Objective To identify the clinical features and pathogenic variants in two unrelated families with gna-thodiaphyseal dysplasia(GDD),a rare genetic bone disorder.Methods Facial and limb deformities and skeletal morphology were observed in the probands and their family members.Peripheral blood samples(3-4 mL)were col-lected from the probands and their parents.Genomic DNA was extracted by standard phenol-chloroform method.Whole exome sequencing(WES)was performed to screen for candidate pathogenic gene variants of the probands.PCR-Sanger sequencing was used to validate the candidate pathogenic variants in the probands and their family members.The pathogenic variants responsible for GDD in the target families were determined through co-segregation of the pathogenic variants in the affected families,evolutionary conservation at the mutation sites,population allele frequency analysis and bioinformatics analysis.Results Heterozygous missense variants in the ANO5 gene were identified in both GDD probands.In family 1,the pathogenic variant was c.1 066T＞G located in the exon 11 of the ANO5 gene,while in family 2,the pathogenic variant was c.1 553G＞A located in the exon 15 of the ANO5.These two variants resulted in the substitutions of amino acid cysteine with glycine at position 356(p.Cys356Gly)and amino acid glycine with glutamic acid at position 518(p.Gly518Glu)in the ANO5 protein,respectively.Conclusions This study first identified the pathogenic variant c.1 066T＞G(p.Cys356Gly)in Chinese population,provided important evidence for prediction of disease prognosis and development of potential prenatal genetic diagnosis.

Objective:To explore the genetic etiology of a fetus with cryptophthalmos detected by prenatal ultrasonography.Methods:A fetus undergoing induced labor at 32nd gestational week due to absence of bilateral eye fissures detected by prenatal ultrasonography in January 2017 was selected as the study subject. Umbilical cord blood sample from the fetus and peripheral blood samples from its parents were collected for the extraction of genomic DNA. Pathogenic variants were screened through whole exome sequencing (WES) and verified by Sanger sequencing. Pathogenicity of candidate variants was verified by bioinformatic analysis and protein structure simulation. Based on the results of genetic testing, prenatal diagnosis was provided to the couple upon their subsequent pregnancy.Results:The couple had four adverse pregnancies previously. The aborted fetus was the fifth, with fused bilateral upper and lower eyelids, poorly developed eyeballs, adhesion of the cornea with the upper eyelid, low-set ears, and abnormal plantar creases, and was diagnosed with cryptophthalmos. WES and Sanger sequencing revealed that the fetus has harbored compound heterozygous variants of the FREM2 gene, namely c. 4537G>A (p.D1513N) and c.7292C>T (p.T2431M). Both variants were unreported associated with cryptophthalmos previously. Protein structure simulation showed that they may lead to loss of hydrogen bonds in the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PM1_Supporting+ PM2_Supporting+ PM5+ PP3+ PP4; PM2_Supporting+ PM3+ PP3+ PP4). The mother was performed prenatal diagnosis in her sixth pregnancy based on the variants detected in this family, and delivered a daughter with normal phenotype. Conclusion:The FREM2: c. 4537G>A and c. 7292C>T compound heterozygous variants probably underlay the pathogenesis of cryptophthalmos in this fetus. Above finding has enriched the mutational spectrum of the FREM2 gene.

Background Currently,the diagnosis of depressive disorder relies on symptomatology,which is greatly influenced by subjective factors such as clinicians' experience.Finding more accurate and reliable quantitative diagnostic methods is currently an urgent problem.Objective To explore the value of Fisher discriminant function based on inflammatory cytokines in the diagnosis of depressive disorder,so as to provide references for clinical diagnosis.Methods A total of 136 patients diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders,fifth edition(DSM-5)criteria,who underwent inpatient treatment at Hebei Mental Health Center from April 2020 to November 2020,were enrolled as study group.67 healthy participants matched for age and gender,was recruited during the same period.Serum levels of inflammatory cytokine were measured using enzyme-linked immunosorbent assay(ELISA).Fisher discriminant model was employed to establish a discriminant function for inflammatory cytokines exhibiting significant statistical differences between study group and control group,which was then validated.Results The levels of pro-inflammatory cytokines interleukin-1β(IL-1β),interleukin-6(IL-6),interferon-γ(INF-γ)and tumor necrosis factor-α(TNF-α)were higher in the study group compared with control group,with statistically significant differences(U=9.115,5.239,4.431,5.428,P<0.01).Conversely,the levels of anti-inflammatory cytokines interleukin-4(IL-4),interleukin-10(IL-10)and interleukin-13(IL-13)were lower in the study group compared with control group,with statistically significant differences(U=7.398,7.331,7.614,P<0.01).The retrospective test in Fisher discriminant function achieved a correct discrimination rate of 89.66%,and the cross validation achieved a correct discrimination rate of 88.67%.Conclusion The Fisher discriminant function developed in this study may serve as a valuable auxiliary method in the diagnosis of depressive disorder.

Objective To investigate the effect of laparoscopic Roux-en-Y gastric bypass surgery(LRYGB)in the treatment of obese diabetes.Methods The clinical data of 20 obese diabetic patients who received LRYGB from 2012 to 2018 in the Minimally Invasive and Herniac Abdominal Surgery Center of Xinjiang People's Hospital were retrospectively analyzed.Result The all 20 surgeries were successfully completed,and 1 case was converted to open surgery.The surgical time ranged from 60 to 420 minutes,with an average of(150±105.64)minutes,the intraoperative blood loss ranged from 20 to 100,with an average of(37.5±20.99)ml,and the postoperative hospital stay ranged from 5 to 15,with an average of(8.25±2.51)days.Complications occurred in 7 cases(35.00％)within 5 years after surgery,all of which were Clavien Dindo grade Ⅱ.The body weight,BMI,glycosylated blood glucose,fasting blood glucose,and the percentage of total weight loss(TWL％)at 1,3,and 5 postoperatively improved compared with those before surgery(P＜0.05).15 cases(75.00％)of type 2 diabetes were completely relieved by LRYGB 5 years after operation.Conclusion Laparoscopic gastric bypass surgery is an effective way to reduce weight and blood sugar in obese patients with type 2 diabetes.

OBJECTIVE To evaluate the correlation between 5-HTR1A gene C- 1019G polymorphism and the efficacy of antidepressants. METHODS PubMed，Embase，Cochrane Library ，CNKI，Wanfang database ，CBM and VIP database were searched for domestic and foreign literatures on the correlation between 5-HTR1A gene C- 1019G polymorphism and antidepressant efficacy. The retrieval time limit was from the inception to February 2022. According to different outcome measures of drug response，Stata 14.0 and RevMan 5.4 software were used for meta-analysis of efficacy group and remission group ，respectively. RESULTS A total of 18 literature were included. The combined results showed that among recessive gene model in valid group ， the correlation of 5-HTR1A gene C- 1019G polymorphism with the efficacy of antidepressants had statistically significance in Asian population（GG vs. CG+CC ，OR＝0.751，95％CI＝0.585-0.964，P＝0.024）. There was statistical significance in the correlation of 5-HTR1A gene C- 1019G polymorphism and the efficacy of antidepressants in China （GG vs. CG+CC ，OR＝0.677，95％CI＝ 0.508-0.901，P＝0.007）. There was no statistical significance in the correlation of 5-HTR1A gene C- 1019G polymorphism and the efficacy of antidepressants in remission group （P＞0.05）. CONCLUSIONS In the effective group ，5-HTR1A gene C- 1019G polymorphism is correlated with the efficacy of antidepressants in the Asian population and the Chinese population ；while in the remission group ，it is not proved that this polymorphism is correlated with the efficacy of antidepressants.

Objective:To analyze the change trend of survival rate after hip fragility fracture in Tianjin Hospital from 2015 to 2021, and the influence of gender, marital status, age and number of complications on survival rate.Methods:From January 1, 2015 to December 31, 2021, a total of 12,570 patients with fragility fracture of hip were retrieved, including 3,934 males and 8,636 females. The age at admission was 74.11±9.50 years and 74.62±8.99 years respectively. By comparing the ID number with the Tianjin population information database, 2,054 cases died, including 804 males and 1,250 females, aged 81.34±7.88 years and 81.92±7.42 years respectively at the time of death. Acquire the patient's survival status, calculate the cumulative survival rate at 3 month intervals, study the change rule of the cumulative survival rate over time, and use Kaplan-Meier method to calculate the cumulative survival rate of the whole population and the impact of gender, marital status, age, and number of complications on the survival rate.Results:The median survival time of all the dead people after fracture was 13(3, 31) months, including 11(2, 27) months for males and 15(4, 32) months for females. Joinpoint regression showed that 9 months after the hip fragility fracture was the break point of the survival rate. The mortality rate changed significantly within 9 months after fracture (the annual change rate was 47%), and slowed down 9 months later (the annual change rate was 1%). There was a statistically significant difference in trend detection before and after the break point ( P<0.05). The age at admission was 80.11±7.71 years for the dead and 73.36±9.01 years for the non dead, with a statistically significant difference ( t=31.80, P<0.001). After normalization, the number of complications was 0.20±0.93 among the dead and 0.00±0.87 among the non dead, with a statistically significant difference ( t=88.81, P<0.001). The survival rate of men after hip fracture is lower than that of women, the number of people without spouse is lower than that of people with spouse, the number of people with more than 70 years old is lower than that of people with less than 70 years old, and the number of complications ≥2 people is lower than that of people with less than 1 complication, all of which are statistically significant ( P<0.05). Conclusion:The survival rate within 9 months after the occurrence of hip fragility fracture decreased significantly, and it needs to be tracked and managed for at least 9 months to effectively reduce the risk of death; Male, no spouse, age>70 years old, number of complications ≥2 will increase the risk of death after hip fragility fracture, leading to reduced survival rate of patients.

Post-stroke depression (PSD) is one kind of the common mental diseases after stroke, and the prevention and treatment of PSD are very difficult. TREK-1, a two-pore domain potassium channel, is an important target in the pathogenesis of stroke and PSD, and it is closely related to neuroprotection and emotion regulation; inhibition of activity of TREK-1 channel can exert significant antidepressant effect. In recent years, TREK-1 channel blocker Spadin and Spadin analogs are discovered, and they have a relatively significant effect on ischemic stroke and PSD. In this paper, the research progress on the discovery, efficacy and therapeutic value of Spadin and Spadin analogs in PSD are summarized as follows.

[Abstract] Objective: To observe the short-term efficacy and safety of Apatinib combined with radiotherapy and concurrent docetaxel and cisplatin chemotherapy in driver-gene-negative non-small cell lung cancer (NSCLC) patients with brain metastases. Methods: A total of 72 NSCLC patients with brain metastases, who were treated in our hospital from June 2018 to June 2019, were enrolled in this study. The driver gene was proved to be negative by next generation sequencing (NGS). The patients were divided into control group (36 cases) and treatment group (36 cases) by Digital random grouping method.The control group received 2 cycles of chemotherapy with docetaxel and cisplatin and concurrent radiotherapy for brain metastases, and the treatment group was given Apatinib anti-angiogenic treatment based on the regimen in control group. Primary study endpoints: confirmed objective response rate (cORR) and disease control rate (DCR); Secondary study endpoints: progression-free survival (PFS), quality of life (QOL) score, serum carcinoembryonic antigen (CEA), vascular endothelial growth factor (VEGF), and incidence of adverse drug events (AE). Results: Compared with the control group, cORR and DCR in treatment group were significantly improved [41.67% (15/36) vs 33.33% (12/36), 80.56% (29/36) vs 69.44% (25/36), all P<0.05], the median PFS was significantly prolonged (5.9 vs 4.6 months, P<0.05), and serum CEA and VEGF levels were significantly reduced [(16.5±2.3) vs (22.9±3.7) ng/ml, (291.6±42.6) vs (479.3±50.2) ng/L, all P<0.05], while the QOL score was slightly increased, but the difference was not statistically significant [(69.5±8.5) points vs (64.1±7.3) points, P>0.05]. There was no statistically significant difference in the incidence of acute brain edema, gastrointestinal reaction, bone marrow suppression, and liver dysfunction between the two groups of patients (all P>0.05); however, the incidences of oral mucositis, hand-foot syndrome, hypertension and proteinuria in the treatment group were significantly higher than those in the control group (all P<0.05). Conclusion: The efficacy of Apatinib combined with radiochemotherapy in driver-negative NSCLC patients with brain metastases is significantly better than that of radiochemotherapy alone, and the adverse reactions can be controlled. It is worthy of clinical recommendation.

Objective To investigate the diagnostic values of procalcitonin (PCT),high sensitive C-reactive protein (hs-CRP),white blood cell (WBC)and percentage of neutrocyte (NEU％)in Gramnegative and Gram-positive bacterial blood stream infection in early stage of sepsis in order to investigate the correlation between PCT and APACHE lⅡ score as well as between PCT and SOFA score,and the prognostic value in assessment of Gram-negative and Gram-positive bacterial blood stream infection.Methods Clinical data of patients admitted to ICU from January 2012 through December 2014 were retrospectively analyzed.A total of 124 sepsis patients with blood stream infection were checked with PCT,hs-CRP,WBC and NEU％ tests,and APACHE Ⅱ score and SOFA score were calculated.The differences in APACHE Ⅱ score and SOFA score were compared between Gram-negative group (n =41) and Gram-positive group (n =83).The correlation between PCT and APACHE Ⅱ score as well as between PCT and SOFA score was analyzed.The differences in diagnostic values of PCT,hs-CRP,WBC and NEU％ between Gram-negative group and Grampositive group were analyzed by using receiver operating characteristic (ROC) curve and it was plotted to assess the prognostic values of PCT,hs-CRP,WBC and NEU％ for septic patients with blood stream infection.Results Compared with Gram-positive group,the levels of PCT [.55.32 (22.01,97.11) vs.2.13 (0.27,5.27)] (P ＜0.01),hs-CRP [105.09 (69.97,186.12) vs.70.54 (42.37,138.63)] (P=0.508),NEU％ [88.30 (75.79,93.52) vs.55.32 (22.01,97.11)] (P=0.302) were higher but WBC was lower [13.59 (10.74,17.58) vs.13.73 (11.32,20.90)] (P=0.058) in Gram-negative group.The ROC curve analysis of PCT showed the area under the curve (AUC) was 0.867 (95％ CI:0.789-0.946).When the optimal cutoff point of PCT was 17.48 ng/mL,the largest Youden's index was found to be 0.661 with 76.9％ sensitivity and 89.2％ specificity.Between two groups,there were significant differences in APACHE Ⅱ score and SOFA score (27.46 ± 9.60 vs.23.67 ± 7.74,P =0.020;8.05 ±3.38 vs.6.59-±3.45,P =0.028).There was significant difference in diagnostic value between PCT and SOFA (r =0.536,P =0.036) in Gram-negative group but no significant difference in Gram-positive group.Conclusions Higher PCT levels are found in Gram-negative group and it can play a role in differntiation between the Gram-negative group and Gram-positive group rather than hs-CRP,WBC and NEU％.PCT can be a better indicator for evaluation of severity of sepsis as well as for prognosis of sepsis patients with Gram-negative bacterium infection.

Objective To investigate the diagnostic value of serum homocysteine in the diagnosis of colon cancer.Methods The performance rate method was used to detect the level of serum homocysteine(Hcy) in colon cancer group(50 cases) who were treated in Beijing Tiantan Hospital Affiliated to Capital Medical University from March 2011 to June 2016 and control group(50 cases).The expression of independent samples t test was used to analysis of the difference of the Hcy levels between the two groups.The ROC curve was used to evaluate the value of Hcy in diagnosis of colon cancer.Results The serum Hcy level in colon cancer group was (18.6±8.9) μmol/L,in healthy control group was (10.7±4.3) μmol/L,colon cancer group serum Hcy levels were significantly higher than those of healthy control group,there was significant difference(t=5.627,P<0.01).AUC of ROC curve was 0.775,cut-off value of 18.5 μmol/L,sensitivity was 0.50,specificity was 0.94,95%CI was 0.682-0.868(P<0.01).Conclusion Serum Hcy can be used as a reference index of the diagnosis of colon cancer.