Effect of nourishing and purging fire Chinese herbal mixture on delaying light-induced premature puberty in rats.

OBJECTIVE: To elucidate the mechanism of the nourishing Yin and purging fire Chinese herbal mixture (NYPF) in delaying light-induced premature puberty in rats. METHODS: Twenty-one days old female Sprague-Dawley rats were randomly assigned to normal group (N), long light exposure group (L), NYPF and normal saline group (NS). Rats in the L, NYPF and NS groups were exposed to 16 h: 350 lux light/8 h: dark, while rats in the N group were exposed to 12 h: 50 lux light/12 h: dark. NYPF and normal saline was administered to the rats in the NYPF group or NS group, respectively, from day 21. Five rats in every group were sacrificed at 9 p.m. on day 28 (P28), on the day when rat's vulva opened in the L group (L-VO), on the day when the first estrous interphase occurred in rats of L group (L-E1), and on the day when the second estrous interphase occurred in rats of L group (L-E2), respectively. RESULITS: On day 34, all rats in the L group, 80% of rats in the NS group, 40% of rats in the N group, and 20% of rats in the NYPF group showed complete opening of the vulva. At P28, mRNA level of hypothalamic kisspeptin (Kiss-1) in the L group was significantly higher than that in the N group (P < 0.05). The rats in the L and NS groups had significantly lower hypothalamic arginine-phenylalanine-amide (RFamide)-related peptide 3 (RFRP-3) mRNA levels than those in the N group (P < 0.05), whereas RFRP-3 mRNA level was significantly higher in the NYPF group than that in the L group (P < 0.05). At L-VO, the ovarian index of the L and NS groups was significantly higher than that of the N group (P < 0.05) and estradiol (E2) level of the NYPF group was significantly lower than that of the N and NS groups (P < 0.05); hypothalamic Kiss-1 mRNA level in the L and NS groups was significantly higher than that in the N and NYPF groups (P < 0.05), whereas hypothalamic RFRP-3 mRNA level in the L, NYPF, and NS groups was significantly lower than that in the N group (P < 0.05). At L-E1, E2 level of the L and NS groups was significantly higher than that of the N group (P < 0.01), whereas it was significantly lower in the NYPF group than that of the N, L, and NS groups (P < 0.01), and serum luteinizing hormone level of the L and NS groups was significantly higher than that of the N group (P < 0.05); levels of serum melatonin and ovarian melatonin receptor 1 (MT-1) mRNA in the L, NYPF, and NS groups were significantly lower than those in the N group (P < 0.05). At L-E2, the uterine organ index of the NYPF group was significantly lower than that of the L group (P < 0.05); and ovarian MT-1 mRNA level of the L and NS groups was significantly lower than that in the N group (P < 0.05). CONCLUSIONS: NYPF can delay puberty onset in rats exposed to strong light for a prolonged duration, and regulation of the gene expression of Kiss-1 and RFRP-3 in the hypothalamus has been suggested as one of the mechanisms.

[Prognostic value of the Second Revision of the International Staging System in patients with newly diagnosed transplant-eligible multiple myeloma].

Objective: To verify the predictive value of the Second Revision of the International Staging System (R2-ISS) in newly diagnosed patients with multiple myeloma (MM) who underwent first-line autologous hematopoietic stem cell transplantation (ASCT) in a new drug era in China. Methods: This multicenter retrospective cohort study enrolled patients with newly diagnosed MM from three centers in China (Beijing Chao-Yang Hospital, Capital Medical University; the First Affiliated Hospital, Sun Yat-Sen University, and the Second Affiliated Hospital of Naval Medical University) from June 2008 to June 2018. A total of 401 newly diagnosed patients with MM who were candidates for ASCT were enrolled in this cohort, all received proteasome inhibitor and/or immunomodulator-based induction chemotherapy followed by ASCT. Baseline and follow-up data were collected. The patients were regrouped using R2-ISS. Progression-free survival (PFS) and overall survival (OS) were analyzed. The Kaplan-Meier method was used to analyze the survival curve and two survival curves were compared using the log-rank test. Cox regression analysis were performed to analyze the relationship between risk factors and survival. Results: The median age of the patients was 53 years (range 25-69 years) and 59.5% (240 cases) were men. Newly diagnosed patients with renal impairment accounted for 11.5% (46 cases). According to Revised-International Staging System (R-ISS), 74 patients (18.5 %) were diagnosed with stage Ⅰ, 259 patients (64.6%) with stage Ⅱ, and 68 patients (17.0%) with stage Ⅲ. According to the R2-ISS, the distribution of patients in each group was as follows: 50 patients (12.5%) in stage Ⅰ, 95 patients (23.7%) in stage Ⅱ, 206 patients (51.4%) in stage Ⅲ, and 50 patients (12.5%) in stage Ⅳ. The median follow-up time was 35.9 months (range, 6-119 months). According to the R2-ISS stage, the median PFS in each group was: 75.3 months for stage Ⅰ; 62.0 months for stage Ⅱ, 39.2 months for stage Ⅲ, and 30.3 months for stage Ⅳ; and the median OS was not reached, 86.6 months, 71.6 months, and 38.5 months, respectively. There were statistically significant differences in PFS and OS between different groups (both P<0.001). Multivariate Cox regression analysis showed that stages Ⅲ and Ⅳ of the R2-ISS were independent prognostic factors for PFS (HR=2.37, 95%CI 1.30-4.30; HR=4.50, 95%CI 2.35-9.01) and OS (HR=4.20, 95%CI 1.50-11.80; HR=9.53, 95%CI 3.21-28.29). Conclusions: The R2-ISS has significant predictive value for PFS and OS for transplant-eligible patients with MM in the new drug era. However, the universality of the R2-ISS still needs to be further verified in different populations.

[Discussion on surgical treatment mode of diabetic foot wounds].

Diabetic foot wounds have a high incidence and uneven therapeutic effect, so it is necessary to explore the suitable treatment mode of diabetic foot wounds. The existing surgical treatment modes for diabetic foot wounds include the multi-disciplinary team (MDT) cooperation mode and the "five-in-one comprehensive limb salvage" treatment mode. These two modes have their own advantages, but are inconvenient to some extent. In response to this problem, the author's team proposed the wound surgical integrated treatment (WSIT) mode based on years of experience in repairing diabetic foot wounds, emphasizing the perioperative management by MDT, and the local wound management by WSIT team, which significantly improved the diagnosis and treatment efficiency of patients with diabetic foot wounds.

[Research advances on the application of free flaps in repairing diabetic foot ulcers].

Free flaps have been successfully used in the repair of diabetic foot ulcers (DFUs), which can reduce amputation rate, maintain normal gait of patients, and improve life quality of patients. However, there are still many challenges in the repair of DFUs with free flaps, and many problems need to be solved. This paper summarizes the selection of patients, preoperative cautions, types of flaps, methods of vascular anastomosis, clinical effects, and existing problems in using free skin flaps for repairing DFUs.

Sex difference in the expression of PD-1 of non-small cell lung cancer.

Evidence increasingly indicated that lung cancer incidence in female individuals continue to rise, and women have a higher risk to develop adenocarcinoma than men. Male and female individuals differ in their innate and adaptive immune responses, and there are sex differences in response to the PD-1/PD-L1-dependent blocking immunotherapy. Whether the differential expression of PD-1 between genders affect the response to blocking treatment is currently unknown. In this study, we examined sex differences in serum sPD-1, mPD-1 expression on T cells, and sex hormone levels in non-small cell lung cancer (NSCLC) patients. Our results revealed a higher level of sPD-1 and expression of PD-1 on CD4+T cell in female patients than in male patients; we identified that serum sPD-1 level and the expression of mPD-1 on T cells were significantly reduced in NSCLC; we also found that serum testosterone level increased in female patients compared with control subjects and that increased testosterone downregulated the expression of mPD-1 on T cell. These findings provide a better understanding of the differences in PD-1 expression between genders in NSCLC patients and the effect of sex hormones on PD-1 expression and supply evidence for early lung cancer diagnosis and responsiveness to immune checkpoint inhibitors.

[The prognostic relationship between CD56 expression and newly diagnosed multiple myeloma].

Objective: To evaluate the prognostic value of CD56 expression in newly diagnosed MM (NDMM). Methods: A total of 332 NDMM patients were enrolled in Beijing Chaoyang Hospital, Capital Medical University from January 1, 2011 to January 1, 2021, with a median age of 60 years and a male to female ratio of 1.2∶1. CD56 expression on myeloma cells was detected by flow cytometry before induction therapy. Overall survival (OS) and progression-free survival (PFS) data were collected. In order to reduce the confounding factors, the propensity score matching technique was used to match CD56 positive versus negative patients at a ratio of 1∶1. Results: Among 332 patients, CD56 positivity rate was 65.1% (216/332). Patients with CD56 expression had significantly longer median OS (58.4 vs. 43.1 months, P=0.024) and PFS (28.7 vs. 24.1 months, P=0.013) than those with negative CD56. Univariate Cox proportional hazards regression analyses showed that CD56 expression was positively correlated with OS (HR=0.644, 95%CI 0.438-0.947, P=0.025) and a favorable prognostic factor for PFS (HR=0.646, 95%CI 0.457-0.913,P=0.013). The favorable effect of CD56 expression on PFS was confirmed in multivariate analysis (HR=0.705, 95%CI 0.497-0.998, P=0.049), but OS was not affected (P>0.05).In the propensity score matching analysis, 194 patients with 97 in each group were identified. CD56 positivity consistently predicted longer PFS (34.2 vs.25.1 months, P=0.047), but not OS (63.4 vs.43.1 months, P=0.056). Conclusion: These results demonstrate that CD56 expression is a favorable prognostic factor for PFS of newly diagnosed MM patients.

[Establishment and preliminary application of a recombinase-aided isothermal amplification assay-based multiplex nucleic acid assay for detection of three Echinococcus species].

OBJECTIVE: To establish a multiplex nucleic acid assay for rapid detection of Echinococcus multilocularis, E. granulosus and E. shiquicus based on the recombinase-aided isothermal amplification assay (RAA) and to preliminarily assess its diagnostic efficiency. METHODS: The mitochondrial genomic sequences of E. multilocularis (GenBank accession number: NC_000928), E. granulosus (GenBank accession number: NC_044548) and E. shiquicus (GenBank accession number: NC_009460) were used as target sequences, and three pairs of primers were designed based on the RAA primer design principle and synthesized for the subsequent multiple RAA amplification. The genomic DNA of E. multilocularis, E. granulosus and E. shiquicus at different concentrations and the recombinant plasmids containing the target gene at various concentrations were amplified to evaluate the diagnostic sensitivity of the multiplex RAA assay, and the genomic DNA of E. multilocularis, E. granulosus, E. shiquicus, Taenia multiceps, T. saginata, T. asiatica, Dipylidium caninum, T. hydatigena, Toxocara canis, Fasciola hepatica, T. pisiformis, Mesocestoides lineatus and Cryptosporidiumn canis was detected using the multiplex RAA assay to evaluate its specificity. In addition, the reaction condition of the multiplex RAA assay was optimized, and was then employed to detect the tissues with echinococcosis lesions, simulated canine fecal samples and field captured fox fecal samples to examine its application values. RESULTS: The multiplex RAA assay was effective to specifically amplify the mitochondrial gene fragments of E. multilocularis, E. granulosus and E. shiquicus within 40 min at 39 °C, with sequence lengths of 540, 430 bp and 200 bp, respectively. This multiplex RAA assay showed the minimum detection limits of 2.0, 2.5 pg/µL and 3.1 pg/µL for detection of the genomic DNA of E. multilocularis, E. granulosus and E. shiquicus, and presented the minimum detection limit of 200 copies/µL for detection of the recombinant plasmids containing E. multilocularis, E. granulosus and E. shiquicus target genes. This multiplex RAA assay was effective to simultaneously detect single and multiple infections with E. multilocularis, E. granulosus and E. shiquicus, but failed to amplify the genomic DNA of T. multiceps, T. saginata, T. asiatica, D. caninum, T. hydatigena, T. canis, F. hepatica, T. pisiformis, M. lineatus and C. canis. In addition, the optimized multiplex RAA assay was effective to detect all positive samples from the tissue samples with echinococcosis lesions, simulated canine fecal samples and field captured fox fecal samples, which was fully consistent with the detection of the single PCR assay. CONCLUSIONS: A sensitive and specific multiplex nucleic acid assay for rapid detection of E. multilocularis, E. granulosus and E. shiquicus has been successfully established.

[Autologous stem cell transplantation improve the survival of newly diagnosed multiple myeloma patients].

Objective: To evaluate the effect of autologous stem cell transplantation (auto-HSCT) on treatment remission and survival of newly diagnosed multiple myeloma (MM) patients. Methods: A total of 243 new diagnosed MM patients (age ≤65 years) who had received auto-HSCT were selected, and 176 MM patients (age ≤65 years) who had not received auto-HSCT were selected as the control group to evaluate the effect of auto-HSCT on the remission and survival. To balance the distribution of prognostic factors between auto-HSCT and non-auto-HSCT patients, the propensity score matching technique was used to reduce the bias between groups in a 1∶1 scale, 64 in each group, and correlation analysis was performed. Results: A total of 128 patients (64 cases in each group) were screened by propensity score matching analysis. 64 patients received auto-HSCT after induction therapy. After auto-HSCT, 24 patients (37.5%) obtained sCR, 16 patients (25.0%) obtained CR, 15 patients (23.4%) obtained VGPR, and 9 patients (14.1%) obtained PR. The efficacy of patients with auto-HSCT was significantly better than that of non-auto-HSCT patients (P=0.032) . Progression-free survival (PFS) and overall survival (OS) were significantly longer in auto-HSCT patients compared with non-auto-HSCT patients[PFS: 42.2 (95% CI 29.9-54.5) months vs 22.4 (95% CI 17.1-27.7) months, P=0.007; OS: 87.6 (95% CI 57.3-117.9) months vs 53.9 (95% CI 36.1-71.7) months, P=0.011]. Multivariate analysis confirmed that auto-HSCT had a favorable effect on OS (HR=0.448, 95%CI 0.260-0.771, P=0.004) and PFS (HR=0.446, 95%CI 0.280-0.778, P=0.003) . Conclusion: These results demonstrated that auto-HSCT was a favorable prognostic factor for newly diagnosed MM patients.

Papillary craniopharyngioma in a patient following resection of nonfunctioning pituitary adenoma: illustrative case.

BACKGROUND: Although craniopharyngioma and pituitary adenoma are common tumors of the sellar or suprasellar region, the development of papillary craniopharyngioma in the same sellar region after resection of a nonfunctioning pituitary adenoma has not been reported. OBSERVATIONS: Here the authors report the first case of craniopharyngioma that developed long after resection of a pituitary adenoma. A 66-year-old male patient underwent endoscopic transsphenoidal resection for a large sellar mass, which histopathologically confirmed the diagnosis of a pituitary adenoma. He had an excellent recovery after surgery. For several years, he had no clinical or imaging evidence of tumor recurrence and then was lost to follow-up. Seven years after the initial surgery, the patient returned with a one-month history of visual field defects, and imaging confirmed a heterogeneous, cystic suprasellar mass. Endoscopic transsphenoidal resection of the tumor was performed, and histological examination showed it to be a papillary craniopharyngioma. LESSONS: Neurosurgeons should be aware that after pituitary adenoma resection, a recurrent mass could be a craniopharyngioma, with implications for very different management recommendations.

Isatuximab as monotherapy and combined with dexamethasone in patients with relapsed/refractory multiple myeloma.

This phase 2 study evaluated isatuximab as monotherapy or combined with dexamethasone in relapsed/refractory multiple myeloma (RRMM). Patients had RRMM refractory to an immunomodulatory drug (IMiD) and a proteasome inhibitor (PI) or had received ≥3 prior lines of therapy incorporating an IMiD and PI. Patients received isatuximab either as monotherapy (20 mg/kg on days 1, 8, 15, and 22 [once weekly] of cycle 1 followed by 20 mg/kg on days 1 and 15 of subsequent cycles; Isa group) or in combination with dexamethasone (40 mg/d [20 mg/d in patients aged ≥75 years] once weekly; Isa-dex group). Treated patients (N = 164) had received a median of 4 (range, 2-10) prior treatment lines. Patients received a median of 5 (1-24) and 7 (1-22) treatment cycles; at data cutoff, 13 (11.9%) of 109 and 15 (27.3%) of 55 patients remained on treatment in the Isa and Isa-dex arms, respectively. Overall response rate (primary efficacy end point) was 23.9% in the Isa arm and 43.6% in the Isa-dex arm (odds ratio, 0.405; 95% confidence interval, 0.192-0.859; P = .008). Median progression-free survival and overall survival were 4.9 and 18.9 months for Isa, and 10.2 and 17.3 months for Isa-dex. Infusion reactions (mostly grade 1/2) and hematologic abnormalities were the most common adverse events. There was a similar incidence of grade 3 or higher infections in both groups (22.0% and 21.8%). In conclusion, addition of dexamethasone to isatuximab increased response rates and survival outcomes with no detrimental effect on safety. This trial was registered at www.clinicaltrials.gov as #NCT01084252.

Hypomethylation of CTCFL promoters as a noninvasive biomarker in plasma from patients with hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the third deadliest cancer in the world with high morbidity and poor prognosis. CTCFL (CCCTC-binding factor like) is a member of the cancer testis antigen (CTA) family with oncogenic properties. To demonstrate whether the hypomethylation of CTCFL promoters in plasma could be used as a noninvasive biomarker to predict poor prognosis of HCC, we extracted cell-free DNA from the plasma and detected the methylation status of CTCFL in 43 HCC, 5 liver cirrhosis and 6 benign lesion samples using methylation specific PCR (MSP). Our study indicated that the hypomethylation of CTCFL promoters in HCC plasma samples (60.4%) was significantly different from that in benign lesion plasma samples (16.7%) with a p-value of 0.043. Analysis of clinicopathological data showed that the methylation status of CTCFL promoters was significantly correlated with microvascular involvement (MVI) (p=0.001) and postoperative recurrence (p=0.031). Furthermore, clinical prognosis data of 347 HCC patients from The Cancer Genome Atlas (TCGA) database displayed that the hypomethylated group had worse overall survival than the hypermethylated group (p=0.0056). In conclusion, we provide evidence that the hypomethylation of CTCFL promoters in cell-free DNA is a biomarker for monitoring HCC patients, which can be used as a noninvasive prediction index for tumor recurrence and provide the individualized decision-making for clinicians.

MicroRNA-34a suppresses neuronal apoptosis and alleviates microglia inflammation by negatively targeting the Notch pathway in spinal cord injury.

OBJECTIVE: The purpose of this study was to investigate role of inhibition of microRNA-34a (miR-34a) in neural damage and repair after spinal cord injury, and to explore the underlying mechanism. MATERIALS AND METHODS: In BV2 microglia, we conducted classical activation using lipopolysaccharide (LPS) and pre-treatment using miR-34a mimics. The expressions of miR-34a, Notch 1, and Jagged 1 were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Moreover, the protein expressions of inflammatory microglia markers were evaluated by Western blotting. In vivo, SCI model was successfully established in rats. Subsequently, the expression levels of miR-34a, Notch 1, and Jagged 1 levels within 1 week were measured by qRT-PCR. Meanwhile, protein expressions of inflammatory mediators were determined by enzyme-linked immunosorbent assay (ELISA) assay. Immunofluorescence was conducted to display the activation degree of microglia and residual neural structure. Furthermore, locomotor function recovery was estimated using BBB rating scale. RESULTS: Compared with the only LPS-activated group, pre-treatment of miR-34a mimics significantly decreased the expressions of Notch 1 and Jagged 1. Similarly, the protein expressions of CD11b and iNOS were significantly down-regulated. In vivo, the levels of Notch 1 and Jagged 1 within 1 week increased significantly, while miR-34a was negatively regulated following spinal cord injury (SCI). Furthermore, the contents of interleukin-1 beta (IL-1ß) and IL-6 were reduced with the treatment of miR-34a mimics when compared with SCI group. With the treatment of miR-34a, the number of inflammatory microglia decreased significantly, and the remaining neural structure was similarly improved. In addition, locomotor function recovery of hindlimbs in rats was significantly ameliorated after the administration of miR-34a mimics. CONCLUSIONS: Increase of miR-34a suppresses neuronal apoptosis and alleviates microglia inflammation by negatively targeting the Notch pathway, thereby improving neural recovery and locomotor function.

[The investigation and prognosis in patients with non-alcoholic fatty liver disease and coronary vulnerable plaque].

Objective: To investigate the prevalence and prognosis of non-alcoholic fatty liver disease (NAFLD) complicated with coronary vulnerable plaque (VP). Method: Consecutive patients were included who had undergone coronary artery CT angiography (CCTA) from January 1, 2011 to January 30, 2015 at the First People's Hospital of Neijiang. NAFLD was diagnosed according to the liver imaging findings (liver/spleen CT ratio≤1.0) and clinical data. Baseline data, diagnosis, vulnerable plaque were recorded and followed up. The end points included all-cause death rate, cardiac death rate, non-fatal myocardial infarction rate, and elective coronary revascularization rate. Result: A total of 1 069 patients were eventually recruited in this study, including 316 (29.6%) cases diagnosed as NAFLD. In patients with NAFLD, 130 (41.1%) cases had vulnerable plaque, which was significantly higher than 217 of 753 non-NAFLD patients (28.8%) (P<0.01). The percentages of spotty calcification, low attenuation plaque, positive remodeling and napkin ring sign in NAFLD cohort were 36.5%, 14.2%, 17.6% and 6.8% respectively, while those corresponding in non-NAFLD cohort were 18.4%, 6.3%, 5.8% and 3.2% respectively. The proportion of each vulnerable feature in NAFLD cohort was significantly higher than that in the non-NAFLD cohort, with P values of 0.016, 0.028, 0.019 and 0.042, respectively. The cardiac mortality rate in NAFLD group was significantly higher than and that of non-NAFLD group (7.0% vs. 3.6%, P=0.044). Multivariate Cox analysis suggested that NAFLD was not an independent risk factor for cardiac death. NAFLD subgroup (n=316) was divided into VP positive group (NAFLD+VP+, n=130) and VP negative group (NAFLD+VP-, n=186). The mean follow-up time was 4.6±1.3 years. All-cause mortality rate, cardiac death rate, elective coronary artery reconstruction rate, non-fatal myocardial infarction rate in NAFLD+VP+group were 20.8%, 12.3%, 25.4%, 13.8% respectively, which were significantly higher than those corresponding rates in NAFLD+VP-group (5.9%, 3.2%, 8.6%, 6.5%) (P<0.01, 0.002,<0.01, and 0.032 respectively). Conclusion: The incidences of cardiac mortality, elective coronary revascularization, and non-fatal myocardial infarction are significantly higher in patients with NAFLD than those without. NAFLD combined with vulnerable plaque of coronary arteries predicts worse prognosis.

Vitamin D-supplemented yogurt drink reduces Candida infections in a paediatric intensive care unit: a randomised, placebo-controlled clinical trial.

BACKGROUND: The prevalence of Candida infections in paediatric intensive care units (PICUs) has dramatically increased as a result of resistance to conventional anti-fungal treatments. Because vitamin D has been shown to exhibit fungicidal activity against Candida infection in an in vitro antimicrobial screening, we aimed to investigate the effect of vitamin D on Candida infections in the PICU. METHODS: Four hundred sixteen eligible children aged between 12 months to 5 years old admitted to the PICU, who were on broad-spectrum antibiotic therapy, participated in the study. Patients were randomly assigned to two study groups, receiving a plain yogurt drink (placebo group) or supplemented with 300 IU day-1 vitamin D (VD group). Primary outcome was defined as the incidences of Candida colonisation (Candida isolated from rectal swab) 14 days after enrollment. Secondary outcome measures were Candida growth in blood (candidaemia) and urine (candiduria). RESULTS: The prevalence of candiduria as well as candidaemia was significantly lower in the VD-treated group (26 cases) than in the placebo group (62 cases). The mean (SD) length of PICU stay was obviously lowered in the VD group [11.8 (1.2) days] compared to the placebo group [15.2 (2.3 days)], whereas cases of patient death were similar between the two groups. CONCLUSIONS: Supplementation of vitamin D effectively reduces infections of Candida in children who were critically ill and on broad-spectrum antibiotic treatment.

[Experimental studies on the repair and restitution of cartilage by cartilage acellular extracellular matrix and adipose tissue-derived stem cells].

Objective: To investigate the effects of the repair and restitution of ear-shaped cartilage by adipose tissue-derived stem cells(ADSC) and cartilage acellular extracellular matrix. Methods: ADSC were extracted by digesting with collagenase type II from the adipose tissue from 32 patients with adiposity whose fats were drawn, and were cultured and subcultured in vitro. The natural biological scaffolds were prepared by acellular method using porcine ear cartilage, and then the second generation ADSC(5.0×10(7)/ml) were inoculated on the preformed natural bio-scaffold scaffold by culturing in vitro for 3 days to form a cell scaffold complex. 32 New Zealand white rabbits were randomly divided into the experimental groups, the control group A, the control group B and the control group C. All New Zealand white rabbits were modeled by ear cartilage defects. The cell scaffolds composite was implanted into the experimental group of the ear cartilage defects of rabbits, the ADSC were implanted into the control group A, the cartilage acellular extracellular matrix scaffold was implanted into the control group B and the control group C was modeled only by ear cartilage defects. After 16 weeks, the animals were sacrificed and the repair effect was observed by gross appearance and histological examinations including HE, Toluidine blue staining, Safranin O and typeⅡ collagen staining. Its were quantitatively analyzed by positive staining results of type Ⅱ collagen. Ear cartilage tissue elasticity was detected. SPSS 17.0 software was used to analyze the data. Results: The cartilage defects in the experimental group were repaired well by general shape observation and those in the control group was filled in with granulation tissue. There were significant differences between the experimental group and the control group in the wet weight(P<0.05). HE staining showed that cartilage cavities formed in articular cartilage defects, and only the fibrous tissue was filled with the ear cartilage defect in the control groups. In the repair area, Toluidine blue staining, Safranin O and type Ⅱ collagen staining were positive in the experimental group, and negative in the control groups. There was no significant difference between the experimental group and the normal ear cartilage in the ear cartilage elastic constant detection(P>0.05). Conclusions: The mechanics and histology of rabbit ear neonatal cartilage constructed by ADSC combined with cartilage acellular matrix are close to normal ear cartilage. Cartilage acellular matrix material combined with adipose-derived stem cells has good repair and reconstruction ability for ear cartilage defects, which possesses potential clinical application value.

Metastatic Subdural Hematoma with Dural Metastasis Secondary to Poorly Differentiated Adenocarcinoma of Unknown Origin.

BACKGROUND: Metastatic subdural hematoma with dural metastasis in the setting of an underlying malignancy is a rare condition that is difficult to diagnose and associated with a poor prognosis. Knowledge of this rare entity is of a paramount importance to neurosurgeons, as its diagnosis may affect the management plan and overall survival. Here, we report a rare case of atraumatic subdural hematoma with dural metastasis in a patient with poorly differentiated adenocarcinoma of unknown origin. CASE DESCRIPTION: A 34-year-old man presented with an insidious onset of headaches, severe light headedness, progressive low back pain, and generalized weakness for 2 weeks. On imaging, he was found to have left-sided acute on chronic subdural hematoma with midline shift. The patient underwent surgical evacuation of the hematoma and the subdural membrane was biopsied. Histopathologic examination revealed metastatic poorly differentiated adenocarcinoma of unclear origin. A full metastatic workup was unremarkable. CONCLUSIONS: Metastatic subdural hematoma with dural metastasis should be included in differential diagnosis of subdural hematoma, especially in patients with atypical presentation and in the presence of an underlying malignancy, as it may affect the management plan and overall survival.

[The clinic experience of implantable diaphragm pacer in a patient with high cervical spinal cord injury and literature review].

Objective: To report the use of implantable diaphragm pacer (IDP) in a patient with high cervical spinal cord injury(HCSCI). Methods: A 14-year-old male patient, who suffered from a HCSCI at C2 neurological level and had been on a ventilator for 2 years, received IDP in August 2017 at China Rehabilitation Research Center. A systematic literature review was performed on IDP in patients with HCSCI in Pubmed, CNKI, and Wanfang databases, using the keywords: phrenic nerve and electrical stimulation and spinal cord injury; IDP and spinal cord injury; breathing pacemaker system and spinal cord injury. All fields were covered from 1970/01/01 to 2018/01/01 in Pubmed, from 1981/01/01 to 2018/01/01 in CNKI, and from 1900/01/01to 2018/01/01 in Wanfang. Results: No spontaneous breathing was observed preoperatively in the patient. The electrical response of phrenic nerves was intact on the right, but unresponsive on the left. We got started with the IDP at 4 weeks after surgery. The threshold voltage of the right hemidiaphragm pacing was 0.1 V and at the level of 0.7 V with an optimal effect. No significant diaphragmatic contraction was found at left side with the extent up till 0.7 V. The maximum tidal volume was 840 ml when electrical stimulation was given at an intensity of 0.7 V bilaterally. The bilateral stimulation voltage at 0.1-0.2 V, pacing frequencies at 9 beats/min in bed, or at 12 beats/min on wheelchair, were set to maintain the tidal volume at the level of (435±32) ml. After 2-week adaptive training, the patient could wean from the ventilator for 12 hours and had a normal blood gas analysis. At 6 week after surgery, with the aid of IDP, the patient could get out in wheelchair for outdoor activities. By literature review, we found 78 English papers, including 6 clinical trials, 10 reviews, and 11 Chinese papers, consisting of 8 reviews, 1 study in animal, and 2 news reports. Extensive contents, such as preoperative evaluation, preoperative preparation, surgical procedures, complications, surgical outcomes, and animal model studies of IDP were involved. The indications of IDP reported by literature were: (1) central alveolar hypoventilation; (2) Sleep apnea syndrome (Biot's respiration); (3) Respiratory failure induced by brainstem injury or disease; (4) Respiratory failure induced by spinal cord injury or disease above C3 level. Conclusion: Our case study confirmed the therapeutic effect of IDP on patients with respiratory failure caused by HCSCI.

Optimizing Live Kidney Donor Workup: A Decision Analysis Approach.

BACKGROUND: Screening potential live kidney donors is an intense process for both candidates and the healthcare system. It is conventionally implemented using a standard generic protocol. Efficiencies in this process could potentially be achieved using personalized protocols that are optimized for a given candidate. Aim: To create personalized protocols (by age, sex, and paired exchange status) and evaluate them relative to the standard generic protocol. METHODS: Two personalized protocols were created. One sequenced tests according to probability (high to low) of excluding a given candidate. The other sequenced tests according to the expected cost (low to high) per exclusion. Test costs and exclusion probabilities were extracted predominantly from Australian sources. These were integrated into a decision analysis incorporating Markov processes. This estimated the expected financial cost and expected number of tests performed to exclude an ineligible candidate in the standard generic and personalized protocols. RESULTS: The standard generic protocol consistently ranked poorest in terms of expected costs and expected tests per exclusion across all ages, sexes, and paired exchange status. Compared with the most efficient personalized protocol, the standard generic protocol was on average A$1767.49 more expensive and required 3.53 more tests. CONCLUSIONS: Personalized protocols enhance the ability of a kidney transplant unit to effectively exclude live kidney donor candidates more quickly and cost effectively compared with the conventional standard generic protocol.

Curcumin converts Foxp3+ regulatory T cells to T helper 1 cells in patients with lung cancer.

The regulatory T cells (Treg) play an important role in the tumor tolerance. The methods to regulate the Treg population in cancer-bearing hosts are limited currently. The effect of curcumin on inhibiting cancer has been recognized, but the mechanism remains elusive. This study tests a hypothesis that administration of curcumin down regulates Tregs in lung cancer (LC) patients. In this study, a group of LC patients was treated with curcumin. The peripheral Tregs and T helper (Th) 1 cells were analyzed by flow cytometry. The mechanism by which curcumin regulated the Tregs was observed by cell culture approaches. The results showed that the frequency of peripheral Treg was markedly higher in LC patients than that in healthy subjects, which was suppressed after treating with curcumin for 2 weeks. The peripheral Th1 cells were increased in LC patients after the curcumin therapy. The data of the in vitro experiments showed that curcumin converted the LC patient-isolated Tregs to Th1 cells via repressing the gene transcription of forkhead protein-3 and increasing the expression of interferon-γ. In conclusion, curcumin can convert LC patient-isolated Tregs to Th1 cells. The results suggest that curcumin may improve the antitumor immunity by regulating the tumor specific immune tolerance.

CGI-99 promotes breast cancer metastasis via autocrine interleukin-6 signaling.

Metastatic relapse remains largely incurable and a major challenge of clinical management in breast cancer, but the underlying mechanisms are poorly understood. Herein, we report that CGI-99 is overexpressed in breast cancer tissues from patients with metastatic recurrence within 5 years. High CGI-99 significantly predicts poorer 5-year metastasis-free patient survival. We find that CGI-99 increases breast cancer stem cell properties, and potentiates efficient tumor lung colonization and outgrowth in vivo. Furthermore, we demonstrate that CGI-99 activates the autocrine interleukin-6 (IL-6)/STAT3 signaling by increasing the accumulation and activity of RNA polymerase II and p300 cofactor at the proximal promoter of IL-6. Importantly, delivery of the IL-6-receptor humanized monoclonal antibody tocilizumab robustly abrogates CGI-99-induced metastasis in vivo. Finally, we find that high levels of CGI-99 are significantly correlated with STAT3 hyperactivation in breast cancer patients. These findings reveal a potential mechanism for constitutive activation of autocrine IL-6/STAT3 signaling and may suggest a novel target for clinical intervention in breast cancer.