The major histocompatibility complex(MHC)is closely related to immune regulation.MHC shows distinct genetic polymorphism,and there are also species differences in MHC restriction.The human MHC is called human leukocyte antigen(HLA),and the mouse MHC is called H-2.The construction of humanized MHC transgenic mouse models is an important strategy to overcome the differences in MHC among species and simulate the characteristics of a human immune response.MHC transgenic mice are mainly divided into MHC Ⅰ or MHC Ⅱ single-transgenic mouse models and MHC Ⅰ and MHC Ⅱ double-transgenic mouse models.The development of HLA Ⅰ transgenic mouse model went through three stages,at present,the strategy of knocking out H-2Kb and H-2Db or murine β2m is adopted to eliminate the competitive inhibition of HLA Ⅰ molecules by endogenous H-2 class Ⅰ molecules.In the construction of an HLA Ⅱtransgenic mouse model,the β strand of murine origin is knocked out and HLA Ⅱ class genes are inserted.With the optimization of construction strategies,MHC transgenic mouse models have been applied to epitope vaccine development,tumor treatment,and genetic disease-association studies,becoming a powerful tool for preclinical trials.In this paper,we summarize the relevant data on MHC transgenic mouse models,as well as the construction strategies used for MHC transgenic mouse models and their application in vaccine development and disease treatment.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:To investigate the clinical characteristics, treatment and prognosis of newly-treated patients with primary central nervous system lymphoma (PCNSL).Methods:Clinical data of 117 newly-treated PCNSL patients who were admitted to the First Hospital of Jilin University, the Fifth Medical Center of Chinese PLA General Hospital, Harbin Medical University Cancer Hospital, and Cancer Hospital of Chinese Academy of Medical Sciences & Peking Union Medical College from August 2009 to February 2018 were retrospectively analyzed. The patients' age, sex, Eastern Cooperative Oncology Group (ECOG) physical status (PS) score, pathological type, involvement of deep brain tissue, number of lesions, cerebrospinal fluid protein concentration, International Extranodal Lymphoma Study Group (IELSG) score, Memorial Sloan Kettering Cancer Center (MSKCC) score, treatment strategy, and response after the first-line therapy were analyzed using univariate and multivariate Cox proportional hazards models to identify the independent influencing factors for progression-free survival (PFS) and overall survival (OS) of PCNSL patients. Kaplan-Meier method was used for survival analysis.Results:In 117 newly-treated PCNSL patients, 59 cases (50.4%) presented with increased intracranial pressure or focal neurological symptoms at diagnosis; there were 65 cases (55.6%) with single lesions and 52 cases (44.4%) with multiple lesions; 1 patient (0.9%) had lymphoma of T-cell origin, and 116 cases (99.1%) had diffuse large B-cell lymphoma (DLBCL). Among 95 evaluable patients, 41 patients (43.2%) achieved complete remission (CR), 20 patients (21.1%) achieved partial remission (PR), 16 patients (16.8%) achieved stable disease (SD), and 18 patients (18.9%) had progressive disease (PD). In 117 patients with median follow-up of 66.0 months (95% CI 57.9-74.1 months), the median PFS and OS were 17.4 months (95% CI 11.5-23.3 months) and 45.6 months (95% CI 20.1-71.1 months), respectively. The 2-, 3- and 5-year PFS rates were 41.2%, 28.6% and 19.3%, and OS rates were 63.7%, 52.4% and 46.3%, respectively. Univariate Cox regression analysis showed that baseline high-risk MSKCC score group was an adverse prognostic factor for PFS ( P = 0.037), and the first-line chemotherapy with ≥4 cycles of high-dose methotrexate (HDMTX), HDMTX in combination with rituximab, ≥4 cycles of rituximab in combination with HDMTX, and achieving CR or ≥PR after the first-line treatment reduced the risk of disease progression and prolonged the PFS time (all P <0.01); age >60 years old, ECOG-PS score of 2-4 points, elevated cerebrospinal fluid protein concentration, high-risk IELSG score, and high-risk MSKCC score were adverse prognostic factors for OS, and ≥4 cycles of HDMTX and achieving CR or ≥PR after the first-line treatment were favorable factors for OS. Multivariate Cox regression analysis verified that rituximab in combination with HDMTX (yes vs. no: HR = 0.349, 95% CI 0.133-0.912, P = 0.032) and achieving ≥PR after the first-line chemotherapy (yes vs. no: HR = 0.028, 95% CI 0.004-0.195, P < 0.001) were independent favorable factors for PFS; age >60 years old (>60 years old vs. ≤60 years old: HR = 10.878, 95% CI 1.807-65.488, P = 0.009) was independent unfavorable factor for OS, while ≥4 cycles of HDMTX treatment (≥4 cycles vs. <4 cycles: HR = 0.225, 95% CI 0.053-0.947, P = 0.042) was independent favorable factor for OS. Conclusions:The older the PCNSL patients at initial treatment, the worse the prognosis. Intensive and continuous treatment for achieving deeper remission may be the key for improving the outcome of PCNSL patients.

Objective:To detective the cut-off values of amino acid levels in premature infants in Sichuan.Methods:Data of newborns screening for inherited metabolic diseases (IMD) by tandem mass spectrometry in Sichuan Province from January 2018 to December 2019 were retrospectively analyzed.They were divided into premature infant group ( n=2 264, 1 312 males and 952 females) and full-term infant group ( n=53 275, 28 269 males and 25 006 females). The cut-off values of amino acids in dry blood spots were expressed as percentage ( P0.5 - P99.5), and rank sum test was used for comparison between preterm and full-term infants. Results:(1) The distribution of 11 amino acids [alanine (ALA), arginine (ARG), citrulline (CIT), glycine(GLY), leucine (LEU), methionine (MET), ornithine (ORN), phenylalanine (PHE), proline (PRO), tyrosine (TYR) and valine (VAL)] in premature infants were abnormal.(2) The cut-off values of amino acids in premature infants were as follows: ALA: 135.20-552.33 μmol/L, ARG: 1.34-47.04 μmol/L, CIT: 5.66-32.02 μmol/L, GLY: 181.48-909.93 μmol/L, LEU : 71.10-283.29 μmol/L, MET: 4.21-34.51 μmol/L, ORN: 40.58-293.76 μmol/L, PHE: 23.60-106.30 μmol/L, PRO: 77.76-358.24 μmol/L, TYR: 27.52-352.91 μmol/L, VAL: 53.74-228.37 μmol/L.(3) The cut-off values of amino acid in full-term infants were as follows: ALA: 135.20-552.33 μmol/L, ARG: 1.30-42.73 μmol/L, CIT: 5.92-30.35 μmol/L, GLY: 208.17-980.09 μmol/L, LEU: 72.91-287.49 μmol/L, MET: 4.27-33.90 μmol/L, ORN: 48.40-305.59 μmol/L, PHE: 27.63-92.27 μmol/L, PRO: 97.38-372.75 μmol/L, TYR: 40.19-276.54 μmol/L, VAL: 65.75-237.92 μmol/L.(4) Except for PHE ( Z=-0.58, P>0.05), the other indicators were significantly different between 2 groups [ALA ( Z=-15.32, P<0.05), ARG ( Z=-5.62, P<0.05), CIT ( Z=-5.86, P<0.05), GLY ( Z=-14.52, P<0.05), LEU ( Z=-5.62, P<0.05), MET ( Z=-5.22, P<0.05), ORN ( Z=-13.01, P<0.05), PRO ( Z=-22.09, P<0.05), TRY ( Z=-2.09, P<0.05), VAL ( Z=-17.82, P<0.05)]. Conclusions:The establishment of the cut-off values of amino acids in premature infants in Sichuan provides a theoretical basis for laboratory diagnosis of IMD screening, which enhances the accuracy of diagnosis and avoids excessive medical treatment.

Objective:To investigate the correlation between global burden of small vessel disease(CSVD) on MRI and impaired spatial navigation in patients with CSVD.Methods:Patients with CSVD admitted to the Department of Neurology, Nanjing Jiangning Hospital from November 2020 to June 2022 were selected as the research subjects. The global burden of CSVD was scored according to the head MRI findings, and was divided into mild group (0-1 points), moderate group (2 points), and severe group (3-4 points). All patients were tested for spatial navigation function. Multivariate linear regression model was used to analyze the correlation between the global burden of CSVD and the spatial navigation function.Results:A total of 101 patients with CSVD were enrolled, including 37 patients in the mild group (36.6%), 28 in the moderate group (27.7%), and 36 in the severe group (35.6%). Age, glycosylated hemoglobin, total cholesterol, low-density lipoprotein cholesterol and creatinine, as well as the proportions of hypertension, diabetes, previous stroke or transient ischemic attack in the moderate group and the severe group were significantly higher than those in the mild group, while the high-density lipoprotein cholesterol was significantly lower than that in the mild group (all P<0.05). The spatial navigation function test showed that the environment + self-navigation, self-navigation and environment navigation functions of the moderate group and the severe group decreased significantly compared with the mild group (all P<0.05). Multivariate linear regression analysis showed that after adjusting for age, sex, hypertension, previous stroke or transient ischemic attack history and years of education, the global burden of CSVD and environment + self-navigation ( β=0.518, P<0.001), self-navigation ( β=0.481, P<0.001) and environmental navigation ( β=0.699, P<0.001) function had significant correlation. Conclusion:The global burden of CSVD is correlated with spatial navigation functions.

Er: YAG laser bleaching is a new tooth bleaching method compared with traditional bleaching technology. The Er: YAG laser significantly improves the bleaching efficiency, has the advantages of high safety, short treatment time and excellent bleaching effect and is widely used in clinical operations. This paper summarizes the working principle and bleaching characteristics of Er: YAG laser bleaching technology and its effect on tooth structure. The existing literature suggests that the high absorption of water and hydroxyapatite by the Er: YAG laser makes it work well on water-bearing tissues and dental tissues. When it is absorbed by the bleaching agent on the tooth surface, it accelerates the catalytic oxidation-reduction reaction and selectively acts on the pigment particles deposited on the tooth, thereby achieving the effect of tooth bleaching. Er: YAG laser bleaching can be applied to most discolored teeth. The bleaching process is rapid and effective. During the bleaching process, for the dental pulp tissue, the temperature of the pulp cavity is lower than the critical value of 5.6 ℃, causing no pathological damage to the dental pulp tissue. For the hard tissues of the teeth, laser irradiation will cause changes in the chemical composition of calcium and phosphorus. The enamel presents a unique lava-like shape, and the bonding strength of the tooth increases after bleaching. Compared with other lasers, the Er: YAG laser has a wavelength close to the peak of water, and adding other ingredients to the bleaching agent is not required. Almost all the energy is used for the bleaching agent, with no damage to the surrounding tissues.

Objective:To explore the change characteristics of amino acid levels in neonates, so as to provide theoretical basis for accurate clinical interpretation.Methods:By preliminary screening and diagnosis from 32 855 newborns, 32 843 samples were collected using tandem mass spectrometry to inherited metabolic disease (IMD) scree-ning in Sichuan Province from January to December 2018.Afterwards, according to gestational age (1 363 premature infants, 31 468 full-term infants and 12 overdue infants), blood collection time (3-7 days old, 3 095 cases, 8-28 days old, 1 637 cases, and more than 28 days old, 248 cases) and season (7 737 cases in the first quarter, 11 428 cases in the second quarter, 5 482 cases in the third quarter, and 8 196 cases in the fourth quarter), neonates were divided into different study groups.The difference of amino acid level in each group was compared, and the correlation between various influencing factors and metabolic index was analyzed.Results:(1) The distribution of 11 amino acids [alanine(ALA), arginine(ARG), citrulline(CIT), glycine(GLY), leucine+ isoleucine+ hydroxyproline (LEU+ ILE+ PRO-OH), methionine(MET), ornithine(ORN), phenylalanine(PHE), proline(PRO), tyrosine(TYR), and valine(VAL)] in neonates showed non-normally distribution.(2)The distribution of 11 amino acids in different gestational age were tested by nonparametric test, except for PHE( H=0.61, P>0.05)and TYR( H=2.02, P>0.05), and other indicators were significantly different [ALA( H=187.11, P<0.05), ARG( H=23.60, P<0.05), CIT( H=22.90, P<0.05), GLY( H=85.18, P<0.05), LEU( H=56.42, P<0.05), MET( H=18.74, P<0.05), ORN( H=129.27, P<0.05), PRO( H=344.40, P<0.05), and VAL( H=272.92, P<0.05)]. (3) The distribution of 11 amino acids in different blood collection time were significantly different [ALA( H=65.19, P<0.05), ARG( H=404.48, P<0.05), CIT( H=502.13, P<0.05), GLY( H=1 719.44, P<0.05), LEU( H=396.41, P<0.05), MET( H=199.39, P<0.05), ORN( H=31.26, P<0.05), PHE( H=325.49, P<0.05), PRO( H=70.09, P<0.05), TYR( H=159.29, P<0.05), and VAL( H=102.52, P<0.05)]. (4) The distribution of 11 amino acids in different birth seasons were significantly different [ALA( H=401.37, P<0.05), ARG( H=3 229.03, P<0.05), CIT( H=65.45, P<0.05), GLY( H=597.82, P<0.05), LEU( H=1 120.42, P<0.05), MET( H=10 515.18, P<0.05), ORN( H=1 275.23, P<0.05), PHE( H=2 260.17, P<0.05), PRO( H=319.57, P<0.05), TYR( H=884.37, P<0.05), and VAL( H=1 824.49, P<0.05)]. Conclusion:According to different gestational age, season and blood collection time, the metabolism of amino acids in neonates was different.When using tandem mass spectrometry for detection, appropriate interpretation criteria should be selected based on different conditions.

Objective To detect phosphorylated-extracellular signal-regulated kinase (p-ERK1/2) protein expression in epithelial ovarian cancer and cell lines,and to examine the effects of mitogen-activated protein kinase (MAPK) kinase (MEK) inhibitor AZD6244 on cell proliferation,apoptosis as well as cell cycle of ovarian cancer cells.To explore the function and significance of MAPK/extracellular signal-regulated kinase (ERK) signaling pathway in the development of ovarian cancer.Methods (1) A total of 104 cases of patients with ovarian cancer who accepted the treatment of gynecological surgery and being confirmed by pathological examination in First Affiliated Hospital,Dalian Medical University from January 2004 to December 2013 were selected.The expressions of p-ERK1/2 protein were detected by immunohistochemistry in ovarian cancer specimens,and the relationship between the expressions of p-ERK1/2 and the clinical features of patients was analyzed.(2) p-ERK1/2 and other related proteins were determined by western blot in various ovarian cancer cells,including SKOV3,OV2008,C13,A2780S,A2780CP,OVCAR4,OVCAR5,OVCAR8 and CAOV3 treated with or without MEK inhibitor.The cellular proliferation,apoptosis and cell cycle of ovarian cancer cells after treatment with MEK inhibitor were analyzed by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry,respectively.Results (1) The immunohistochemical method showed that p-ERK1/2 between low grade serous carcinoma and clear cell carcinoma were not significantly higher expressed (P＞0.05).However,a lower level of the p-ERK1/2 expression were observed among high grade serous carcinoma,mucinous carcinoma and endometrioid carcinoma (all P＜0.05).There was no significant correlation between the protein expression of p-ERK1/2 and patients' age,pathological stage of surgery,and preoperative serum CA125 level (P＞0.05).(2) Western blot showed that the protein p-ERK1/2 was widely expressed in various ovarian cancer cell lines such as SKOV3,OV2008,C13,A2780S,A2780CP,OVCAR4,OVCAR5,OVCAR8 and CAOV3.After treatment with AZD6244 (5,10 μmol/L),the level of p-ERK 1/2 in OVCAR5 and OVCAR8 decreased significantly in dose-dependent manner.Additionally,we found a reduction of the expression level of cyclin D 1,caspase-3 and appeared cleaved poly adenosine diphosphate ribose polymerase (PARP) in OVCAR5 and OVCAR8,compared with control groups.MTT assays showed that OVCAR5,OVCAR8 and A2780S were differently inhibited in the dose-dependent manner after being treated with different concentrations of AZD6244 (0,2.5,5,10,25,50 and 100 μmol/L,all P＜0.05).Further tested by flow cytometry,the results showed that AZD6244 (5,10 μmol/L) was able to induce the apoptosis of OVCAR5,OVCAR8 and A2780S,as well as G0/G1 phase arrest,both in a dose-dependent manner (P＜0.05).Conclusions As the main active and functional unit of MAPK/ERK signaling pathway,p-ERK1/2 protein is expressed in both the tissues and various ovarian cancer cell lines.AZD6244 could down-regulated the expression of p-ERK1/2 in ovarian cancer cells,accompanied by the decreased proliferation and increased cell apoptosis of ovarian cancer cells.In conclusion,MAPK/ERK signaling pathway might play a role in the development and progression of ovarian cancer,and may be provide a novel option for molecular targeted therapies of the disease.

Objective: To investigate the effects of calcium supplementation during the pregnancy and early infancy stage on body mass index (BMI) and gut microbiota in the infants. Methods: A total of 1 752 healthy pregnant women and their infants (breast feeding) in two maternal and child health care hospitals of Beijing were chosen as the subjects in this study from May to October 2016. Questionnaires were used to obtain the general information and supplementation of calcium and vitamin D in mothers and their infants. The body length and weight of infants at birth and 6 months were recorded to calculate the BMI. The random number table method was used to randomly select 40 infants from each group for gut microbiota analysis (If less than 40 infants were all included in this study, 23 infants in the pregnancy and early infancy would be all treated with calcium supplements. There were 6 infants who was not added calcium during the pregnancy but added in the early infancy). Then it was compared that the effects of calcium supplementation during the pregnancy and early infancy on the BMI and gut microbiota composition of infants were determined at birth and 6 months. Results: Compared to the group with no calcium supplementation during the pregnancy ((12.76±1.23), (17.68±0.76)kg/m²), the BMI of infants at birth and 6 months in the group with calcium supplementation during the pregnancy ((13.51±0.47), (17.91±0.23)kg/m²) were significantly higher(P<0.05). In the group with maternal calcium supplementation, the BMI at 6 months ((18.63±0.52)kg/m²), BMI increment ((5.71±0.54)kg/m²) and the content of lactobacillus (21.04%±3.68%) in the only calcium supplementation subgroup in the early infancy were higher than those in only vitamin D supplementation subgroup ((17.69±0.89) kg/m², (4.17±1.01) kg/m² and 12.28%±3.86%) (P<0.05). In the group without maternal calcium supplementation, the content of lactobacillus (20.15%±4.87%) in the only calcium supplementation subgroup were also higher than those in only vitamin D supplementation subgroup (14.64%±3.71%) (P<0.05). Conclusion Appropriate calcium supplementation during the pregnancy is good for the growth and development of the fetus. Calcium supplementation in the early infancy could increase the BMI of infants, and promote the growth of intestinal lactobacillus.

Objective: To assess the incidence and characteristics of thyroid dysfunction during anti-Programmed cell death 1 receptor (PD-1) antibody SHR-1210 therapy in patients with advanced solid tumor. Methods: The medical records of 98 patients who initiated SHR-1210 treatment between April 27, 2016 and June 8, 2017 in the phase 1 trial to evaluate the safety, efficacy, and pharmacokinetics of SHR-1210 in patients with advanced solid tumors were retrospectively reviewed. Serological tests of thyroid stimulating hormone (TSH) and free thyroxine (fT4) were measured at baseline and prior to each SHR-1210 administration. Results: A total of 86 patients had normal thyroid function before the first dose of SHR-1210 treatment. Nine out of 86 (10.5%) patients developed new onset hypothyroidism from euthyroid state. 12 patients presented thyroid dysfunction at baseline, 10 of whom were subclinical hypothyroid and 2 were hypothyroidism. Four out of 10 patients developed hypothyroidism from subclinical hypothyroid. Most patients with hypothyroidism were asymptomatic. Thyroid dysfunction occurred early (median, 55days) after the initiation of SHR-1210. The severity of hypothyroidism were all grade 1-2. No grade 3-4 hypothyroidism occurred. No patients discontinue the treatment of SHR-1210 due to clinical impact of the thyroid dysfunctions. Conclusions: Thyroid-related adverse events were common during anti-PD-1 antibody SHR-1210 treatment . The incidence of hypothyroidism is lower in patients with euthyroid state than in patients with thyroid dysfunction at baseline during SHR-1210 treatment . Thyroid function can be improved after thyroid hormone replacement. During SHR-1210 treatment, it is necessary to pay attention to monitor the thyroid function, especially in the patients with thyroid dysfunction at baseline. Trial registration Chinese Clinical Trial Registry, 2016L01455