[Retrospective clinical study on cryopreservation-free integrated autologous hematopoietic stem cell transplantation model for newly diagnosed multiple myeloma].

Objective: To explore the efficacy and safety of cryopreservation-free integrated autologous hematopoietic stem cell transplantation (HSCT) model for patients with multiple myeloma. Methods: A total of 96 patients with newly diagnosed multiple myeloma (NDMM) between July 31, 2020, and December 31, 2022, were retrospectively analyzed, of which 41 patients in the observation group received integrated non-cryopreserved transplantation mode. After hematopoietic stem cells were mobilized and collected, melphalan was started immediately for pre-transplant conditioning, and non-cryopreserved grafts from the medical blood transfusion refrigerator were directly injected intravenously into the patient within 24-48 h after the melphalan conditioning. The control group consisted of 55 patients who received traditional transplantation mode. After hematopoietic stem cells were collected, stem cell cryopreservation was performed in liquid nitrogen, and then the transplant plans were started at the right time. All patients received mobilization of autologous hematopoietic stem cells using the G-CSF combined with the plerixafor. Results: ① A total of 34 patients (82.9% ) with VGPR plus CR in the observation group were significantly higher than 33 patients (60.0% ) in the control group (P=0.016). ②Compared with the control group, the incidence of grade 1 oral mucosal inflammation was higher in the observation group (P<0.001) ; however, the incidence of grades 2 and 3 oral mucosal inflammation was lower (P=0.004, P=0.048), and neither group experienced grade 4 or above oral mucosal inflammation. The incidence of grade 1 diarrhea was higher in the observation group (P=0.002), whereas the incidence of grade 3 diarrhea was lower (P=0.007). No statistically significant difference was observed in the incidence of grade 4 diarrhea (P=0.506), and neither group experienced grade 5 diarrhea. ③ The incidence of bacterial infection in the observation group was lower than that in the control group (34.1% vs 65.5%, P=0.002), whereas no statistically significant difference was observed in the incidence of fungal infection (29.3% vs 31.4%, P=0.863) and viral infection (4.88% vs 3.64%, P=0.831). ④No statistically significant difference was observed in the implantation time of granulocytes and platelets between the observation and control groups [10 (8-20) days vs 11 (8-17) days, P=0.501; 13 (10-21) days vs 15 (10-20) days, P=0.245]. ⑤ All patients did not receive lenalidomide treatment 100 days post-transplantation. At 30 days post-transplantation, the CTL, NK, and Th cell counts in the observation group were lower than those in the control group (P<0.001, P=0.002, P=0.049), and the NKT cell counts were higher than those in the control group (P=0.024). At 100 days post-transplantation, the CTL, NKT, and Th cell counts in the observation group were higher than those in the control group (P=0.025, P=0.011, P=0.007), and no statistically significant difference in NK cell counts was observed between the two groups (P=0.396). ⑥ The median follow-up was 18 (4-33) months. The overall 2-year survival rates of the observation and control groups post-transplantation were 91.5% and 78.2%, respectively (P=0.337). The recurrence-free survival rates were 85.3% and 77.6%, respectively (P=0.386), and the cumulative recurrence rates were 9.8% and 16.9%, respectively (P=0.373) . Conclusion: In NDMM, the cryopreservation-free integrated autologous HSCT model can achieve similar therapeutic effects as traditional transplantation models, with lower rates of severe mucosal inflammation and infection compared with traditional transplantation models.

Interplay of metabolic dysfunction-associated fatty liver disease and papillary thyroid carcinoma: insights from a Chinese cohort.

PURPOSE: Thyroid cancer is one of a set of extrahepatic cancers that closely linked to metabolic dysfunction-associated fatty liver disease (MAFLD). However, the connection between MAFLD and the characteristics of papillary thyroid cancer (PTC) remains unexplored. METHODS: Between Jan 2020 and Oct 2022, surgical cases of PTC patients were examined at the first Affiliated Hospital of Wenzhou Medical University. Clinical data extracted from the electronic medical system underwent a rigorous comparison between two groups, classified based on MAFLD criteria, using logistic regression analysis. RESULTS: In this study of 4,410 PTC patients, 18.3% had MAFLD. MAFLD emerged as a distinct risk factor for lymph node metastasis (OR = 1.230, 95% CI 1.018-1.487) in this cohort, especially in females (OR = 1.321, 95% CI 1.026-1.702) and those with BMI ≥ 23 kg/m2 (OR = 1.232, 95% CI 1.004-1.511). The presence of MAFLD was found to significantly elevate the risk of BRAF V600E mutation in both subgroups characterized by FIB-4 score ≥ 1.3 (OR = 1.968, 95% CI 1.107-3.496) and BMI < 23 kg/m2 (OR = 2.584, 95% CI 1.012-6.601). Moreover, among the subset of individuals without non-alcoholic fatty liver disease (NAFLD), it was noted that MAFLD considerably increased the likelihood of tumor multifocality (OR = 1.697, 95% CI 1.111-2.592). Nevertheless, MAFLD did not exhibit any correlation with increased tumor size, extra-thyroidal extension (ETE), or later TNM stage in PTC. CONCLUSION: In this cross-sectional study, we discovered a significant association between MAFLD and increased occurrences of lymph node metastasis. Furthermore, MAFLD was linked to a higher chance of BRAF V600E mutation and the presence of multiple tumors in certain subgroups.

[A prospective study on application of human umbilical cord mesenchymal stem cells combined with autologous Meek microskin transplantation in patients with extensive burns].

Objective: To investigate the effects of human umbilical cord mesenchymal stem cells (hUCMSCs) combined with autologous Meek microskin transplantation on patients with extensive burns. Methods: The prospective self-controlled study was conducted. From May 2019 to June 2022, 16 patients with extensive burns admitted to the 990th Hospital of PLA Joint Logistics Support Force met the inclusion criteria, while 3 patients were excluded according to the exclusion criteria, and 13 patients were finally selected, including 10 males and 3 females, aged 24-61 (42±13) years. A total of 20 trial areas (40 wounds, with area of 10 cm×10 cm in each wound) were selected. Two adjacent wounds in each trial area were divided into hUCMSC+gel group applied with hyaluronic acid gel containing hUCMSCs and gel only group applied with hyaluronic acid gel only according to the random number table, with 20 wounds in each group. Afterwards the wounds in two groups were transplanted with autologous Meek microskin grafts with an extension ratio of 1∶6. In 2, 3, and 4 weeks post operation, the wound healing was observed, the wound healing rate was calculated, and the wound healing time was recorded. The specimen of wound secretion was collected for microorganism culture if there was purulent secretion on the wound post operation. In 3, 6, and 12 months post operation, the scar hyperplasia in wound was assessed using the Vancouver scar scale (VSS). In 3 months post operation, the wound tissue was collected for hematoxylin-eosin (HE) staining to observe the morphological changes and for immunohistochemical staining to observe the positive expressions of Ki67 and vimentin and to count the number of positive cells. Data were statistically analyzed with paired samples t test and Bonferronni correction. Results: In 2, 3, and 4 weeks post operation, the wound healing rates in hUCMSC+gel group were (80±11)%, (84±12)%, and (92±9)%, respectively, which were significantly higher than (67±18)%, (74±21)%, and (84±16)% in gel only group (with t values of 4.01, 3.52, and 3.66, respectively, P<0.05). The wound healing time in hUCMSC+gel group was (31±11) d, which was significantly shorter than (36±13) d in gel only group (t=-3.68, P<0.05). The microbiological culture of the postoperative wound secretion specimens from the adjacent wounds in 2 groups was identical, with negative results in 4 trial areas and positive results in 16 trial areas. In 3, 6, and 12 months post operation, the VSS scores of wounds in gel only group were 7.8±1.9, 6.7±2.1, and 5.4±1.6, which were significantly higher than 6.8±1.8, 5.6±1.6, and 4.0±1.4 in hUCMSC+gel group, respectively (with t values of -4.79, -4.37, and -5.47, respectively, P<0.05). In 3 months post operation, HE staining showed an increase in epidermal layer thickness and epidermal crest in wound in hUCMSC+gel group compared with those in gel only group, and immunohistochemical staining showed a significant increase in the number of Ki67 positive cells in wound in hUCMSC+gel group compared with those in gel only group (t=4.39, P<0.05), with no statistically significant difference in the number of vimentin positive cells in wound between the 2 groups (P>0.05). Conclusions: The application of hyaluronic acid gel containing hUCMSCs to the wound is simple to perform and is therefore a preferable route. Topical application of hUCMSCs can promote healing of the autologous Meek microskin grafted area in patients with extensive burns, shorten wound healing time, and alleviate scar hyperplasia. The above effects may be related to the increased epidermal thickness and epidermal crest, and active cell proliferation.

[LASS2/TMSG1 overexpression inhibits proliferation and promotes apoptosis of human lung cancer A549 cells possibly by upregulating ceramide and p38 MAPK to activate a signaling cascade].

OBJECTIVE: To investigate the effects of LASS2/TMSG1 gene overexpression on proliferation and apoptosis of human lung cancer A549 cells and explore the possible mechanism. METHODS: We examined LASS2/TMSG1 expression level in a previously constructed A549 cell line overexpressing LASS2/TMSG1 using Western blotting. The proliferation and apoptosis of the cells were detected using colony-forming assay, CCK-8 assay, Hoechst/PI double staining and flow cytometry. Fourteen nude mice were randomized into 2 groups (n=7) to receive subcutaneous injection of A549 cells with or without LASS2/TMSG1 overexpression on the back of the neck, and the cell proliferation in vivo was observed. The expression levels of p38 MAPK protein and p-p38 MAPK protein in the xenografts were detected with Western blotting. ELISA was used to detect the levels of ceramide and p38 MAPK protein in cultured A549 cell supernatants and the xenografts in nude mice. RESULTS: Compared with the negative control cells, A549 cells with LASS2/TMSG1 overexpression had significantly lowered proliferation ability in vitro with increased early apoptosis rate (P < 0.05), and showed obvious growth inhibition after inoculation in nude mice(P < 0.05). Western blotting showed that in both cultured A549 cells and the xenografts in nude mice, LASS2/TMSG1 gene overexpression significantly increased the expression levels of p38 MAPK protein and p-p38 MAPK protein (P < 0.05); the results of ELISA also revealed significantly increased levels of ceramide and p38 MAPK protein in the cell supernatant andxenografts as well (P < 0.05). CONCLUSION: Overexpression of LASS2/TMSG1 gene can significantly inhibit the proliferation and promote early apoptosis of human lung cancer A549 cells both in vitro and in vivo possibly by upregulating the expressions of ceramide and p38 MAPK protein to activate a signal transduction cascade.

[International multi-center evaluation of a rapid antigen test based on gold immunochromatographic assay for detection of severe acute respiratory syndrome coronavirus 2].

Objective: The gold immunochromatographic assay for detection of SARS-CoV-2 antigen was evaluated by international multi-center clinical trial. Methods: A total of 1 855 clinical parallel samples with valid test results (for nucleic acid and antigen tests, respectively) were collected from nine countries, including Germany, the United Kingdom, Ukraine, France, India, Thailand, Malaysia, the United States of America and Brazil, with sampling period from January 3 to September 22, 2021. These samples were detected by SARS-CoV-2 antigen test kit (colloidal gold immunochromatography assay) and nucleic acid detection kit (real-time fluorescent quantitative reverse transcription polymerase chain reaction). Positive coincidence rates [(number of antigen-positive cases/nucleic acid-positive cases)×100%], negative coincidence rates [(number of antigen-negative cases/nucleic acid-negative cases)×100%], total coincidence rates [(number of cases with consistent results for both antigen and nucleic acid detection/number of total cases) ×100%], as well as Kappa values were calculated. The differences of the above indictors among different countries were evaluated by the coefficient of variation. The detection rates of the antigen test for samples with different cycle threshold values (Ct values) for the nucleic acid detection, different characteristics and different mutant strains were analyzed. Results: For all samples, the positive, negative, and total coincidence rate between the antigen test and nucleic acid assay was 90.8% (569/627), 99.7% (1 224/1 228) and 96.7% (1 793/1 855), respectively, and the consistency coefficient Kappa value was 0.924. Among these countries, the coefficient of variation for positive coincidence rates (except for Malaysia with a lot of samples with Ct value>30), negative coincidence rates (except for France without negative samples) and total coincidence rates (except for France) was 6%,<1%, and 6%, respectively. When Ct values were less than 25, the detection rates of antigen test were 83.3%-100% for each countries (the coefficient of variation was 6%); the total detection rate and the coefficient of variation was 93.4% (428/458) and 5%, respectively, for asymptomatic infected persons and cases within 7 days post onset of symptoms; the total detection rate for various SARS-CoV-2 mutant strains was 97.5% (119/122); and it showed negative results for samples from cases infected with other viruses, including influenza A virus subtype H1N1, influenza B virus, respiratory syncytial virus subgroups A and B, coxsackievirus 16, human metapneumovirus, parainfluenza virus types 1 and 4, Epstein-Barr virus and adenovirus. Conclusion: The SARS-CoV-2 antigen test kit showed excellent authenticity, and there were few differences for its indictors among nine countries, therefore it can meet the needs of large-scale early screening of SARS-CoV-2 infection.

[International multi-center evaluation of a rapid antigen test based on gold immunochromatographic assay for detection of severe acute respiratory syndrome coronavirus 2].

Objective: The gold immunochromatographic assay for detection of SARS-CoV-2 antigen was evaluated by international multi-center clinical trial. Methods: A total of 1 855 clinical parallel samples with valid test results (for nucleic acid and antigen tests, respectively) were collected from nine countries, including Germany, the United Kingdom, Ukraine, France, India, Thailand, Malaysia, the United States of America and Brazil, with sampling period from January 3, 2021 to September 22, 2021. These samples were detected by SARS-CoV-2 antigen test kit (colloidal gold immunochromatography assay) and nucleic acid detection kit (real-time fluorescent quantitative reverse transcription polymerase chain reaction). Positive coincidence rates [(number of antigen-positive cases/nucleic acid-positive cases)×100%], negative coincidence rates [(number of antigen-negative cases/nucleic acid-negative cases)×100%], total coincidence rates [(number of cases with consistent results for both antigen and nucleic acid detection/number of total cases) ×100%], as well as Kappa values were calculated. The differences of the above indictors among different countries were evaluated by the coefficient of variation. The detection rates of the antigen test for samples with different cycle threshold values (Ct values) for the nucleic acid detection, different characteristics and different mutant strains were analyzed. Results: For all samples, the positive, negative, and total coincidence rate between the antigen test and nucleic acid assay was 90.8% (569/627), 99.7% (1 224/1 228) and 96.7% (1 793/1 855), respectively, and the consistency coefficient Kappa value was 0.924. Among these countries, the coefficient of variation for positive coincidence rates (except for Malaysia with a lot of samples with Ct value>30), negative coincidence rates (except for France without negative samples) and total coincidence rates (except for France) was 6%,<1%, and 6%, respectively. When Ct values were less than 25, the detection rates of antigen test were 83.3%-100% for each countries (the coefficient of variation was 6%); The total detection rate and the coefficient of variation was 93.4% (428/458) and 5%, respectively, for asymptomatic infected persons and cases within 7 days post onset of symptoms; the total detection rate for various SARS-CoV-2 mutant strains was 97.5% (119/122); and it showed negative results for samples from cases infected with other viruses, including influenza A virus subtype H1N1, influenza B virus, respiratory syncytial virus subgroups A and B, coxsackievirus 16, human metapneumovirus, parainfluenza virus types 1 and 4, Epstein-Barr virus and adenovirus. Conclusion: The SARS-CoV-2 antigen test kit showed excellent authenticity, and there were few differences for its indictors among nine countries, therefore it can meet the needs of large-scale early screening of SARS-CoV-2 infection.

[The role and mechanism of lncRNA C9ORF139 targeting miR-24-3P/TAOK1 in regulating the proliferation of acute myeloid leukemia cells].

Objective: To investigate the role and mechanism of long non-coding RNA (lncRNA) C9ORF139 targeting micro RNA(miR)-24-3P/TAOK1 in regulating the proliferation of acute myeloid leukemia (AML) cells. Methods: AML cells HL-60 and THP-1 were purchased from the Chinese Academy of Sciences and divided into 4 groups:group A was negative control group (siNC group), group B was interference C9ORF139 group (siC9ORF139 group), group C was siC9ORF139+miR-24-3p inhibitor group, and group D was miR-24-3P+TAOK1 overexpression group (oe-TAOK1 group). Real-time fluorescence quantitative reverse transcription PCR was used to detect the expression levels of AML cell lines of HL-60 and THP-1 in four groups. Cell Counting Kit-8 assay was performed to measure cell proliferation. Flow cytometry was applied to analyze cell apoptosis. Transwell test was applied to detect cell migration and invasion ability. Western blot was used to detect p-serine/threonine kinase (p-raf) and p-mitogen activation proteinkinase (p-MEK), p-extracellular regulatory protein kinase (p-ERK) expression. The luciferase reporter gene plasmid was constructed to verify the binding ability of C9ORF139,miR-24-3P and TAOK1.Nude mice were inoculated with subcutaneous tumor cells of HL-60 (group A) and HL-60 (group B). Results: After the C9ORF139 gene was knocked down and cultured for 120 h, The cell proliferation ability (0.62±0.02, 0.82±0.02), migration ability (0.22±0.03, 0.05±0.01), invasion ability (0.20±0.02, 0.13±0.03) of group B were all lower than that of group A (1.30±0.02, 1.83±0.07; 0.99±0.02, 0.99±0.02; 1.00±0.01, 1.00±0.01) (all P<0.05). When co-transfected with miR-24-3 inhibitor, cell proliferation ability, migration ability and invasion ability were all higher in group B (all P<0.05). When co-transfected with miR-24-3P and oe-TAOK1 plasmid, cell proliferation ability, migration ability and invasion ability were all higher than group B (all P<0.05).When the C9ORF139 gene in the cells was knocked down, the apoptosis level of group B (28.56±8.07, 17.74±1.91) were higher than those of group A (0.31±0.27, 2.49±0.33)(all P<0.05); when co-transfected with miR-24-3P inhibitor, the apoptosis level (2.34±0.09, 3.06±0.06) were lower than those in group B (all P<0.05); when co-transfected with miR-24-3P and oe-TAOK1 in the plasmid group, the apoptosis level (2.16±1.29, 4.80±0.37) were also lower than those of group B (all P<0.05). In HL-60 and THP-1 cells, when C9ORF139 was not mutated, the luciferase activity of miR-24-3P group was lower than that of the miR-NC group (P<0.05). When the binding site with miR-24-3p in C9ORF139 sequence was mutated, the luciferase activity in miR-24-3p group was equivalent to that in miR-NC group (P>0.05).When TAOK1 was not mutated; the luciferase activity of miR-24-3P group was lower than that of group A (P<0.05). When the binding site with miR-24-3p in TAOK1 sequence was mutated, the luciferase activity in miR-24-3p group was equivalent to that in miR-NC group (P>0.05).When the C9ORF139 gene in HL-60 cells was knocked down and cultured for 72 h, the phosphorylation expression levels of Raf, MEK and ERK molecules in group B were significantly lower than those in group A (all P<0.05). By day 14, the tumor volume in the group A was greater than the tumor cell volume in the group B [(284.49±57.61) vs (125.70±18.64) mm3, P=0.017]. The tumor weight of HL-60 in group A was heavier than that of group B [(847.80±159.36) vs (408.40±113.16) mg, P=0.001]. Conclusions: LncRNA C9ORF139 regulates TAOK1 by sponging miR-24-3P to promote the proliferation, invasion and migration of acute myeloid leukemiacell.In vivo experiments have confirmed that the expression of C9ORF139 can promote the growth of subcutaneous tumors in AML nude mice.

[Prognostic value of preoperative platelet parameters in locally advanced renal cell carcinoma].

OBJECTIVE: To explore the prognostic value of preoperative platelet parameters in locally advanced renal cell carcinoma for the risk stratification of such patients. METHODS: Clinical data of patients with locally advanced renal cell carcinoma in the Third Hospital of Peking University from January 2015 to December 2017 were collected. The patients were divided into progression group and progression-free group according to follow-up data, and preoperative platelet parameters and clinical data between the two groups were compared. The optimal cut-off value of platelet parameters was determined by receiver operating characteristic curve (ROC) and analyzed by Kaplan-Meier survival curve. Cox proportional hazards model was used to analyze the independent risk factors of PFS. Time dependent ROC curve, net reclassification index (NRI), and integrated discrimination improvement (IDI) were used to evaluate the improvement of SSIGN model by incorporating platelet parameters. RESULTS: Of the 215 patients, 192 (89.3%) were followed up for a median of 36 months. Sixty-four patients (29.8%) had disease progression during the follow-up, and the median PFS was 46 months. In progression group, the platelet count (PLT) was higher [(250.72 ± 88.59)×109/L vs. (227.27 ± 66.94)×109/L, P=0.042] and the platelet distribution width (PDW) was lower [(12.01 ± 2.27)% vs. (13.31 ± 2.74)%, P = 0.001] than that of progression-free groups. 285×109 /L and 12.65% as the best cut-off values of PLT and PDW, the median PFS of PLT≤285×109 /L group was significantly longer than that of PLT>285×109 /L group (53 months vs. 41 months, P=0.033), and the median PFS of PDW>12.65% group was also significantly longer than that of PDW≤12.65% group (56 months vs. 41 months, P < 0.001). Multivariate analysis showed that preoperative PDW (HR=0.735, P < 0.001), nuclear grade Ⅲ to Ⅳ (HR=2.425, P=0.001) and sarcomatoid differentiation (HR=3.101, P=0.008) were independent risk factors for PFS. The area under the curve of PDW combined with SSIGN model was larger than that with the original SSIGN model [0.748 (95%CI: 0.662－0.833) vs. 0.678 (95%CI: 0.583－0.773), P=0.193], NRI was 0.262 (P=0.04), and IDI was 0.085 (P=0.01), indicating that the predictive ability of PDW combined with SSIGN model was improved. CONCLUSION: Preoperative high PLT and low PDW are associated with adverse prognosis of locally advanced renal cell carcinoma, and PDW is an independent risk factor. Therefore, preoperative PDW could serve as biomarker for risk stratification of locally advanced renal cell carcinoma.

Evaluating the efficacy of recombinant human bone morphogenic protein-2 in the treatment of alveolar clefts with autologous bone grafting using computer-aided engineering techniques.

Recent studies have indicated the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) to be a viable adjunctive to alveolar cleft reconstruction owing to its osteoinductive capacity. This study aimed to evaluate the efficacy of rhBMP-2 in the treatment of alveolar cleft with autologous bone grafts by precise volumetric analysis. Twenty-six patients (aged 8-14) with unilateral alveolar clefts were enrolled in this comparative study. Patients were divided into two groups: the iliac crest bone graft (ICBG) was placed at the side of the cleft in the control group (ICBG group), and rhBMP-2 was mixed with the ICBG in the rhBMP-2 group (BMP group). Helical computed tomographic images were obtained preoperatively and 12 months postoperatively. The datasets were reconstructed as three-dimensional (3D) images using Mimics software and processed using Geomagic Wrap. The newly formed bone of the alveolar cleft was segmented by identifying the differences between preoperative and postoperative 3D images. In the ICBG group, the volume of newly formed bone ranged from 0.25 to 0.88 cm3, and the mean (SD) bone formation percentage was 42.01% (15.57%). In the BMP group, the volume of newly formed bone ranged from 0.34 to 1.09 cm3, and the bone formation mean (SD) percentage was 55.79% (11.84%). There was a statistically significant difference between the two groups in terms of the postoperative percentage of bone formation (p = 0.022). Thus, rhBMP-2 combined with an autologous bone graft is a promising technique to improve the results of secondary alveolar bone grafting.

[Suprapubic-assisted laparoendoscopic single-site surgery in nephroureterectomy A case series of 4 patients].

Objective: To evaluate the feasibility and clinical value of suprapubic-assisted laparoendoscopic single-site surgery (SA-LESS) in nephroureterectomy using method of transvaginal natural orifice specimen extraction (NOSE) (SA-LESS+TV-NOSE NU). Methods: Four patients (three cases of renal pelvic carcinoma and one case of ureteral carcinoma) undergoing SA-LESS+TV-NOSE NU were enrolled between April 2015 and January 2016. After general anesthesia, the patients were placed in the lithotomy position with the affected side elevated by 60°. Two trocars were inserted at the medial margin of umbilicus, and the third one was inserted into abdominal cavity at the superior margin of pubic symphysis. The operation was performed under a direct vision with a 5.4 mm 0° flexible-tip laparoscope. Firstly, the distal ureter was isolated completely and blocked by a Hem-O-lok clip. Then, the laparoscopic nephrectomy was performed according to the standard method. Finally, the bladder cuff excision was executed and the incision was sutured. The intact specimen was placed inside a homemade bag and removed through the incision at posterior vaginal fornix. Results: All the procedures were successfully performed. The median operative time was 150 (range: 120 to 210) minutes, and the median estimated blood loss was 180 (range: 80 to 350) ml. No major perioperative complications occurred. The mean visual analogue score (VAS) of 24 hours and 48 hours after operation were 3.25 (range: 2 to 5) and 2.25 (range: 2 to 3). All the patients resumed ambulation on postoperative day 1. Pelvic drainage tube was removed on postoperative day 2-4. On postoperative day 7, urethral catheter was removed. The patients were discharged on postoperative day 7-9. During the follow-up of 20-29 months, the patient recovered well with no case of incisional hernia and pelvic, abdominal infections. The vaginal fornix incision healed well, and the umbilical and suprapubic puncture scars were not obvious. All the patients completed the patient-assessed acromegaly symptom questionnaire PASQ. The average PSAQ score of 3 months after surgery was 34.5. Three of them restarted their sex lives, with an average female sexual function index score of 16.0, which was not significantly different with that of preoperation (15.6). There was no tumor recurrence, metastasis and implantation in all cases. Conclusion: SA-LESS+TV-NOSE NU is safe and feasible for upper tract urothelial carcinoma with faster postoperative recovery, less pain, shorter hospitalization time, better cosmetic results, and does not cause negative effect on the female sexual function.

[Single-center study of laparoscopic radical nephrectomy with Mayo 0-2 level inferior vena cava thrombectomy].

OBJECTIVE: To investigate the safety and feasibility of laparoscopic treatment for renal carcinoma with Mayo 0-2 level venous thrombosis. METHODS: From January 2015 to February 2018, 58 renal carcinoma cases with venous thrombus underwent laparoscopic radical nephrectomy with inferior vena cava thrombectomy in Department of Urology, Peking University Third Hospital, of which, 51 cases were male, and 7 female, aged 29-82 years. According to the Mayo grade classification, 20 cases were level 0, 20 cases were level 1, and 18 cases were level 2, with left side being 22 cases, and right side 36 cases. The patients except for those complicated with hemorrhagic diseases, cardiac and pulmonary insufficiency, or those who could not tolerate anesthesia and surgical contraindications, underwent the operation after comprehensive examinations. RESULTS: The 58 cases of renal tumor with venous tumor emboli were successfully completed with the surgeries, including 50 cases of totally laparoscopic surgery, 8 cases of laparoscopy surgery from convert to open (among the patients who were converted to open surgery, 7 were complicated with grade 2 tumor thrombus and 1 with grade 1 tumor thrombus). The main reasons for converting to open surgery were huge tumors (the largest of which was about 16 cm in diameter), severe adhesion and difficulty of separation. For different patients, different surgical methods and procedures were adopted according to the tumor direction and the different grade of tumor thrombus. Radical nephrectomy combined with vena cava tumor thrombus removal was performed in 55 cases and segmental resection of vena cava in 3 cases. The operation time was 132-557 min, and blood loss was 20-3 000 mL. Post-operative pathological types: 51 cases were clear cell carcinoma, 5 cases were type 2 of papillary carcinoma, 1 case was squamous cell carcinoma, and 1 case was chromophobe cell tumor. In the study, 47 cases were followed up for 1-36 months, and 4 cases died (the survival time was 5-15 months, with an average of 10.2 months). CONCLUSION: Laparoscopic radical nephrectomy with inferior vena cava thrombectomy is a reasonable choice for renal tumor with Mayo 0-2 level venous thrombosis. For different tumor directions and different grades of tumor thrombus, an appropriate operation plan can give the maxim benefit to the patients with skillful surgeons.

[Clinicopathological analysis of patients with papillary renal cell carcinoma].

OBJECTIVE: To investigate the clinicopathological features,treatment and prognosis of patients with papillary renal cell carcinoma (PRCC) and PRCC-complicated with tumor thrombus. METHODS: Single center retrospective analysis of 75 patients with PRCC treated from January 2012 to October 2017 was performed. There were 55 males and 20 females at an age range of 24-82 years. Sixteen PRCC patients were complicated with tumor thrombus. All the patients were with a surgery and had clear pathological diagnosis and detailed follow-up data. The clinicopathological features, prognosis and influencing factors of the patients with PRCC and PRCC complicated with tumor thrombus were analyzed and summarized. RESULTS: The average age of the 75 patients was(56.05±11.59)years,the average body mass index (BMI) was (26±3) kg/m², and the average tumor maximum diameter was (5.17±3.85) cm. There were significant differences between tumor maximum diameter larger than 7 cm and less than 7 cm (69.6% vs. 94.4%, P<0.001), lymph node metastasis and no lymph node metastasis (<38% vs. 98%, P<0.001), adrenal metastasis and no adrenal metastasis (0% vs. 95.3%, P<0.001), pulmonary metastasis and no pulmonary metastasis (0% vs.90.7%, P<0.001), complicated with and without tumor thrombus (<66.4% vs. 93.5%, P<0.001) on the effect of 3-year survival rate of the PRCC patients. In this study, there were 16 patients with type 2 PRCC complicated with tumor thrombus. There were significant differences in concomitant symptoms (62.5% vs. 22.0%, P=0.005), maximum tumor diameter (68.8% vs.13.3%, P<0.001), adrenal metastasis (18.8% vs. 0.02%, P=0.029), pulmonary metastasis (18.8% vs. 0%, P=0.008), nuclear grade (P<0.001) and pathological type (100% vs. 44.1%, P<0.001) between the PRCC patients with and without tumor thrombus. CONCLUSION: There were significant differences in tumor diameter,lymph node metastasis,adrenal metastasis, pulmonary metastasis,pathological type, nuclear grade and tumor thrombus in the effect of the 3-year survival rate of PRCC patients. PRCC patients with tumor thrombus were more commonly suffered from type 2 PRCC, for whom the tumor diameter was larger,the nuclear grade was higher,and the distance metastasis happened more easily.

[Association between polymorphism in notch signaling pathway and lung cancer risk].

Objective: To analyze the relationship between single nucleotide polymorphisms (SNP) of Notch signaling pathway and susceptibility to lung cancer. Methods: The present study was a hospital-based case-control study. All 1 121 patients of lung cancer diagnosed by histopathology three hospitals in Fujian and Nanjing were selected as cases from January 2006 to December 2012. At the same time, 1 121 healthy population from other departments of the hospital to visit patients or community, excluding those with tumor, chronic disease, and immediate family members of lung cancer, were enrolled in control group. A uniform questionnaire was used to collect general information. Matrix-assisted laster desorption ionization time of flight mass spectrometry (MALDI-TOF-MS) was used to identify the polymorphisms of 9 SNP (Notch3 rs3815188, Notch4 rs915894, Notch4 rs520692, DLL1 rs1033583, JAG1 rs8708, JAG2 rs9972231, HEY1 rs1046472, HEY2 rs3734637, HES2 rs11364) in 1 121 lung cancer patients and 1 121 healthy controls. The association between SNP and lung cancer was analyzed by χ(2) and logistic regression model. Results: The average age of cases and controls was (58.70±10.73) and (58.98±10.85) years old. The OR for genotype AC carriers of HEY1 rs1046472 was 0.80 (95%CI: 0.66-0.97) when comparing with genotype CC. The OR for genotype AC+AA carriers of HEY1 rs1046472 was 0.81 (95% CI: 0.67-0.98) when comparing with genotype CC. The OR for genotype AC carriers of HEY2 rs3734637 was 0.82 (95%CI: 0.67-0.99) when comparing with genotype AA. In the stratified analysis, Notch3 rs3815188, DLL1 rs1033583, JAG1 rs8708, JAG2 rs9972231, HEY1 rs1046472, HEY2 rs3734637, HES2 rs11364 were associatied with the risk of lung cancer, P were 0.041, 0.030, 0.043, 0.003, 0.004, 0.026 and 0.038, respectively.The interactions analysis done by logistic regression model showed JAG1 rs8708 and family history, JAG2 rs9972231 and BMI had interaction in the study, OR were 2.07 (95% CI:1.21-3.52) and 1.73 (95% CI:1.21-2.47), respectively. Conclusion: Notch3 rs3815188, DLL1 rs1033583, JAG1 rs8708, JAG2 rs9972231, HEY1 rs1046472, HEY2 rs3734637 and HES2 rs11364 were significantly associated with susceptibility to lung cancer.

Placental mitochondrial biogenesis and function was slightly changed by gestational hypercholesterolemia in full-term pregnant women.

It was reported that high blood cholesterol levels increased the susceptibility to mitochondrial dysfunction. This study hypothesized that the gestational hypercholesterolemia (HC) could induce the mitochondrial dysfunction in term human placenta. The eligible pregnant women were recruited from Xuanwu Hospital in Beijing during their first prenatal visit (before their 10th week of pregnancy). In total, 19 pregnant women whose serum total cholesterol levels were higher than 7.25 mm at third trimester (measured at 36-38 weeks) were selected as gestational HC. Other 19 pregnant women with normal cholesterol level matched with age, pre-gestational body mass index, and the neonatal gender were included as the control group. Full-term placenta samples were collected. The mitochondrial DNA (mtDNA) copy number, messenger RNA (mRNA) expression of cytochrome c oxidase subunit I, adenosine triphosphate monophosphatase 6 (ATP6ase), citrate synthase, peroxisome proliferator-activated receptor-γ (PPARγ) co-activator 1α, PPARγ co-activator 1ß and estrogen-related receptor-α, and the activity of mitochondrial respiratory chain enzyme complex were measured. Pregnancy outcomes were obtained by extraction from medical records and the labor ward register. The results showed that only placental mtDNA copy number and mRNA expression of ATP6ase were significantly decreased in HC group. No significant differences were detected of other measurements between the two groups. These findings indicated that gestational HC might not induce the damage of placental function seriously.

Novel lncRNA Erbb4-IR Promotes Diabetic Kidney Injury in db/db Mice by Targeting miR-29b.

Transforming growth factor-ß/Smad signaling plays an important role in diabetic nephropathy. The current study identified a novel Smad3-dependent long noncoding RNA (lncRNA) Erbb4-IR in the development of type 2 diabetic nephropathy (T2DN) in db/db mice. We found that Erbb4-IR was highly expressed in T2DN of db/db mice and specifically induced by advanced glycosylation end products (AGEs) via a Smad3-dependent mechanism. The functional role of Erbb4-IR in T2DN was revealed by kidney-specific silencing of Erbb4-IR to protect against the development of T2DN, such as elevated microalbuminuria, serum creatinine, and progressive renal fibrosis in db/db mice, and to block AGE-induced collagen I and IV expression in mouse mesangial cells (mMCs) and mouse tubular epithelial cells (mTECs). Mechanistically, we identified that the Erbb4-IR-microRNA (miR)-29b axis was a key mechanism of T2DN because Erbb4-IR was able to bind the 3' untranslated region of miR-29b genomic sequence to suppress miR-29b expression at transcriptional level. In contrast, silencing of renal Erbb4-IR increased miR-29b and therefore protected the kidney from progressive renal injury in db/db mice and prevented mTECs and mMCs from AGE-induced loss of miR-29b and fibrotic response in vitro. Collectively, we identify that Erbb4-IR is a Smad3-dependent lncRNA that promotes renal fibrosis in T2DN by suppressing miR-29b. Targeting Erbb4-IR may represent a novel therapy for T2DN.

An in-situ thermally regenerated air purifier for indoor formaldehyde removal.

Formaldehyde is a common indoor pollutant that is an irritant and has been classified as carcinogen to humans. Adsorption technology is safe and stable and removes formaldehyde efficiently, but its short life span and low adsorption capacity limit its indoor application. To overcome these limitations, we propose an in-situ thermally regenerated air purifier (TRAP) which self-regenerates as needed. This purifier has four working modes: cleaning mode, regeneration mode, exhaust mode, and outdoor air in-take mode, all of which are operated by valve switching. We developed a real-scale TRAP prototype with activated carbon as adsorbent. The experimental testing showed that the regeneration ratios for formaldehyde of TRAP were greater than 90% during 5 cycles of adsorption-regeneration and that through the 5 cycles, there was no damage to the adsorption material as confirmed by scanning electron microscope (SEM) and Brunauer-Emmett-Teller (BET) tests. The total energy consumption by the prototype for purifying 1000 m3 indoor air was 0.26 kWh. This in-situ thermal-regeneration method can recover the purifier's adsorption ability through at least five cycles.

Regenerative approaches for cartilage repair in the treatment of osteoarthritis.

Osteoarthritis (OA) as a debilitating affliction of joints currently affects millions of people and remains an unsolved problem. The disease involves multiple cellular and molecular pathways that converge on the progressive destruction of cartilage. Activation of cartilage regenerative potential and specific targeting pathogenic mediators have been the major focus of research efforts aimed at slowing the progression of cartilage degeneration and preserve joint function. This review will summarize recent key discoveries toward better understanding of the complex mechanisms behind OA development and highlight the latest advances in basic and clinical research in the approach for cartilage regeneration. Prospectively, more potent therapeutic strategies against progressive cartilage deterioration may use a combination of cytotherapy, pharmacotherapy, and bioscaffoldings for improved chondrogenic differentiation and stem/progenitor cell homing as well as the concomitant reduced enzymatic matrix degradation and inflammation. Further, treatments need to be provided with increased preciseness of targeted therapy. One might expect that the regenerative therapies could potentially control or even possibly cure OA if performed at early stages of the disease.