Objective:To investigate the correlation factors of complete clinical response in idiopathic inflammatory myopathies(IIMs)patients receiving conventional treatment.Methods:Patients diagnosed with IIMs hospitalized in Peking University People's Hospital from January 2000 to June 2023 were in-cluded.The correlation factors of complete clinical response to conventional treatment were identified by analyzing the clinical characteristics,laboratory features,peripheral blood lymphocytes,immunological indicators,and therapeutic drugs.Results:Among the 635 patients included,518 patients finished the follow-up,with an average time of 36.8 months.The total complete clinical response rate of IIMs was 50.0％(259/518).The complete clinical response rate of dermatomyositis(DM),anti-synthetase syn-drome(ASS)and immune-mediated necrotizing myopathy(IMNM)were 53.5％,48.9％and 39.0％,respectively.Fever(P=0.002)and rapid progressive interstitial lung disease(RP-ILD)(P=0.014)were observed much more frequently in non-complete clinical response group than in complete clinical re-sponse group.The aspartate transaminase(AST),lactate dehydrogenase(LDH),D-dimer,erythrocyte sedimentation rate(ESR),C-reaction protein(CRP)and serum ferritin were significantly higher in non-complete clinical response group as compared with complete clinical response group.As for the treat-ment,the percentage of glucocorticoid received and intravenous immunoglobin(IVIG)were significantly higher in non-complete clinical response group than in complete clinical response group.Risk factor analysis showed that IMNM subtype(P=0.007),interstitial lung disease(ILD)(P=0.001),eleva-ted AST(P=0.012),elevated serum ferritin(P=0.016)and decreased count of CD4+T cells in peripheral blood(P=0.004)might be the risk factors for IIMs non-complete clinical response.Conclu-sion:The total complete clinical response rate of IIMs is low,especially for IMNM subtype.More effec-tive intervention should be administered to patients with ILD,elevated AST,elevated serum ferritin or decreased count of CD4+T cells at disease onset.

Objective:To explore the clinical characteristics and outcomes of type 2 autoimmune pancreatitis (AIP) and compare with type 1 AIP.Methods:Clinical data of the patients diagnosed with type 2 AIP by the International Consensus on diagnostic criteria of AIP at Peking Union Medical College Hospital from January 2001 to December 2022 were retrospectively analyzed, and type 1 AIP patients diagnosed in Peking Union Medical College Hospital from January 1985 to December 2016 were collected as controls. The clinical symptoms, treatments and follow-ups were analyzed.Results:A total of 25 patients with type 2 AIP were included, of which 16 cases (64.0%) were pathologically confirmed cases (13 cases by endoscopic ultrasound puncture, 2 cases by surgery, and 1 case by interventional puncture), and 9 cases (36.0%) were suspected. The average age of onset was 40 years old. Most patients ( n=23, 92.0%) had abdominal pain along with emaciation to a various degree. Among them, 3 cases primarily presented as acute pancreatitis. Two cases were diagnosed after surgery for pancreatic masses. Eighteen cases were complicated with inflammatory bowel disease, including 16 cases with ulcerative colitis, one case with Crohn's disease, and one case with indeterminate colitis. All patients had typical imaging manifestations, including 13 cases (52.0%) with diffuse pancreatic enlargement, 12 cases (48.0%) with focal or multifocal pancreatic lesions, and 5 cases (20.0%) with simultaneous focal pancreatic masses and diffuse enlargement. All patients had normal serum IgG4 levels, anti-neutropil cytoplasmic antibodies (ANCA) positivity rate was 35.3% (6/17), and anti-nuclear antibody (ANA) positivity rate was 29.2% (7/24). Two surgical patients recovered well after surgery, and the other patients all achieved clinical and imaging relief after hormone therapy, and no recurrence was seen during follow-up. Compared with type 1 AIP, type 2 AIP had younger onset age, main manifestation as abdominal pain without jaundice, rare involvement with extra-pancreatic organs, the lesions mainly located in the intestine and normal IgG4 level with statistically significant differences. The recurrence rate of type 2 AIP was lower than that of type 1 AIP (0 vs 16%). Conclusions:Type 2 AIP has different clinical characteristics from type 1 AIP. Due to the lack of specific serum markers, the diagnosis is more difficult. It responds well to glucocorticoids and has a low recurrence rate.

Objective Improving the limb management strategy for patients undergoing coronary intervention through radial artery puncture and observe the application effect,and to provide scientific basis for the prevention of limb complications.Methods From March 2023 to February 2024,patients who underwent coronary intervention in the Cardiovascular Department of a Tertiary A hospital in Wenzhou City were selected.They were randomly di-vided into an experimental group of 241 cases and a control group of 236 cases using a random number table method.After surgery,they were all treated with a rotary hemostatic device for compression hemostasis.The experi-mental group implement improvement strategies for surgical limb management,specifically underwent a reverse Bar-beau test upon returning to the ward after surgery to achieve non-occlusive compression,followed by decompression every hour.The compression intensity of the control group was guided by palpating the distal radial artery pulsa-tion,and the first decompression was performed 1 hour after surgery,followed by decompression at intervals of every 2 hours.The main evaluation indicators are the incidence of surgical limb complications and simplified Chinese version of General Comfort Questionnaire(GCQ)scores in 2 groups of patients,while the secondary evaluation indi-cators are the duration of compression and the number of decompression times in both groups.Results The inci-dence of postoperative complications in the experimental group was 14.11%,which was statistically significant com-pared to 44.49%in the control group(χ2=53.308,P<0.001).The GCQ score of the experimental group was(77.71±5.43)points,which was higher than(74.66±5.83)points in the control group,and the difference was statistically signif-icant(t=-3.354,P=0.001).The compression duration of(172±52)minutes and decompression frequency of 2(2,3)in the experimental group were lower than(289±60)minutes and 4(3,4)in the control group,and the differences were statistically significant(P<0.001).Conclusion The non-occlusive compression method of the radial artery based on the reverse Barbeau test can significantly reduce limb complications in patients undergoing coronary inter-vention,shorten the duration of hemostatic compression,reduce the number of depressions,and improve patient com-fort.It provides objective basis for nursing staff to evaluate the intensity of hemostatic compression and the timing of decompression.

Human genetic resources include specimen samples and related information. The application and regulation of human genetic resources in China started at the end of the 20th century and have progressed rapidly. However， many challenges remain. In this paper， we reviewed the current status of sample conservation and management and provided recommendations for further development of human genetic resources in China. The aim is to effectively protect and rationally utilize China's human genetic resources， safeguard national security and people's health， and promote the building of a community of common health for mankind.

【Objective】 To investigate the clinical and genetic characteristics of hemolytic disease of the newborn(HDN) induced by anti-M complicated with pyruvate kinase deficiency (PKD) disease. 【Methods】 The clinical data of a pregnant woman with unexplained adverse pregnancy outcome in the third trimester were retrospectively analyzed, and neonate anemia status and blood transfusion were followed up. With informed consent, peripheral blood of the neonate and her parents were collected for serological tests and disease-related gene target sequence capture and sequencing. The clinical and genetic characteristics of HDN induced by anti-M or PKD were reviewed. 【Results】 The neonate presented severe anemia, hepatosplenomegalism, hyperbilirubinemia at birth, and was confirmed MN combined with ABO neonatal hemolysis by serological tests. The neonate recovered by receiving blood exchange and phototherapy treatments, but he needed to receive blood transfusion each month because of hemolytic anemia. Genetic analysis showed that the neonate had compound heterozygous mutations (c. 1096C>T; c. 941T>C) of PKLR gene inherited from her parents. 【Conclusion】 The clinical manifestations of PKD are similar to that of HDN caused by anti-M in the early stage of the disease. Clinicians should exclude the metabolic diseases of red blood cells when diagnosing severe HDN caused by anti-M.

Drug metabolism and pharmacokinetics (DMPK) is an important branch of pharmaceutical sciences. The nature of ADME (absorption, distribution, metabolism, excretion) and PK (pharmacokinetics) inquiries during drug discovery and development has evolved in recent years from being largely descriptive to seeking a more quantitative and mechanistic understanding of the fate of drug candidates in biological systems. Tremendous progress has been made in the past decade, not only in the characterization of physiochemical properties of drugs that influence their ADME, target organ exposure, and toxicity, but also in the identification of design principles that can minimize drug-drug interaction (DDI) potentials and reduce the attritions. The importance of membrane transporters in drug disposition, efficacy, and safety, as well as the interplay with metabolic processes, has been increasingly recognized. Dramatic increases in investments on new modalities beyond traditional small and large molecule drugs, such as peptides, oligonucleotides, and antibody-drug conjugates, necessitated further innovations in bioanalytical and experimental tools for the characterization of their ADME properties. In this review, we highlight some of the most notable advances in the last decade, and provide future perspectives on potential major breakthroughs and innovations in the translation of DMPK science in various stages of drug discovery and development.

Objective:To compare the safety and efficacy of terbutaline and nifedipine for acute intrapartum fetal resuscitation (IUFR).Methods:This was a prospective randomized controlled study involving 110 pregnant women with non-reassuring fetal heart rate tracings (NRFHT) during delivery at Guangzhou Women and Children's Medical Center between January and April 2021. These women were randomly allocated to receive subcutaneous terbutaline sulphate (0.25 mg, terbutaline group) or oral nifedipine (10 mg, nifedipine group), with 55 subjects in each group. Hemodynamic parameters including blood pressure, heart rate, and oxygen saturation before and 5, 15 and 30 min after treatment as well as the success rate of intrapartum resuscitation, the onset time of medication, and the incidence of postpartum hemorrhage were analyzed using t test, Chi-square test or Fisher's exact test. Results:Two groups both showed no significant difference in the mean arterial pressure or oxygen saturation before or after treatment (all P>0.05). The heart rate was not affected in nifedipine group at any time points ( P>0.05). While the patients treated with terbutaline showed accelerated maternal heart rate 5, 15 and 30 min after administration as compared with the baseline[(97.0±20.2), (99.2±13.8), (91.8±12.6) vs (81.7±11.3) bpm, all P<0.001], but it began to decrease at 30 min, with a drop of 6.4 bpm compared with that at 15 min (95% CI: 1.5-11.2, P<0.05). None of the pregnant women had adverse reactions requiring medical intervention. The rates of successful acute resuscitation were similar in the two groups [terbutaline: 78.2% (43/55) vs nifedipine: 70.9% (39/55), χ 2= 0.77, P=0.381]. Terbutaline had a shorter onset time than nifedipine in slowing the frequency of contractions and returning fetal heart rate to class Ⅰ category [2(1-6) vs 6(1-10) min, U=2 348.50, P<0.001]. No significant difference was found between the two groups in terms of NRFHT-indicated cesarean section, assisted vaginal delivery, or second dose of tocolysis within 1 h (all P>0.05) nor in blood loss volume, postpartum hemorrhage rate, low Apgar score, low umbilical artery pH value (pH<7.2), neonatal asphyxia rate, or neonatal intensive care admission rate (all P>0.05). Conclusion:Terbutaline spends less time than nifedipine to take effect and may be an alternative for acute IUFR without significant adverse outcomes.

In order to study the signal pathway secreting type Ⅰ interferon in porcine alveolar macrophages (PAMs) infected with porcine circovirus type 2 (PCV2), the protein and the mRNA expression levels of cGAS/STING pathways were analyzed by ELISA, Western blotting and quantitative reverse transcriptase PCR in PAMs infected with PCV2. In addition, the roles of cGAS, STING, TBK1 and NF-κB/P65 in the generation of type I interferon (IFN-I) from PAMs were analyzed by using the cGAS and STING specific siRNA, inhibitors BX795 and BAY 11-7082. The results showed that the expression levels of IFN-I increased significantly at 48 h after infection with PCV2 (P<0.05), the mRNA expression levels of cGAS increased significantly at 48 h and 72 h after infection (P<0.01), the mRNA expression levels of STING increased significantly at 72 h after infection (P<0.01), and the mRNA expression levels of TBK1 and IRF3 increased at 48 h after infection (P<0.01). The protein expression levels of STING, TBK1 and IRF3 in PAMs infected with PCV2 were increased, the content of NF-κB/p65 was decreased, and the nuclear entry of NF-κB/p65 and IRF3 was promoted. After knocking down cGAS or STING expression by siRNA, the expression level of IFN-I was significantly decreased after PCV2 infection for 48 h (P<0.01). BX795 and BAY 11-7082 inhibitors were used to inhibit the expression of IRF3 and NF-κB, the concentration of IFN-I in BX795-treated group was significantly reduced than that of the PCV2 group (P<0.01), while no significant difference was observed between the BAY 11-7028 group and the PCV2 group. The results showed that PAMs infected with PCV2 induced IFN-I secretion through the cGAS/STING/TBK1/IRF3 signaling pathway.
Animals ; Cells, Cultured ; Circovirus ; Interferon Type I/genetics* ; Macrophages, Alveolar/virology* ; Membrane Proteins/metabolism* ; Nucleotidyltransferases/metabolism* ; Signal Transduction ; Swine

OBJECTIVE：To e stablish the method for simultaneous determination of 10 kinds of active components in Tibetan medicine Siwei jianghuang prescription ，and to optimize its decoction technology. METHODS ：HPLC method was adopted. Using soaking time ，the amount of added water ，decoction time and decoction times as factors ，comprehensive score of the contents of 10 kinds of components and solid extracts rate as response values ，one the basis of single factor test ，Box-Behnken response surface method was used to optimize its decoction technology. RESULTS ：The linear range of gallic acid ，corilagin，magnoflorine， ellagic acid ， hydrochloric jatrorrhizine ， hydrochloride palmatine ， hydrochloride berberine ， bisdemethoxycurcumin， demethoxycurcumin and curcumin were 0.280 6-1.683 6，0.289 6-1.737 6，0.320 8-1.924 8，0.116 0-0.696 0，0.018 9-0.113 5， 0.013 3-0.079 9，0.092 3-0.553 8，0.025 5-0.153 0，0.036 1-0.216 3，0.041 0-0.245 7 µg（all r were 0.999 9），respectively. The limits of quantitation were 0.28，14.48，3.21，11.60，1.89，4.44，0.46，0.26，0.36，0.41 ng，respectively. The limits of detection were 0.11，4.14，1.24，3.32，0.58，1.33，0.13，0.09，0.14，0.12 ng，respectively. RSDs of precision ，stability and reproducibility tests were all lower than 3％. The recoveries were 92.56％-103.69％（RSDs were 0.90％-3.81％，n＝6）. The optimal decoction technology included soaking 60 min，adding 8-fold（mL/g）water，decoction for twice ，lasting for 65 min each time. In 6 validation tests ，comprehensive scores were 3.323 2-3.422 4，and the absolute value of the relative error with the predicted value （3.437 4）was less than 2％.CONCLUSIONS：Established method is simple and repeatable ，and can be used for simultaneous determination of 10 kinds of active components in Siwei jianghuang prescription. Optimized decoction technology is stable and feasible.

Objective: To compare the clinical features between the 2 cohorts developing myelodysplastic syndrome or acute myeIogenous Ieukemia in Philadelphia chromosome-negative cells (Ph^- MDS/AML) and maintaining disease stable in the patients with Philadelphia chromosome-positive chronic myeloid Ieukemia (Ph⁺ CML) who had clonal chromosomal abnormalities in Philadelphia chromosome-negative metaphases (CCA/Ph^-) during tyrosine kinase inhibtor (TKI) - therapy. Methods: We retrospectively analyzed Ph⁺ CML patients who developed CCA/Ph^- during TKI-therapy from May 2001 to December 2017. Results: Data of CCA/Ph^- 63 patients, including 7 progressing to Ph^- MDS/AML and 56 remaining disease stable were collected. Compared with those with stable disease, patients with Ph^-MDS/AML had lower hemoglobin (P=0.007) and platelet (P=0.006) counts, and higher proportion of peripheral blasts (P<0.001) when the first time CCA/Ph^- was detected, and more mosonomy 7 abnormality (5/7, 71.4%) when MDS or AML was diagnosed; meanwhile, trisomy 8 (32/56, 57.1%) was more common in those with stable disease. Outcome of the patients with Ph^- MDS/AML were poor. However, most of those with CCA/Ph^- and stable disease had optimal response on TKI-therapy. Conclusions A few patients with Ph⁺ CML developed CCA/Ph^- during TKI-therapy, most of them had stable disease, but very few patients developed Ph^- MDS/AML with more common occurrence of monosomy 7 or unknown cytopenia. Our data suggested the significance of monitoring of peripheral blood smear, bone marrow morphology and cytogenetic analysis once monosomy 7 or unknown cytopenia occurred.