Aim To investigate the effect of dipeptidyl peptidase-4 inhibitor(DPP-4i)on serum creatinine(Cr)in patients with type 2 diabetes mellitus(T2DM).Methods A systematic search was performed across data-bases of PubMed,Embase,Cochrane Library and Web of Science,and randomized controlled trials(RCT)of DPP-4i therapy for regulating Cr in T2DM patients was included.A fixed-effect or random-effect model was used for data fitting,heterogeneity was quantitatively evaluated according to the index of I2,and sensitivity analysis and publication bias testing were performed by using the standard methods.Results After searching the database through the system,12 RCTs were included,with a total of 2 276 participants.Due to the potential heterogeneity,a random effect model was used for data fitting.DPP-4i treatment could mildly increase Cr levels in T2DM patients(WMD:0.15 mg/L,95％CI:0.03～0.27,I=1 8％,P=0.02),and the results showed statistical differences.According to sensitivity testing,the results of Meta-analysis were relatively reliable.No publication bias was observed according to Begg's and Egger's tests.Conclusions The use of DPP-4i for hypoglycemic treatment in T2DM patients may result in mild elevation of blood Cr lev-els.Further multicenter studies with larger samples are needed in the future to explore the clinical significance of DPP-4i treatment induced changes in Cr levels.

Objective To explore the mechanism underlying ITGB1-induced drug resistance in gastric cancer based on the circRNA-miRNA-ITGB1 regulatory network.Methods Tumor tissue samples were collected from 21 patients with gastric cancer.The ITGB1 gene expression levels were determined using real-time fluorescent quantitative polymerase chain reaction,and circRNA sequencing was performed to compare the differences in circRNAs between patients with low and high ITGB1 expression.BGC-823 cells were trans-fected with si-circ_0027189,si-miR-455,or si-NC and divided into the si-circ_0027189,si-miR-455,or si-NC groups,respectively.The circ_0027189,miR-455,and ITGB1 expression levels in each group and the sensitivity to oxaliplatin were measured.Results The circRNA regulatory network showed that circ_0027189 regulated ITGB1 expression through miR-455.Compared to the si-NC group,the si-circ_0027189 group exhibited decreased expression levels of circ_0027189 and ITGB1,increased expression levels of miR-455,and reduced sensitivity to oxaliplatin.In contrast,the si-miR-455 group showed decreased expression levels of miR-455,increased expression levels of ITGB1,and enhanced sensitivity to oxaliplatin compared to the si-NC group.Conclusion circ_0027189 can increase ITGB1 expression levels by targeting miR-455 expression,ultimately increasing drug resistance in gastric cancer cells.

Objective:To summarize the clinical manifestations, gene variations, diagnosis and treatment of 3 cases with SLC35A2 variations characterized by congenital glycosylation disorder Ⅱm (CDG Ⅱm). Methods:A total of 3 patients admitted to the Department of Pediatrics of Xiangya Hospital of Central South University in China from 2018 to 2020 were examined in detail. The studies till January 2022 were searched with key words of "congenital disorders of glycosylation Ⅱm", " SLC35A2" and "CDG Ⅱm" in both English and Chinese in the databases of China National Knowledge Infrast Ructure (CNKI), Wanfang, Online Mendelian Inheritance in Man and PubMed, and the clinical manifestations, genetic variation, treatments and prognosis of patients with SLC35A2 mutation were summarized. Results:The patients all presented with intractable infantile spasm and global developmental delay, onset in infancy. A variety of antiepileptic treatments had temporary and partial efficacy. Otherwise, proband 2 and 3 presented with abnormal glutamic-pyruvic transaminase and increased platelets. Funduscopy showed dysplasia of the retinal pigment epithelium in both eyes, and they both received D-galactose treatment. A total of 22 relevant case reports, including 99 patients, were collected. The 99 patients all were heterozygous mutations, and a total of 75 different variation sites were reported. The clinical manifestations were characterized by global developmental delay or mental retardation ( n=89), epileptic seizure ( n=75), hypotonia ( n=57), facial deformity ( n=57), skeletal abnormality ( n=50), visual impairment ( n=42), elevated glutamic-pyruvic transaminase ( n=31), gastrointestinal symptoms ( n=28), skin deformity ( n=26), microcephaly ( n=23) and congenital heart disease ( n=12). Craniocerebral magnetic resonance imaging may be normal in the early stage. With age, magnetic resonance imaging may show abnormal white matter signals, brain atrophy, dysplasia of corpus callosum, delayed myelination, enlargement of lateral ventricle, brain stem atrophy and so on. Studies have shown that galactose treatment may be effective. Conclusions:SLC35A2 variants lead to CDG Ⅱm, whose clinical manifestations mainly include epileptic encephalopathy and global developmental delay. Multiple antiepileptic therapies can temporarily or partially control seizures, while oral galactose may improve the clinical symptoms, showing its prospect as a dietary therapy.

Objective:To investigate the clinical efficacy of anterior approach combined with blocking plates and screws in the management of acetabular fracture involving the quadrilateral area.Methods:A retrospective case series analysis was performed for 16 patients with acetabular fracture involving the quadrilateral area admitted to First and Second Affiliated Hospital of Guangxi Medical University from January 2017 to January 2019. There were 12 males and 4 females，with the age of 21-66 years［（45.3±10.6）years］. According to Letournel-Judet classification，there were 9 patients with bi-column fracture，6 with anterior and posterior traverse fracture and 1 with anterior column fracture. A total of 9 patients were operated via the ilioinguinal approach and 7 via the lateral-rectus approach. Reduction and fixation of the pelvis and acetabulum were performed，using 3.5 mm cortical bone screws or plates to block the internal displacement of fracture in the quadrilateral body. The incision length，operation time and intraoperative blood loss were recorded. The quality of fracture reduction was assessed according to the Matta reduction criteria at postoperative 2 days and hip function by the modified Merle D'Aubigne-Postel score at postoperative 3 months and 12 months. Postoperative complications were observed.Results:All patients were followed up for 13-24 months［（16.1±2.9）months］. The ilioinguinal approach and lateral-rectus approach showed surgical incision of 12-26 cm［（18.6±4.0）cm］and 8-15 cm［（10.7±2.3）cm］，respectively. The operation time was 107-215 minutes［（159.2±27.8）minutes］and the intraoperative blood loss was 200-2，300 ml［（853.1±489.7）ml］. According to Matta reduction criteria，the results were excellent in 9 patients and good in 7. Three months after operation，the modified Merle D'Aubigne-Postel score was 11-18 points［（15.2±2.2）points］，which showed the results were excellent in 4 patients，good in 7，fair in 4 and poor in 1，with the excellent and good rate of 69%. Twelve months after operation，the modified Merle D'Aubigne-Postel score was 13-18 points［（16.9±1.4）points］，which showed the results were excellent in 7 patients，good in 8 and fair in 1，with the excellent and good rate of 94%. The liquefaction of post-surgical incision was seen in a patient，bladder injury in a patient，lateral femoral cutaneous nerve injury in a patient，and heterotopic ossification in a patient. There was no loosening or breakage of the internal fixation.Conclusion:For acetabular fracture involving the quadrilateral area，anterior approach combined with blocking plates and screws can prevent the displacement of quadrilateral fracture and attain satisfactory reductiongood hip function recovery and few complications.

Objective:To analyze the clinical manifestation, laboratory examination, treatment and prognosis of congenital factor Ⅺ (FⅪ) deficiency.Methods:The clinical data of 80 patients with congenital FⅪ deficiency in our hospital from September 2006 to October 2020 were analyzed retrospectively.Results:Among the 80 patients, there were 33 males (41.3%) and 47 females (58.8%) , with a median age of 32 (2-66) years. Twenty-eight cases (35.0%) had bleeding events, including 11 cases of spontaneous bleeding (13.8%) , 9 cases of ecchymosis or bleeding after skin trauma (11.3%) , 9 cases of postoperative bleeding (11.3%) . Among the female patients, there were 11 cases of menorrhagia (23.4%) and 1 case of bleeding after vaginal delivery (2.1%) . Laboratory examination were characterized by prolonged activated partial thromboplastin time (APTT) , normal prothrombin time (PT) , and decreased FⅪ activity (FⅪ∶C) . Nine patients (11.3%) were tested for FⅪ gene (F11) with 11 mutations. Twenty-seven patients (33.8%) received fresh frozen plasma (FFP) treatment, 15 patients (18.8%) were received for prophylaxis with no bleeding occurred during and after operation.Conclusion:Most patients with congenital FⅪ deficiency have no or mild bleeding symptoms. There was no significant correlation between FⅪ∶C and the severity of bleeding symptoms, and there was a well consistency between FⅪ∶C and F11 homozygous or heterozygous mutation type. Prophylactic infusion of FFP can effectively reduce the risk of operative bleeding.

Objective:To analyze the clinical phenotype and molecular pathogenesis of nine patients with hereditary factor Ⅴ (FⅤ) deficiency.Methods:Nine patients with hereditary FⅤ deficiency who were admitted to the Institute of Hematology and Blood Diseases Hospital from April 1999 to September 2019 were analyzed. The activated partial thromboplastin time, prothrombin time, and FⅤ procoagulant activity (FⅤ∶C) were measured for phenotypic diagnosis. High-throughput sequencing was employed for the F5 gene mutation screening, Sanger sequencing was adopted to confirm candidate variants and parental carrying status, Swiss-model was used for three-dimensional structure analysis, and ClustalX v.2.1 was used for homologous analysis.Results:The FⅤ∶C of the nine patients ranged from 0.1 to 10.6. Among them, eight had a hemorrhage history, with kin/mucosal bleeding as the most common symptom (three cases, 37.5%) , whereas one case had no bleeding symptom. There were five homozygotes and four compound heterozygotes. A total of 12 pathogenic or likely pathogenic mutations were detected, of which c.6100C>A/p.Pro2034Thr, c.6575T>C/p.Phe2192Ser, c.1600_1601delinsTG/p. Gln534*, c.4713C>A/p.Tyr1571*, and c.952+5G>C were reported for the first time.Conclusion:The newly discovered gene mutations enriched the F5 gene mutation spectrum associated with hereditary FⅤ deficiency. High-throughput sequencing could be an effective method to detect F5 gene mutations.

Objective:To investigate the clinical type and gene mutations, clinical manifestations, laboratory tests, diagnosis, and fibrinogen replacement therapy of congenital fibrinogen disorders.Methods:Clinical data of 146 patients with congenital fibrinogen disorders diagnosed from April 2000 to November 2020 were retrospectively analyzed.Results:Among the 146 patients, 61 (41.8%) men and 85 (58.2%) women had a median age of 33.5 years at the time of consultation. 34 patients (34.7%) were found to suffer from the disease due to bleeding symptoms, 33 patients (33.7%) due to preoperative examination. 55 patients (56.1%) had at least one bleeding symptom, and 42 patients (42.9%) had no bleeding symptoms. There is a negative correlation between fibrinogen activity concentration and bleeding ISTH-BAT score (rs=-0.412, P=0.001) . A total of 34 gene mutations were detected in 56 patients, of which 84.1% were missense mutations, and 16 new mutations were found. FGA Exon2 and FGG Exon8 mutations accounted for 71.4% of all mutation sites. Patients with afibrinogenemia were younger, with a median age of 2 (1-12) years, an ISTH-BAT score of 4, and patients with dysfibrinogenemia had significantly longer thrombin time (TT) , with a median of 28.5 (19.2-36.6) s. The 1 hour in vivo recovery (IVR) after fibrinogen infusion was (127.19±44.03) %, and the 24 hour IVR was (101.78±43.98) %. In addition to the obvious increase in the concentration of fibrinogen activity, the TT and the prothrombin time (PT) both decreased significantly, and the TT decreased more significantly, with an average decrease of 15.2% compared to the baseline after 24 hours of infusion. Conclusion:Most patients with congenital fibrinogen disorders have mild or no bleeding symptoms. Patients with afibrinogenemia have more severe symptoms. There is a negative correlation between the fibrinogen and the degree of bleeding. Genetic testing is helpful for the diagnosis of disease classification. FIB∶C/FIB∶Ag<0.7 can be used as a basis for clinical diagnosis. The TT can be used as the basis for the diagnosis of dysfibrinogenemia and the effectiveness of fibrinogen infusion.

Objective:To investigate the expression of coxsackievirus-adenovirus receptor (CAR) in thymic carcinoma and the relationship between CAR and the antitumor activity of oncolytic adenovirus H101.Methods:The expression of CAR in thymic carcinoma tissues and cells were detected by RT-qPCR and Western blot. H101 expression and virus titers in Bcap-37, MP59 and T1889 cells after infection were detected by RT-qPCR and 50% tissue culture infectious dose (TCID 50). The proliferation activity and apoptosis rates of T1889 cells infected with H101 at different multiplicity of infection (MOI) were detected by CCK-8 and flow cytometry. CAR expression in T1889 cells treated with different concentrations of trichostatin A (TSA), a histone deacetylase inhibitor, was detected. H101 expression and virus titers in the TSA-treated and H101-infected cells were detected. Cell activity was detected by CCK-8. The phosphorylation levels of MARK and ERK1/2 and the expression of CAR at protein level in TSA-treated or TSA+ TBHQ (ERK activator) treated cells were detected. Results:CAR expression at both mRNA and protein levels were significantly lower in thymic carcinoma tissues than in adjacent normal tissues ( P<0.01), and lower in MP59 and T1889 cells than in thymic epithelial cells (TEC) and Bcap-37 cells ( P<0.01). H101 expression in MP59 and T1889 cells and the titers of H101 in culture supernatants were significantly lower than those in Bcap-37 cells ( P<0.01). Compared with Bcap-37 cell, the activity of MP59 and T1889 cells was significantly increased and the apoptosis rates were significantly decreased 48 h after H101 infection ( P<0.01). The expression of CAR at both mRNA and protein levels in T1889 cells treated with different concentrations of TSA increased in a dose-dependent manner. When T1889 cells were treated with 0.25 μmol/L of TSA, the expression of H101 at mRNA level and H101 titers were significantly increased ( P<0.05); the phosphorylation levels of MAPK and ERK1/2 proteins were continuously decreased; the expression of CAR was continuously increased. Compared with the TSA treatment group, the expression of CAR at protein level in the TSA+ TBHQ treatment group decreased significantly ( P<0.01), and the p-ERK1/2/ERK1/2 ratio increased significantly ( P<0.01). Conclusions:TSA could up-regulate CAR expression in thymic carcinoma by inhibiting the MARK/ERK1/2 pathway, thereby enhancing the antitumor activity of H101.

Objective:To explore the safety and short-term and long-term efficacy of robot-assisted radical esophageal cancer surgery.Methods:A prospective randomized controlled trial was conducted. Patients who were preoperatively diagnosed as stage 0-IIIB esophageal squamous cell carcinoma and suitable for minimally invasive surgery in our hospital from January 1, 2014 to June 30, 2018 were prospectively enrolled. Those of age ≥75 years having received preoperative neoadjuvant therapy, contradicted to anesthesia or operation due to severe complications, with history of thoracotomy or laparotomy, with concurrent malignant tumors, without complete informations or refusing to participate in this study were excluded. Participants were randomly divided into the thoracoscopy-laparoscopy group and the robot group using a random number table in ratio of 1:1. Preoperative clinicopathological data, surgical data and postoperative outcomes were recorded. The patients were followed up mainly by telephone. Follow-up endpoint was recurrence of esophageal cancer and death. Kaplan-Meier method was used to estimate survival rate. The survival difference between the two groups was analyzed using the log-rank test.Results:According to above criteria, a total of 192 esophageal cancer patients were enrolled finally, including 144 males and 48 females with mean age of (61.9±8.6) years. The robot group had 94 cases, including 72 males and 22 females with mean age of (61.3±8.2) years, and the thoracoscopy-laparoscopy group had 98 cases, including 72 males and 26 females with mean age of (62.4±9.1) years. There were no significant differences in baseline data between the two groups (all P>0.05). Operation was abandoned in one case in each group due to extensive pleural cavity metastasis and one case in each group was converted to thoracotomy. The success rate of operation was 97.9% (92/94) in the robot group and 98.0% (96/98) in the thoracoscopy-laparoscopy group (χ 2=0.002, P=0.996). The number of lymph nodes dissected in the robot group was significantly higher than that in the thoracoscopy-laparoscopy group (29.2±12.5 vs. 22.8±13.3, t=3.433, P=0.001), while there were no significant differences in operative time, intraoperative blood loss, R0 resection rate, postoperative 30-day mortality, postoperative hospital stay, ICU stay, time to withdrawal of chest drainage tube, ICU readmission, and postoperative morbidity of complications between the two groups (all P>0.05). The median follow-up time was 21 (3 to 57) months. During the follow-up, 3 cases and 4 cases were lost, and 2 cases and 3 cases died of other diseases in the robot group and in the thoracoscopy-laparoscopy group respectively. Recurrence occurred in 39 cases during follow-up, including 14 recurrences in the robotic group with 1- and 3-year recurrence-free survival rates of 92.4% and 87.6% respectively and the median recurrence time of 15 (9 to 42) months. There were 25 recurrences in the thoracoscopy-laparoscopy group with 1- and 3-year recurrence-free survival rates of 81.7% and 67.9% respectively and the median recurrence time of 9 (3 to 42) months. There was significant difference in recurrence-free survival between the two groups (χ 2=4.193, P=0.041). Conclusions:The robotic surgical system has good oncology effect and surgical safety in the radical operation of esophageal cancer, which deserves further research and promotion.

Objective:To explore the pathogenesis, clinical characteristics, laboratory findings, diagnosis, treatment, and prognosis of congenital factor Ⅶ (FⅦ) deficiency.Methods:Clinical data of 43 patients with congenital FⅦ deficiency diagnosed from April 1999 to September 2019 were retrospectively analyzed.Results:There were 27 females and 16 males. Median age was 16 (1-70) years. Family history was found in 6 cases. There were 29 (67.4%) cases with bleeding symptoms, most common of which were mucocutaneous bleeding (13 cases, 30.2%) , oral bleeding (13 cases, 30.2%) , and epistaxis (9 cases, 20.9%) . Menorrhagia occurred in 11 cases (47.6% of female patients who were in fertile age) . Laboratory findings were characterized by significantly prolonged prothrombin time (PT) , normal partial thromboplastin time (APTT) , and decreased FⅦ activity (FⅦ∶C) . Ten cases received gene mutation analysis and 3 new mutations were found. Fourteen cases (32.6%) were treated with prothrombin complex concentrates (PCC) , 12 (27.9%) with fresh frozen plasma (FFP) , and 3 (7.0%) with human recombinant activated FⅦ (rFⅦa) . Twenty cases (46.5%) with no or mild bleeding symptoms did not receive any replacement therapy. Previous bleeding symptoms recurred in 5 patients (11.6%) , 8 females still had heavy menstrual bleeding, and 9 patients (20.9%) were lost to follow-up.Conclusion:Most patients with congenital FⅦ deficiency have mild or no bleeding symptoms, but have a tendency to excessive bleeding after surgery or trauma. There is no significant correlation between FⅦ∶C and severity of bleeding symptoms. Prophylaxis should be applied in patients with severe bleeding symptoms and rFⅦa is the first choice. Gene mutation test is significant for screening, diagnosis, and prognosis prediction of the disease.