Objective To investigate the efficacy and safety of tyrosine kinase inhibitor(TKI)combined with immune checkpoint inhibitor as the second-line therapy for advanced hepatocellular carcinoma(HCC).Methods A retrospective analysis was performed for the clinical data of 63 patients with advanced HCC who were admitted to Department of Interventional Radiology,The First Affiliated Hospital of Soochow University,from January 2018 to December 2022,and all patients experienced progression/intolerance after transcatheter arterial chemoembolization combined with first-line TKI and were switched to second-line TKI with or without immune checkpoint inhibitor.The 32 patients receiving second-line TKI with immune checkpoint inhibitor were enrolled as combination group,and the 31 patients receiving second-line TKI alone were enrolled as single treatment group.Modified Response Evaluation Criteria in Solid Tumors was used to evaluate tumor response,and Common Terminology Criteria for Adverse Events 5.0 was used to evaluate adverse events.The Kaplan-Meier method was used to calculate median overall survival(mOS)and median progression-free survival(mPFS)for the two groups,and the two groups were compared in terms of objective response rate(ORR)and disease control rate(DCR).The chi-square test was used for comparison of baseline data and follow-up results between groups.Results The median follow-up time was 16.5(3.2-53.4)months for the 63 patients.The combination group had an mOS of 24.3(95%confidence interval[CI]:20.0-28.6)months and an mPFS of 9.8(95%CI:7.5-12.1)months,while the single treatment group had an mOS of 15.8(95%CI:11.4-20.1)months and an mPFS of 4.1(95%CI:3.2-4.9)months,and there were significant differences in mOS and mPFS between the two groups(P=0.029 and 0.038).The combination group had an ORR of 47%and a DCR of 84%,while the single treatment group had an ORR of 19%and a DCR of 65%;there was a significant difference in ORR between the two groups(P=0.021),but with no significant difference in DCR between the two groups(P=0.070).As for adverse events,4 patients(12.5%)in the combination group and 3(10.0%)in the single treatment group experienced grade Ⅲ-Ⅳ serious adverse events,with no fatal drug reactions in either group,and there was no significant difference in the incidence rate of adverse events between the two groups(P=0.783).Conclusion Compared with TKI alone,TKI combined with immune checkpoint inhibitor has a more significant therapeutic effect as the second-line therapy for advanced HCC,without increasing serious adverse reactions.

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.

ObjectiveTo investigate the distribution of traditional Chinese medicine （TCM） syndrome types and influencing factors of protein-energy wasting （PEW） in chronic kidney disease （CKD） undergoing maintenance hemodialysis （MHD）. MethodsAccording to diagnostic criteria， 164 patients with MHD were divided into PEW group and non-PEW group. The clinical data of all patients were collected， including general information such as gender， age， height and weight， disease characteristics such as course， cormobidity， and haemodialysis duration， laboratory indicators such as blood routine， liver function， renal function， electrolyte， blood lipid， grip strength， and the four examinations. Logistic regression analysis was used to find the influencing factors of PEW by taking the clinical indicators with significant differences between the two groups （P＜0.05） as the independent variables， diagnosis of PEW as the dependent variable， and normal values as the reference. ResultsOut of 164 patients with MHD， there were 96 （58.5%） cases in PEW group and 68 cases （41.5%） in non-PEW group. Compared to the non-PEW group，PEW group had increased age， ratios of bedrest， deep vein preservation， edema， and low grip strength， percentages of comorbidities type 2 diabetes， cardiovascular and cerebrovascular diseases，infections and anemia， and levels of alanine aminotransferase and permine amin aminotransferase， as well as decreased body mass index， self-care ratio，internal arteriovenous fistula， red blood cell count， hemoglobin， serum total protein， serum albumin levels （P＜0.05）. The PEW group had significantly higher frequency of poor appetite and digestion， abdominal distension， fear of cold and preference of warmth， weak breathing and fatigue， poor appetite， oliguria， nausea and vomiting than non-PEW group （P＜0.05）. The incidence of both yin and yang deficiency syndrome and damp-turbidity syndrome were significantly higher in the PEW group than the non-PEW group， while that of liver-kidney yin deficiency syndrome and stirring of wind syndrome were lower （P＜0.05）. Logistic regression analysis showed that low BMI （＜22 kg/m²）， inability to take care of oneself， low grip strength，low serum albumin （＜38 g/L）， infection， older age， fear of cold and cold limbs，and poor appetite were the risk factors of PEW in patients undergoing MHD （P＜0.05）. ConclusionThe root syndrome of MHD-PEW patients is both yin and yang deficiency， concurrent with damp-turbidity syndrome. Low BMI， low serum albumin， infection and older age may be the influencing factors of PEW in patients undergoing MHD.

Whether Fanconi anemia (FA) heterozygotes are predisposed to bone marrow failure and hematologic neoplasm is a crucial but unsettled issue in cancer prevention and family consulting. We retrospectively analyzed rare possibly significant variations (PSVs) in the five most obligated FA genes, BRCA2, FANCA, FANCC, FANCD2, and FANCG, in 788 patients with aplastic anemia (AA) and hematologic malignancy. Sixty-eight variants were identified in 66 patients (8.38%). FANCA was the most frequently mutated gene (n = 29), followed by BRCA2 (n = 20). Compared with that of the ExAC East Asian dataset, the overall frequency of rare PSVs was higher in our cohort (P = 0.016). BRCA2 PSVs showed higher frequency in acute lymphocytic leukemia (P = 0.038), and FANCA PSVs were significantly enriched in AA and AML subgroups (P = 0.020; P = 0.008). FA-PSV-positive MDS/AML patients had a higher tumor mutation burden, higher rate of cytogenetic abnormalities, less epigenetic regulation, and fewer spliceosome gene mutations than those of FA-PSV-negative MDS/AML patients (P = 0.024, P = 0.029, P = 0.024, and P = 0.013). The overall PSV enrichment in our cohort suggests that heterozygous mutations of FA genes contribute to hematopoietic failure and leukemogenesis.
Anemia, Aplastic/genetics* ; Epigenesis, Genetic ; Fanconi Anemia/genetics* ; Germ Cells ; Hematologic Neoplasms/genetics* ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Retrospective Studies

Objective:To evaluate the efficacy of embedding suture in pterygium excision combined with autologous conjunctival transplantation, and to compare the differences between embedding suture, continuous suture and intermittent suture.Methods:A randomized controlled study was conducted.One hundred and twenty patients (120 eyes) with primary pterygium, who underwent pterygium excision combined with autologous conjunctival transplantation in Shanghai Aier Eye Hospital from May to July 2020, were enrolled.The patients were randomly divided into the embedding suture group, continuous suture group and interrupted suture group, with 40 eyes in each group.The operation duration was recorded and the patients received follow-up visit at 0.5, 1, 3, 7, 10, 14 days and 1, 3 and 6 months after the operation.The five-point method was used to record the postoperative pain score.The corneal epithelial healing was evaluated by sodium fluorescein staining.The complications such as graft detachment, graft displacement or pterygium recurrence were observed with a slit lamp microscope.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Shanghai Aier Eye Hospital (No.SHAIER2020RB03). Written informed consent was obtained from each subject before any medical examination.Results:The operation time of continuous suture, interrupted suture and embedding suture was (14.45±2.78), (16.28±2.24) and (16.58±2.22) minutes, respectively, and the overall difference was statistically significant ( F=8.98, P<0.05). The operation time of continuous suture was significantly shorter than that of interrupted suture and embedding suture (both at P<0.017), and there was no significant difference between embedding suture and interrupted suture ( P>0.017). There was a statistically significant overall difference in pain scores among the three groups at various time points after the operation ( P<0.05). At 0.5, 1, 3, 7 and 10 days after the operation, the pain scores of embedding suture were lower than those of continuous suture and interrupted suture (all at P<0.05). On the 7th day after the operation, there was no significant difference in the unhealed rate of corneal epithelium among the three groups ( P=1.000). On the 10th day after the operation, the corneal epithelia of the three groups were all healed.During the six months after the operation, no complications such as displacement, detachment, necrosis, infection of graft and eye movement disorder occurred in the three groups.There was no significant difference in the recurrence rate of pterygium ( P=1.000). Conclusions:Embedding suture method can effectively reduce the irritation symptoms after pterygium conjunctival transplantation, and has stable fixation of implants.Compared with the traditional interrupted suture, it does not increase the recurrence rate, incidence of adverse reactions, operation time and economic burden of patients.

Objective:To analyze the HIV-1 drug resistance and related influencing factors of HIV antiviral therapy failures.Methods:Plasma samples were collected from the HIV/AIDS patients who had failed after antiviral therapy for one year at least from 2019 to 2020 for drug resistance gene detection and gene subtype determination, and the influencing factors were analyzed.Results:Among 479 successful samples, 284 had drug resistance gene mutation, the success rate of amplification was 84.18%, the mutation rate was 59.29%, the main gene subtype was CRF01_AE. The related factors of drug resistance gene mutation are CD4 + T lymphocyte count (CD4 count) ( χ2=18.01, P<0.001), HIV-1 subtype ( χ2=10.83, P =0.029) and treatment duration (month) ( χ2=6.24, P=0.044)during drug resistance test. Nucleoside reverse transcriptase inhibitor (NRTI)/non-nucleoside reverse transcriptase inhibitor (NNRTI) double resistance accounted for 54.23%, NNRTI drug resistance accounted for 34.86%, protease inhibitor (PI) drug resistance accounted for 4.23%, NRTI drug resistance accounted for 2.82%, PI/NNRTI double drug resistance accounted for 2.46%, PI/NRTI/NNRTI triple drug resistance accounted for 1.41%. NNRTI mutation mainly occurred at K103N, Y181C, G190A sites. NRTI mutation mainly occurred at M184V, K65R, K70R sites. PI mutation mainly occurred at M46L and Q58E sites. High resistance to nevirapine (NVP) accounted for up to 76.76% of patients with NNRTI resistance. Among the patients with NRTI resistance, 46.83% were highly resistant to emtricitabine (FTC)/lamivudine (3TC). There was no high resistance to PI among 284 drug resistant patients. Conclusions:Patients with low CD4 count, longer treatment time, BC subtype and CRF01_AE subtype had a higher incidence of drug resistance mutations in HIV/AIDS patients in Shanxi province. Most of them are mixed with multi-gene coding region mutations and have high resistance to FTC/3TC and NVP.

Objective:To evaluate the effect of preoperative respiratory muscle exercise combined with intraoperative lung protective ventilation strategy on atelectasis in elderly patients undergoing robot-assisted radical prostatectomy.Methods:In the prospective study, a total of 45 patients aged 65-80 years undergoing scheduled robot-assisted radical prostatectomy in First Hospital of Shanxi Medical University from August 2020 to November 2020 were divided into three groups( N=15, each): respiratory muscle exercise combined with lung protective ventilation strategy group(combined group), lung protective ventilation strategy group(pulmonary protective group)and conventional ventilation strategy(control group). Heart rate, systolic blood pressure, diastolic pressure, and pulse oxygen saturation as well as blood gas analysis of arterial blood and the calculated oxygenation index were measured and recorded immediately after establishing invasive artery monitoring in operating room, 10 min after endotracheal intubation, 1 h after the flexitic position, 30 min after tracheal extubation, 24 h after operation in all three groups of patients.The lung compliance values, peak airway pressure, and end-tidal carbon dioxide were recorded at 10 minutes after tracheal intubation, 30 minutes after tracheal extubation, 1 hour after succession position.A single-slice chest CT scan was performed at 1 h after surgery while satisfying the anesthesia recovery steward score ≥ 5.And the percentage of atelectasis area was calculated. Results:The American Society of Anesthesiologisits(ASA)classification of patients was 11/4, 12/3, and 11/4 in the combination group, lung protection group and control group respectively, and the difference was not statistically significant( χ2=0.127, P>0.05). Oxygenation index(mmHg)(1 mmHg=0.133 kPa)at 24 h after surgery was significantly higher in the combined group(351.1±11.2)than in lung protection group(337.0±13.4)( t=3.287, P<0.05). Atelectasis area(Median, Interquartile range)assessed by CT imaging at 30 min after tracheal extubation was 1.92(0.77)% in the combination group, 2.09(1.13)% in lung protection group, and 3.01(1.01)% in control group, with statistically significant difference( χ2 values, 26.036, 12.313, both P<0.05). Atelectasis area at 30 minutes after tracheal extubation was statistically significant smaller in the combination group than in lung protection group( χ2=6.240, P<0.05). Conclusions:Preoperative respiratory muscle exercise combined with intraoperative lung protective ventilation strategy can achieve the better effect of lung protection, reduce the degree of perioperative atelectasis in elderly patients, and improve oxygenation function.

OBJECTIVE: To detect fusion gene with pathological significance in a patient with refractory and relapsed acute B cell lymphoblastic leukemia (B-ALL) and to explore its laboratory and clinical characteristics. METHODS: Transcriptome sequencing was used to detect potential fusion transcripts. Other laboratory results and clinical data of the patient were also analyzed. RESULTS: The patient was found to harbor TCF3 exon 17-ZNF384 exon 7 in-frame fusion transcript. The minimal residual disease (MRD) has remained positive after multiple chemotherapy protocols including CD19-, CD22- targeted chimeric antigen receptor T cells immunotherapy. The patient eventually achieved complete remission and sustained MRD negativity after allogeneic hemopoietic stem cell transplantation (allo-HSCT). CONCLUSION Transcriptome sequencing can effectively detect potential fusion genes with clinical significance in leukemia. TCF3-ZNF384 positive B-ALL has unique laboratory and clinical characteristics, may not well respond to chemotherapy and immunotherapy, and is more likely to relapse. Timely allo-HSCT treatment may help such patients to achieve long-term disease-free survival. TCF3-ZNF384 positive B-ALL is not uncommon in pediatric patients but has not been effectively identified.
B-Lymphocytes ; Basic Helix-Loop-Helix Transcription Factors/genetics* ; Child ; Hematopoietic Stem Cell Transplantation ; Humans ; Laboratories ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy* ; Trans-Activators/genetics* ; Transcriptome

Objective:To investigate the infection spectrum revealed by metagenomics high-throughput next-generation sequencing (mNGS), and to provide a reference for infection diagnosis after allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:A total of 64 patients who developed systemic or local infection symptoms after allo-HSCT in Hebei Yanda Lu Daopei Hospital from January 2018 to November 2018 were enrolled. Gene sequences of pathogenic microorganisms in blood, cerebrospinal fluid and bronchoalveolar fluid specimens were detected by using mNGS. The pathogenic microorganisms or suspected pathogens were determined based on the clinical manifestations of patients.Results:There were 97 samples of mNGS detection for 64 patients who underwent allo-HSCT. The most common gram-positive bacteria were staphylococcus haemolyticus (19 times) and staphylococcus (14 times), and the most common gram-negative bacterium was acinetobacter baumannii (8 times). The most common viruses were cytomegalovirus, EB virus and Torque teno virus (35, 22 and 23 times, respectively), and the most common fungi were malassezia globus (14 times) and candida parapsilosis (8 times). There were 3 mycobacterium tuberculosis complexes detected in 3 patients with acute myeloid leukemia who received allo-HSCT. Mycoplasma orale was detected in one patient's sputum, and none parasite was detected.Conclusion:mNGS can comprehensively reveal the infection spectrum of hematologic diseases after allo-HSCT, especially for pathogenic microorganisms that are rare or difficult to cultivate, and it can effectively help the diagnosis of clinically infectious pathogens.

OBJECTIVE: To explore the mechanism of METHODS: Healthy male DBA/1 mice were used for CIA modeling. Twenty-five CIA mice with successful modeling and similar arthritis index (AI) scores were randomized equally into model group (CIA), methotrexate (MTX) group, and low-, medium-, and high-dose XWGD groups (0.975, 1.95, and 3.9 g/mL, respectively), with another 5 normal mice as the normal control group. The mice in normal control and CIA groups were given saline once a day, those in MTX group were given 0.1 mg/mL MTX once a week, and those in XWGD groups were treated daily via garage of XWGD containing crude drugs of different doses for 28 consecutive days. The AI score and HE staining were used to evaluate the changes in the joints of the CIA mice. The effect of XWGD on Th1, Th17, MDSC, G-MDSC and M-MDSC cells were evaluated with flow cytometry. RESULTS: Treatment with MTX and different doses of XWGD significantly decreased the AI score of the mice and relieved joint inflammation as compared with the model group ( CONCLUSIONS XWGD can improve joint inflammation in CIA mice by increasing the percentages of G-MDSC cells and decreasing the percentages of M-MDSC, Th1 and Th17 cells, and a high dose of XWGD can produce an equivalent therapeutic effect to methotrexate but with better safety.
Animals ; Arthritis, Experimental/drug therapy* ; Arthritis, Rheumatoid/drug therapy* ; Male ; Methotrexate ; Mice ; Mice, Inbred DBA ; Th17 Cells