[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.

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.

[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.

[Clinical application of combined infratemporal fossa approaches for internal carotid artery in petrous bone reconstruction for large lateral skull base tumors].

Objective: By summarizing the technical points and therapeutic outcomes of combing infratemporal fossa approach (IFA) and internal carotid artery (ICA) reconstruction for the colossal skull base tumor invading ICA in petrous bone, the clinical application value was discussed. Methods: Five patients (2 males, 3 females,aging from 27 to 55 years old) who received surgeries between July 2015 and May 2017 for lateral skull base pathology involved petrous ICA using technique combined IFA and pre-reconstruction, were reviewed. Results: Among the five patients, three were paraganglioma of head and neck, one was carotid aneurysms, and one was recurrent adenoid cystic carcinoma (ACC). The median tumor size in the largest cross-section was 60 mm × 51 mm (range, 28 mm × 22 mm-72 mm × 58 mm). Complete excision was achieved with IFA and ICA reconstruction. The median blood loss volume was 1 000 ml (range, 600-2 500 ml). Four cases showed no new long-term neurologic sequelae, while one showed hemiplegia due to graft vessel occlusion. Except for the one with ACC having facial nerve cut, others achieved good facial nerve function of HB grade Ⅰ to Ⅱ during 3 to 12 months, follow-up. No tumor recurrence was observed over the median duration of follow-up for above 36 months (range, 36-58 months). Conclusion: For lesions involved superior part of ICA, which is unable to separate from ICA, IFA and ICA reconstruction can achieve complete excision.

[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.

[Epidemiological characteristics of COVID-19 in Gansu province].

Objective: To understand the epidemiological characteristics of COVID-19 cases in different epidemic stages in Gansu province. Methods: Epidemiological investigation was conducted to collect the information of confirmed COVID-19 cases, including demographic, epidemiological and clinical information. Results: As of 25 February 2020, a total of 91 confirmed COVID-19 cases had been reported in Gansu. The epidemic of COVID-19 in Gansu can be divided as three different stages, i.e. imported case stage, imported-case plus indigenous case stage, and indigenous case stage. A total of 63 cases were clustered cases (69.23%), 3 cases were medical staff infected with non-occupational exposure. The initial symptoms included fever (54.95%, 50/91), cough (52.75%, 48/91), or fatigue (28.57%, 26/91), the proportion of each symptom showed a decreasing trend along with the three epidemic stages, but only the differences in proportions of fever (trend χ2=2.20, P<0.05) and fatigue (trend χ2=3.18, P<0.05) among the three epidemic stages were statistically significant. The cases with critical severe symptoms accounted for 42.85% (6/14), 23.73% (14/59) and 16.67% (3/18), respectively, in three epidemic stages, showed a decreasing trend (H=6.45, P<0.05). Also, the incubation period prolonged along with the epidemic stage (F=51.65, P<0.01), but the intervals between disease onset and hospital visit (F=5.32, P<0.01), disease onset and diagnosis (F=5.25, P<0.01) became shorter along with the epidemic stage. Additionally, the basic reproduction number (R0) had decreased from 2.61 in imported case stage to 0.66 in indigenous case stage. Conclusions: The COVID-19 epidemic in Gansu was caused by the imported cases, and about 2/3 cases were clustered ones. No medical worker was observed to be infected by occupational exposure. With the progression of COVID-19 epidemic in Gansu, the change in initial symptom and incubation period suggests, the early screening cannot only depend on body temperature monitoring.

[Epidemiological and spatial-temporal distribution of several natural focus diseases in Gansu province, 2014-2018].

Objective: To analyze the epidemiological and spatial-temporal distribution of Brucellosis, epidemic encephalitis B and hemorrhagic fever with renal syndrome (HFRS) in Gansu province during 2014-2018 so as to provide evidence for the prevention and control of those diseases. Methods: A database was established in Gansu province from 2014 to 2018, using the geographical information system. A spatial distribution map was drawn, with trend analysis and space-time clustering used to study the 3-dimention of the diseases, by using both ArcGIS 10.5 and SaTScan 9.6 softwares. Results: Results from the trend surface analysis showed that the incidence of Brucellosis decreased gradually from north to south parts while the U type curve could reflect the distribution from the east to the west areas. Incidence of epidemic encephalitis B decreased significantly from south to north areas in the province, with incidence higher in the eastern than in the mid-west region. Difference on the incidence of HFRS was not significantly visible in the eastern and western regions, while the incidence was slightly higher in the southern than the northern parts of the province. Spatial and space-time clustering did exist among the 3 diseases in Gansu from 2014 to 2018. The areas with clusters of Brucellosis appeared in the eastern parts during 2014-2015, including 19 counties. The areas with secondary clusters of Brucellosis were seen in the Hexi district, including 4 counties, during 2017-2018. The areas with high incidence of epidemic encephalitis B were clustered in the middle and southeast areas, including 32 counties, during 2017-2018. Areas with most clusters of HFRS appeared in Min county of Dingxi city in 2018, with the areas of secondary clusters in 8 counties of the eastern areas in 2018. Conclusions: The overall incidence rates of the 3 natural focus diseases were in a upward trend and showing obvious characteristics on spatial clustering. According to the distributive characteristics, effective measures should be developed accordingly.

[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.

[The application of three-dimensional printing technique combined with three-dimensional reconstruction in mandibular fracture].

Objective:To explore the value and significance of the combination of 3D printing and spiral CT three-dimensional reconstruction in the diagnosis and treatment of common mandibular fractures. Method:Forty patients with mandibular fracture were collected. They were randomly divided into traditional operation group and 3D printing combined with three-dimensional reconstruction operation group. The differences between the two groups were compared according to the operation time and the recovery of fracture. Result:The operation time and trauma of 3D printing combined with three-dimensional reconstruction group were significantly better than those of traditional operation group, and the former was better than the latter （P<0.05）. Conclusion: 3D printing combined with three-dimensional reconstruction operation method realized the concept of individualized, precise and minimally invasive comprehensive treatment, which is worthy of clinical promotion.

Retigabine protects the blood-brain barrier by regulating tight junctions between cerebral vascular endothelial cells in cerebral ischemia-reperfusion rats.

OBJECTIVE: To investigate the effect of retigabine on the blood-brain barrier permeability in rats with cerebral ischemia-reperfusion and its mechanism. MATERIALS AND METHODS: A total of 90 Sprague-Dawley (SD) rats were selected to prepare a rat model of focal cerebral ischemia-reperfusion. The blood flow changes were detected using a laser Doppler flow meter, the percentage of the cerebral infarction volume was measured by means of the triphenyl tetrazolium chloride (TTC) staining, the effect of retigabine on the permeability of the blood-brain barrier after cerebral ischemia-reperfusion was examined via Evans blue (EB) staining, and the state of tight junctions between endothelial cells was determined via the transmission electron microscopy (TEM) technique. Immunohistochemistry was used to detect the effects of retigabine on the distribution and expressions of tight junction-associated proteins in the cerebral ischemia-reperfusion blood-brain barrier. Western blotting was adopted to examine the changes in the expressions of related proteins in cerebral ischemia-reperfusion tissues. RESULTS: At 48 h and 96 h after cerebral ischemia-reperfusion, retigabine notably reduced the cerebral infarction volume of rats, and the tight junctions between microvascular endothelial cells in the ischemic area opened up, the permeability of the blood-brain barrier was remarkably increased, and the permeability of the blood-brain barrier was significantly reduced under the action of retigabine. The expressions of claudin-5, occludin, and ZO-1 in the blood-brain barrier of the ischemic brain tissue significantly declined, and retigabine notably increased the expressions of three proteins and their distributions along the microvessels. At 3 h, 24 h, 48 h, and 96 h after cerebral ischemia-reperfusion, the expressions of the MMP-2 protein and MMP-9 protein in the ischemic brain tissue were evidently increased, which were inhibited by retigabine. Moreover, the expressions of the PKCδ protein in the ischemic brain tissue were markedly increased, which were significantly inhibited by retigabine. CONCLUSIONS: The regulatory roles of retigabine in the distribution and expressions of claudin-5, occludin, and ZO-1 may be associated with the inhibition of the expressions of the MMP-2, MMP-9, and PKCδ proteins.

[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.

[Study on early warning threshold values for 7 common communicable diseases in Gansu province, 2016].

Objective: To optimize the warning threshold values of common communicable diseases in Gansu province, and improve the early warning effect. Method: An early warning model was set up for influenza, scarlet fever, other infectious diarrheal diseases, dysentery, typhoid and paratyphoid, viral hepatitis type E and hand foot and mouth disease (HFMD) respectively in Gansu by using the moving percentile method and cumulative sum method. By calculating the sensitivity, specificity, predictive value of positive test, predictive value of negative test, Youden' index and receiver-operating characteristic curve, the optimum early warning threshold values for communicable diseases in Gansu were selected. Results: The optimum early warning boundary values of influenza, scarlet fever, other infectious diarrheal diseases, dysentery, typhoid and paratyphoid, and viral hepatitis type E were P(90), P(80), P(95), P(90), P(80) and P(90) respectively. The optimum early warning parameters of HFMD were k=1.2, H=5σ. Under the optimum early warning boundary values/parameters, the early warning sensitivities of influenza, scarlet fever, other infectious diarrheal diseases, dysentery, typhoid and paratyphoid, viral hepatitis type E and HFMD were 86.67%, 100.00%, 91.67%, 100.00%, 100.00%, 100.00% and 100.00%, the specificities were 86.49%, 62.22%, 75.00%, 100.00%, 97.92%, 89.13% and 74.47%. The predictive values of positive test were 72.22%, 29.17%, 52.38%, 100.00%, 80.00%, 54.55% and 29.41%, and the predictive values of negative test were 94.12%, 100.00%, 96.77%, 100.00%, 100.00%, 100.00% and 100.00%, and the Youden' indexes were 0.73, 0.62, 0.67, 1.00, 0.98,0.89 and 0.74. Receiver-operating characteristic curve showed that the values/parameters of this warning boundary were the points closest to the upper left of the coordinate diagram. Conclusion: The early warning thresholds of influenza, other infectious diarrheal diseases, dysentery and hepatitis E in Gansu may be raised appropriately and the early warning parameters of HFMD need to be adjusted to improve the effectiveness of early warning.

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.

[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.