Objective: To analyze the causes of abnormal blood agglutination caused by high-titer cold antibodies in blood donors from a serological perspective. Methods: The donor's blood type was identified using the tube method. Direct antiglobulin test (DAT), indirect antiglobulin test (IAT), and antibody titer detection were performed on the samples. Results: The blood type of the donor was type B, and the DAT was negative. No complement components were detected on the surface of the donor's red blood cells. The supernatant of the suspended red blood cells was clear without abnormal coloration, and the agglutinated clumps were intact and difficult to dissociate. The antibody was identified as an IgM-type anti-IH cold agglutinin. At 4℃, this antibody reacted with autologous red blood cells, adult group B red blood cells, adult group O red blood cells, cord blood group B red blood cells and cord blood group O red blood cells, with a stronger reaction intensity observed with group O cells than with B cells. The titers were 512, 128, 256, 32 and 128, respectively. Conclusion: High-titer anti-IH can cause abnormal agglutination of blood at low temperatures. During blood distribution and clinical use, the appearance of blood products shall be strictly inspected to prevent the release of non-conforming blood products.

Tailored lipid nanoparticles (LNPs)-mediated small interfering RNA (siRNA) nanomedicines show promise in treating liver disease, such as acute liver injury (ALI) and non-alcoholic steatohepatitis (NASH). However, constructing LNPs that address biosafety concerns, ensure efficient delivery, and target specific hepatic subcellular fractions has been challenging. To evade above obstacles, we develop three novel self-degradable "gemini-like" ionizable lipids (SS-MA, SS-DC, SS-MH) by incorporating disulfide bonds and modifying the length of ester bond and tertiary amino head. Our findings reveal that the disulfide-bond-bridged LNPs exhibit reduction-responsive drug release, improving both biosafety and siRNA delivery efficiency. Furthermore, the distance of ester bond and tertiary amino head significantly influences the LNPs' pK _a, thereby affecting endosomal escape, hemolytic efficiency, absorption capacity of ApoE, uptake efficiency of hepatocytes and liver accumulation. We also develop the modified-mannose LNPs (M-LNP) to target liver macrophages specifically. The optimized M-MH_LNP@TNFα exhibits potential in preventing ALI by decreasing tumor necrosis factor α (TNFα) levels in the macrophages, while MH_LNP@DGAT2 could treat NASH by selectively degrading diacylglycerol O-acyltransferase 2 (DGAT2) in the hepatocytes. Our findings provide new insights into developing novel highly effective and low-toxic "gemini-like" ionizable lipids for constructing LNPs, potentially achieving more effective treatment for hepatic diseases.

Objective:To explore the effect of preoperative gamma-glutamyl transferase to albumin ratio (GAR) on prognosis of patients with Barcelona clinic liver cancer (BCLC)stage 0-A hepatocellular carcinoma (HCC) after microwave ablation (MWA).Methods:The clinical data of 201 patients with BCLC stage 0 to A who underwent MWA at two centers of Jiaxing Second Hospital and Shengjing Hospital of China Medical University from January 2011 to December 2018 were retrospectively analyzed, including 152 males and 49 females, aged (57.5±9.6) years. X-tile software was used to divide patients into a low GAR group ( n=84, GAR<0.9) and a high GAR group ( n=117, GAR≥0.9). Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival comparison. Univariate and multivariate Cox regression analysis was used to evaluate the relationship between GAR and prognosis. Results:The cumulative survival rates at 1, 3 and 5 years postoperatively were 98.7%, 93.8%, 78.5% for the low GAR group, which were superior to that 97.2%, 87.1%, 70.2% for the high GAR group, and the difference was statistically significant ( χ2=11.89, P=0.001). The recurrence-free survival rates at 1, 3 and 5 years after surgery between the two groups was no significant difference ( χ2=1.70, P=0.192). Multivariate analysis revealed that high GAR ( HR=2.723, 95% CI: 1.508-4.914, P=0.001) was independent risk factors for overall survival after MWA in patients with BCLC stages 0 to A HCC. Male gender ( HR=1.959, 95% CI: 1.127-3.305, P=0.017) and tumor diameter ≥2 cm ( HR=1.547, 95% CI: 1.008-2.373, P=0.046) were independent risk factors for recurrence after MWA in patients with BCLC stages 0 to A HCC. Univariate analysis, GAR≥0.9 was not associated with postoperative recurrence ( HR=1.315, 95% CI: 0.869-1.989, P=0.195). Conclusion:Preoperative GAR (≥0.9) is an independent risk factor affecting overall survival in patients with BCLC stages 0 to A HCC after MWA.

Objective:To explore the efficacy and safety of olverembatinib in treatment of chronic myeloid leukemia (CML) progressed to acute lymphoblastic leukemia with D241E mutation.Methods:The diagnosis and treatment of a patient with D241E mutant CML progressed to acute lymphoblastic leukemia admitted to the Fourth People's Hospital of Jinan in December 2018 were retrospectively analyzed, and relevant literature was reviewed.Results:The patient was a 47-year-old female, and her blood test result was abnormal during physical examination. She was diagnosed as CML and received treatment with imatinib and dasatinib for 2 years. The disease progressed to philadelphia chromosome (Ph)-positive acute B-lymphoblastic leukemia with BCR-ABL mutation (a D241E mutation). After 3 courses of chemotherapy combined with a targeted drug (ponatinib), the patient achieved complete remission, while the minimal residual disease continued to be positive. The patient received 1 course of chemotherapy combined with olverembatinib from the 4th course of treatment. After olverembatinib monotherapy maintenance therapy for 36 months, the patient achieved molecular complete remission with minimal residual disease. The patient developed complications such as skin pigmentation and elevated lipid levels, but all complications were tolerable.Conclusions:The application of olverembatinib in D241E mutant CML progressed to acute lymphoblastic leukemia can help patients obtain sustained molecular biological remission and good safety.

Objective:To observe the clinical efficacy of Tuina(Chinese therapeutic massage)plus Liu Zi Jue for adenoid hypertrophy(AH)due to Qi deficiency of lung and spleen and its effects on the adenoid-nasopharyngeal cavity ratio(A/N value)and traditional Chinese medicine(TCM)constitution scale score.Methods:A total of 64 children with AH due to Qi deficiency of the lung and spleen were randomized into a trial group and a control group,with 32 cases in each group.The trial group was treated with Tuina plus Liu Zi Jue,and the control group was treated with Tuina alone.The Tuina manipulations were the same in the two groups.Tuina treatment was performed 3 times a week,with an interval of at least 1 d.Liu Zi Jue was performed 2 sets each time and 5 times a week.After 8 weeks of treatment and at the 2-month follow-up,the clinical efficacy was compared between the two groups,and the changes in the main clinical symptom score,A/N value,and TCM constitution scale score were observed.Results:After treatment,the total effective rate of the trial group and the control group was 96.9%and 93.8%,respectively.The difference between the two groups was not statistically significant(P>0.05).At the follow-up,the total effective rate of the trial group was 93.8%,higher than 90.6%in the control group(P<0.05).After treatment and at the follow-up,the main clinical symptom score in both groups was lower than that before treatment(P<0.05);at the follow-up,the main clinical symptom score in the trial group was lower than that in the control group(P<0.05).After treatment,the A/N value in both groups was lower than that before treatment(P<0.05),and the value in the trial group was lower than that in the control group;however,the difference between the two groups was not statistically significant(P>0.05).After treatment and at the follow-up,the TCM constitution scale score in both groups was lower than that before treatment(P<0.05);the score after treatment in the trial group was lower than that in the control group(P<0.05).Conclusion:Tuina plus Liu Zi Jue can effectively improve the main clinical symptoms in children with AH due to Qi deficiency of lung and spleen,reduce the A/N value and TCM constitution scale score,with stable efficacy.

Objective:To observe the clinical efficacy of Tuina(Chinese therapeutic massage)plus Liu Zi Jue for adenoid hypertrophy(AH)due to Qi deficiency of lung and spleen and its effects on the adenoid-nasopharyngeal cavity ratio(A/N value)and traditional Chinese medicine(TCM)constitution scale score.Methods:A total of 64 children with AH due to Qi deficiency of the lung and spleen were randomized into a trial group and a control group,with 32 cases in each group.The trial group was treated with Tuina plus Liu Zi Jue,and the control group was treated with Tuina alone.The Tuina manipulations were the same in the two groups.Tuina treatment was performed 3 times a week,with an interval of at least 1 d.Liu Zi Jue was performed 2 sets each time and 5 times a week.After 8 weeks of treatment and at the 2-month follow-up,the clinical efficacy was compared between the two groups,and the changes in the main clinical symptom score,A/N value,and TCM constitution scale score were observed.Results:After treatment,the total effective rate of the trial group and the control group was 96.9%and 93.8%,respectively.The difference between the two groups was not statistically significant(P>0.05).At the follow-up,the total effective rate of the trial group was 93.8%,higher than 90.6%in the control group(P<0.05).After treatment and at the follow-up,the main clinical symptom score in both groups was lower than that before treatment(P<0.05);at the follow-up,the main clinical symptom score in the trial group was lower than that in the control group(P<0.05).After treatment,the A/N value in both groups was lower than that before treatment(P<0.05),and the value in the trial group was lower than that in the control group;however,the difference between the two groups was not statistically significant(P>0.05).After treatment and at the follow-up,the TCM constitution scale score in both groups was lower than that before treatment(P<0.05);the score after treatment in the trial group was lower than that in the control group(P<0.05).Conclusion:Tuina plus Liu Zi Jue can effectively improve the main clinical symptoms in children with AH due to Qi deficiency of lung and spleen,reduce the A/N value and TCM constitution scale score,with stable efficacy.

Objective:To explore the effect of preoperative gamma-glutamyl transferase to albumin ratio (GAR) on prognosis of patients with Barcelona clinic liver cancer (BCLC)stage 0-A hepatocellular carcinoma (HCC) after microwave ablation (MWA).Methods:The clinical data of 201 patients with BCLC stage 0 to A who underwent MWA at two centers of Jiaxing Second Hospital and Shengjing Hospital of China Medical University from January 2011 to December 2018 were retrospectively analyzed, including 152 males and 49 females, aged (57.5±9.6) years. X-tile software was used to divide patients into a low GAR group ( n=84, GAR<0.9) and a high GAR group ( n=117, GAR≥0.9). Kaplan-Meier method was used for survival analysis, and log-rank test was used for survival comparison. Univariate and multivariate Cox regression analysis was used to evaluate the relationship between GAR and prognosis. Results:The cumulative survival rates at 1, 3 and 5 years postoperatively were 98.7%, 93.8%, 78.5% for the low GAR group, which were superior to that 97.2%, 87.1%, 70.2% for the high GAR group, and the difference was statistically significant ( χ2=11.89, P=0.001). The recurrence-free survival rates at 1, 3 and 5 years after surgery between the two groups was no significant difference ( χ2=1.70, P=0.192). Multivariate analysis revealed that high GAR ( HR=2.723, 95% CI: 1.508-4.914, P=0.001) was independent risk factors for overall survival after MWA in patients with BCLC stages 0 to A HCC. Male gender ( HR=1.959, 95% CI: 1.127-3.305, P=0.017) and tumor diameter ≥2 cm ( HR=1.547, 95% CI: 1.008-2.373, P=0.046) were independent risk factors for recurrence after MWA in patients with BCLC stages 0 to A HCC. Univariate analysis, GAR≥0.9 was not associated with postoperative recurrence ( HR=1.315, 95% CI: 0.869-1.989, P=0.195). Conclusion:Preoperative GAR (≥0.9) is an independent risk factor affecting overall survival in patients with BCLC stages 0 to A HCC after MWA.

Objective:To compare the prognosis of percutaneous versus laparoscopic microwave ablation in patients with hepatocellular carcinoma (HCC) classified as Barcelona Clinic Liver Cancer (BCLC) stage 0 to A, and evaluate the impact of these two ablation modalities on treatment outcome.Methods:Clinical data of 198 patients with HCC of BCLC stages 0 to A undergoing microwave ablation treatment at the Second Hospital of Jiaxing and Shengjing Hospital of China Medical University from January 2011 to December 2018 were retrospectively analyzed, including 149 males and 49 females, aged (57.4±9.6) years. Patients were divided into two groups based on the treatment modality: percutaneous microwave ablation group ( n=133) and laparoscopic microwave ablation group ( n=65). Survival rates were calculated using the Kaplan-Meier method, and the log-rank test was used to compare survival rates. Univariate and multivariate analyses were performed using Cox regression to assess the impacts of percutaneous and laparoscopic microwave ablation on prognosis. Results:The median overall survivals for the percutaneous and laparoscopic microwave ablation groups were 54 months and 77 months, respectively. The 1-, 3-, and 5-year cumulative survival rates postoperatively were 95.6%, 67.3%, 47.4% for the percutaneous group, and 100.0%, 79.9%, 60.4% for the laparoscopic group, respectively, with the latter showing superior cumulative survival rates ( χ2=4.53, P=0.033). The median recurrence-free survival (RFS) was 27 months for the percutaneous group and 52 months for the laparoscopic group. The 1-, 3-, and 5-year RFS postoperatively were 67.4%, 41.1% and 32.8% for the percutaneous group, and 81.5%, 58.1%, and 46.7% for the laparoscopic group, respectively, with the latter showing superior RFS, and the difference was statistically significant ( χ2=7.20, P=0.007). Multivariate analysis indicated that percutaneous microwave ablation was associated with an increased risk of death ( HR=2.475, 95% CI: 1.423-4.305, P=0.001) and recurrence ( HR=1.996, 95% CI: 1.255-3.176, P=0.004). Conclusion:Laparoscopic approach was superior to percutaneous microwave ablation in patients with HCC of BCLC stages 0 to A, and percutaneous microwave ablation could be a risk factor for poor prognosis in these patients.

The construction of a medication safety culture is important for medication safety management and rational drug use.The construction of medication safety culture standards is formulated based on relevant national policies and regulations,accreditation standards for hospitals,expert opinions,the current situation,and the development trend of the healthcare industry.With scientificity,general applicability,instructive guidance,and practicality,they standardized basic requirements,management processes,and improvement of the construction of medication safety culture.To facilitate understanding and the implementation of the standards,we describe the process of standards formulation and explain the key points of the standards.

Objective:To establish an HPLC-MS/MS method for the determination of related impurities in traz-odone hydrochloride API.Methods:The impurities were separated on an Agilent ZORBAX Eclipse Plus C18column(2.1 mm x 100 mm,1.8 μm)using a gradient elution of 0.1％formic acid solution and acetonitrile at a flow rate of 0.2 mL·min-1 at column temperature of 30 ℃,and determined by electrospray ionization source(ESI)com-bined with multiple reaction detection(MRM)in the positive ion mode.Results:The related impurities(triazol-opyridone,trazodone N-oxide,dechlorinated trazodone,4-ethyltrazodone,and trazodone isobutyl ether analogue)in trazodone hydrochloride API were determined.The linear relationship of five impurities was good in correspond-ing concentration ranges with correlation coefficients(r)of more than 0.999 5.The average recoveries varied be-tween 91.9％and 99.4％with RSD ≤3.9％.Trazodone N-oxide and dechlorinated trazodone were detected in all three batches,and extremely trace amounts of 4-ethyltrazodone were detected in two batches.Conclusion:The es-tablished method can determine the content of five related impurities in trazodone hydrochloride API,and can more effectively evaluate and control the quality of trazodone hydrochloride API.