[Efficacy and safety of daratumumab in patients with relapsed/refractory multiple myeloma].

Objective: To investigate the efficacy and safety of daratumumab in relapsed/refractory multiple myeloma (RRMM) patients. Methods: Fifty-two RRMM patients treated with daratumumab from September 2019 to November 2021 in West China Hospital were retrospectively enrolled, including 31 males and 21 females. The mean age of these patients at the first diagnosis of multiple myeloma was (58±10) years. According to the dosage of daratumumab, patients were divided into low dosage group (n=10) and high dosage group (n=42). Overall response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse event rates were investigated. Univariate and multivariate analysis of potential factors were conducted. Results: Of the 52 patients, 8 received daratumumab monotherapy, 27 received daratumumab plus immuno-modulatory drug (IMiD) treatment, 4 received daratumumab plus proteosome inhibitor (PI) treatment, and 11 received daratumumab plus dexamethasone treatment. The diagnosis age of high dosage group patients was (57±9) years, which was significantly younger than that of low dosage group [(66±10) years] (P=0.009). The baseline creatinine level of high dosage group patients [M (Q1, Q3)] was 91 (68, 196) µmol/L, which was significantly higher than that of low dosage group [66 (51, 76) µmol/L] (P=0.021). There was no significant difference in other baseline clinical characteristics, previous treatment regimens, previous lines of treatment, and regimen and cycles of daratumumab between the high dosage group and low dosage group (all P>0.05). The ORR for the 52 patients was 71.2% (37/52). The ORR for daratumumab plus IMiD group was 81.5% (22/27), which was significantly higher than that in monotherapy or dexamethasone group [ORR: 52.6% (10/19), P=0.036). With a median follow-up [M (Q1, Q3)] of 7 (5, 26) months, the median PFS for overall cohort was 17 (95%CI: 9.6-24.4) months. The median PFS for daratumumab plus IMiD group was 26 (95%CI: 6.0-46.0) months, which was significantly better than that in monotherapy or dexamethasone group [12 (95%CI: 3.5-20.5) months] (HR=0.231, 95%CI: 0.075-0.715, P=0.011). Higher diagnosis age was the risk factor of progression (HR=1.085, 95%CI: 1.016-1.158, P=0.014), while more cycles of daratumumab treatment was the protective factor of progression (HR=0.669, 95%CI: 0.495-0.904, P=0.009). There was no significant influence of daratumumab dosage on progression (high dosage vs low dosage, HR=1.016, 95%CI: 0.221-4.668, P=0.984). The median OS for overall cohort was 26 (95%CI: 13.1-38.9) months. Higher serum calcium was the independent risk factor of death (HR=12.190, 95%CI: 1.170-127.048, P=0.037). There was no significant influence of daratumumab dosage on death (high dosage vs low dosage, HR=0.818, 95%CI: 0.171-3.917, P=0.802). Adverse events included infections (43.2%, 16/37), infusion-associated reactions (29.7%, 11/37), and thrombocytopenia (27.0%, 10/37). Conclusions: Daratumumab is effective to treat RRMM. The dosage of daratumumab has no significant influence on prognosis when used in combined treatment. The incidence of adverse events is relatively low, with a favorable safety profile.

[Progress and prospect of the treatment of lower extremity arteriosclerosis obliterans].

In the past five years,both advancements and new problems were seen in the treatment of lower extremity arteriosclerosis obliterans.The Global Vascular Guidelines published in 2019 have given us comprehensive suggestions for the diagnosis and treatment of critical limb threatening ischemia(CLTI),but the grading and treatment suggestions for CLTI should be generalized.As to endovascular treatment,drug coated balloons have been found to be effective for limb salvage and graft patency in femoropopliteal and infra-popliteal artery occlusive diseases.As to surgical revascularization,persistent education and surveillance are necessary to maintain the practical quality of this fundamental technique.Inframalleolar bypass could achieve good graft patency and limb salvage rate for in CLTI patients.Regional anesthesia has been found to have lower risk than general anesthesia for lower extremity surgical revascularization.Percutaneous deep vein arterialization might be helpful for limb salvage in patients with non-option CLTI.A brief review about the treatment of lower extremity arteriosclerosis obliterans is performed based on latest literatures and institutional experience.Understanding the present situation and development trend is important for peripheral vascular practitioners.

[Transmission routes of 2019-novel coronavirus (2019-nCoV)].

Since the outbreak of COVID-19 in Wuhan, China, at the end of 2019, it has demonstrated China's ability to identify unknown pathogens. At present, reports showed that the main transmission routes are respiratory droplets and indirect contact, other vertical transmission routes have yet to be confirmed. This review discusses the possible transmission routes of 2019-novel coronavirus (2019-nCoV), based on currently research, the main transmission routes are respiratory droplets and indirect contact, fecal-oral might bepossible, while aerosol, tear (conjunctival) and mother-to-fetus still have yet to be confirmed, providing a reference basis for 2019-nCoV prevention and control and public protection.

[Radical vulvectomy and inguinal lymphadenectomy using a single incision for the treatment of vulvar malignancy].

Objective: To describe a novel procedure of radical vulvectomy and inguinal lymphadenectomy using a single incision (RVIL-SI) for the treatment of vulvar malignancy. Methods: In March, 2019, two cases affected with vulvar cancer (the first one is stage ⅢA squamous cell carcinoma and the second one is stage ⅠB with malignant melanoma) underwent this novel procedure, which was characterized by the combination of radical vulvectomy and bilateral inguinal lymphadenectomy without making additional incisions in groin areas. The boundaries of femoral triangle could be exposed perfectly using the initial incision of radical vulvectomy and the combined superficial and deep groin lymph node dissection were done subcutaneously from medial to lateral. Preoperative data and short term follow-up outcomes were collected. Results: The RVIL-SI was successfully conducted in two patients without any incisions of groin. The great saphenous veins were all spared. The operative time, average blood loss and median total regional lymph nodes of two cases were close. No major intraoperative complications occurred. Micrometastasis in one right superficial inguinal node was found in the first case with ipsilateral huge cancer lesion. No drain tube was left in inguinal areas intraoperatively. On postoperative day 3, the second case suffered mild lymphocele of right groin, which was resolved via repeated percutaneous needle puncture followed by elastic compression. Postoperative hospital stay of two cases were 10 and 11 days, respectively. With no skin complication at the time of writing this report. Conclusion: Our preliminary experience with the RVIL-SI has confirmed the reproducibility and minimal invasive therapeutic potential in the treatment for patients with vulvar cancer. But this novel procedure is in its infancy stage. Although short-term results are encouraging, a larger series with longer follow-up are required to fully evaluate the therapeutic efficacy.

Dietary butylated hydroxytoluene improves lipid metabolism, antioxidant and anti-apoptotic response of largemouth bass (Micropterus salmoides).

A 10-week growth trail was conducted to investigate the efficacy and tolerance of dietary butylated hydroxytoluene (BHT) by evaluating inflammation, apoptosis and hepatic disease related to oxidative stress in largemouth bass (Micropterus salmoides). Four experimental diets were prepared with BHT supplement levels of 0 (B0), 150 (B150), 300 (B300) and 1500 (B1500) mg/kg, in which B150 was at the maximum recommended level established by European Union Regulation, and the B300 and B1500 levels were 2 and 10-fold of B150, respectively. Each diet was fed to 6 replicates with 30 largemouth bass (initial body weight, IBW = 6.20 ± 0.01 g) in each tank. The BHT inclusion level did not affect the specific growth rate, but fish in the B150 group showed the lowest feed conversion rate (P < 0.05). BHT inclusion significantly decreased the levels of plasma TC, TG, LDL, ALT and AKP, and increased the (HDL-C)/TC ratio (P < 0.05). Plasma MDA was significantly decreased in the B150 group and GSH-Px was extremely enhanced in each BHT inclusion group (P < 0.05). Hepatic T-AOC was significantly enhanced and O2- was significantly decreased in each BHT inclusion group compared to the B0 group (P < 0.05), as well as hepatic MDA was significantly decreased in B1500 group (P < 0.05). Dietary BHT inclusion down-regulated the hepatic mRNA levels of inflammation, apoptosis and fibrosis related genes, including TNFα, TGF-ß1, α-SMA, IL8, IL11ß and caspase-9. Moreover, BHT could improve hepatic lipid metabolism via up-regulating the mRNA levels of APOA1, CYP7A1, CYP8B1, and down-regulating the mRNA levels of PPAR-γ and APOB. Histological examination of the liver morphology with H&E and Sirius Red staining showed that BHT inclusion decreased necrotic degenerative changes and collagen deposition in largemouth bass. An immunofluorescence examination revealed significantly decreased cleaved caspase-3 signals in the BHT groups. In conclusion, the results demonstrated that ROS induces hepatic cell apoptosis and fibrosis via the intrinsic pathway of apoptosis by activating caspase-9 in the mitochondria and then initiates apoptosis by activating caspase-3. Consuming 2.32-23.80 mg/kg·bw/d (150-1500 mg/kg in diet) of BHT effectively improved the plasma and hepatic lipid metabolism, antioxidant response as well as reduced ROS production, protecting hepatic cells from injury. It is implied that even a 10-fold increase of the maximum level of BHT (150 mg/kg) is safe for the largemouth bass.

[Surgical technique and outcomes of uteri retrieval from brain-dead multi-organ donors: a preclinical research of human uterine transplantation].

Objective: To evaluate the surgical technique and outcomes of uteri retrieval from brain-dead multi-organ donors.This study is a preclinical research of human living uterine transplantation. Methods: From May, 2015 to May, 2017, four uteri retrieval procedures, characterized with radical hysterectomy and uterine vascular pedicles dissection, were performed in multi-organ brain-dead donors.The uterus was the third authorized organ after the kidney and liver retrieval procedures in the first two cases.The uterine pedicles included the uterus, ovaries, fallopian tubes, the upper one-third of the vagina and internal iliac vessels or external iliac vessels.The perfusion of the uterus was conducted after the retrieval for evaluating the availability, followed by histopathological examination of the uterine issues per 30 minutes. Results: Since the uterine vein was quite difficult to identify and dissect in the first two case, which result in the rupture of triple uterine veins.Therefore, the uterine venous vessels including uterine vein connected with internal iliac vein and internal iliac arteries were selected as vascular grafts and dissected successfully in the last two cases, which could be perfused with the mixture of 4 ℃ heparinized physiological saline through each artery because of shortening the surgical time and arranging the uterine procurement as the first authorized organ procedure.Mean (SD) operative time was 152.5±39.0 min (115-215 min, n=4). Conclusion: Our preliminary experience indicated that the uterus could be retrieved from the brain-dead multi-organ donors and transplanted to the recipient.The attempt of skeletonizing the uterine veins should be replaced by dissection of internal iliac vein.

[Comparative analysis of open surgical repair and endovascular aortic repair in the treatment of abdominal aortic aneurysm implicated visceral arteries].

Objective: To evaluate the value of open surgery repair and endovascular aortic repair in the treatment of abdominal aortic aneurysm which implicate visceral arteries. Methods: From January 2012 to October 2016, 26 patients were reviewed. According to the treatment, they were divided into open surgery group (n=7) and endovascular repair group(n=19). Then, the characteristics and relative data of follow-up of the two groups were analysis. Results: In open surgery group, there were 7 patients. All of them were men, median age 58(41-62) years and 1 patient were older than 75 years. And in endovascular repair group, there were 19 patients(14 men) of median age 72(66-76) years, 8 patients were older than 75 years. Patients in endovascular repair group were significantly older than who were in open surgery group (Z=-13.06, P<0.05). Complications of open surgery group and endovascular repair group were 57.14% and 15.79% respectively. There was no statistically significant difference (χ(2)=3.13, P>0.05). During follow-up, the diameters of aneurysm which planted stents were smaller than before. Conclusions: In the treatment of abdominal aortic aneurysm implicated visceral arteries, open surgery is mainly suitable for the patients with low-risk. But the rate of complications was high. By contrast, endovascular aortic repair with small trauma and high safety, has becoming the first choice.

[The analysis of risk factors and outcomes of carotid endarterectomy for carotid artery stenosis].

Objective: To evaluate the early and long-term outcomes of carotid endarterectomy for carotid artery stenosis and analyse the risk factors for the outcomes. Methods: A retrospective review of 369 patients underwent carotid endarterectomy(CEA) in Peking Union Medical College Hospital from Oct 2006 to Nov 2012 was conducted. Clinical data including general conditions, perioperative and follow-up outcomes were collected. Results: Three hundred sixty-nine patients underwent 407 CEAs. The long-term follow-up rate (≥30 d) was 89.9% and follow-up period was 11.8-48.3 months. Among 407 CEAs, patients with symptomatic carotid artery stenosis, carotid stenosis over 70% and contralateral severe carotid stenosis occupied 78.0%(317/407), 98.4%(400/407) and 12.04%(49/407) respectively. Total early complications (<30 d) of stroke, cardiac events and death was 3.93% (16/407). Univariate analysis showed no risk factor had significant effect on early complications (P>0.05). Total long-term complications of stroke, cardiac events and death was 8.7% (32/366). Univariate analysis showed that total long-term complication rate of smoking group was higher than non-smoking group (12.1% vs 5.1%, P<0.05), contralateral carotid artery stenosis group was higher than opposite one (28.6% vs 8.0%, P<0.05). Multivariate Logistic regression showed the HR of long-term complications rate in patients aged over 65 years, smoking history, myocardial infarction and contralateral carotid stenosis were 2.59, 2.66, 2.48 and 6.06, respectively. Conclusions: CEA is safe method for the treatment of carotid stenosis. To CEA, age over 65 years, smoking history, myocardial infarction and contralateral carotid stenosis are risk factors for long-term adverse outcomes.

Karyotype studies on Lycoris radiata populations from China.

Lycoris radiata is an important medicinal and ornamental plant of China. In the present study, somatic chromosome counts and karyotype analyses, which are important aspects of plant phylogeny and evolution, were performed in 466 individuals from 25 L. radiata populations by root tip squash method. Chromosome counts revealed that 10 populations were diploid (2n = 2x = 22) and 15 were triploid (2n = 3x = 33). Except for one diploid population containing some triploid plants, the remaining 24 populations showed a single cytotype. Karyotype analysis showed that the karyotypes of L. radiata varied in different populations and even within the same population. However, based on the Stebbins' system, the karyotype of all the populations could be classified in 4A classes. The cluster analysis and ordination methods demonstrated that the L. radiata populations grouped in two major clusters. Previous research has shown that the triploid strain of L. radiata is a genetically identical species. However, the cluster analysis revealed that the triploid strains clustered in two groups instead of one, which indicates that these strains may not be identical species, genetically. This study is expected to improve the understanding of the genetic diversity in L. radiata and provide a basis for future studies on species differentiation, speciation, and taxonomy.

[Risk factors for long-term result of endovascular treatment for auto-immune disease related abdominal aorta pseudo-aneurysm].

Objective: To summarize results of endovascular treatment for auto-immune disease related abdominal aorta pseudo-aneurysm(AIPA), and to analysis clinical predictors of long term major adverse clinical events(MACE). Methods: Retrospectively collected endovascular treatment for AIPA cases in Peking Union Medical College Hospital within 2000 to 2015. Twenty-nine cases with AIPA treated by endovascular therapy were enrolled in this study. Twenty five cases were male, range from 23 to 67 years old, mean age was (39.3±11.4) years old.Demographic characters, locations of aneurysms, type to auto-immune disease, immuno medical therapy, operation strategy and long term follow-up data were reported. Statistical analysis was made to verify clinical predictors of long-term MACE. Results: Among the 29 cases, 22 cases with bechet's disease, 4 cases with Takayasu's arteritis, 2 cases with systemic lupus erythematosus, 1 cases with polyarteritis nodosa. Eight cases had ruptured or pending ruptured pesudo-aneurysms, the rest 21 cases had dull pain or no overt symptome. Twenty-four cases had infra-renal artery aneurysms, two were para-and supra-renal artery, two were supra-celiac artery, and the rest one had multiple aneurysms involved thoracic and abdominal aorta.All the cases received regular immune medical therapy except the three emergency cases. All the operations were under general anaesthesia. Nineteen cases underwent classical Endovascular aortic aneurysm repair (EVAR), 5 cases underwent fenestration EVAR, the rest 5 cases underwent hybrid procedure. All the 29 operations were successful, without conversion to open surgery. Major peri-operation complication included 3 incision infection, 3 pulmonary infection. No death occurred. All the cases received regular follow-up from 1 to 120 months. There were five recurrence of pseudo-aneurysm, 1 case suffered from iliac limb occlusion. 5 cases received re-intervention procedure. No occlusion of revascularizal visceral artery was found during follow-up. There were 3 deaths during follow-up, with 1 aneurysm related death, the rest died due to other reasons. Single factors logical regressions analysis showed discontinuing immune medicine therapy and age no less than 40 years significantly related long-term MACE(P<0.05). Meanwhile, type of original auto-immune disease, none classical EVAR were not significant related to MACE. Conclusions: Endovascular therapy is safe and effective for AIPA. Regular peri-operation and long-term immunotherapy is key to success.

[Prevalence of asymptomatic carotid artery stenosis in patients with arteriosclerosis obliterans of lower extremities and risk factor analysis].

OBJECTIVE: To evaluate the prevalence of asymptomatic carotid artery stenosis in patients with arteriosclerosis obliterans of lower extremities, and evaluate its effect on the treatment strategies for lower extremity artery lesions. METHODS: Totally 348 patients with arteriosclerosis obliterans of lower extremities who had no cerebrovascular symptoms or events in the past were enrolled from September 2012 to September 2014 in the Department of Vascular Surgery, Peking Union Medical College Hospital. Preoperative color doppler ultrasonography results of carotid arteries and demographic characteristics were retrospectively collected. The peak systolic velocity and the presence of plaque on gray-scale in the internal carotid arteries were used for diagnosing and grading internal carotid artery stenosis. A stenosis ≥50% was diagnosed as carotid artery stenosis. Binary logistic regression analysis was used to evaluate related risk factors. Treatment strategies for the artery lesions of lower extremities were compared between those with and without asymptomatic carotid artery stenosis. RESULTS: Seventy-seven (22.1%) patients were found to have carotid artery stenosis. Forty-four (12.6%) patients were found to have a stenosis ≥70% or occlusion. Smoking (OR=2.122, 95% CI: 1.143-3.940), coronary artery disease (OR=1.939, 95% CI: 1.058-3.552) and hypertension (OR=1.882, 95% CI: 1.025-3.457) were found to be related risk factors. In patients combined with asymptomatic carotid stenosis, open surgery with general anesthesia was less frequently used than those without asymptomatic carotid stenosis (6.5% vs 18.1%, χ(2)=6.142, P=0.013). CONCLUSIONS: Prevalence of asymptomatic carotid artery stenosis is high in patients with arteriosclerosis obliterans of lower extremities. Smoking, coronary artery disease and hypertension are related risk factors.

Modified radical vaginal hysterectomy for cervical cancer treatment.

OBJECTIVES: The aim of this study was to modify vaginal radical hysterectomy (VRH), design a series of surgical instruments specialised for this procedure, and to study the feasibility, morbidity, and outcome of cervical cancer patients treated with modified laparoscopic-assisted radical vaginal hysterectomy (LARVH). MATERIALS AND METHODS: A total of 86 patients with early-stage cervical cancer (IB 1-IAl) underwent modified VRH and laparoscopic pelvic lymphadenectomy and para-aortic lymphadenectomy. Special instruments and modified procedures were used in VRH. Data were collected on operating time, blood loss, ureter separation time, nodal count, hospital stay, and complication recurrence and survival rates. RESULTS: All patients successfully completed LARVH. Median operating time was 238 minutes, mean blood loss was 283 ml, median time for ureter separation was 18.5 minutes, median time to post-operative exhaustion was 23 hours, urine recovery was 10.3 days, and median hospital stay was 9.2 days. On average, 23.2 lymph nodes were harvested. Except for one case of left internal iliac vein with intraoperative and postoperative complications, no other major complications occurred, particularly no bladder and ureter injury. Surgical margins were negative in all cases. After median follow-up of 46 months, recurrence rate and overall survival for 84 patients were 3.57% and 97.62%, respectively. DISCUSSION: Modified VRH with laparoscopic pelvic lymphadenectomy is an oncologically valid alternative for early stage cervical cancer treatment with minimal intraoperative and postoperative complications. The modification of this procedure and special instruments can enhance the feasibility and the safety of treatment.

Molecular cloning and functional characterization of a mouse ccl6 analog gene in the rat.

Suppression subtractive hybridization was used to analyze differential expression of genes in rat peritoneal macrophages after granulocyte macrophage colony-stimulating factor treatment. We identified and cloned the mouse C10 analog gene in the rat, and named it as ccl6. The full-length cDNA of rat ccl6 was 467 bp, which contains a single-open reading frame and encodes 116 amino acid residues. Compared with other C-C chemokines, the rat ccl6 gene had an unusual four-exon genome structure instead of the typical three exons, it had the highest homology with murine ccl6. The rat ccl6 gene was localized on chromosome 10, where most of the C-C chemokine superfamily members are located. The recombinant rat C-C chemokine ligand 6 (CCL6) protein was expressed by the pGEX4T-1 plasmid in Escherichia coli BL21. The purified recombinant protein had bioactivity similar to that of mouse CCL6, which is a chemoattractant for macrophages and lymphocytes, but not for neutrophils.

Effects of different specimen pretreatment methods on the measurement of thyrotropin stimulating hormone in serum.

OBJECTIVE: The pre-analysis processing method of serum samples plays a very important role in the assurance of the quality of the entire test and the accuracy of the results. This study illustrates the importance of pretreatment methods of serum samples for the test results by comparing the effects of different pretreatment methods on the measurement of thyroid stimulating hormone (TSH) concentration in serum. SUBJECTS AND METHODS: In this study, the concentrations of TSH of 37 patients' serum, which were treated in six different ways including the reverse mixing times after blood collection, clotting time and conditions, centrifugal speed and time, were detected on Automatic Chemiluminescence Immunoassay Analyzer, and a comparative analysis of the different results was performed. RESULTS: For serum samples containing coagulants, the test results were significantly affected if the samples were not reversed mixing after collection. The abnormal results would be obtained with insufficient coagulation time, low reaction temperature, low centrifuge speed and insufficient centrifugation time. CONCLUSIONS: The pre-analysis processing of serum samples is the beginning of the entire inspection process. The quality of the entire inspection will not be guaranteed if the pre-analysis processing method is irregular. Therefore, clinical laboratories should pay more attention to the pretreatment process of samples to ensure the quality of the entire inspection process.

New evaluation of the thermodynamics stability for bcc-Fe.

The thermodynamic properties for bcc-Fe were predicted by combination of the first-principles calculations, the quasiharmonic approximation, the CALPHAD method and the Weiss molecular field theory. The hybrid method considers the effects of the lattice vibration, electron, intrinsic magnetism and external magnetic fields on the thermodynamic properties at finite temperature. Combined with experimental data, the calculated heat capacity without external magnetic fields was used to verify the validity of the hybrid method. Close to the Fermi level the high electronic density of states leads to a significant electronic contribution to free energy. Near the Curie temperature lattice vibrations dominant the Gibbs free energy. The order of the other three excitation contributions to Gibbs free energy from high to low is: intrinsic magnetism > electron > external magnetic fields. The investigation suggests that all the excitation contributions to Gibbs free energy are not negligible which provides a correct direction for tuning the thermodynamic properties for Fe-based alloy.