[Objective]To evaluate the efficacy and safety of total oral regimens containing pomalidomide as a second-line treatment strategy in multiple myeloma.[Methods]A total of 22 patients with multiple myeloma placed on total oral regimens containing pomalidomide as a second-line therapy from March 2020 to December 2023 were retrospectively analyzed to evaluate the treatment response,survival and safety.[Results]The median age of the 22 patients was 71.5 years old. The total oral treatment regimens containing pomalidomide included IPD (7 cases),PCD (11 cases),XPD (2 cases),and PD (2 cases). The median number of treatment cycles was 14. Among the 13 patients with prior lenalidomide exposure,ORR was 53.85％,of which 23.08％ was ≥VGPR. In 9 patients without prior lenalidomide exposure,the ORR was 77.78％,and of which 55.56％ was ≥VGPR. There was no significant difference in ORR between these two groups (P=0.38). In 12 patients with high genetic risk,the ORR was 50％,and ≥VGPR was 16.67％. The median follow-up time was 10.6 months. Disease progressed in 10 patients and death occurred in 6 patients of them. The median progression free survival (PFS) was not reached (not reached and 10.6 months in non-lenalidomide-exposure patients or lenalidomide-exposure patients,respectively).The high grade treatment-related adverse events (AEs)(≥3 ) were reported in 18.18％ patients,including granulocytopenia,thrombocytopenia,and pulmonary infection. There was no treatment-related death.[Conclusion]Total oral regimens containing pomalidomide as a second-line therapy is generally effective and safe for multiple myeloma patients.

Copper is a trace element essential for the maintenance of normal physiological functions in cardiovascular system,and its transport and metabolisms are regulated by various copper proteins such as copper-based enzymes,copper chaperones and copper transporters.The disturbance of copper level or abnormal expression of copper proteins are closely associated with the development of cardiovascular diseases such as atherosclerosis,hypertension,ischemic heart disease,myocardial hypertrophy and heart failure.Thus,intervention of copper ion signaling pathways is expected to be an effective measure for treating cardiovascular diseases.Some copper complexes,such as trientine,copper-aspirinate complex and copper(Ⅱ)diethyldithiocarbamate,have been found to play a role in the prevention and treatment of cardiovascular diseases and possess potential prospects.Exploring the role of copper in maintaining normal cardiovascular status and the potential application of copper complexes in the treatment of cardiovascular diseases may lay a foundation for finding new targets for prevention and treatment of various cardiovascular diseases,and provide new ideas for clinical treatment of cardiovascular diseases.

The current outpatient payment method based on fee-for-service induced serious demand, which increased the waste of medical insurance fund. The authors briefly introduced ambulatory patient groups(APG)with the same concept of diagnosis-related groups. According to the current situation of outpatient medical insurance payment and the degree of informatization in China, suggestions are put forward: launch a pilot project first and starting with chronic disease to promote reform; improve the quality of outpatient electronic medical records, and develop APG suitable for China; under the background of aging, cooperate with the total budget to ensure the security of medical insurance.

Objective: To evaluate the clinical effects of vitrectomy with or without fovea-sparing internal limiting membrane peeling on macular foveoschisis (MF) secondary to pathologic myopia. Methods: A non-randomized controlled study was adopted.Twenty-three patients (25 eyes) with refractive error ≥-8.00 DS and MF either combined with foveal retinal detachment or epi-macualr membrane or lamellar macular hole.The subjects were divided into non-internal limiting membrane peeling group (11 patients /11 eyes) who underwent triamcinolone (TA) assisted vitrectomy and fovea-sparing internal limiting membrane peeling group (12 patients/14 eyes) who underwent TA assisted vitrectomy with fovea-sparing internal limiting membrane peeling.The baseline data such as age, best corrected visual acuity (BCVA), refractive error, axial length were not significant difference between the two group.Main outcomes were BCVA, remission of MF defined by optical coherence tomographyc OCT as well as complications.This study followed the Declaration of Helsinki and this protocol was approved by Ethic Committee of Xiamen Eye Center of Xiamen University (NO.XMYKZX-2016-YWS-007). Results: All patients completed follow-up for more 6 months.BCVA (LogMAR) was 0.47±0.30 in non-internal limiting membrane peeling group and 0.40±0.33 in fovea-sparing internal limiting membrane peeling group, showing no significant difference between the two groups (t=0.66, P=0.52). Complete remission of MF was achieved in 22 eyes.The remission time in non-internal limiting membrane peeling group was 2.5 (1.8, 9.3) months, and 1.0 (1.0, 3.8) months in fovea-sparing internal limiting membrane peeling group, no statistical significance was obtained between the two groups (U=35.00, P=0.09). One eye had post-operative macular hole in non-internal limiting membrane peeling group, accounting for 9%, while in fovea-sparing internal limiting membrane peeling group, one eye had macular hole, accounting for 7%, and one eye had rhegmatogenous retinal detachment post-operatively, accounting for 7%. Conclusions MF can be resolved by vitrectomy while complete remission can achieved more quickly when combined with fovea-sparing internal limiting membrane peeling.

Objective: To observe the clinical efficacy of digital 3D heads-up display viewing system(3D viewing system) and intraoperative OCT (iOCT) in vitrectomy for myopic foveoschisis (MF). Methods: A retrospective, consecutive case series. From October 2018 to May 2019, Nineteen eyes of 19 consecutive patients with MF diagnosed in Xiamen Eye Center of Xiamen University who underwent vitrectomy were included in this study. There were 7 males and 12 females, with the mean age of 54.47±11.38 years. The average axial length was 30.40±2.30 mm, the mean logMAR BCVA was 0.56±0.31, the mean central foveal thickness (CFT) was 317.80±151.9.32 μm, the mean max retinal thickness (maxRT) was 556.7±143.7 μm. All the surgeries performed combined with 3D viewing system with iOCT. The standard 25G pars planar vitrectomy were performed with removing the posterior vitreous and indocyanine green (ICG) staining of internal limiting membrane (ILM) and air-fluid exchange. Thirteen of 19 eyes underwent fovea-sparing ILM peeling and the other 6 eyes not. The average follow-up was 4.2±1.4 months. All the patients were on regular follow-up to document the changes on BCVA, anatomical changes in macula, CFT and maxRT. Paired t test was used to compare BCVA, CFT and maxRT before and after surgery. Results: The fine images of macula were clearly shown on the 3D viewing system in all eyes. The electronic green filter enhanced the contrast sensitivity of ICG stained images. Clear images of macula were captured by iOCT in all eyes. The average surgical time was 35.5±8.2 min. On the last follow-up, 16 of 19 eyes with MF resolved. The mean CFT was 178.5±103.5 μm, the maxRT was 341.8±83.8.16 μm, and the mean logMAR BCVA was 0.35±0.22. The differences of CFT, maxRT and logMAR BCVA before and after surgery were statistically significant (t=4.181, 7.154, 5.129; P<0.001). Minimal invisible full thickness macular hole were detected in 2 eyes by iOCT and repaired with auto serum or ILM flap covering. There was no complication associated with the 3D viewing system. Conclusions 3D viewing system provides improved contrast and crystal clear macular image stain with ICG in pathological myopia. iOCT can detect the minimal invisible full thickness macular hole during surgery. Both may contribute to improved MF closure rate and BCVA.

Objective: To study the shift of oVEMP frequency tuning of unilateral Meniere′s disease, by analyzing oVEMP of air-conducted tone bursts in various frequencies. Methods: From May 2016 to October 2017, 33 patients with unilateral Meniere′s from Aerospace Center Hospital were tested for oVEMP in 500 Hz and 1 000 Hz air-conducted tone bursts respectively, and 20 healthy subjects(40 ears), matched for age and sex, were used as healthy control. The amplitudes of the N1-P1 wave and the frequency amplitude ratios of 500/1 000 Hz in affected ears, unaffected ears and normal ears were compared; and receiver operating characteristic curve was analyzed for frequency amplitude ratios of 500/1 000 Hz. Results: By the 500 Hz tone-burst stimulus, the provocation rates of the oVEMP were 84.9%(28/33), 93.9%(31/33) and 97.5%(39/40) in affected ears, contralateral ears and the ears of normal controls, respectively. By the stimulus of 1 000 Hz tone-burst, the provocation rates of the oVEMP were 81.8%(27/33), 87.9%(29/33) and 82.5% (33/40) in affected ears, contralateral ears and normal control ears, respectively. Amplitudes of N1-P1 waveforms in 500 Hz air-conducted tone bursts in affected ears were under normal control ears and contralateral ears. There was significant difference between affected ears and healthy control ears (P<0.05). Amplitudes of N1-P1 waveforms in contralateral ears were also significantly smaller than those in normal control ears (P<0.05). There were no significant differences in amplitudes of N1-P1 waveforms between affected ears, contralateral ears and normal control ears in 1 000 Hz tone bursts stimulus(P>0.05). Frequency amplitude ratios of 500/1 000 Hz in affected ears were significantly under contralateral and normal control ears (P<0.05). According to ROC, the frequency amplitude ratio critical value of frequency tuning was set as 1.17, the positive rate of frequency tuning shift in affected ears was 54.5%(18/33) and significantly higher than in contralateral ears(18.2%, 6/33, χ²=9.429, P=0.002) and normal control ears (7.5%, 3/40, χ²=19.530, P=0.000). In contrast, there was no significant difference in the incidence of frequency tuning shift between contralateral ears and normal ears(χ²=1.909, P=0.167). Conclusions Frequency tuning oVEMP with Meniere′s disease will be changed.Frequency tuning of oVEMP with Meniere′s disease shifts from low frequency region to high frequency region in comparison with healthy people. Frequency amplitude ratio is helpful for diagnosis of Meniere′s disease.

To investigate changes in the angiotensin converting enzyme 2 (ACE2) and angiotensin (1-7) [Ang (1-7)] and to explore the role of ACE2-Ang (1-7)-Mas receptor axis in hypertension with heart failure with preserved ejection fraction (HFPEF).
 Methods: A total of 70 patients with primary hypertension and preserved left ventricular ejection fraction (LVEF>50%) were recruited and patients were divided into a hypertension group (HBP) and a heart failure with preserved ejection fraction group (HFpEF) according to the diagnostic criteria of HFpEF. Thirty-five healthy participants were selected randomly as a control group. Enzyme linked immunosorbent assays (ELISA) method was used to detect concentration of Ang (1-7), ACE2, angiotensin II (Ang II), brain natriuretic peptide (BNP) in plasma. Male Sprague- Dawley (SD) rats was randomly divided into 2 groups: An HFpEF group (n=16) and a sham group (n=8). Rats (n=8) in the AAC group were given Ang (1-7) [0.5 mg/(kg.d), intraperitoneally] for 6 weeks, and the rest were given equal dose normal saline. Then all the rats were killed, and the hearts were taken out for hematoxylineosin (HE) staining. The protein expressions of angiotensin converting enzyme (ACE), ACE2, and Mas receptor were detected by Western blot.
 Results: The BNP and Ang II were significantly increased in the HBP group and the HFpEF group compared with the control group (P<0.01). There were not significantly different in levels of ACE2 and Ang (1-7) between the HBP group and control group (P>0.05), whereas those levels were significantly increased in the HFpEF group compared with the HBP group and control group (P<0.01). HE staining showed obvious hypertrophy of myocardial cell in the AAC group compared with the sham group. Hypertrophy of myocardial cell in the AAC+Ang (1-7) group was significantly higher than that in the AAC group. Expressions of ACE, ACE2, and Mas receptor proteins were significantly higher in the AAC group than those in the sham group (P<0.05), while the expressions of ACE2 and Mas receptor proteins in the AAC+Ang (1-7) group were significantly higher than those in the AAC group (P<0.05). There was no significant difference in the ACE protein expression between groups (P>0.05).
 Conclusion: ACE2 and Ang (1-7) are important predictive factors for the severity of heart failure and myocardial remodeling of HFpEF with hypertension; ACE2-Ang (1-7)-Mas receptor axis may play a protective role in preventing myocardial remodeling in HFpEF with hypertension.
Angiotensin I ; physiology ; Angiotensin II ; Animals ; Atrial Remodeling ; physiology ; Case-Control Studies ; Enzyme-Linked Immunosorbent Assay ; Heart Failure ; metabolism ; physiopathology ; Humans ; Hypertension ; metabolism ; physiopathology ; Male ; Peptide Fragments ; physiology ; Peptidyl-Dipeptidase A ; physiology ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Receptors, G-Protein-Coupled ; physiology ; Stroke Volume ; Ventricular Function, Left ; physiology ; Ventricular Remodeling ; physiology

Objective To investigate the gene mutations in benign familial infantile epilepsy(BFIE)in Chi-na. Methods Data of all BFIE probands and their family members were collected from Peking University First Hospital and other three hospitals between October 2006 and June 2017. Clinical phenotypes of affected members were analyzed. Genomic DNA was extracted from peripheral blood samples with standard protocol. Mutations in PRRT2 were screened using Sanger sequencing. For families that PRRT2 mutations were not detected by Sanger sequencing,candidate gene mutations were further screened by next - generation sequencing. Results A total of 71 families including 227 affected members were collected. Genetic testing led to the identification of gene mutations in 52 families (52 / 71,73. 2％). Forty - three families had PRRT2 mutations (43 / 71,60. 6％),including 40 families with frameshift mutations(hotspot mutations c. 649_650insC and c. 649delC were detected in 29 families and 6 families,respectively),one family with nonsense mutation,one family with a loss of a stop codon,and one family with a microdeletion of the gene. C. 560_561insT and c. 679C > T were novel PRRT2 mutations. Five families had SCN2A mutations. All SCN2A mutations were missense mutations(c. 668G > A,c. 752T > C,c. 1307T > C,c. 4835C > G,c. 1737C > G). Mutation c. 752T > C, c. 1307T > C,c. 4835C > G,and c. 1737C > G were novel mutations. Three families had KCNQ2 mutations. All KCNQ2 mutations were missense mutations(c. 775G > A,c. 237T > G,c. 1510C > T). Mutation c. 237T > G and c. 1510C > T were novel mutations. One family had a novel GABRA6 mutation c. 523G > T. In 71 BFIE families,16 families had mem-bers who showed paroxysmal kinesigenic dyskinesias(PKD)and subclassified as infantile convulsions with paroxysmal choreoathetosis syndrome(ICCA). Fifteen ICCA families were found having PRRT2 mutations (15 / 16,93. 8％). The remaining ICCA family was not detected with any pathogenic mutation. Conclusion There is high frequency of gene mutations in BFIE families. Mutations in KCNQ2,SCN2A,and PRRT2 are genetic causes of BFIE. PRRT2 is the main gene responsible for BFIE. GABRA6 mutation might be a new cause of BFIE.

[Objective] To explore the risk factors for mortality of bloodstream infections in the patients with hematologic diseases,so as to provide evidence for reasonable and effective application of treatments.[Methods] The clinical data of 242 cases of bloodstream infections who were hospitalized from Jan 2012 to Jun 2016 were analyzed retrospectively,then the analysis was performed for risk factors.The statistical analysis was processed by SPSS 19.0.[Results] A total of 266 strains of pathogens were isolated,including 99 strains of gram-positive bacteria,accounting for 37.2％,and 164 strains of gram-negative bacteria,accounting for 61.7％.Multivariate analysis showed that the significant independent risk factors for mortality were active states of hematologic diseases (P =0.007,OR =5.622,95％ CI 1.586 ～ 19.924),presentation with septic shock(P =0.007,OR =4.978,95％ CI 1.560 ～15.884),cardiac insufficiency (P =0.001,OR =11.878,95％ CI 2.760 ～ 51.120),level of albumin less than 35 g/L (P =0.036,OR =3.468,95％ CI 1.087 ～ 11.066),polymicrobial infection (P =0.010,OR =6.024,95％ CI 1.540 ～ 23.563),and Staphylococcus haemolyticus (P =0.001,OR =19.308,95％ CI 3.392 ～ 109.888)/Enterococcus (P =0.002,OR =15.266,95％ CI 2.817 ～82.728) infection.The survival curves show that the inappropriate initial antimicrobial therapy group or presentation with any one of the independent risk factors had a lower probability of survival than the control group.[Conclusions] Bloodstream infections in patients may cause high mortality rate,so it is necessary that we use antibiotic reasonably and spare no effort to reduce the mortality rate by appropriate application of antimicrobial therapy and effective intervention of the risk factors.

The craniospinal radiotherapy method was studied by using the whole body positioning frame and base dose plan compensation (BDPC) technique.11 patients with central nervous system malignancies in our hospital were studied. Use whole body positioning frame with the head - neck shoulder and body membrane to immobilize posture, then use BDPC for the intensity-modulated radiotherapy. Target area conformability index(CI), homogeneity index (HI), dose of endangerment organ (OAR) and beam connecting dose distribution are evaluated. The use of base-dose-compensation intensity-modulated plan combined with whole-body positioning technology improves the target area conformability and target uniformity, simplifies the design of craniospinal radiotherapy, improves the placement accuracy and ensure good placement repeatability. We measure beam connecting dose distribution. Cold and hot spots do not appear, and calculated values are basically identical. The application of whole-body positioning technique combined with BDPC optimization method in the treatment of the craniospinal radiotherapy meets the clinical requirements of dosimetry. Moreover, it is simple and can improve the treatment planning efficiency.