohort who were free of atherosclerotic lesions on carotid artery at baseline. Daily concentrations of pollutants were predicted at both residential and work addresses based on land-use regression model. With additional consideration of personal indoor and outdoor activity patterns at both addresses and exposure to ambient pollutants from traffic transportation, individual time-weighted concentration was calculated. Indoor exposure was estimated by infiltrated ambient pollutants (based on infiltration factors and land-use regression model). Personal activity patterns included type, time, location, and frequency. Exposure to ambient pollutants from different traffic transportations was estimated by the average outdoor pollutant concentrations at both residential and work addresses combined within filtration factors and time spent on commuting. Multiple linear regression was conducted to assess the association of time-weighted individual pollutant exposure and the central position of CIMT progression. Quantile regression was applied to explore the relationship between time-weighted individual pollutant exposure and the progression of CIMT on different percentiles. Results The median value of CIMT progression was 369.49 μm·year−1. PM2.5, PM10, SO2, and O3 were associated with CIMT progression in the multiple linear regression model. The largest effect sizes of PM2.5, PM10, and SO2 were obtained for one-year exposure (regression coefficient: 66.910, 64.077, and 191.070, respectively), and two-year exposure for O3 (regression coefficient: 62.197). The results of quantile regression demonstrated different effect sizes for pollutants among different percentiles on CIMT progression. Significant associations between CIMT progression and PM2.5 from P30 to P50, CO from P10 to P40, and PM10 from P30 to P60 were observed. Two-year and three-year exposures to NO2 (P10, P20 and P40) were also associated with CIMT progression. The association between SO2 and the progression of CIMT was proved on all percentiles, and larger effect sizes of one-year and two-year exposures to SO2 (except P90) were demonstrated with increasing percentiles. The upward trend for the coefficients was clearly presented from P50 to P80. Specifically, the coefficient of two-year exposure to SO2 ranged from 136.583 (P50) to 277.330 (P80). No statistically significant association was observed between O3 and CIMT progression on any percentile (P>0.05), and the results were inconsistent with those of the multiple linear regression. Conclusion Individual time-weighted exposures to PM2.5, PM10, SO2, NO2, and CO have the potential to promote the progression of CIMT, and the adverse effect of ambient pollution on atherosclerotic lesion is identified.

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.

An analysis on the compatibility principle and efficacy characteristics of Wumei Pill from the perspective of "Tang-Ye-Jing-Fa Map" / 国际中医中药杂志

Wumei Pill is a classic insect repellent prescription, which is used for ascaris lumbricoides and diarrhea. It is considered to be a representative prescription for the treatment of simultaneous occurrence of cold and heat syndromes. Its prescription is mainly composed of sour drugs ( Mume Fructus and bitter wine) and pungent drugs ( Aconiti Lateralis Radix Praeparataaconite, Cinnamomi Ramulus, Sichuan pepper, Angelicae Sinensis Radix, Zingiberis Rhizoma, and Asari Radix et Rhizoma), supplemented by bitter drugs ( Coptidis Rhizoma and Phellodendri Chinensis Cortex) and sweet drugs ( Ginseng Radix et Rhizoma and honey). From the point of view of "Tang-Ye-Jing-Fa Map", the role of liver is to disperse, whose deficiency leads to limb syncope, and excess leads to the full of hypochondrium and abdominal pain. The pungent herbs can tonify the liver-deficiency, the sour herbs can dispel the liver-excess, and sweet herbs can relive them both. The role of spleen is to moderate, whose deficiency leads to fatigue and weakness, and excess leads to the vomiting and diarrhea. The sweet herbs can tonify the spleen-deficiency, the pungent herbs can dispel the spleen-excess, and bitter herbs can relive them both. Therefore, the function of Wumei Pills is located in the liver and spleen, giving consideration to the heart and lung. It is used for the deficiency and excess mixed syndrome of liver and spleen, which is mainly characterized by chest and flank abdominal pain, limb chills, diarrhea, muscle and pulse contracture and the symptoms of the parts along the liver meridian. It is commonly used in the treatment of ascaris, diarrhea, impotence, depression. At the same time, it can also be used for the treatment of diseases about heart and lung, and cough, anxiety and other diseases.

Association between air quality index and brachial-ankle pulse wave velocity in Beijing / 环境与职业医学

Background Few studies have investigated the association between air pollution and arterial stiffness in Chinese population, and the findings are inconsistent. The problem of multicollinearity exists when modeling multiple air pollutants simultaneously. Objective To investigate potential association between air quality index (AQI) and population brachial-ankle pulse wave velocity (baPWV) in Beijing. Methods This study retrieved medical examination data of 2971 participants from the Beijing Health Management Cohort, who were under 60 years old and not yet retired, from January 1, 2015 to December 31, 2019. The most recent medical examination data available were utilized for this analysis. AQI data from 35 air pollution monitoring sites in Beijing and meteorological data (including atmospheric pressure, air temperature, wind speed, and relative humidity) from 16 meteorological monitoring stations from January 1, 2014 to December 31, 2019 were collected. An average AQI exposure level for 365 d before the date of physical examination for each participant was computed using inverse distance weighting. Multiple linear regression analysis was employed to investigate the relationship between AQI and baPWV in Beijing, after adjusting for confounding variables including age, gender, body mass index, mean arterial pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting blood glucose, atmospheric pressure, temperature, wind speed, relative humidity, medication history of diabetes, medication history of hypertension, cardiovascular disease, education, smoking status, drinking status, and physical activity intensity. Subgroup analysis was performed by age, sex, presence of diabetes, and presence of hypertension. Results AQI demonstrated an overall decreasing trend during the study period and was lower in the northern regions and higher in the southern regions of Beijing. After adjusting the confounding variables, each 10 unit increase in AQI was associated with 6.18 (95%CI: 1.25, 11.10) cm·s−1 increase in baPWV in all participants, 8.05 (95%CI: 2.32, 13.79) cm·s−1 increase in the participants <50 years, 15.82 (95%CI: 8.33, 23.31) cm·s−1 increase in the female group, 10.10 (95%CI: 4.66, 15.55) cm·s−1 increase in the participants without diabetes, and 9.41 (95%CI: 4.21, 14.62) cm·s−1 increase in the participants without hypertension. However, there was no statistically significant association observed between AQI and baPWV in the age group ≥50 years, the male group, the diabetic group, and the hypertensive group (P>0.05). Conclusion An increase in long-term AQI levels is associated with an elevation in the degree of arterial stiffness. Individuals under 50 years old, females, without hypertension or diabetes are susceptible populations to arterial stiffness when being exposed to air pollution. Improving air quality may contribute to prevent arterial stiffness.

Design and Verification of Human Metabolic Measurement System Based on STM32 / 中国医疗器械杂志

A high-precision human metabolic measurement system is designed. The system uses STM32F103 as the main control chip to acquire oxygen, carbon dioxide and flow signals to calculate four quantitative indicators: oxygen consumption(VO2), carbon dioxide production(VCO2), respiratory entropy(RQ) and resting energy metabolism(REE), and finally uses an upper computer to display the calculation results.In this paper, the signal acquisition circuit design was carried out for the oxygen sensor, carbon dioxide sensor and flow sensor, and the validity of the device was verified with the American machine MGCDiagnositcs using Bland-Altman analysis method, and the results showed that the four parameters of VO2,VCO2, RQ and REE of both devices fell in the agreement interval of more than 95%. The device thus provides accurate metabolic measurements and offers an effective tool for the field of general health and clinical nutrition support in China.

Evaluating the risk factors of inferior alveolar nerve injury following removal of the mandibular third molars / 中华口腔医学杂志

Objective: To evaluate the risk factors of inferior alveolar nerve injury (IANI) after surgical removal of the mandibular third molars (M3) and present a new risk scoring system to predict the probability of IANI. Methods: Patients who underwent extraction of M3 in the Stomatology Hospital, Zhejiang University School of Medicine from April 2017 to December 2019 were involved. The investigators enrolled a sample composed of 949 mandibular third molars. Prediction model was used for univariate and multivariate analysis of gender, age, M3, inferior alveolar canal (IAC), and the contact between M3 and IAC, to assess the risk factors of IANI. Combined with the risk factors determined by the outcomes of prediction model, the risk scoring system was constructed. The diagnostic performance of each cut-off score was examined to conduct a risk stratification of IANI risk scores. The predictive ability and reliability of the model were evaluated. Results: In prediction model, twenty nine cases (4.4%, 29/664) experienced postoperative IANI. Number of root (P<0.01), depth of impaction (P<0.05), contact between M3 and IAC (P<0.01) and their contact position (P<0.05) were statistically significant as contributing risk factors of IANI. Specifically, the incidence of temporary IANI was higher in those who aged under 25 years (P<0.001), while female suffer more permanent injury (P<0.05). Based on the IANI risk scoring system, patients were stratified into low-risk, middle-risk and high-risk groups at cutoff scores of 3 and 4. The area under the receiver operator characteristic curve of the risk scoring system were 0.81 [95%CI (0.70-0.90), P=0.002] and 0.80 [95%CI (0.68-0.92), P=0.007] towards good discrimination. Conclusions: Age, gender, number of root, depth of impaction, and contact between M3 and IAC were risk factors of IANI. IANI risk scoring system might help in preoperative assessment, recognition of high-risk cases and decision-making to reduce IANI.

Screening methods of traditional Chinese medicine for coronary heart disease and angina pectoris: an exploration based on core outcome set and fuzzy comprehensive evaluation / 中国中药杂志

It was pointed out in Opinions on Promoting the Inheritance, Innovation and Development of Traditional Chinese Medicine issued by the State Council in 2019 that 100 varieties of traditional Chinese medicine(TCM) with unique curative effects should be screened out within about three years. Due to the multi-component and multi-target mechanisms of TCM varieties, it is difficult to directly and simply evaluate their multi-dimensional clinical value using methods applicable to chemical or biological agents. The heterogeneity of outcomes for similar TCM makes it difficult to determine the advantages of similar products. The fuzzy comprehensive evaluation method that is developed on the basis of core outcome set and fuzzy mathematics for clinical efficacy evaluation of TCM may solve these problems. This study developed a fuzzy comprehensive evaluation model for the clinical efficacy evaluation of Chinese patent me-dicines for coronary heart disease and angina pectoris, and selected the previous normative studies with complete or incomplete data for verifying the model application. The results showed that original studies with complete data failed to evaluate and compare the comprehensive efficacy of different interventions. The original research only mentioned the advantages and disadvantages of different interventions in different aspects. The comprehensive clinical efficacy of three different interventions obtained through fuzzy comprehensive evaluation was all graded as level Ⅱ. The original research with incomplete data drew the same conclusions as the fuzzy comprehensive evaluation, and the results of fuzzy comprehensive evaluation can provide more comprehensive information. Therefore, the fuzzy comprehensive evaluation shows the products with overall advantages of clinical efficacy, which may become a feasible method for the screening of TCM.

Research of proliferation inhibition and apoptosis promotion mechanism of brusatol on H1299 cells / 中国药理学通报

Aim To preliminarily investigate the effect of brusatol(BRU), the monomer components fromChinese medicines on H1299 cells and its mechanisms.Methods CCK-8 and EdU staining experiment were used to detect the effect of BRU on cell prolifera-tion.Clone formation experiment was performed to measure the effect of drugs on cell clone formation.Hoechst33258 staining experiment and flow cytometry were employed to observe the cell apoptosis.Western blot assay was used to detect the protein expression levels of Bcl-xL, Bax, Bcl-2, cleaved-caspase-3, caspase-3, Gadd45α, PI3K, p-PI3K, Akt, p-Akt and NF-κB-p65.Results CCK-8 assay revealed that the inhibitory effect of H1299 cells gradually increased with the rising of BRU concentration and action time.Compared with control group, the EdU incorporation rate of the BRU treatment group decreased significantly.Treated with different concentrations of BRU for 24 h, the clone formation rate was significantly reduced in a concentration-dependent manner.Hoechst33258 experiment and flow cytometry showed that BRU could induce apoptosis in H1299 cell nucleus and increase its apoptotic rate.Western blot results revealed that BRU could significantly up-regulate the protein levels of Bax, cleaved-caspase-3, Gadd45α, and significantly down-regulate the expression of Bcl-xL, Bcl-2, caspase-3.In addition, BRU could significantly decrease the expression level of p-PI3K, p-Akt, NF-κB-p65 in cell nucleus.Conclusions BRU can inhibit the proliferation and induce apoptosis of H1299 cells in a concentration and time-dependent manner.The mechanism may be related to the inhibition of PI3K/Akt signaling pathway and the nuclear shuttle of NF-κB-p65.

Mathematical Model for Analyzing Five Flavor Compatibility-transformation Theory in Tangye Jingfatu / 中国实验方剂学杂志

Objective:<italic>Auxiliary Verse on Drugs and</italic> <italic>methods</italic> <italic>for Zang-Fu Organs （Fuxingjue Wuzangyongyao Fayao）</italic> written by TAO Hong-jing from the Liang dynasty covered many contents from<italic> </italic>a missing prescription book<italic> Classic of Decoction （Tangye Jingfa）</italic>， including a map revealing the compatibility principle of Chinese herbs， namely the Tangye Jingfatu. Represented by a centrosymmetric pentagon， the map describes a unique theoretical system for deficiency-excess syndrome differentiation of five Zang organs （liver， heart， spleen， lung and kidney） and the tonification-purgation and compatibility theory of five flavors （pungent， salt， sweet， sour and bitter）. Each Zang organ fixedly corresponds to one "property" flavor （purgation）， one "function" flavor （tonification） and one "transformation" flavor （harmonization） resulting from the combination of the former two. For example， the liver can be purged by sour， tonified by pungent， and moderated by sweet transformed by the combination of sour with pungent. The heart can be purged by bitter， tonified by salt， and astringed by sour transformed by the combination of bitter with salt. The spleen can be purged by pungent， tonified by sweet， and dried by bitter transformed by the interaction between pungent and sweet. The lung can be purged by salt， tonified by sour， and dispersed by pungent transformed by the combination of salt with sour. The kidney can be purged by sweet， tonified by bitter， and moistened by salt transformed by the combination of sweet with bitter. This study selected appropriate mathematical tools to analyze the fixed relationship between "property" flavor， "function" flavor and "transformation" flavor among the five Zang organs in “Tangye Jingfatu” and establish a mathematical model revealing the compatibility-transformation relationship among five flavors. Method:Based on the group representation of five elements （wood， fire， earth， metal， and water）， the correlations of "property" flavor， "function" flavor， and "transformation" flavor with five elements’ generation-restriction were deduced based on matrix calculation and group theory. The three-dimensional calculation method for vector product was expanded for establishing the mathematical operator of five flavors' compatibility-transformation. Result:<bold>and</bold> Conclusion:There is a mapping relationship of the purging， tonifying， and harmonizing functions represented by the "property" flavor， "function" flavor， and "transformation" flavor of the five zang organs in the "Tangye Jingfatu" with the five elements' generation-restriction. The established mathematical operator contributes to explaining the fixed collocations of five flavor transformation. Based on such algorithm， the tonifying and purging characteristics of five flavors in 10 representative classic prescriptions have been clearly expounded.

The phantom study of bismuth shielding combined with organ tube current modulation in brain CT / 中华放射医学与防护杂志

Objective:To evaluate the application value of bismuth shielding combined with organ tube current modulation (X-care) in brain CT scanning by measuring the radiation dose of sensitive organs.Methods:The head and neck phantom was scanned with Siemens dual source CT at the same volume CT dose index (CTDI vol) by X-care, bismuth shielding and x-care combined with bismuth shielding, and by dual energy CT angiography (DE-CTA) with and without bismuth shielding. The CT values of cerebral vessels, adjacent brain tissues and cerebrospinal fluid and image noise were measured, and the contrast noise ratio of cerebral vessels and brain parenchyma was calculated. Organ dose equivalent ( HT) was calculated by placing thermoluminescent personal dosimeter (TLD), and CTDI vol and dose length product (DLP) were recorded after each scan. Results:Under the same CTDI vol, the mean values of HT, lens with X-care, Bi shielding and X-care combined with Bi shielding were(37.89 ± 2.00), (42.20 ± 2.96) and (28.21 ± 1.31) mSv, respectively, significantly lower than those of conventional sequence scanning( F=186.52, P<0.05). The values of HT, thyroid with Bi shielding and X-care combined with Bi shielding were (0.77 ± 0.07) and (0.89 ± 0.08) mSv, lower than those of routine brain scan and X-care( F=103.26, P<0.05). The values of HT, lens and HT, thyroidof DE-CTA with bismuth shielding were (11.56 ± 1.04) and (0.32 ± 0.03) mSv, respectively, significantly lower than those without bismuth shielding( t=5.07, P<0.05). There was no significant difference in noise and CNR in routine brain scan between with and without X-care, bismuth shielding and X-care combined with bismuth shielding. There was no significant difference in noise and CNR in dual energy CTA scanning between with and without Bi shielding. Conclusions:Using bismuth shielding and organ tube current modulation, we can significantly reduce organ dose of lens and thyroid during brain CT scanning without sacrificing the image quality.

Methods for development of a core outcome set for clinical trials integrating traditional Chinese medicine and Western medicine / 中西医结合学报

Clinical trial outcome reporting differs between studies integrating traditional Chinese medicine (TCM) and Western medicine, so that some clinical trials are not eligible for inclusion in a systematic review. The excluded studies are therefore less widely disseminated, and even valid studies are less likely to yield impact. This problem may be addressed by developing core outcome sets (COSs) for integrative medicine in specific healthcare areas. The first stage of development is to define the scope of the COS for integrative medicine, the second stage is to establish the need for such a COS, and the third stage is to develop a protocol and register the COS. The final stage involves three steps: (i) development of a comprehensive list of outcomes (including efficacy outcomes and safety outcomes and TCM syndromes) using systematic review, qualitative or cross-sectional research, and reviews of package inserts and medical records; (ii) merging and grouping of outcomes within domains; (iii) conducting two rounds of Delphi survey and consensus meetings with a range of stakeholders. The final COS will include a general COS and core TCM syndrome- set. Development of COSs for clinical trials of integrative medicine may help to standardize outcome reporting and reduce publication bias in the future.

The misdiagnosis reported about a case of adrenal alveolar echinococcosis / 中华泌尿外科杂志

The clinical data of a case of adrenal alveolar echinococcosis treated and misdiagnosed in our hospital were reported retrospectively. The pre-operative CT examination of this patient showed that the liver S7 segment-the right adrenal gland area showed irregular masses of mixed density lesions, the boundary was unclear, consider the possibility of liver hydatid. During the operation, hydatid was found to only invade the liver capsule, and the primary lesion was the adrenal gland. The right adrenal gland and lesion were resected by urological surgeons. The pathological diagnosis was adrenal alveolar echinococcosis. When the imaging examination considers hepatic alveolar echinococcosis, and the lesion is mainly in the right adrenal gland area, it should be considered that the primary lesion could be in the adrenal gland.

Correlation between anti-mitochondrial antibodies and clinical serological and cirrhotic markers of primary biliary cholangitis / 中华消化杂志

Objective:To explore the correlation between the level of anti-mitochondrial antibody (AMA) and clinical indicators of first visited primary biliary cholangitis (PBC) patients with positive AMA.Methods:From January 2013 to December 2016, the clinical data of 1 323 patients with positive AMA and/or AMA-M2 detected for the first time were collected through the Information System of Peking University People′s Hospital. Among them, 183 were detected by indirect immunofluorescence assay, 431 were measured by immunoblotting, and 709 were determined by enzyme-linked immunosorbent assay (ELISA). Patients were divided into undiagnosed PBC group (non-PBC group, 973 cases) and newly diagnosed PBC group (new-PBC group, 350 cases including 268 cases of non-liver cirrhosis and 82 cases of liver cirrhosis); among 709 cases detected by ELISA, there were 567 cases in the non-PBC group and 142 cases in the new-PBC group (115 cases of non-liver cirrhosis PBC group and 27 cases of liver cirrhosis PBC group). Among 183 cases determined by indirect immunofluorescence assay, there were 118 cases in the non-PBC group and 65 cases in the new-PBC group. Among them 69 cases with low AMA titer (1∶40—1∶80) (53 cases of non-PBC group and 16 cases of new-PBC group), 95 cases with medium titer (1∶160—1∶320) (59 cases of non-PBC group and 36 cases of new-PBC group) and 19 cases with high titer (≥1∶640) (six cases of non-PBC group and 13 cases of new-PBC group). AMA levels among groups were compared, and its correlation with clinical serology and cirrhosis indicators of PBC including immunoglobulin (Ig)G, IgM, platelet, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptadase (GGT), alkaline phosphatase (ALP), serum total protein, serum albumin, total bilirubin (TBil), total cholesterol (TC), and aspartate aminotransferase to platelet ratio index (APRI) and fibrosis (Fib-4) was analysed. Mann-Whitney U test, Kruskal-Wallis test, and linear regression analysis were performed for statistical analysis. Results:By ELISA method, the median titer of AMA-M2 of 709 patients was 53 RU/mL, the serum AMA and AMA-M2 levels of new-PBC group were both higher than those of non-PBC group (1∶320 vs. 1∶80, 180 RU/mL vs. 47 RU/mL), and the differences were statistically significant ( χ2 = 14.111, Z = -7.531, both P < 0.01). In non-PBC group, the AMA-M2 value was positively correlated with age, serum IgG, IgM, AST, GGT, ALP, serum total protein and TC, all of which were statistically significant ( Rho = 0.114, 0.108, 0.337, 0.089, 0.197, 0.086, 0.121 and 0.073, all P<0.05). In new-PBC group, AMA-M2 value was positively correlated with age, IgM, serum total protein and TC, however was negatively correlated with platelet count, all of which were statistically significant ( Rho = 0.218, 0.483, 0.230, 0.161, and -0.183, all P<0.05). The median values of serum AMA and AMA-M2 of PBC without liver cirrhosis group were both tended to be lower than those of PBC with liver cirrhosis (1∶160 vs. 1∶320; 174 RU/mL vs. 495 RU/mL), however the differences were not statistically significant (both P>0.05). AMA-M2 value of patients in PBC with liver cirrhosis group was positively correlated with IgM level ( r = 0.38, P = 0.039), but was not correlated with APRI and Fib-4 (all P > 0.05). The median of AMA value of 183 patients who underwent indirect immunofluorescence test was 1∶160. In non-PBC group, the IgM levels of patients with low, medium and high AMA titers gradually increased (the median levels were 1.2, 1.7 and 1.8 g/L, respectively); in new-PBC group, the levels of IgM, GGT and ALP of patients with low, medium and high AMA titers gradually increased (median IgM levels were 1.5, 3.7 and 4.1 g/L, respectively; GGT levels were 144, 182 and 317 U/L, respectively; and ALP levels were 137, 168 and 221 U/L, respectively), and the differences were statistically significant ( χ2 =6.260, 7.081, 8.030, 15.226, all P<0.05). In non-PBC group, the median level of serum AMA-M2 of men was lower than that of women (41 RU/L vs. 50 RU/L), and the difference was statistically significant ( Z = -2.945, P = 0.003). In new-PBC group, the median level of serum AMA-M2 of men tended to be lower than that of women (113 RU/mL vs. 206 RU/mL), but the difference was not statistically significant ( P=0.257). Conclusion:Serum AMA level is correlated with many clinical parameters and may be related with the disease severity in patients with PBC.

Correlation between anti-mitochondrial antibodies and clinical serological and cirrhotic markers of primary biliary cholangitis / 中华消化杂志

Objective@#To explore the correlation between the level of anti-mitochondrial antibody (AMA) and clinical indicators of first visited primary biliary cholangitis (PBC) patients with positive AMA.@*Methods@#From January 2013 to December 2016, the clinical data of 1 323 patients with positive AMA and/or AMA-M2 detected for the first time were collected through the Information System of Peking University People′s Hospital. Among them, 183 were detected by indirect immunofluorescence assay, 431 were measured by immunoblotting, and 709 were determined by enzyme-linked immunosorbent assay (ELISA). Patients were divided into undiagnosed PBC group (non-PBC group, 973 cases) and newly diagnosed PBC group (new-PBC group, 350 cases including 268 cases of non-liver cirrhosis and 82 cases of liver cirrhosis); among 709 cases detected by ELISA, there were 567 cases in the non-PBC group and 142 cases in the new-PBC group (115 cases of non-liver cirrhosis PBC group and 27 cases of liver cirrhosis PBC group). Among 183 cases determined by indirect immunofluorescence assay, there were 118 cases in the non-PBC group and 65 cases in the new-PBC group. Among them 69 cases with low AMA titer (1∶40—1∶80) (53 cases of non-PBC group and 16 cases of new-PBC group), 95 cases with medium titer (1∶160—1∶320) (59 cases of non-PBC group and 36 cases of new-PBC group) and 19 cases with high titer (≥1∶640) (six cases of non-PBC group and 13 cases of new-PBC group). AMA levels among groups were compared, and its correlation with clinical serology and cirrhosis indicators of PBC including immunoglobulin (Ig)G, IgM, platelet, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltranspeptadase (GGT), alkaline phosphatase (ALP), serum total protein, serum albumin, total bilirubin (TBil), total cholesterol (TC), and aspartate aminotransferase to platelet ratio index (APRI) and fibrosis (Fib-4) was analysed. Mann-Whitney U test, Kruskal-Wallis test, and linear regression analysis were performed for statistical analysis.@*Results@#By ELISA method, the median titer of AMA-M2 of 709 patients was 53 RU/mL, the serum AMA and AMA-M2 levels of new-PBC group were both higher than those of non-PBC group (1∶320 vs. 1∶80, 180 RU/mL vs. 47 RU/mL), and the differences were statistically significant (χ2 = 14.111, Z = -7.531, both P < 0.01). In non-PBC group, the AMA-M2 value was positively correlated with age, serum IgG, IgM, AST, GGT, ALP, serum total protein and TC, all of which were statistically significant (Rho = 0.114, 0.108, 0.337, 0.089, 0.197, 0.086, 0.121 and 0.073, all P<0.05). In new-PBC group, AMA-M2 value was positively correlated with age, IgM, serum total protein and TC, however was negatively correlated with platelet count, all of which were statistically significant (Rho = 0.218, 0.483, 0.230, 0.161, and -0.183, all P<0.05). The median values of serum AMA and AMA-M2 of PBC without liver cirrhosis group were both tended to be lower than those of PBC with liver cirrhosis (1∶160 vs. 1∶320; 174 RU/mL vs. 495 RU/mL), however the differences were not statistically significant (both P>0.05). AMA-M2 value of patients in PBC with liver cirrhosis group was positively correlated with IgM level (r = 0.38, P = 0.039), but was not correlated with APRI and Fib-4 (all P > 0.05). The median of AMA value of 183 patients who underwent indirect immunofluorescence test was 1∶160. In non-PBC group, the IgM levels of patients with low, medium and high AMA titers gradually increased (the median levels were 1.2, 1.7 and 1.8 g/L, respectively); in new-PBC group, the levels of IgM, GGT and ALP of patients with low, medium and high AMA titers gradually increased (median IgM levels were 1.5, 3.7 and 4.1 g/L, respectively; GGT levels were 144, 182 and 317 U/L, respectively; and ALP levels were 137, 168 and 221 U/L, respectively), and the differences were statistically significant (χ2 =6.260, 7.081, 8.030, 15.226, all P<0.05). In non-PBC group, the median level of serum AMA-M2 of men was lower than that of women (41 RU/L vs. 50 RU/L), and the difference was statistically significant (Z = -2.945, P = 0.003). In new-PBC group, the median level of serum AMA-M2 of men tended to be lower than that of women (113 RU/mL vs. 206 RU/mL), but the difference was not statistically significant (P=0.257).@*Conclusion@#Serum AMA level is correlated with many clinical parameters and may be related with the disease severity in patients with PBC.

Clinical application effects of portable visual retractor in superficial temporal fascia flap harvesting / 中华烧伤杂志

Objective@#To explore the clinical application effects of portable visual retractor in superficial temporal fascia flap harvesting.@*Methods@#From January 2010 to June 2019, 27 patients meeting the inclusion criteria and planning to perform operation of superficial temporal fascia flap harvesting were admitted to the Department of Plastic and Reconstructive Surgery of the First Clinical Medical Center of the People′s Liberation Army General Hospital. The patients were divided into traditional surgical method group [6 males and 3 females, aged (34±14) years], cold light source retractor group [6 males and 4 females, aged (35±16) years], and portable visual retractor group [7 males and 1 female, aged (30±14) years] according to way of superficial temporal fascia flap harvesting. The superficial temporal fascia flaps of patients in traditional surgical method group were resected by traditional way of resection, and the superficial temporal fascia flaps of patients in cold light source retractor group and portable visual retractor group were resected at assistance of cold light source retractor and portable visual retractor, respectively. Length of incision, operation time, intraoperative blood loss volume, postoperative drainage volume, and postoperative complication of patients in 3 groups were observed and recorded. Data were processed with Fisher′s exact probability test, one-way analysis of variance, least significant difference test, Kruskal-Wallis H test, and Bonferroni correction.@*Results@#The length of incision of patients in visual retractor group was (3.6±0.8) cm, significantly shorter than (12.6±1.6) cm in traditional surgical method group and (5.8±0.9) cm in cold light source retractor group (P<0.05). The incision length of patients in traditional surgical method group was significantly longer than that in cold light source retractor group (P<0.05). The operation time of patients in visual retractor group was 24.0 (23.3, 25.8) min, significantly shorter than 35.0 (30.5, 36.5) min in traditional surgical method group and 28.5 (26.8, 30.5) min in cold light source retractor group (H=16.5, 9.8, P<0.05). The operation time of patients in traditional surgical method group was significantly longer than that in cold light source retractor group (H=6.6, P<0.05). The intraoperative blood loss volume was (26±3) mL of patients in visual retractor group, significantly less than (34±4) mL in traditional surgical method group and (30±6) mL in cold light source retractor group (P<0.05). The intraoperative blood loss volume of patients in traditional surgical method group was significantly more than that in cold light source retractor group (P<0.05). The postoperative drainage volumes of patients in visual retractor group, cold light source retractor group, and traditional surgical method group were (33±4), (34±6), and (31±7) mL, respectively, and there were no significantly statistical differences in postoperative drainage volumes among patients in the three groups (F=0.3, P>0.05). There were no severe complications such as ischemia and necrosis of superficial temporal fascia flaps in patients of the three groups. One patient in cold light source retractor group had subcutaneous hematoma after operation, which was improved by removing stitches and hematoma.@*Conclusions@#Superficial temporal fascia flap harvesting at the assistance of portable visual retractor has the advantages of clear visual field, simple operation, short operation time, small incision, and less intraoperative blood loss.

Research progress of PD-1/PD-L1 in head and neck squamous cell carcinoma / 中国肿瘤临床

Head and neck squamous cell carcinoma (HNSCC) is a kind of malignant tumor characterized by metastasis and local invasion. Its recurrence rate is high after surgery and radiotherapy, and the prognosis and quality of life are poor. In recent years, programmed death-1 (PD-1) inhibitors have been recommended in National Comprehensive Cancer Network (NCCN) guidelines for the treatment of recurrent, unresectable, and metastatic HNSCC, and their efficacy has been remarkable. PD-1 inhibitors constitute a new treatment for the patients with advanced HNSCC who are refractory to platinum-based chemotherapy and can increase the probability of surgical resection, reduce the risk of postoperative dysfunction, and improve the survival and quality of life. This article reviews the structure and mechanism of the PD-1/PD-L1 immunocheckpoint, as well as research progress on its inhibitors in the treatment of HNSCC.

Identification of related substances of midazolam hydrochloride by LC-MS / 中国药科大学学报

@#This study aimed to identify the related substances of midazolam hydrochloride by liquid chromatography-mass spectrometry (LC-MS). To separate the related substances of midazolam hydrochloride, gradient elution was performed using acetonitrile and 25 mmol/L of ammonium acetate (pH was adjusted to 5.5 with acetic acid) as mobile phase on Thermo BDS Hypersil C18 column (100 mm × 4.6 mm, 2.4 μm). The accurate mass and elemental composition of the parent ions and their product ions of related substances were determined by electrospray-ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF/MS). The structures of the related substances were identified by spectral analysis and process synthesis, and some of them were further confirmed by reference substances. Under the established HPLC condition, midazolam hydrochloride and its related substances were adequately separated, and 22 major related substances were detected and identified by hyphenated techniques in midazolam hydrochloride and its stressed samples, of which 8 were recorded as impurities in the United States Pharmacopeia. The LC-MS techniques can effectively separate and identify the related substances of midazolam hydrochloride and provide reference for the establishment of storage condition, optimization of synthetic processes and quality control.

Expression of CREB in children with recurrent wheezing and its effect on ORMDL3 gene expression / 中国当代儿科杂志

OBJECTIVE@#To study the expression level of cAMP response element-binding protein (CREB) in children with recurrent wheezing under three years of age and its effect on the expression of the serum orosomucoid 1-like protein 3 (ORMDL3) gene.@*METHODS@#Thirty-six children with recurrent wheezing under three years of age who visited the hospital from June 2017 to June 2019 were selected as the recurrent wheezing group. Twenty-four healthy children from physical examination were selected as the control group. The CREB expression level in peripheral blood was measured by quantitative real-time PCR. Human bronchial epithelial cells (BEAS-2B) were cultured, and dual-luciferase reporter assay and quantitative real-time PCR were used to investigate the effects of overexpression and siRNA interference of CREB on the promoter activity and mRNA expression of the ORMDL3 gene in the BEAS-2B cells.@*RESULTS@#The expression level of CREB in the recurrent wheezing group was significantly higher than that in the control group (P<0.001). In BEAS-2B cells, overexpression of CREB significantly up-regulated the promoter activity and mRNA expression of the ORMDL3 gene (P<0.05), while siRNA interference of CREB significantly reduced the promoter activity and mRNA expression of the ORMDL3 gene (P<0.05).@*CONCLUSIONS@#The expression of CREB is increased in children with recurrent wheezing, and CREB may be involved in the pathogenesis of recurrent wheezing by regulating expression of the ORMDL3 gene.