[Objective] To investigate the functional differences and potential effects of chromatin spatial structure in patients with normal karyotype and complex karyotype multiple myeloma. [Methods] High-throughput chromosome conformational capture (Hi-C) analysis was performed on plasma cells of 1 case with 1q21 complex karyotype and 1 case with normal karyotype multiple myeloma, and the differences in three-dimensional genome structure between the two patients were analyzed, and the transcriptome characteristics of plasma cells were combined to investigate the differential features through gene functional enrichment. [Results] A/B switch occurred in 36% of the chromatin compartments in two cases, and 1 041 genes in patient with complex karyotype had B/A switch. About 3 500 topological association domains (TADs) were identified in each sample, and there was no significant difference. The number of loops identified in complex karyotype sample was 1 069, which was 1/6 of the normal sample, and there were significant differences in the number of three different types of loops, which to some extent reflected the loss of genome stability. Transcriptome analysis showed significant differences in expression profiles between the two patients, and a total of 6 150 differentially expressed genes (3 303 up-regulated genes and 2 847 down-regulated genes) were identified. [Conclusion] Compared with patient with normal karyotype, patient with 1q21 complex karyotype multiple myeloma exhibit significant changes in the spatial structure of plasma cell chromatin at different levels, which leads to changes in gene expression and activation of pathways related to cancer progression.

Objective:To study the time consumption of clinical trial projects in each link of contract signing in medical institutions and its influencing factors, to provide a reference for further optimizing the clinical trial management process and improving the efficiency of contract signing.Methods:All of the review records of projects that signed clinical trial contracts at Peking Union Medical College Hospital from January 1st, 2018 to December 31st, 2021 were retrospectively analyzed by comparing the time consumption in each link before signing the contracts and the frequency of contract reviews. Multiple linear regressions were applied to multivariate analyze the influence of different factors on contract signing.Results:A total of 761 clinical trial contracts signed at Peking Union Medical College Hospital from 2018 to 2021 were included in this study, and the average time consumption of contract signing was 127.0 days, among which the consumption of contract review by the hospital was 10.5 days and by sponsors was 99.0 days. The time consumption of contract signing has been decreasing in recent 4 years, from 154.0 days in 2018 to 104.0 days in 2021. The phase of clinical trials, category of sponsors, frequency of contract reviews, and different policies of the institutions were the main influencing factors for contract signing time ( P<0.05). Conclusions:Clinical trial institutions should optimize the contract approval progress, provide agreement templates and targeted service, and strengthen propaganda and information system construction, to improve the efficiency of reviewing and signing clinical trial contracts.

Long non-coding RNA (lncRNA) is a class of highly conserved transcript with a length of more than 200 nucleotides, which is of great significance for the occurrence, development, diagnosis and treatment of malignant tumors. The abnormal expression of linc01410 in malignant tumors can affect the occurrence and development of malignant tumors by regulating the biological processes such as proliferation, migration and epithelial-mesenchymal transformation of malignant tumor cells, acting on related signaling pathways such as nuclear factor-κB and Notch or through exosome pathways.

Objective:To explore the effectiveness, safety and cost between urinary follicle stimulating hormone (uFSH) and recombinant follicle stimulating hormone (rFSH) in controlled ovarian stimulation (COS) in China.Methods:Data were collected from 16 reproductive centers in China covering oocytes collection time from May 1, 2015 to June 30, 2018. Eligible patients were over 18 years old, adopting COS with uFSH (uFSH group) or rFSH (rFSH group) as start gonadotropins (Gn), and using in vitro fertilization (IVF) and (or) intracytoplasmic sperm injection for fertilisation, excluding frozen embryo recovery cycle. Generalised estimating equation was used to address the violation of independency assumption between cycles due to multiple IVF cycles for one person and clustering nature of cycles carried out within one center. Controlling variables included age, body mass index, anti-Müllerian hormone level, cause of infertility, ovulation protocol, type of fertilisation, number of embryos transferred, number of days of Gn use.Results:Totally 102 061 cycles met eligibility criteria and were included in the analyses. In terms of effectiveness, after controlling relevant unbalanced baseline characteristics, compared with rFSH group, the high oocyte retrieval (>15 oocytes was considered high retrieval) rate of uFSH group significantly decreased in gonadotropin-releasing hormone agonist protocol ( OR=0.642, P<0.01) and in gonadotropin-releasing hormone antagonist protocol ( OR=0.556, P=0.001), but the clinical pregnancy rate per transfer cycle and the live birth rate per transfer cycle significantly increased ( OR=1.179, OR=1.169, both P<0.01) in both agonist and antagonist protocols. For safety, multiple analysis result demonstrated that in the agonist protocol, compared with rFSH group, the incidence of moderate to severe ovarian hyperstimulation syndrome of uFSH group significantly decreased ( OR=0.644, P=0.002). The differences in ectopic pregnancy rate and multiple pregnancy rate between the uFSH and rFSH groups were not significant ( P=0.890, P=0.470) in all patients. In terms of cost, compared with rFSH group, the uFSH group had lower total Gn costs for each patient ( P<0.01). Conclusion:For patients who underwent COS, uFSH has better safety, and economic profiles over rFSH in China.

Objective:To explore the feasibility of applying plasma with same blood group as kidney donor to ABO incompatible kidney transplantation(ABOi-KT)preconditioning of blood group O recipients with high-titer anti-A/B preformed antibody(IgM/IgG titer ≥1∶256).Methods:A total of 15 cases of blood group O ABOi-KT recipients with high-titer anti-A/B were recruited and divided into two groups of AB( n=8)and kidney donor's blood(KD, n=7)according to plasma type for plasma exchange during preconditioning phase. Clinical data of preconditioning and post-KT were recorded. Results:They received plasmapheresis(PP)(8.1±2.5)sessions in preconditioning phase, including double plasma filtration(DFPP)(4.0±1.4)sessions and plasma exchange(PE)(4.1±2.0)sessions, PP frequency was(0.8±0.1)sessions per day. No hemolysis reaction occurred during preconditioning phase. Anti-A/B titers declined as expected and fulfilled the ABOi-KT criteria(IgM/IgG titers ≤1∶8). KT was performed successfully without antibody-mediated rejection. All of them survived with normal renal function within 90 days post-KT. Levels of serum creatinine at Day 7/30/90 post-KT were(92.9±30.4), (96.2±25.9)and(103.1±28.4)μmol/L; anti-A/B IgM titers at Day 7/30/90 post-KT 1∶1-1∶32, 1∶1-1∶64 and 1∶1-1∶32; anti-A/B IgG titers at Day 7/30/90 post-KT 1∶1-1∶64, 1∶1-1∶64 and 1∶1-1∶32 respectively. No significant differences existed in count/frequency of PP sessions, levels of serum creatinine or anti-A/B titers at each observation point between AB and KD groups( P>0.05). Conclusions:Plasma with the same blood group as kidney donor is feasible for maximizing the intensity of ABOi-KT preconditioning. Favorable outcomes may be achieved through an intensified desensitization strategy on blood group O recipients with high-titer anti-A/B preformed antibody. The potential risks and long-term outcomes should be further explored.

Background::Dermatophagoides pteronyssinus is a common allergen causing allergic diseases in China. The aim of this study was to evaluate the efficacy and safety of D. pteronyssinus extracts produced by Peking Union Medical College Hospital (PUMCH) for the skin prick test (SPT) in the diagnosis of D. pteronyssinus allergy. Methods::A total of 910 subjects with allergic diseases were prescribed D. pteronyssinus SPT and specific sIgE (sIgE) test among the Outpatients of Department of Allergy, PUMCH from August 10, 2015 to August 30, 2017. Receiver operating characteristic curve (ROC) analysis was performed according to the results of D. pteronyssinus-sIgE detection. The accuracy of D. pteronyssinus extracts used for SPT in the diagnosis of D. pteronyssinus allergy was evaluated under different cutoff values. Adverse events after SPT were recorded to evaluate safety. Results::There were 796 and 618 subjects in the full analysis set (FAS) and the per protocol set (PPS), respectively. The areas under the curve of FAS and PPS were 0.871 and 0.873, respectively. According to the ROC of PPS, the optimal and 95% specificity diagnostic cutoff values of D. pteronyssinus SPT mean wheal diameter were 3.25 and 3.75 mm, respectively. No adverse events occurred. Conclusion::The extracts of D. pteronyssinus for SPT were simple, highly accurate, and safe and should be considered for recommendation in the clinical diagnosis of D. pteronyssinus allergy.

Objective:To evaluate the effect of transcutaneous electrical acupoint stimulation (TEAS) on perioperative anxiety and postoperative pain in living kidney donors (LKDs).Methods:Seventy-two American Society of Anesthesiologists physical status Ⅰ or Ⅱ LKDs, aged 18-64 yr, with body mass index of 18-28 kg/m 2, undergoing living kidney transplantation, were selected, and divided into 2 groups ( n=36 each) using a random number table method: TEAS group (group T) and sham stimulation group (group S). In group T, TEAS was performed on the forenoon at 1 day before surgery (T 0), at 30 min before anesthesia induction on the morning of the operation day (T 1) and on the forenoon at 1 day after surgery (T 2) at bilateral Neiguan, Taichong and Yintang with a frequency 2-100 Hz, disperse-dense waves and current intensity 6-15 mA, and each TEAS lasted for 30 min.Only electrode patches were applied at the same acupoint and at the same time point, but no stimulation was applied in group S. In T and S groups, brachial venous blood samples were collected before each stimulation for measurement of the plasma 5-hydroxytryptamine (5-HT) concentration.The Hospital Anxiety Depression Scale-Anxiety subscale (HADS-A) scores at T 0, T 1, T 2, on day 3 after surgery (T 3) and before discharge (T 4) in the 2 groups were recorded.The consumption of anesthetics during operation, laryngeal mask airway removal time, requirement for rescue analgesia within 72 h after surgery and the development of postoperative complications were recorded.The LKDs were followed up by telephone at 3 months after surgery (T 5) to record the scores of HADS-A and Leeds Assessment of Neuropathic Symptoms and Sign (LANSS) scale. Results:Compared to group S, the incidence of anxiety was significantly decreased T 1, T 2 and T 3, the incidence of rescue analgesia within 72 h after surgery was decreased, plasma concentration of 5-HT was increased at T 1 and T 2, the incidence of postoperative nausea and vomiting was decreased, and the time to first flatus was shortened in group T ( P<0.05). There was no significant difference in the consumption of anesthetics during operation, laryngeal mask airway removal time, and the incidence of anxiety and neuropathic pain within 3 months after surgery between the 2 groups ( P>0.05). Conclusion:TEAS can relieve early preoperative and postoperative anxiety and alleviate postoperative pain in LKDs.

OBJECTIVE：To provide scientifi c evidence for improving the quality standard of Mongolian medicine Juniperus rigida. METHODS ：Totally 10 batches of J. rigida from different places were taken as samples to observe their characters and identify them by microscope ；TLC method was adopted to qualitatively identify isoquercitrin ，quercitrin，amentoflavone， podocarpusflavone A and hinokiflavone ；the contents of total ash ，acid-insoluble ash ，ethanol-soluble extract and heavy metals were determined by related method stated in 2020 edition of Chinese Pharmacopeia （part Ⅳ）. The contents of above 5 components in samples were determined by HPLC. RESULTS ：The powder of J. rigida was green or yellowish green ，polygonal tracheids ， closely arranged in longitudinal with unequal stomatal ；epidermal cells were nearly rectangular ；sclerenchyma cells were quasi rectangular and the wall beadedly thickening. Results of TLC showed that the spots of the same color were found in the corresponding positions of chromatogram for test sample and substance control. The contents of total ash ，acid-insoluble ash and ethanol-soluble extract in 10 batches of samples were 7.37％-11.18％，0.75％-2.98％，16.55％-26.42％，respectively；average contents were 8.51％，1.27％，22.35％. The contents of lead ，arsenic，cadmium，mercury and copper were 2.00-5.44，0.65-1.65， 0.044-0.100，0.034-0.160，4.59-6.79 mg/kg，respectively；average conte nts were 3.73，0.97，0.078，0.061，5.23 mg/kg. The linear ranges of isoquercitrin ，quercitrin，amentoflavone，podocarpus- flavone A and hinokiflavone were 4.98-20.02，49.99-199.96， 19.94-99.96，9.99-40.00，20.20-159.98 μg/mL（all r＞0.999 7）； com RSDs of precision ，repeatability and stability （24 h） tests were all less than 3.00％（n＝6）；the average recoveries were 话：0993-2057878。E-mail：Tanghuishz@qq.com 100.62％-102.96％，RSDs were 1.21％-1.88％（n＝6）. Average contents of the above-mentioned 5 compounds in 10 batches of samples were 0.089-0.379，1.379-4.250，1.077-2.026，0.162-0.423， 0.016 9-0.117 0 mg/g，respectively. CONCLUSIONS ：The qualitative and quantitative analysis methods of Mongolian medicine J. rigida are established. It is preliminarily proposed that the total ash content shall not exceed 10.22％，the acid-insoluble ash content shall not exceed 1.53％，ethanol-soluble extract content shall not be less than 17.88％，heavy metal lead should not exceed 5 mg/kg，arsenic should not exceed 2 mg/kg，cadmium should not exceed 0.3 mg/kg，mercury should not exceed 0.2 mg/kg，copper should not exceed 20 mg/kg.

In order to explore the treatment of Her-2 positive breast cancer patients who failed in multi-line treatments, we retrospectively analyzed the clinical data of a patient with refractory Her-2 positive breast cancer.The patient was initially diagnosed as Her-2 positive advanced breast cancer.After six line treatment in the outer hospital, the patient′s condition was basically in a progressive state.The breast tumor was broken and purulent, the lung metastasis increased, and the patient′s quality of life was poor.The patient was admitted to Department of Breast Surgery of Affiliated Suqian Hospital of Xuzhou Medical University, after MDT discussion, we gave pyrrolotinib combined with capecitabine treatment, the chest wound healed gradually, the lung metastasis gradually reduced, and the quality of life was better.A retrospective analysis of this case showed that pyrrolidine combined with capecitabine may bring hope to Her-2 positive breast cancer patients who failed to receive multi-line therapies, especially those who failed to target therapy.

Background and aim:Real-world data on the effectiveness and safety of treatment with the direct-acting antiviral agent-based regimen are limited on the Chinese mainland.The aim of this study was to conduct a multicenter,prospective,real-world study of ombitasvir/paritaprevir/ritonavir(OBT/PTV/r)combined with dasabuvir(DSV)in hepatitis C virus(HCV)genotype 1b-infected non-cirrhotic or compensated cirrhotic Chinese adult patients. Materials and methods:Genotype 1b-infected patients were enrolled at eight sites in China.Patients received 25/150/100 mg of OBT/PTV/r once daily combined with 250 mg of DSV twice daily for 8 weeks or 12 weeks.Sustained virological response at 12 weeks post-treatment(SVR12)and the incidence of adverse events were assessed.We have also evaluated the effect of intensive questioning of patients who were overdue for SVR12 testing.Intention-to-treat(1TT)and modified 1TT(mITT)populations were used in the analysis. Results:One hundred forty patients were included,among whom 90.0％(126/140)were newly diag-nosed,9.3％(13/140)had compensated cirrhosis,92.9％(130/140)received 12 weeks of treatment,and 7.1％(10/140)received 8 weeks of treatment.In the mITT population,the virological response rate at week 4 was 96.4％(108/112),and at the end of treatment was 100％(102/102).Among these patients,139 patients completed 12 weeks of treatment,and 73 patients were followed-up.All followed-up patients achieved SVR12.There was no adverse event-related discontinuation.Serious adverse events during treatment were reported in two(1.4％)patients,and none were considered to be drug-related.Sixty-six(47.1％)patients did not return to receive the HCV RNA test at 12 weeks post-treatment. Conclusions:The rate of SVR12 was consistent with Phase Ⅲ clinical studies.OBT/PTV/r combined with DSV showed effectiveness in Chinese adult patients,and both tolerability and safety profile were favorable.However,patient compliance should be further improved in the real world.