OBJECTIVE To assess the performance of non-invasive prenatal testing (NIPT) based on massive parallel sequencing. METHODS A total of 10 275 maternal blood samples were collected. Fetal chromosomal aneuploides were subjected to low coverage whole genome sequencing. Patients with high risks received further prenatal diagnosis. The outcome of all patients were followed up. RESULTS High-throughput sequencing detected 72 pregnancies with fetal autosomal chromosomal aneuploidy, including 57 cases of trisomy 21, 14 cases of trisomy 18, and 1 case of trisomy 13. The positive predictive value for trisomies 21 and 18 were 98.25% and 91.67%, respectively. Comparing its performance in intermediate or high risk pregnancies, advanced maternal age pregnancies and volunteering to test pregnancies, the positive predictive value were 100%, 95%, 90% and 50%, respectively. The follow up result was only 1 case of 21 trisomy false negative with high risk. For the 56 cases of trisomy 21, the high risk group accounted for 55%, advanced maternal age accounted for 29%, the intermediate risk referred to 14%, the volunteering to test group accounted for 2%. CONCLUSION The performance of NIPT for trisomies 21, 18 and 13 was satisfactory. The method can be used for women with advanced gestational age. NIPT has offered an ideal secondary screening method for those with an intermediate or high risk, and can reduce the rate of birth defects.

PURPOSE: To demonstrate the feasibility, safety, and technical strategies of hand-assisted laparoscopic complete mesocolic excision (HAL-CME) and to compare oncological outcomes between HAL-CME and the open approach (O-CME) for right colon cancers. METHODS: Patients who were scheduled to undergo a right hemicolectomy were divided into HAL-CME and O-CME groups. Measured outcomes included demographic variables, perioperative parameters, and follow-up data. Demographic variables included age, sex distribution, body mass index (BMI), American Society of Anesthesiologists (ASA) physical status classification, previous abdominal surgery, tumor localization, and potential comorbidities. Perioperative parameters included incision length, operative time, blood loss, conversion rate, postoperative pain score, postoperative first passage of flatus, duration of hospital stay, total cost, number of lymph nodes retrieved, TNM classification, and postoperative complications. Follow-up data included follow-up time, use of chemotherapy, local recurrence rate, distant metastasis rate, and short-term survival rate. RESULTS: In total, 150 patients (HAL-CME, 78; O-CME, 72) were included. The groups were similar in age, sex distribution, BMI, ASA classification, history of previous abdominal surgeries, tumor localization, and potential comorbidities. Patients in the HAL-CME group had shorter incision lengths, longer operative times, less operative blood loss, lower pain scores, earlier first passage of flatus, shorter hospital stay, higher total costs, similar numbers of lymph nodes retrieved, similar TNM classifications, and a comparable incidence of postoperative complications. The 2 groups were also similar in local recurrence rate, distant metastasis rate, and short-term survival rate. CONCLUSION: The results demonstrate that the HAL-CME procedure is a safe, valid, and feasible surgical method for right hemicolon cancers.
Body Mass Index ; Classification ; Colectomy ; Colonic Neoplasms ; Comorbidity ; Drug Therapy ; Flatulence ; Follow-Up Studies ; Hand-Assisted Laparoscopy ; Humans ; Incidence ; Laparoscopy ; Length of Stay ; Lymph Node Excision ; Lymph Nodes ; Mesocolon ; Methods ; Neoplasm Metastasis ; Operative Time ; Pain, Postoperative ; Postoperative Complications ; Recurrence ; Sex Distribution ; Survival Rate

OBJECTIVE: To determine the relationship between intravoxel incoherent motion (IVIM) imaging derived quantitative metrics and serum soluble CD40 ligand (sCD40L) level in an embolic canine stroke model. MATERIALS AND METHODS: A middle cerebral artery occlusion model was established in 24 beagle dogs. Experimental dogs were divided into low- and high-sCD40L group according to serum sCD40L level at 4.5 hours after establishing the model. IVIM imaging was scanned at 4.5 hours after model establishment using 10 b values ranging from 0 to 900 s/mm². Quantitative metrics diffusion coefficient (D), pseudodiffusion coefficient (D*), and perfusion fraction (f) of ischemic lesions were calculated. Quantitative metrics of ischemic lesions were normalized by contralateral hemisphere using the following formula: normalized D = D(stroke) / D(contralateral). Differences in IVIM metrics between the low- and high-sCD40L groups were compared using t test. Pearson's correlation analyses were performed to determine the relationship between IVIM metrics and serum sCD40L level. RESULTS: The high-sCD40L group showed significantly lower f and normalized f values than the low-sCD40L group (f, p < 0.001; normalized f, p < 0.001). There was no significant difference in D*, normalized D*, D, or normalized D value between the two groups (All p > 0.05). Both f and normalized f values were negatively correlated with serum sCD40L level (f, r = −0.789, p < 0.001; normalized f, r = −0.823, p < 0.001). However, serum sCD40L level had no significant correlation with D*, normalized D*, D, or normalized D (All p > 0.05). CONCLUSION: The f value derived from IVIM imaging was negatively correlated with serum sCD40L level. f value might serve as a potential imaging biomarker to assess the formation of microvascular thrombosis in hyperacute period of ischemic stroke.
Animals ; CD40 Ligand* ; Diffusion ; Dogs ; Infarction, Middle Cerebral Artery ; Magnetic Resonance Imaging* ; Perfusion ; Stroke* ; Thrombosis

Paget's disease of bone (PDB) is a common metabolic bone disease that is characterized by aberrant focal bone remodeling, which is caused by excessive osteoclastic bone resorption followed by disorganized osteoblastic bone formation. Genetic factors are a critical determinant of PDB pathogenesis, and several susceptibility genes and loci have been reported, including SQSTM1, TNFSF11A, TNFRSF11B, VCP, OPTN, CSF1 and DCSTAMP. Herein, we report a case of Chinese familial PDB without mutations in known genes and identify a novel c.163G>C (p.Val55Leu) mutation in FKBP5 (encodes FK506-binding protein 51, FKBP51) associated with PDB using whole-exome sequencing. Mutant FKBP51 enhanced the Akt phosphorylation and kinase activity in cells. A study of osteoclast function using FKBP51V55L KI transgenic mice proved that osteoclast precursors from FKBP51V55L mice were hyperresponsive to RANKL, and osteoclasts derived from FKBP51V55L mice displayed more intensive bone resorbing activity than did FKBP51WT controls. The osteoclast-specific molecules tartrate-resistant acid phosphatase, osteoclast-associated receptor and transcription factor NFATC1 were increased in bone marrow-derived monocyte/macrophage cells (BMMs) from FKBP51V55L mice during osteoclast differentiation. However, c-fos expression showed no significant difference in the wild-type and mutant groups. Akt phosphorylation in FKBP51V55L BMMs was elevated in response to RANKL. In contrast, IκB degradation, ERK phosphorylation and LC3II expression showed no difference in wild-type and mutant BMMs. Micro-CT analysis revealed an intensive trabecular bone resorption pattern in FKBP51V55L mice, and suspicious osteolytic bone lesions were noted in three-dimensional reconstruction of distal femurs from mutant mice. These results demonstrate that the mutant FKBP51V55L promotes osteoclastogenesis and function, which could subsequently participate in PDB development.
Acid Phosphatase ; Animals ; Asian Continental Ancestry Group ; Bone Diseases, Metabolic ; Bone Remodeling ; Bone Resorption ; Femur ; Humans ; Mice ; Mice, Transgenic ; Osteitis Deformans* ; Osteoblasts ; Osteoclasts ; Osteogenesis ; Phosphorylation ; Phosphotransferases ; Tacrolimus Binding Proteins ; Transcription Factors

PURPOSE: Numerous studies have assessed the association of SP110 gene variants with tuberculosis (TB), but the results were inconsistent. Through a comprehensive review and meta-analysis, our study aimed to clarify the nature of genetic risks contributed by 11 polymorphisms for the development of TB. MATERIALS AND METHODS: Through searching PubMed, web of science, China National Knowledge Infrastructure (CNKI) databases, a total of 11 articles including 13 independent studies were selected. The pooled odd ratios (ORs) along with their corresponding 95% confidence interval (CI) were estimated for allelic comparisons, additive model (homozygote comparisons; heterozygote comparisons), dominant model and recessive model. We also assessed the heterogeneity across the studies and publication bias. RESULTS: The results of combined analysis revealed a significantly increased risk of TB for single nucleotide polymorphism (SNP) rs9061 in all five comparisons (allelic comparisons: OR=1.28, 95% CI=1.14–1.44, p<0.0001; homozygote comparisons: OR=2.84, 95% CI=1.84–4.38, p<0.00001; heterozygote comparisons: OR=1.23, 95% CI=1.05–1.43, p=0.009; dominant model: OR=1.32, 95% CI=1.14–1.53, p=0.0003; recessive model: OR=2.26, 95% CI=1.18–4.34, p=0.01). In subgroup analysis, the risk of TB associated with SNP rs9061 appeared to be increased. Moreover, increased risk of TB was also found in Asian subgroup of SNP rs11556887, while decreased risk of TB appeared in large sample size subgroup of SNP rs1135791. No significant association was observed between other SNPs and the risk of TB. CONCLUSION: Our meta-analysis suggested that the variant of SNP rs9061 might be a risk factor for TB.
Alleles ; Asian Continental Ancestry Group/genetics ; China ; Confidence Intervals ; Genetic Predisposition to Disease ; Heterozygote ; Homozygote ; Humans ; Minor Histocompatibility Antigens/*genetics ; Nuclear Proteins/*genetics ; Odds Ratio ; *Polymorphism, Single Nucleotide ; Risk Factors ; Tuberculosis, Pulmonary/*genetics

Colorectal cancer (CRC) is one of the leading causes of death worldwide. Thus, the development of new therapeutic targets for CRC treatment is urgently needed. SGK1 is involved in various cellular activities, and its dysregulation can result in multiple cancers. However, little is known about its roles and associated molecular mechanisms in CRC. In present study, we found that SGK1 was highly expressed in tumor tissues compared with peri-tumor samples from CRC patients. In vitro experiments revealed that SGK1 overexpression promoted colonic tumor cell proliferation and migration and inhibited cell apoptosis induced by 5-fluorouracil (5-FU), while SGK1 shRNA and inhibitors showed the inverse effects. Using CRC xenograft mice models, we demonstrated that knockdown or therapeutic inhibition of SGK1 repressed tumor cell proliferation and tumor growth. Moreover, SGK1 inhibitors increased p27 expression and promoted p27 nuclear accumulation in colorectal cancer cells, and p27 siRNAs could attenuate the repression of CRC cell proliferation induced by SGK1 inhibitors. Collectively, SGK1 promotes colorectal cancer development via regulation of CRC cell proliferation, migration and survival. Inhibition of SGK1 represents a novel strategy for the treatment of CRC.
Animals ; Apoptosis ; Cause of Death ; Cell Proliferation ; Colon ; Colorectal Neoplasms* ; Fluorouracil ; Heterografts ; Humans ; In Vitro Techniques ; Mice ; Repression, Psychology ; RNA, Small Interfering

OBJECTIVETo explore the protective effects of Tibetan medicine Zuo-Mu-A Decoction (, ZMAD) on the blood parameters and myocardium of high altitude polycythemia (HAPC) model rats.

METHODSForty male Wistar rats were randomly divided into 4 groups by a random number table, including the normal, model, Rhodiola rosea L. (RRL) and ZMAD groups (10 in each group). Every group was raised in Lhasa to create a HAPC model except the normal group. After modeling, rats in the RRL and the ZMAD groups were administered intragastrically with RRL (20 mL/kg) and ZMAD (7.5 mL/kg) once a day for 2 months, respectively; for the normal and the model groups, 5 mL of distilled water was administered intragastrically instead of decoction. Then routine blood and hematologic rheology parameters were taken, levels of erythropoietin and 8-hydroxy-2'-deoxyguanosine (8-OHdG) were tested, and ultrastructural change in the left ventricular myocardium was observed using transmission electron microscopy.

RESULTSCompared with the model group, ZMAD significantly reduced the red blood cell count, hemoglobin levels, whole blood viscosity at low/middle shear rates, plasma viscosity, erythrocyte electrophoretic time, erythropoietin and 8-OHdG levels, and also increased the erythrocyte deformation index (P<0.05). There was no difference in all results between the RRL and the ZMAD groups. The cardiac muscle fibers were well-protected, mitochondrial matrix swelled mildly and ultrastructure changes were less prominent in the ZMAD group compared with the model group.

CONCLUSIONZMAD has significant protective effects on the blood parameters against HAPC, and also has the beneficial effect in protecting against myocardial injury.

Currently, there are increasing debates on the necessity of health instruments in Chinese medicine (CM) emerging in China. This study aims to reevaluate its status and values. Analyzing the causes, limits, advantages, and properties characters of health instruments in CM, it is found that weak fundamental research, incomplete self-awareness, and complicated social factors are the primary causes of debates. A comprehensive analysis showed health instruments in CM have health evaluation benefits to people from a dominant Chinese culture, meet the requirements of cultural background, and bring long-term value to Chinese instrument researches. However, its values and status should be treated differently depending on various subtypes. Although little theoretical and practical evidences proved that patients-reported health instruments in CM should be proposed independently, the doctors- and nurses-reported questionnaires are necessary. With this in mind, the study group proposes the 'Chinese cultural instruments (CCIs)' and 'health-related CCIs'. The latter one aims to evaluate the health status of people in a dominant Chinese culture. The CCIs theory represents Chinese instrument researches on a larger regional and higher level, and resolves the debates on instruments between CM and Western medicine in China. Health instruments in CM bring more scientific and social benefits for Chinese instrument researches. However, it does not include cultural demands, and lacks scientific significance. CCIs have all its virtues, and add solutions to the latter's theory bottleneck and scientific debates, thus bringing increased benefits to clinical assessment in complementary and alternative medicine researches.
China ; Culture ; Dissent and Disputes ; Humans ; Medicine, Chinese Traditional ; methods ; standards ; Patient Outcome Assessment ; Research Design ; standards ; Self Report ; Surveys and Questionnaires ; standards

To observe the protective effects of Lycium barbarum polysaccharides (LBP) on cerebral ischemia reperfusion injury in mice and explore its mechanism. Common carotid artery thread was used to cause middle cerebral artery ischemia, and the thread was taken out after 2 h ischemia to achieve cerebral ischemia reperfusion injury in mice. Therefore, the transient middle cerebral artery occlusion (tMCAO) models were established to observe the effects of LBP (25,50, 100 mg•kg⁻¹) on neurological outcome, infarct size and water contents. HE staining was used to observe its effects on neurocytes of cerebral tissues in mice. Western blotting was used to evaluate the protein expression levels of NF-κB p65. ELISA was used to evaluate the levels of TNF-α, IL-6 and IL-1β in the serum. According to the results, LBP markedly improved neurologic deficits, and decreased infarct size and water contents at 24 h after reperfusion in mice. Pathological section of brain tissues also proved its protective effects on neurocytes. Western blot analysis indicated that LBP markedly down-regulated the protein level of NF-κB p65. ELISA indicated that LBP decreased the levels of TNF-α, IL-6 and IL-1β in the serum 24 h after reperfusion.In conclusion, LBP has protective effects on cerebral ischemia reperfusion injury in mice, and this effect may be associated with inhibiting NF-κB and inflammatory reactions.