Objective:To analyze the clinical manifestations and explore the etiology in a family with congenital aniridia and to analyze the influence of candidate variants on the protein structure.Methods:A pedigree investigation was performed.A Han Chinese family with congenital aniridia of two generations consisting of three members from Henan Province, including one patient diagnosed with congenital aniridia, was identified and studied following their admission to Henan Eye Hospital in June 2023.A thorough medical history was obtained for the patient and their family members.Comprehensive ophthalmologic examinations were conducted, including visual acuity, intraocular pressure, anterior segment photography, color fundus photography, ultrasound biomicroscopy, and optical coherence tomography, etc.Peripheral blood samples were obtained from the family members and whole exome sequencing (WES) was performed on the patient and validated by Sanger sequencing for other members.The pathogenicity and protein structure of newly identified variant sites were analyzed.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of Henan Eye Hospital (No.HNEECKY-2023[06]).Written informed consent was obtained from each subject.Results:The proband is a 23-year-old male presenting with poor binocular vision, aniridia, corneal degeneration, mild lens opacity, shallow anterior chamber, elevated intraocular pressure, peripheral retinal degeneration, and macular dysplasia.The clinical phenotype of the proband's parents did not show any significant abnormality.WES identified a heterozygous frameshift and nonsense varint c. 734_735del (p.Arg245Asnfs*20) in exon 10 of the PAX6 gene, which consisited of two bases deletion at positions 734 to 735, resulting in the mutation of its arginine at position 245 to asparagine and the early appearance of a termination codon at the next 19 amino acids.The variant had not been identified in the HGMD, Clinvar, 1 000 Genomes, and gnomAD databases.Neither of the proband's parents carried the variant, consistent with the pattern of family co-segregation.Substructural analysis using the SMART tool indicated that the variant is situated within the HOX domain.Amino acid conservation analysis demonstrated that the arginine residue at position 245 in the PAX6 gene is highly conserved across multiple species, including human, house mouse, domestic dog, African clawed frog, and macaque.The variant was classified as pathogenic (PVS1+ PS2+ PM2+ PP3) based on the ACMG standards and guidelines for the interpretation of sequence variants.Protein structure analysis revealed the absence of both the homologous domain and the proline-serine-threonine-rich domain in the PAX6 protein. Conclusions:A novel pathogenic variant, c.734_735del (p.Arg245Asnfs*20), in the PAX6 gene has been identified in a family affected by congenital aniridia.This variant results in the deletion of both the PAX6 protein homology domain and the proline-serine-threonine-rich domain.

With the accelerated aging society in China, the incidence of biliary surgical diseases in the elderly has increased significantly. The clinical characteristics of these patients indicate that improving treatment outcomes and realizing healthy aging are worthy of attention. How to effectively improve the treatment effect of geriatric biliary surgical diseases has attracted widespread attention. This paper reviews and comments on the hotspots and difficulties of biliary surgery in older patients from six aspects: (1) higher morbidity associated with an aging society, (2) prevention and control of pre-operative risks, (3) extending the indications of laparoscopic surgery, (4) urgent standardization of minimally invasive surgery, (5) precise technological progress in hepatobiliary surgery, and (6) guarantee of peri-operative safety. It is of great significance to fully understand the focus of controversy, actively make use of its favorable factors, and effectively avoid its unfavorable factors, for further improving the therapeutic effects of geriatric biliary surgical diseases, and thus benefits the vast older patients with biliary surgical diseases. Accordingly, a historical record with the highest age of 93 years for laparoscopic transcystic common bile duct exploration has been created by us recently.
Humans ; Aged ; Aged, 80 and over ; Biliary Tract Surgical Procedures ; Gallstones ; Laparoscopy ; Treatment Outcome ; Aging ; Retrospective Studies

Objective:The purpose of this study was to explore the critical values of monitored indexes of perioperative major adverse cardiac events(MACE), so as to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function to further improve the perioperative safety of elderly patients with biliary diseases.Methods:The clinical data of 246 elderly patients with biliary diseases in our hospital from May 2016 to February 2022 were collected.According to whether MACE occurred during the perioperative period, they were divided into the MACE group and the non-MACE group.The differences of clinical data, the monitoring indexes of postoperative cardiac function, and the coagulation function between the two groups were compared and analyzed.Logistic regression was used to analyze the independent risk factors of perioperative MACE, the cut-off value of the receiver operating characteristic(ROC)curve was calculated, and the Logistic multivariate prediction model was established.Results:In the MACE compared with the non-MACE group, age, postoperative complications and mortality, postoperative hospital stay, and the levels of postoperative high sensitivity troponin-I(Hs-TnI), creatine kinase isoenzyme(CK-MB), myoglobin(MYO), B-type natriuretic peptide(BNP), and D-dimer(D-D)were significantly increased(all P<0.05). Multivariate Logistic regression showed that postoperative BNP and D-D were two independent risk factors for perioperative MACE, and their cut-off values in the ROC curve were 382.65 pg/mL and 0.975mg/L respectively.The Logistic multivariate prediction model established by the Logistic regression equation was P= ex/(1+ ex), X=-5.710+ 0.003X 1+ 0.811X 2, where X 1 was the postoperative BNP level and X 2 was the postoperative D-D level.The accuracy, specificity and sensitivity of this prediction model for predicting perioperative MACE were 96.3%(237/246), 100.0%(235/235), and 18.2%(2/11). Conclusions:The Logistic multivariate prediction model established in this study can effectively predict the occurrence of perioperative MACE in elderly patients.Postoperative BNP and D-D were two independent risk factors for perioperative MACE.The cut-off values of BNP and D-D in the ROC curve could be used as critical values for monitoring perioperative MACE.Therefore, it is of great clinical significance to take effective prevention and treatment measures in time to maintain the stability of perioperative cardiac function, and further improve the perioperative safety of elderly patients with biliary diseases.

Objective:To analyze the association between high density lipoprotein cholesterol (HDL-C) and the risk of cardiovascular disease mortality.Methods:A total of 71 618 residents aged over 18 years with complete baseline data, who were filed on the health information big data platform of Yinzhou district, Ningbo city, Zhejiang Province from 2009 to 2014, were selected as the research population. The research population were divided into four groups according to the level of HDL-C: low-level group (HDL-C<1.0 mmol/L), intermediate-level group (1.0 mmol/L≤HDL-C<1.5 mmol/L), medium-high-level group (1.5 mmol/L≤HDL-C<2.0 mmol/L) and high-level group (HDL-C≥2.0 mmol/L). Cox proportional hazard model was used to calculate the risk ratio of cardiovascular diseases mortality in different groups.Results:The study population was followed up for a total of 427 989.4 person-years, follow-up time of (5.98±1.04)years. During the follow-up period, there were 799 deaths due to cardiovascular diseases. After adjusting for confounding factors, compared with the medium-high-level group as the reference group, the HR (95% CI) for cardiovascular diseases mortality was 1.43 (1.13-1.82) in the low-level group and 1.22 (1.02-1.46) in the high-level group. Conclusion:The low level of HDL-C (<1.5 mmol/L) is associated with a higher risk of cardiovascular disease deaths. The level of HDL-C can be used as a biological indicator to monitor the development of cardiovascular diseases and guide treatment.

Objective:To analyze the association between high density lipoprotein cholesterol (HDL-C) and the risk of cardiovascular disease mortality.Methods:A total of 71 618 residents aged over 18 years with complete baseline data, who were filed on the health information big data platform of Yinzhou district, Ningbo city, Zhejiang Province from 2009 to 2014, were selected as the research population. The research population were divided into four groups according to the level of HDL-C: low-level group (HDL-C<1.0 mmol/L), intermediate-level group (1.0 mmol/L≤HDL-C<1.5 mmol/L), medium-high-level group (1.5 mmol/L≤HDL-C<2.0 mmol/L) and high-level group (HDL-C≥2.0 mmol/L). Cox proportional hazard model was used to calculate the risk ratio of cardiovascular diseases mortality in different groups.Results:The study population was followed up for a total of 427 989.4 person-years, follow-up time of (5.98±1.04)years. During the follow-up period, there were 799 deaths due to cardiovascular diseases. After adjusting for confounding factors, compared with the medium-high-level group as the reference group, the HR (95% CI) for cardiovascular diseases mortality was 1.43 (1.13-1.82) in the low-level group and 1.22 (1.02-1.46) in the high-level group. Conclusion:The low level of HDL-C (<1.5 mmol/L) is associated with a higher risk of cardiovascular disease deaths. The level of HDL-C can be used as a biological indicator to monitor the development of cardiovascular diseases and guide treatment.

Objective To study protective and therapeutic measures to improve perioperative safety in extremely elderly patients with biliary diseases.Methods A retrospective case-control study was conducted.The clinical data of elderly patients with biliary diseases treated at the Department of General Surgery,Beijing Electric Power Hospital,from July 2013 to December 2018,were collected.According to age,the patients were divided into the high age (HA) group (≥80.0 years) and the middle-low age (MLA) group (60.0～79.0 years).The related indexes of perioperative safety such as preoperative coexisting diseases,functions of liver,kidney,heart and lung,surgical procedures,intraoperative blood loss,operation time,postoperative hospital stay and postoperative hospital stay were analyzed and compared between the two groups.Results Of the 372 included patients,there were 168 males and 204 females,aged 60.0 to 96.0 (72.0 ± 8.6) years.There were 69 elderly patients (37 males and 32 females) aged 80.0 to 96.0 (84.4 ±3.8) years in the HA group.There were 303 patients in the middle and lower age group (131 men and 172 women),aged 60.0 to 79.0(68.4 ±5.8) years (MLA group).(1) Preoperative coexisting diseases were significantly increased in the HA compared with the MLA group (all P ＜ 0.05),including the proportion of coexisting coronary heart disease [34.8％ (24/69) vs.18.5％ (56/303)],hypertension [68.1％ (47/69)vs.46.9％ (142/303)],chronic bronchitis with emphysema [17.4％ (12/69) vs.3.6％ (11/303)],hypoproteinemia [39.1％ (27/69) vs.26.7％ (81/303)],and anemia [42.0％ (29/69) vs.11.9％ (36/303)].(2) Laboratory examinations:the functions of liver,kidney,heart,lung and blood coagulation were significantly worse in the HA compared with the MLA group (P ＜ 0.05).(3) Surgical procedures:the proportion of open cholecystectomy with transcystic common bile duct exploration (OC + OTCBDE) was higher [17.4％ (12/69) vs.6.9％ (21/303)],while laparoscopic cholecystectomy (LC) was lower [43.5％ (30/69) vs.62.7％ (190/303)],in the HA compared with the MLA group (P ＜0.05,totally).(4) Operative effects:the intraoperative blood loss [30.0 (20.0,75.0) ml vs.20.0 (10.0,30.0) ml],operation time [90.0(72.5,137.5) min vs.77.0(55.0,115.0) min],postoperative hospital stay [10.0(6.0,18.0) d vs.7.0(4.0,11.0) d],and length of hospitalization [17.0(11.5,23.0) d vs.13.0(9.0,19.0) d] were significantly increased or prolonged in the HA compared with the MLA group (all P ＜0.05).(5) Postoperative complications:the incidence of postoperative complications was significantly higher [30.4％ (21/69) vs.12.2％ (37/303)] in the HA compared with the MLA group (P ＜ 0.05).(6) Therapeutic outcomes:there was a cure rate of 95.7％ (66/69) in the HA group,and 97.7％ (296/303)in the MLA group.No significant difference in the therapeutic effects was found between the two groups (P ＞ 0.05).Conclusions Operation in extremely elderly patients with biliary diseases is safe and feasible.The key is to take measures such as actively treating preoperative coexisting diseases,strictly mastering operative indications,reasonably selecting surgical procedures,accurately carrying out precise operation,strictly monitoring and dealing with intraoperative emergency,timely preventing and treating postoperative complications,and especially focusing on maintaining cardiopulmonary function during the perioperative period.

Objective To compare outcomes of laparoscopic radical prostatectomy (LRP) and open radical prostatectomy (ORP) performed in our hospital.Methods A non-randomized,retrospective comparative study was performed to analysis 302 prostate cancer patients from January 2011 to June 2014.One hundred and ten patients underwent LRP and 192 underwent ORP.There were no significant differences between the LRP and ORP groups with respect to patient age,body mass index,PSA level,Gleason Score,clinical T stage and transrectal ultrasonography prostate volume (P ＞ 0.05).The operating time,estimated blood loss,catheter retaining time,hospital stay time,positive surgical margin rate and urinary control rate were compared between the 2 groups.Results The median operative time of the ORP group and the LRP group was 95 min and 120 min,the difference between groups was significant (P ＜ 0.01).The median duration of hospitalization of the 2 groups was 9 d and 6 d,the difference between groups was significant (P＜0.01).ORP group and LRP group's estimated blood loss was 350 ml and 250 ml.Days of tube drainage were 3 d in both groups.Days of urinary catheterization drainage after surgery were 16 d and 15 d,respectively.Positive margin rate was 10.4％ and 12.7％.Urinary continence recovery rates at 3 month were 80.2％ and 70.8％.Urinary continence recovery rates at 6 month were 85.9％ and 87.3％.No significant difference was observed in the above index (P ＞ 0.05).Conclusions Compared with ORP,LRP has shorter hospital stay time and longer operating time.Both LRP and ORP have good outcomes in oncological control and function rehabilitation.Both of them are important procedures to treat localized prostate cancer.

Objective To reassess the treatment of Bosniak category Ⅱ-Ⅲ renal cyst.Methods Sixty-eight cases of Bosniak category Ⅱ-Ⅲ renal cyst were operated from 2005 to 2008 in our institute.The average patient age was 40 years with the average renal cyst diameter of 5.1 cm.There were 37 left lesions and 31 right lesions with 31 cases of category Ⅱ (including 13 cases of category Ⅱ F) and 37 cases of category Ⅲ.Renal unroofing were performed in 49 cases with 9 cases found malignant and followed by radical nephrectomy,19 cases were diagnosed as malignancy preoperatively and nephron sparing surgery or radical nephrectomy were performed in these cases.Results Malignant lesions were found in 21 cases and benign lesions were found in 47 cases.The malignant rate was 9.7％ in category Ⅱ (15.4％ in category Ⅱ F),48.6％ in category Ⅲ.Nine cases were diagnosed benign preoperatively but confirmed malignancy after operation; 7 cases were diagnosed malignancy preoperatively but confirmed benign after operation.Forty-two cases were followed up for 8-65 months with 15 cases of malignancy and 27 cases of benign lesions.The recurrence of renal cyst occurred in 6 cases of benign lesions and recurrence and metastasis occurred in 3 cases of malignancy in 1-5 years.Conclusions It is difficult to draw a therapeutic principle for Bosniak category Ⅱ-Ⅲ renal cyst because of the uncertainty of the lesion.Partial nephrectomy or renal cystectomy is a good choice in the treatment of Bosniak category Ⅱ-Ⅲ renal cysts.

Objective To investigate the safety and efficacy of radical nephrectomy plus inferior vena cava thrombectomy,and to evaluate the efficacy of preoperative temporary inferior vena cava filter placement and intraoperative application of liver transplantation techniques to reveal the inferior vena cava in order to avoid tumor thrombosis shedding and embolism.Methods The data of 42 cases (January 2004 to December 2010) of renal cell carcinoma with subdiaphragmatic thrombus were analyzed retrospectively.All these patients underwent radical nephrectomy plus inferior vena cava thrombectomy.Patients were implanted temporary inferior vena cava filter as preoperative routine.Patients with the tumor thrombi behind the liver were applied liver transplant techniques to free and turn liver to the left in order to reveal inferior vena cava,block blood flow according to priority and then finish the inferior vena cava thrombectomy.The filter was removed postoperatively on the same day,and the patients were followed up as routine.Results The operation of the 42 cases was successful without symptomatic tumor thrombus embolism perioperatively,while 1 case died of severe postoperative lung infection.The average operation time was 220 min (130-320 min),blood loss was 750 ml (200-2500 ml),and 12 cases had blood transfusion with an average of 800 ml (400-2000 ml).Forty-one cases were followed up with an average period of 36 months (6-60 months).Among the 37 cases without preoperative tumor metastasis,15 cases had metastases and 22 cases had disease-free survival.Conclusions Nephrectomy and inferior vena cava thrombectomy could be safe and effective for renal cell carcinoma with subdiaphragmatic thrombosis.Preoperative temporary inferior vena cava filter placement and intraoperative application of liver transplantation techniques to reveal the inferior vena cava can be effective to prevent tumor thrombosis shedding and embolism and improve surgical safety.

Objective To evaluate the hematological adverse events of sunitinib in treatment of advanced renal cell carcinoma.Methods Forty-four male patients and 18 female patients were included in this study.They were all with metastatic renal cell carcinoma and received sunitinib treatment at the dose of 50 mg daily in repeated 6 weeks cycle (4 weeks on and 2 weeks off).Toxicity was assessed every cycle with tumor assessments every 2 cycles via CT or PET-CT.Results Fifty patients (80.6％) had experienced treatment-related hematotoxicity,including leucocytopenia,anemia and thrombocytopenia.Severe hematological adverse events ( grade 3 -4 ) occured in 18 patients ( 29.0％ ) and slight events ( grade 1 - 2 ) in others (51.6％).Most of the hematological adverse events were manageable and reversible and treatment-changes (dose reduction,interruption) were necessary in severe cases.Almost half of the dose reduction (9/21,42.9％ ) were owing to hematotoxicity.Conclusions Sunitinib of 50 mg dose on schedule 4/2 is effective and well-tolerated in advanced renal carcinoma patients.Hematological adverse events are frequent in Chinese patients and can be controlled well.