ObjectiveThis study aims to elucidate the potential mechanism of Zuojinwan in improving liver fibrosis through hepatic tissue metabolomics analysis. MethodsTwenty-four mice were randomly allocated into normal group， model group ， positive drug group （silymarin， 100 mg·kg^-1）， and Zuojinwan group （Zuojinwan solution， 2.5 g·kg^-1）， with per group six mice. Liver fibrosis model was induced via intraperitoneal injection of olive oil solution with 10% carbon tetrachloride （CCl₄） （0.5 μL·g^-1， three times weekly for 8 weeks） in all groups except the normal group. During the final 4 weeks， the silymarin group received silymarin （100 mg·kg^-1） by gavage thrice weekly， while the Zuojinwan group was administered Zuojinwan solution （2.5 g·kg^-1） under the same regimen. After the last administration， the levels of liver fibrosis indicators and liver injury markers in serum were detected. The pathological morphological changes of the liver tissues were observed. The levels of liver fibrosis markers α-smooth muscle actin （α-SMA） and Collagen Ⅰ（ColⅠ） were detected. Metabolomics was analyzed on mice's liver tissues. The mice's serum was collected for metabolomics analysis. ResultsCompared with the model group， Zuojinwan significantly improved indicators related to liver fibrosis and liver injury. Compared with the normal group， the model group showed significantly elevated levels of fibrosis markers such as laminin （LN）， hyaluronic acid （HA）， procollagen typeⅢ （PC-Ⅲ）， and type Ⅳ Collagen （Ⅳ-C）， while liver injury indicators such as alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， alkaline phosphatase （ALP）， lactate dehydrogenase （LDH）， and total bilirubin （TBIL）， exhibited a marked upward trend （P<0.05）. Compared with the model group， the silymarin group showed a significant decrease in the aforementioned indicators （P<0.05）. Notably， compared with the model group， the Zuojinwan group exhibited a significant reduction in all these indicators （P<0.05）， with efficacy comparable to that of the silymarin group. Zuojinwan reduced mRNA and protein levels of α-SMA and ColⅠ in the liver tissue. Metabolomics results revealed that compared with the model group， Zuojiinwan significantly reduced levels of glucose metabolism-related metabolites such as D-fructose 1，6-bisphosphate （FBP）， nicotinamide adenine dinucleotide phosphate （NADPH）， sodium beta-D-fructose 6-phosphate （F6P）， dihydroxyacetone phosphate （DHAP）， fumaric acid， and D-glucose 6-phosphate （G6P） （P<0.05）. Serum enzyme-linked immunosorbent assay （ELISA） was used to detect glucose metabolism indicators and further validate the regulatory effect of Zuojinwan on glucose metabolism. ConclusionThese results suggest that Zuojinwan may improve liver fibrosis by regulating the dysregulated levels of glucose metabolism during the progression of liver fibrosis.

Objective: To explore the genetic basis for a fetus with Dandy-Walker malformation. Methods: G-banding chromosomal karotyping, single nucleotide polymorphism microarray (SNP array) and fluorescence in situ hybridization (FISH) were carried out for the fetus. Chromosomal karyotyping and FISH assay were also carried out for both parents. Results: SNP array has detected a 4266 kb microdeletion at 6p25.3p25.1 in the fetus, which was confirmed by FISH. FISH analysis of the parents demonstrated that the father has carried a cryptic t(6; 14)(p25.1; p13) translocation, while the fetus has a der(6)t(6; 14)(p25.1; p13) derived the paternal translocation. Conclusion The der(6)t(6; 14)(p25.1; p13) probably underlies the Dandy-Walker malformation in the fetus. The 6p25.3p25.1 microdeletion is due to unbalanced gametes produced by the father’s cryptic balanced translocation.

Objective To explore the genetic basis for a child with mentally retardation.Methods G-banding karyotyping,single nucleotide polymorphism array (SNP-array) and fluorescence in situ hybridization (FISH) were performed for the child.Karyotyping and FISH were also carried out for her parents.Results SNP-array has detected a 5077 kb microdeletion at 5q35.2q35.3 and a 4964 kb microduplication at 7q36.2q36.3 in the child.The results were confirmed by FISH.Based on above results,the father was subsequently found to carry a cryptic t(5;7)(q35.2;q36.2) translocation.The child was verified to have inherited a der(5) t(5;7) (q35.2;q36.2) from her father.Conclusion The 5077 kb microdeletion at 5q35.2q35.3 may have predisposed to the Sotos syndrome in the child.SNP-array combined with G-banding karyotyping and FISH can help to detect cryptic chromosomal translocations among patients.

OBJECTIVE: To assess the clinical application of single nucleotide polymorphism microarray (SNP array) in patients with intellectual disability/developmental delay(ID/DD). METHODS: SNP array was performed to detect genome-wide DNA copy number variants (CNVs) for 145 patients with ID/DD in Women's Hospital, Zhejiang University School of Medicine from January 2013 to June 2018. The CNVs were analyzed by CHAS software and related databases. RESULTS: Among 145 patients, pathogenic chromosomal abnormalities were detected in 32 cases, including 26 cases of pathogenic CNVs and 6 cases of likely pathogenic CNVs. Meanwhile, 18 cases of uncertain clinical significance and 14 cases of likely benign were identified, no significant abnormalities were found in 81 cases (including benign). CONCLUSIONS SNP array is effective for detecting chromosomal abnormalities in patients with ID/DD with high efficiency and resolution.
Chromosome Aberrations ; DNA Copy Number Variations ; Genome-Wide Association Study ; Humans ; Intellectual Disability ; diagnosis ; genetics ; Oligonucleotide Array Sequence Analysis ; standards ; Polymorphism, Single Nucleotide

OBJECTIVE: To assess the clinical application of single nucleotide polymorphism microarray (SNP array) in prenatal genetic diagnosis for fetuses with absent nasal bone. METHODS: Seventy four fetuses with absent nasal bone detected by prenatal ultrasound scanning were recruited from Women's Hospital, Zhejiang University School of Medicine during June 2015 and October 2018. The chromosome karyotypes analysis and SNP array were performed. The correlation between absent fetal nasal bone and chromosome copy number variants was analyzed. RESULTS: Among 74 fetuses, 19 were detected to have chromosomal abnormalities, including 16 cases of trisomy-21, 1 case of trisomy-18 and two cases of micro-deletion/duplication. Among 46 cases with isolated absence of nasal bone, 3 had trisomy-21, and 1 had a micro-duplication. Absence of nasal bone in association with nuchal translucency thickening had a higher rate of abnormal karyotypes compared with isolated absence of nasal bone (=32.27,<0.01). CONCLUSIONS Fetuses with absent nasal bone and nuchal translucency thickening are likely to have chromosome abnormalities, and SNP array testing is recommended to exclude the chromosome abnormalities.
Chromosome Aberrations ; Female ; Fetus ; Humans ; Nasal Bone ; abnormalities ; Oligonucleotide Array Sequence Analysis ; standards ; Polymorphism, Single Nucleotide ; genetics ; Pregnancy ; Pregnancy Trimester, First ; Prenatal Diagnosis ; methods

OBJECTIVE: To conduct genetic analysis in a fetus with complex translocation of four chromosomes. METHODS: G-banded chromosome karyotype analysis, single nucleotide polymorphism array (SNP array) and fluorescence hybridization (FISH) were performed in a fetus with multiple malformations. Peripheral blood chromosome karyotype and FISH were also carried out for the parents. RESULTS: The fetal amniotic fluid karyotype was 46, XY, t(12; 13)(q22; q32). SNP array analysis showed that there were 20 192 kb duplication at 1q42.13q44 and 13 293 kb deletion at 15q26.1q26.3 in the fetus. The results of karyotype and SNP array were inconsistent. FISH analyses on the parental peripheral blood samples demonstrated that the mother was a cryptic 46, XX, t(1; 15)(q42.1; q26.1) translocation. The fetus had inherited 46, XY, t(12; 13)(q22; q32) from his father and der(15)t(1; 15)(q42.1; q26.1) from his mother. CONCLUSIONS The 1q42.13q44 duplication and 15q26.1q26.3 deletion may have contributed to the abnormal sonographic features of the fetus. The combination of cytogenetic, SNP array and FISH techniques was beneficial for providing an accurate genetic counseling.
Chromosome Aberrations ; Female ; Fetus ; abnormalities ; Humans ; In Situ Hybridization, Fluorescence ; Karyotyping ; Male ; Polymorphism, Single Nucleotide ; Translocation, Genetic

OBJECTIVE: To diagnose a fetus with Phelan-McDermid syndrome (PMS) using various techniques. METHODS: Single nucleotide polymorphism array (SNP Array), multiplex ligation-dependent probe amplification (MLPA), fluorescence in situ hybridization (FISH) were applied in conjunction for the prenatal diagnosis of the fetus. RESULTS: SNP Array detected a 4.03 Mb microdeletion at 22q13.31q13.33 in the fetus, which was confirmed by FISH and MLPA. FISH analysis of the parents suggested that the 22q13.31q13.33 deletion has a de novo origin. CONCLUSION Combined use of various techniques can enable accurate prenatal diagnosis and genetic counseling.
Chromosome Deletion ; Chromosome Disorders ; diagnosis ; Chromosomes, Human, Pair 22 ; Female ; Fetus ; Humans ; In Situ Hybridization, Fluorescence ; Pregnancy ; Prenatal Diagnosis

Objective: To compare the clinical efficacy of proximal gastrectomy with double tract reconstruction (PG-DT) and total gastrectomy with Roux-en-Y reconstruction (TG-RY) for proximal gastric cancer. Methods: The retrospective study was conducted. Clinicopathological data of 132 patients with proximal gastric cancer confirmed by pathology who underwent PG-DT (n=51) or TG-RY (n=81) by the same surgeon team in Southwest Hospital of Army Military Medical University between January 2006 and December 2016 were collected. Patients with preoperative neoadjuvant therapy, non-R0 resection and non-adenocarcinoma confirmed by pathology were excluded. Observation indicators included intraoperative (operation time and blood loss); postoperative (time to flatus, hospital stay, total complications, metastasis of lymph nodes around distal side of stomach from cases undergoing TG-RY), follow-up (long-term hemoglobin level, incidence of anemia, and survival) parameters. Survival analysis was conducted using the Kaplan-Meier method, and Log-rank test was used to compare survival difference between two groups. Results: No statistically significant differences were found between two groups in the baseline data, including age, gender, BMI, hemoglobin level before operation, postoperative TNM stage, tumor size and histological differentiation between two groups (all P>0.05). There were no significant differences between PG-DT and TG-RY in intraoperative blood loss [200 (200) ml vs. 200 (195) ml, Z=-1.860, P=0.063], time to flatus [(2.7±1.0) days vs. (2.6±1.1) days, t=0.225, P=0.823], postoperative hospital stay [10(3) days vs. 10 (4) days, Z=-0.449, P=0.654] and morbidity of perioperative complications [5.9% (3/51) vs. 8.6% (7/81), χ²=0.081, P=0.775]. Compared with the TG-RY group, PG-DT group had longer total operative time [294 (97) minutes vs. 255 (71) minutes, Z=–3.148, P=0.002]. The hemoglobin data of 42 patients with PG-DT and 56 patients with TG-RY were collected 1 year after operation. The incidence of anemia in PG-DT group was lower than that of TG-RY group [64.2%(27/42) vs. 82.1% (46/56), χ²=4.072, P=0.045], and PG-DT group had higher level of hemoglobin than TG-RY group [(114.4±16.3) g/L vs. (106.6±15.0) g/L, t=2.435, P=0.017]. There were 4 cases (4/81, 4.9%) with metastasis of lymph nodes around distal side of stomach in TG-RY group. All of these 4 tumors were T4 in depth and were more than 5 cm in diameter. The median follow-up period was 26 (1 to 110) months. One-year, 3-year and 5-year survival rates were 93.2%, 65.3% and 55.0% in PG-DT group, and 85.8%, 63.8% and 47.2% in TG-RY group, respectively without significant difference (χ²=0.890, P=0.345). Conclusions Compared with TG-RY, PG-DT has the same safety and feasibility for proximal gastric cancer. Although the operative time is a little longer than TG-RY, PG-DT has advantages in improving the postoperative hemoglobin level.

Objective To compare the clinical efficacy of proximal gastrectomy with double tract reconstruction (PG?DT) and total gastrectomy with Roux?en?Y reconstruction (TG?RY) for proximal gastric cancer. Methods The retrospective study was conducted. Clinicopathological data of 132 patients with proximal gastric cancer confirmed by pathology who underwent PG?DT (n=51) or TG?RY (n=81) by the same surgeon team in Southwest Hospital of Army Military Medical University between January 2006 and December 2016 were collected. Patients with preoperative neoadjuvant therapy, non?R0 resection and non?adenocarcinoma confirmed by pathology were excluded. Observation indicators included intraoperative (operation time and blood loss); postoperative (time to flatus, hospital stay, total complications, metastasis of lymph nodes around distal side of stomach from cases undergoing TG?RY), follow?up (long?term hemoglobin level, incidence of anemia, and survival) parameters. Survival analysis was conducted using the Kaplan?Meier method, and Log?rank test was used to compare survival difference between two groups. Results No statistically significant differences were found between two groups in the baseline data, including age, gender, BMI, hemoglobin level before operation, postoperative TNM stage, tumor size and histological differentiation between two groups (all P>0.05). There were no significant differences between PG?DT and TG?RY in intraoperative blood loss [200 (200) ml vs. 200 (195) ml, Z=-1.860, P=0.063], time to flatus [(2.7±1.0) days vs. (2.6±1.1) days, t=0.225, P=0.823], postoperative hospital stay [10(3) days vs. 10 (4) days, Z=-0.449, P=0.654] and morbidity of perioperative complications [5.9% (3/51) vs. 8.6% (7/81), χ2=0.081, P=0.775]. Compared with the TG?RY group, PG?DT group had longer total operative time [294 (97) minutes vs. 255 (71) minutes, Z=–3.148, P=0.002]. The hemoglobin data of 42 patients with PG?DT and 56 patients with TG?RY were collected 1 year after operation. The incidence of anemia in PG?DT group was lower than that of TG?RY group [64.2%(27/42) vs. 82.1% (46/56), χ2=4.072, P=0.045], and PG?DT group had higher level of hemoglobin than TG?RY group [(114.4 ± 16.3) g/L vs. (106.6±15.0) g/L, t=2.435, P=0.017]. There were 4 cases (4/81, 4.9%) with metastasis of lymph nodes around distal side of stomach in TG?RY group. All of these 4 tumors were T4 in depth and were more than 5 cm in diameter. The median follow?up period was 26 (1 to 110) months. One?year, 3?year and 5?year survival rates were 93.2%, 65.3% and 55.0% in PG?DT group, and 85.8%, 63.8% and 47.2% in TG?RY group, respectively without significant difference (χ2=0.890, P=0.345). Conclusions Compared with TG?RY, PG?DT has the same safety and feasibility for proximal gastric cancer. Although the operative time is a little longer than TG?RY, PG?DT has advantages in improving the postoperative hemoglobin level.

Objective To compare the clinical efficacy of proximal gastrectomy with double tract reconstruction (PG?DT) and total gastrectomy with Roux?en?Y reconstruction (TG?RY) for proximal gastric cancer. Methods The retrospective study was conducted. Clinicopathological data of 132 patients with proximal gastric cancer confirmed by pathology who underwent PG?DT (n=51) or TG?RY (n=81) by the same surgeon team in Southwest Hospital of Army Military Medical University between January 2006 and December 2016 were collected. Patients with preoperative neoadjuvant therapy, non?R0 resection and non?adenocarcinoma confirmed by pathology were excluded. Observation indicators included intraoperative (operation time and blood loss); postoperative (time to flatus, hospital stay, total complications, metastasis of lymph nodes around distal side of stomach from cases undergoing TG?RY), follow?up (long?term hemoglobin level, incidence of anemia, and survival) parameters. Survival analysis was conducted using the Kaplan?Meier method, and Log?rank test was used to compare survival difference between two groups. Results No statistically significant differences were found between two groups in the baseline data, including age, gender, BMI, hemoglobin level before operation, postoperative TNM stage, tumor size and histological differentiation between two groups (all P>0.05). There were no significant differences between PG?DT and TG?RY in intraoperative blood loss [200 (200) ml vs. 200 (195) ml, Z=-1.860, P=0.063], time to flatus [(2.7±1.0) days vs. (2.6±1.1) days, t=0.225, P=0.823], postoperative hospital stay [10(3) days vs. 10 (4) days, Z=-0.449, P=0.654] and morbidity of perioperative complications [5.9% (3/51) vs. 8.6% (7/81), χ2=0.081, P=0.775]. Compared with the TG?RY group, PG?DT group had longer total operative time [294 (97) minutes vs. 255 (71) minutes, Z=–3.148, P=0.002]. The hemoglobin data of 42 patients with PG?DT and 56 patients with TG?RY were collected 1 year after operation. The incidence of anemia in PG?DT group was lower than that of TG?RY group [64.2%(27/42) vs. 82.1% (46/56), χ2=4.072, P=0.045], and PG?DT group had higher level of hemoglobin than TG?RY group [(114.4 ± 16.3) g/L vs. (106.6±15.0) g/L, t=2.435, P=0.017]. There were 4 cases (4/81, 4.9%) with metastasis of lymph nodes around distal side of stomach in TG?RY group. All of these 4 tumors were T4 in depth and were more than 5 cm in diameter. The median follow?up period was 26 (1 to 110) months. One?year, 3?year and 5?year survival rates were 93.2%, 65.3% and 55.0% in PG?DT group, and 85.8%, 63.8% and 47.2% in TG?RY group, respectively without significant difference (χ2=0.890, P=0.345). Conclusions Compared with TG?RY, PG?DT has the same safety and feasibility for proximal gastric cancer. Although the operative time is a little longer than TG?RY, PG?DT has advantages in improving the postoperative hemoglobin level.