Comparison of outcomes after human leukocyte antigen-matched and haploidentical hematopoietic stem-cell transplantation for multiple myeloma Background: Allogeneic stem-cell transplantation (SCT) is a well-established immunotherapeutic strategy for multiple myeloma (MM) with a potent and often sustained graft-vs.-myeloma effect. This multicenter investigation aimed to analyze the complications and survival of haploidentical SCT in patients with MM, and compare the main outcomes with matched-related donors (MRDs). Methods: Haploidentical and MRD SCT was identified from a cohort of 97 patients with MM who received a myeloablative transplantation in 13 hospitals from May 2001 to December 2017. A matched-pair analysis was designed. For each haplo recipient, the recipients were randomly selected from the MRD group and were matched according to the following criteria: year of the hematopoietic SCT (±2 years), disease status at transplantation, and the length of follow-up. Results: Seventy cases received MRD and 27 received haploidentical transplantation. The two groups showed no significant differences regarding age, gender, cytogenetic risk, and diagnostic stage. The cumulative incidences of non-relapse mortality (NRM) at 1 and 3 years based on donor type were 20.5% (95% confidence interval [CI], 10.90–30.10%) and 24.2% (95% CI, 13.81–34.59%) for the MRD group and 16.80% (95% CI, 1.71–31.89%) and 28.70% (95% CI, 8.71–48.69%) for the haplo group, respectively. Cumulative incidence of NRM did not differ significantly between the two groups (χ2 = 0.031, P = 0.861). The cumulative incidences of progression-free survival (PFS) and 1 year and 3 years by type of donors were 59.8% (95% CI, 48.24–71.36%) and 45.4% (95% CI, 33.44–57.36%), and 65.6% (95% CI, 47.18–84.02%) and 26.8% (95% CI, 7.59–46. 01%) for MRD and haploidentical donor, respectively. Cumulative incidence of PFS did not differ significantly between the two groups (χ2 = 0.182, P = 0.670). In multivariate analyses, no statistically significant differences were observed between haploidentical and MRD for relapse, NRM, PFS, and overall survival. There were no statistically differences on main outcomes after haploidentical and MRD. Conclusion: Haploidentical SCT could be performed safely and feasibly for patients with MM in need.

A preliminary cervical cancer screening cascade for eight provinces rural Chinese women: a descriptive analysis of cervical cancer screening cases in a 3-stage framework Background: Cascade analysis is an effective method to analyze the processing data of an event, such as a provided service or a series of examinations. This study aimed to develop a primary cervical cancer screening cascade in China to promote the quality of the screening process. Methods: We designed a cervical cancer screening cascade in China according to the program flow chart. It had three stages, each with two steps and one result. Data from 117,522 women aged 35 to 64 years in the Rural Cervical Cancer Surveillance Project from January 1, 2014, to December 31, 2014, were collected to analyze the main results of the cascade. The data and proportion are used to describe the follow-up of cervical cancer and pre-cancer detection rate. Results: In 2014, 117,522 (80.94% of all cases reported by the Rural Cervical Cancer Surveillance Project) women aged 35 to 64 years had not received cervical cytology in the previous 3 years. The pre-cancer and cancer detection rates were 256.12/100,000 and 16.16/100,000, respectively. A total of 3031 cases failed to follow-up through the screening process, and 1189, 1555, and 287 cases were lost at cervical cytology, colposcopy, and histopathological screening stages, respectively. The estimated cases of pre-cancer and cancer cases would have been 544 and 34, respectively, and the estimated detection rates of pre-cancer and cancer would have been 462.89/100,000 and 28.93/100,000, respectively. Conclusion: In order to increase the detection rate of cervical cancer, cervical cancer screening staff should focus on increasing the rate of follow-up of those who are positive for cervical cancer screening (ie, those with positive cytology results), especially for the 40 to 44 years age range.

Surgical complexity and prognostic outcome of small volume renal cell carcinoma with high-level venous tumor thrombus and large volume renal cell carcinoma with low-level thrombus Background: Radical nephrectomy with thrombectomy is one of the most difficult and complicated urological operations. But the roles of renal tumor volume and thrombus level in surgical complexity and prognostic outcome are not clear. This study aimed to evaluate the surgical complexity and prognostic outcome between the volume of renal cell carcinoma (RCC) and the level of venous tumor thrombus. Methods: The clinical data of 67 RCC cases with renal vein or inferior vena cava (IVC) tumor thrombus from January 2015 to May 2018 were retrospectively analyzed. Among these 67 cases, 21 (31.3%) were small tumors with high-level thrombus (tumor ≤7 cm in diameter and thrombus Neves Level II–IV), while 46 (68.7%) were large tumors with low-level thrombus group (tumor >7 cm in diameter and thrombus Level 0–I). Clinical features, operation details, and pathology data were collected. Univariable and multivariable logistic regression analyses were applied to evaluate the risk factors for small tumor with high-level thrombus. Results: Patients with small tumors and high-level thrombus were more likely to have longer operative time (421.9 ± 135.1 min vs. 282.2 ± 101.9 min, t = 4.685, P < 0.001), more surgical bleeding volume (1200 [325, 2900] mL vs. 500 [180, 1000] mL, U = 270.000, P = 0.004), more surgical blood transfusion volume (800 [0, 1400] mL vs. 0 [0, 800] mL, U = 287.500, P = 0.004), more plasma transfusion volume (0 [0, 800] mL vs. 0 [0, 0] mL, U = 319.000, P = 0.004), higher percentage of open operative approach (76.2% vs. 32.6%, χ2 = 11.015, P = 0.001), higher percentage of IVC resection (33.3% vs. 0%, χ2 = 17.122, P < 0.001), and higher percentage of post-operative complications (52.4% vs. 19.6%, χ2 = 7.415, P = 0.010) than patients with large tumors and low-level thrombus. In multivariate analysis, decreased hemoglobin (Hb) (odds ratio [OR]: 0.956, 95% confidence interval [CI]: 0.926–0.986, P = 0.005) and non-sarcomatoid differentiation (OR: 0.050, 95% CI: 0.004–0.664, P = 0.023) were more likely to form small tumors with high-level tumor thrombus rather than large tumor with small tumor thrombus. The estimated mean cancer-specific survival times of small tumor with high-level thrombus and large tumor with low-level thrombus were 31.6 ± 3.8 months and 32.5 ± 2.9 months, without statistical significance (P = 0.955). After univariate and multivariate Cox proportional hazard survival regression analyses, only distant metastasis (hazard ratio [HR]: 3.839, P = 0.002), sarcomatoid differentiation (HR: 7.923, P < 0.001), alkaline phosphatase (HR: 2.661, P = 0.025), and severe post-operative complications (HR: 10.326, P = 0.001) were independent predictors of prognosis. Conclusions: The level of the tumor thrombus was more important than the diameter of the primary kidney tumor in affecting the complexity of surgery. In the same T3 stage, neither the renal tumor diameter nor the tumor thrombus level was an independent risk factor for prognosis.

Sleep fragmentation as an important clinical characteristic of sleep disorders in Parkinson's disease: a preliminary study Background: Sleep disorders are one of the earliest non-motor symptoms of Parkinson's disease (PD). Sleep disorders could, therefore, have value for recognition and diagnosis in PD. However, no unified classification and diagnostic criteria exist to evaluate sleep disorders by polysomnography (PSG). Utilizing PSG to monitor sleep processes of patients with PD and analyze sleep disorder characteristics and their relationship with demographic parameters could aid in bridging this gap. This preliminary study aimed to evaluate the clinical characteristic of sleep disorders in PD using PSG. Methods: PSG was used to evaluate sleep disorders in 27 patients with PD and 20 healthy volunteers between August 2015 and July 2018 in Fujian Medical University Union Hospital. Total sleep time (TST), sleep efficiency (SE), total wake time, and other parameters were compared between the two groups. Finally, the correlation between sleep disorders and age, disease duration, Unified Parkinson's Disease Rating Scale-III scores, Hoehn-Yahr stage, and levodopa dose were analyzed. The main statistical methods included Chi-square test, two independent samples t test, Fisher exact test, and Pearson correlation. Results: Sleep fragmentation in the PD group was significantly increased (74.1%) while difficulty falling asleep and early awakening were not, as compared to healthy controls. No significant differences were found in time in bed, sleep latency (SL), non-rapid eye movement (NREM) stage 1 (N1), N1%, N2, N2%, N3%, and NREM% between PD and control groups; but TST (327.96 ± 105.26 min vs. 414.67 ± 78.31 min, P = 0.003), SE (63.26% ± 14.83% vs. 76.8% ± 11.57%, P = 0.001), R N3 (20.00 [39.00] min vs. 61.50 [48.87] min, P = 0.001), NREM (262.59 ± 91.20 min vs. 337.17 ± 63.47 min, P = 0.003), rapid-eye-movement (REM) (32.50 [33.00] min vs. 85.25 [32.12] min, P < 0.001), REM% (9.56 ± 6.01 vs. 15.50 ± 4.81, P = 0.001), REM sleep latency (157.89 ± 99.04 min vs. 103.47 ± 71.70 min, P = 0.034) were significantly reduced in PD group. Conclusion: This preliminary study supported that sleep fragmentation was an important clinical characteristic of sleep disorders in PD. Whether sleep fragmentation is a potential quantifiable marker in PD needs to be further investigated in the future study.

Relationship between T-cell receptor α gene polymorphisms and symptomatic differences in patients with narcolepsy type 1 Background: Recent genome-wide association studies have identified an important role of T-cell receptor α (TRA) gene in the development of narcolepsy type 1. However, the role of TRA haplotype polymorphisms in the symptomatic diversity of narcolepsy remains unclear. This study aimed to investigate whether TRA polymorphisms can influence the symptomatic diversity of narcolepsy. Methods: Totally, 903 patients with narcolepsy type 1 were included in the study. Patients were divided into different groups according to their symptoms. First, 13 genotyped single nucleotide polymorphisms in the TRA were assessed for their association with symptoms of narcolepsy. We used the Chi-square test to determine differences in genotype frequencies in patients with narcolepsy. Further, we identified the haplotypes and variations of the TRA and tested their association with the symptoms of narcolepsy using a logistic regression model. Results: According to the results of the logistic regression, TRA haplotypes TG and CT were significantly associated with auditory hallucination, with odds ratios of 1.235 (95% confidence interval [CI], 1.012–1.507) and 1.236 (95% CI, 1.012–1.511), respectively (P < 0.05). Conclusions: The patterns of haplotype in TRA (haplotypes TG and CT) are associated with hypnagogic auditory hallucination in patients with narcolepsy type 1. However, further studies are needed to confirm our results and explore the underlying mechanisms.

Prevalence and associated factors of intra-articular lesions in acute ankle fractures evaluated by arthroscopy and clinical outcomes with minimum 24-month follow-up Background: Acute ankle fractures can lead to high rate of concomitant intra-articular lesions which may compromise clinical results. The purpose of this study was to evaluate the incidence of concomitant intra-articular lesions in acute ankle fractures with arthroscopy. We also sought to analyze the relationship between intra-articular lesions and the fracture type, as well as the severity of the fracture. Methods: It was a retrospective cohort study. From April 2014 to December 2015, we have chosen arthroscopy-assisted open reduction and internal fixation (AORIF) for the treatment of unstable acute ankle fractures. All concomitant intra-articular lesions were assessed and documented carefully and prospectively, such as ligament injuries, osteochondral lesions, and tibiofibular syndesmosis injuries. All fractures were classified according to the Lauge-Hansen classification system. The American Orthopedic Foot and Ankle Society's (AOFAS) ankle-hindfoot scale was used to assess post-operative function. Statistical comparisons between the intra-articular lesions, the fracture type, and the severity of the presenting fracture were performed using a Chi-squared analysis. Results: Data of 36 patients were analyzed in the study, including 23 supination-type fractures and 13 pronation-type fractures. The incidence of tibiofibular syndesmosis injuries, chondral lesions, and loose bodies were 92%, 72%, and 39%, respectively. Avulsion fractures of the anterior tibiofibular syndesmosis were more commonly found in supination-type fractures than pronation-type fracture (45% vs. 15%, χ2 = 5.78, P = 0.02), which would cause mechanical blocking in the anterior portion of the ankle. On the contrary, chondral lesions were more commonly found in the more severe fractures than mild fractures (86% vs. 53%, χ2 = 4.57, P = 0.03). A mean 41.7 months (range, 33.0–51.0 months) of follow-up was achieved. A mean AOFAS's ankle-hindfoot scale was 96.9, and 97.2% of the patients were satisfied with the procedure. Conclusions: Acute ankle fractures have a high incidence of concomitant intra-articular lesions. Avulsion fractures of the anterior tibiofibular syndesmosis are more commonly found in supination-type fractures. Chondral lesions are related to the severity of the fractures, but not with the classification of the fractures. AORIF can be one reliable solution in dealing with the associated injuries seen with acute ankle fractures.

A retrospective analysis of real-world outcomes of elderly Chinese patients with diffuse large B-cell lymphoma Background: Elderly patients with diffuse large B-cell lymphoma (DLBCL) have a worse prognosis than younger patients, and the optimal treatment strategy for this group remains controversial. We conducted a retrospective analysis to investigate the clinical features and outcomes of elderly patients (>60 years) and to assess the impact of clinical and molecular factors on outcome in this age group. Methods: From April 2006 to December 2012, a total of 349 elderly patients with DLBCL from the National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences, and Peking Union Medical College were included in this analysis. Patients were further divided into two age groups (61–69 years and ≥70 years). We compared clinical characteristics and outcomes between groups. Results: Of 349 total patients, 204 (58.5%) were aged 61 to 69 years, and 145 (41.5%) patients were aged 70 years or older. Except for the Eastern Cooperative Oncology Group performance status, clinical characteristics were comparable between the two groups. With a median follow-up of 82 (range, 1–129) months, the 5-year overall survival (OS) and progression-free survival (PFS) rates were 51.9% and 45.8%, respectively. The 5-year OS rates for patients aged 61 to 69 years and those over 70 years were 58.3% and 42.8% (P = 0.007), respectively, and the 5-year PFS rates were 51.0% and 38.6% (P = 0.034). Treatment regimens including rituximab provided a higher 5-year OS rate (63.1% vs. 37.1%, P < 0.001) and PFS rate (56.6% vs. 31.8%, P < 0.001) than chemotherapy alone. For patients aged 61 to 69 years, chemotherapy plus rituximab resulted in a higher 5-year OS rate (66.7% vs. 46.4%, P = 0.002) and PFS rate (60.0% vs. 38.1%, P = 0.002) than chemotherapy alone. For patients aged ≥70 years, there was a marked survival advantage in patients who received chemotherapy plus rituximab (5-year OS rate: 57.7% vs. 25.4%, P < 0.001; 5-year PFS rate: 51.3% vs. 23.9%, P < 0.001) compared with that seen in those who received chemotherapy alone. Multivariate analysis established that stage III/IV disease, elevated lactate dehydrogenase (LDH), initial treatment, and chemotherapy with rituximab were independent risk factors for 5-year OS, and stage III/IV disease, elevated LDH, and chemotherapy with rituximab were independent risk factors for 5-year PFS for elderly patients with DLBCL. Conclusions: In comparison to patients aged 61 to 69 years, those aged ≥70 years have poorer survival. Prolonged survival is obtainable with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP)-like in elderly Chinese patients in all age groups, indicating that the R-CHOP-like regimen should be considered for this population, even for those aged 70 years or older.

Intestinal microbiota composition in patients with amyotrophic lateral sclerosis: establishment of bacterial and archaeal communities analyses Background: Emerging evidences have indicated that the composition of gut microbiota was significantly influenced by central nervous system diseases. The digestion and metabolism disturbances of patients with amyotrophic lateral sclerosis (ALS) might be strongly associated with ALS; however, this has rarely been evaluated in these populations. This study was to evaluate bacterial and archaeal composition of gut flora and the corresponding metabolism performance of these micro-organisms in fecal samples of patients with ALS. Methods: A comparative study was performed on the intestinal microbiota from eight patients with ALS and eight healthy individuals at Huadong Hospital during November 2017 to April 2018; meanwhile, the metabolite concentrations of human endotoxin, short-chain fatty acids (SCFA), NO2-N/NO3-N, and γ-aminobutyric acid were also evaluated by spectrophotometry methods. The correlations between intestinal microbiota and metabolite concentration were compared between the two groups using one-way analysis of variance; the relative abundance of beneficial and harmful micro-organisms in fecal samples was also analyzed. Results: In general, the richness and evenness of bacterial and archaeal communities of healthy individuals were healthier than that of patients with ALS. The phylum Firmicutes/Bacteroidetes ratio, genus Methanobrevibacter showed an enhancive tendency in patients with ALS, whereas the relative abundance of beneficial micro-organisms (genera Faecalibacterium and Bacteroides) presented a significant decrease tendency in patients with ALS. In addition, the average concentrations of human endotoxin, SCFA, NO2-N/NO3-N, and γ-aminobutyric acid in patients with ALS and healthy individuals were 64.2 vs. 65.3 EU/mL, 57.5 vs. 55.3 μg/mL, 5.7 vs. 5.3 ng/mL, and 6.1 vs. 5.4 μmol/L, respectively, indicating that the digestion and metabolism functions of gastrointestinal tract of patients might decline with this disease. Conclusions: The relative abundance of beneficial and harmful micro-organisms respectively showed decrease and increase tendency in patients with ALS.

Endoplasmic reticulum stress and proteasome pathway involvement in human podocyte injury with a truncated COL4A3 mutation Background: Collagen type IV (COL4)-related nephropathy includes a variety of kidney diseases that occur with or without extra-renal manifestations caused by COL4A3-5 mutations. Previous studies revealed several novel mutations, including three COL4A3 missense mutations (G619R, G801R, and C1616Y) and the COL4A3 chr:228172489delA c.4317delA p.Thr1440ProfsX87 frameshift mutation that resulted in a truncated NC1 domain (hereafter named COL4A3 c.4317delA); however, the mutation mechanisms that lead to podocyte injury remain unclear. This study aimed to further explore the mutation mechanisms that lead to podocyte injury. Methods: Wild-type (WT) and four mutant COL4A3 segments were constructed into a lentiviral plasmid, then stably transfected into human podocytes. Real-time polymerase chain reaction and Western blotting were applied to detect endoplasmic reticulum stress (ERS)- and apoptosis-related mRNA and protein levels. Then, human podocytes were treated with MG132 (a proteasome inhibitor) and brefeldin A (a transport protein inhibitor). The human podocyte findings were verified by the establishment of a mus-Col4a3 knockout mouse monoclonal podocyte using clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9) technology. Results: Our data showed that COL4A3 mRNA was significantly overexpressed in the lentivirus stably transfected podocytes. Moreover, the COL4A3 protein level was significantly increased in all groups except the COL4A3 c.4317delA group. Compared to the other test groups, the COL4A3 c.4317delA group showed excessive ERS and apoptosis. Podocytes treated with MG132 showed remarkably increased intra-cellular expression of the COL4A3 c.4317delA mutation. MG132 intervention improved higher ERS and apoptosis levels in the COL4A3 c.4317delA group. Mouse monoclonal podocytes with COL4A3 chr:82717932insA c.4852insA p.Arg1618ThrfsX4 were successfully acquired; this NC1-truncated mutation suggested a higher level of ERS and relatively remarkable level of apoptosis compared to that of the WT group. Conclusions: We demonstrated that excessive ERS and ERS-induced apoptosis were involved in the podocyte injury caused by the NC1-truncated COL4A3 mutation. Furthermore, proteasome pathway intervention might become a potential treatment for collagen type IV-related nephropathy caused by a severely truncated COL4A3 mutation.

Effects of probiotics and prebiotics on intestinal microbiota in mice with acute colitis based on 16S rRNA gene sequencing Background Imbalance of intestinal microbiota was closely related to colitis. Under these circumstances, regulation of enteric flora may be beneficial to the repair of inflammation. We aimed to investigate the effects of probiotics (Bifidobacterium and Lactobacillus), prebiotics and their combination on inflammation, and microflora in mice of acute colitis. Methods C57BL/6J mice were divided into six groups randomly (blank control group, model control group, probiotics group, synbiotics group, lactitol group and probiotics + lactitol group). Each group was given 2.5% dextran sulfate sodium drinking water for 5 days other than the blank control group. Except for the model control group, the other four groups were intervened with probiotics, synbiotics (probiotics and inulin), lactitol, and probiotics + lactitol. Mice were sacrificed after 1 week of gavage, and pathologic scores were calculated. The feces of different periods and intestinal mucosa samples were collected to analyze the differences of intestinal microbiota by 16S rRNA sequencing. Differences of two groups or multiple groups were statistically examined through unpaired Student t test and analysis of variance (ANOVA), respectively. ANOVA, Tukey, Anosim, and metastats analysis were used to compare differences of microbiota among different groups. Results After gavage for 1 week, the pathologic scores of groups with the intervention were significantly lower than those in the model control group, and the difference was statistically significant (P < 0.05). The model control group was higher in the genus of Bacteroides (relative abundance: 0.3679 vs. 0.0099, P = 0.0016) and lower in Lactobacillus (relative abundance: 0.0020 vs. 0.0122, P = 0.0188), Roseburia (relative abundance: 0.0004 vs. 0.0109, P = 0.0157), compared with the blank control group. However, the same phenomenon was not found in groups gavaged with probiotics and lactitol. Compared with model control group, mice with intervention were increased with Bifidobacterium (relative abundance: 0.0172 vs. 0.0039, P = 0.0139), Lachnospiraceae_NK4A136_group (relative abundance: 0.1139 vs. 0.0320, P = 0.0344), Lachnospiraceae_UCG-006 (relative abundance: 0.0432 vs. 0.0054, P = 0.0454), and decreased with Alistipes (relative abundance: 0.0036 vs. 0.0105, P = 0.0207) in varying degrees. The mucosal flora was more abundant than the fecal flora, and genus of Mucispirillum (relative abundance: 0.0207 vs. 0.0001, P = 0.0034) was more common in the mucosa. Lactitol group showed higher level of Akkermansia than model control group (relative abundance: 0.0138 vs. 0.0055, P = 0.0415), probiotics group (relative abundance: 0.0138 vs. 0.0022, P = 0.0041), and synbiotics group (relative abundance: 0.0138 vs. 0.0011, P = 0.0034), while probiotics + lactitol group had more abundant Akkermansia than synbiotics group (relative abundance: 0.0215 vs. 0.0013, P = 0.0315). Conclusions Probiotics and prebiotics reduce the degree of inflammation in acute colitis mice obviously. Mice with acute colitis show reduced beneficial genera and increased harmful genera. Supplementation of probiotics and prebiotics display the advantage of increasing the proportion of helpful bacteria and regulating the balance of intestinal microbiota. Lactitol might promote the proliferation of Akkermansia.