Objective:To explore the clinical and genetic characteristics of two children diagnosed with two rare genetic diseases simultaneously.Methods:Two children with comorbidity of two genetic diseases due to dual genetic mutations diagnosed at the Third Affiliated Hospital of Zhengzhou University respectively in May 2022 and March 2023 were selected as the study subjects. Clinical and genetic data of the two children were retrospectively analyzed. This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-062-01).Results:Child 1 was a 2-year-and-4-month-old boy whose clinical manifestations included facial dysmorphism, developmental delay, short stature, microcephaly, cleft palate, cryptorchidism, hypospadias, recurrent infections and immunological abnormalities. Whole exome sequencing revealed that he had harbored a heterozygous c.6595delT (p.Y2199Ifs*65) variant of the KMT2D gene and a heterozygous c. 1892G>A (p.R631Q) variant of the PIK3R1 gene. This has led to a dual genetic diagnosis of Kabuki syndrome and PI3Kδ-related immunodeficiency type 36. Child 2 was a 15-year-old girl whose clinical manifestations included epilepsy, Albright′s hereditary osteodystrophy, long body trunk, short limbs, hypocalcemia, hyperphosphatemia and hyperparathyroidism. The child also had a family history of short stature. Whole exome sequencing revealed that she had harbored a heterozygous c. 2T>C (p.Met1? ) variant of the GNAS gene and deletion of exons 2 to 6 of the SHOX gene. The two variants have led to dual diagnose of pseudohypoparathyroidism and X-linked idiopathic short stature. Conclusion:When the clinical phenotype of a genetic disease is complex and cannot be fully explained with a single genetic variant, multiple pathogenic variants should be considered, and this may lead to the diagnosis of co-morbid genetic diseases. To adopt or supplement corresponding genetic testing in time and re-analyze the genetic data may facilitate accurate diagnosis of comorbid genetic diseases.

OBJECTIVE: To explore the clinical and genetic characteristics of two children diagnosed with two rare genetic diseases simultaneously. METHODS: Two children with comorbidity of two genetic diseases due to dual genetic mutations diagnosed at the Third Affiliated Hospital of Zhengzhou University respectively in May 2022 and March 2023 were selected as the study subjects. Clinical and genetic data of the two children were retrospectively analyzed. This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-062-01). RESULTS: Child 1 was a 2-year-and-4-month-old boy whose clinical manifestations included facial dysmorphism, developmental delay, short stature, microcephaly, cleft palate, cryptorchidism, hypospadias, recurrent infections and immunological abnormalities. Whole exome sequencing revealed that he had harbored a heterozygous c.6595delT (p.Y2199Ifs*65) variant of the KMT2D gene and a heterozygous c.1892G>A (p.R631Q) variant of the PIK3R1 gene. This has led to a dual genetic diagnosis of Kabuki syndrome and PI3Kδ-related immunodeficiency type 36. Child 2 was a 15-year-old girl whose clinical manifestations included epilepsy, Albright's hereditary osteodystrophy, long body trunk, short limbs, hypocalcemia, hyperphosphatemia and hyperparathyroidism. The child also had a family history of short stature. Whole exome sequencing revealed that she had harbored a heterozygous c.2T>C (p.Met1?) variant of the GNAS gene and deletion of exons 2 to 6 of the SHOX gene. The two variants have led to dual diagnose of pseudohypoparathyroidism and X-linked idiopathic short stature. CONCLUSION When the clinical phenotype of a genetic disease is complex and cannot be fully explained with a single genetic variant, multiple pathogenic variants should be considered, and this may lead to the diagnosis of co-morbid genetic diseases. To adopt or supplement corresponding genetic testing in time and re-analyze the genetic data may facilitate accurate diagnosis of co-morbid genetic diseases.
Child, Preschool ; Female ; Humans ; Male ; Class Ia Phosphatidylinositol 3-Kinase/genetics* ; Comorbidity ; Exome Sequencing ; Mutation ; Rare Diseases/genetics* ; Retrospective Studies ; Adolescent

Objective:This study aimed to clarify clinicopathologic characteristics, postoperative complications, and related risk factors of elderly patients with gastric cancer.Methods:A total of 395 patients(≥65 years old)who underwent radical gastrectomy for gastric cancer in Beijing Hospital from January 2014 to December 2021 were enrolled in this study.The patients were divided into the common elderly group(age<80 years, n=340)and the high-age group(age ≥ 80 years, n=55). Postoperative complications were classified into medical and surgical types.The clinicopathological characteristics and complications were compared between the two groups.Logistic regression models(univariate and multivariate)were used to identify the risk factors for postoperative complications.Results:The common elderly group was 65-79 years old(mean age: 71.5±4.3 years), with 263 male(77.4%); The high-age group was 80-89 years old(mean age: 82.6±2.6 years), with 42 male(76.4%). The comorbidity rate and the number of comorbidities in the high-age group were significantly higher than those in the common elderly group.The American Society of Anesthesiologists(ASA)scores and nutritional risk screening(NRS)2002 scores in the high-age group were significantly higher than those in the common elderly group(both P<0.05), and the activities of daily living(ADL)scores in the high-age group were significantly lower than that in the common elderly group( P<0.001). There were no statistically significant differences in tumor location, degree of differentiation, pathological type, T stage, and N stage between the two groups(all P>0.05). The overall postoperative complication rate in the high-age group was significantly higher than that in the common elderly group(38.2% vs.24.7%, P=0.036); the medical complications were significantly increased in the high-age group(21.8% vs.10.9%, P=0.022), whereas the surgical complications did not increase significantly(25.5% vs.17.1%, P=0.135). Multivariate analysis revealed that the number of comorbidities ≥2( HR=2.502, 95% CI: 1.275-4.911, P=0.008), preoperative NRS 2002 scores ≥5( HR=2.714, 95% CI1.294-5.693, P=0.008), and preoperative ADL scores<100( HR=2.012, 95% CI1.010-4.009, P=0.047)were independent risk factors for medical complications.Additionally, ASA grade ≥ 3( HR=2.586, 95% CI: 1.444-4.632, P=0.001)and proximal or distal gastrectomy( HR=2.397, 95% CI: 1.237-4.574, P=0.009)were independent risk factors for surgical complications. Conclusions:The occurrence of postoperative medical complications in very elderly patients with gastric cancer undergoing radical surgery has increased, while the rate of surgical complications has not increased.Moreover, advanced age itself is not an independent risk factor for postoperative complications.More attention should be paid to medical complications, and the management of commodities and nutritional support should be strengthened during the perioperative period.

Objective:This study aimed to analyze the infection status of viral viruria within one year after kidney transplantation, its impact on renal allograft function, and associated risk factors.Methods:A retrospective case-control study was conducted, involving 370 patients who underwent allogeneic kidney transplantation at Renji Hospital, Shanghai Jiao Tong University School of Medicine, from January 1, 2020 to December 31, 2021. Urinary viral loads of BK virus (BKV), JC virus (JCV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) were detected using PCR fluorescent probe assays. Patients were categorized into infection and non-infection groups. Glomerular filtration rate (GFR) and tacrolimus trough concentration was measured during infections, and clinical data were collected. Univariate analysis was performed to identify risk factors for viral viruria.Results:The 1-year patient survival rate and graft survival rate were both 98.6%. The incidence rates of viral viruria were as follows: JCV (42.7%), BKV (29.7%), CMV (11.6%), and EBV (2.9%), with statistically significant differences among viruses ( P<0.001). Single viral infection accounted for 48% of cases, while co-infections were predominantly BKV+JCV (9%). JCV infection rates remained consistently high throughout the year (22.4%-28.9%), whereas BKV infections peaked at 3 months postoperatively (20.5%). Co-infection with low-load JCV (>2 000 copies/ml) and CMV (>6 000 copies/ml) led to a significant decline in GFR at 6 months post-transplantation [median difference: 16.7 ml/(min×1.73 m2), P=0.019]. Univariate analysis revealed that elevated tacrolimus trough concentration was independent risk factor for BKV (4.90 vs. 4.30 ng/ml, Z=4.29, P<0.001) and JCV infections (5.30 vs. 4.80 ng/ml, Z=4.25, P<0.001). Conclusion:High incidences of JCV and BKV infections were observed post-kidney transplantation. Co-infection with low-load JCV and CMV accelerates renal function impairment, highlighting the critical role of tacrolimus concentration management in reducing viral infection risks.

Objective:To explore the clinical and genetic characteristics of two children diagnosed with two rare genetic diseases simultaneously.Methods:Two children with comorbidity of two genetic diseases due to dual genetic mutations diagnosed at the Third Affiliated Hospital of Zhengzhou University respectively in May 2022 and March 2023 were selected as the study subjects. Clinical and genetic data of the two children were retrospectively analyzed. This study has been approved by the Ethics Committee of the Third Affiliated Hospital of Zhengzhou University (Ethic No. 2021-062-01).Results:Child 1 was a 2-year-and-4-month-old boy whose clinical manifestations included facial dysmorphism, developmental delay, short stature, microcephaly, cleft palate, cryptorchidism, hypospadias, recurrent infections and immunological abnormalities. Whole exome sequencing revealed that he had harbored a heterozygous c.6595delT (p.Y2199Ifs*65) variant of the KMT2D gene and a heterozygous c. 1892G>A (p.R631Q) variant of the PIK3R1 gene. This has led to a dual genetic diagnosis of Kabuki syndrome and PI3Kδ-related immunodeficiency type 36. Child 2 was a 15-year-old girl whose clinical manifestations included epilepsy, Albright′s hereditary osteodystrophy, long body trunk, short limbs, hypocalcemia, hyperphosphatemia and hyperparathyroidism. The child also had a family history of short stature. Whole exome sequencing revealed that she had harbored a heterozygous c. 2T>C (p.Met1? ) variant of the GNAS gene and deletion of exons 2 to 6 of the SHOX gene. The two variants have led to dual diagnose of pseudohypoparathyroidism and X-linked idiopathic short stature. Conclusion:When the clinical phenotype of a genetic disease is complex and cannot be fully explained with a single genetic variant, multiple pathogenic variants should be considered, and this may lead to the diagnosis of co-morbid genetic diseases. To adopt or supplement corresponding genetic testing in time and re-analyze the genetic data may facilitate accurate diagnosis of comorbid genetic diseases.

Objective:This study aimed to clarify clinicopathologic characteristics, postoperative complications, and related risk factors of elderly patients with gastric cancer.Methods:A total of 395 patients(≥65 years old)who underwent radical gastrectomy for gastric cancer in Beijing Hospital from January 2014 to December 2021 were enrolled in this study.The patients were divided into the common elderly group(age<80 years, n=340)and the high-age group(age ≥ 80 years, n=55). Postoperative complications were classified into medical and surgical types.The clinicopathological characteristics and complications were compared between the two groups.Logistic regression models(univariate and multivariate)were used to identify the risk factors for postoperative complications.Results:The common elderly group was 65-79 years old(mean age: 71.5±4.3 years), with 263 male(77.4%); The high-age group was 80-89 years old(mean age: 82.6±2.6 years), with 42 male(76.4%). The comorbidity rate and the number of comorbidities in the high-age group were significantly higher than those in the common elderly group.The American Society of Anesthesiologists(ASA)scores and nutritional risk screening(NRS)2002 scores in the high-age group were significantly higher than those in the common elderly group(both P<0.05), and the activities of daily living(ADL)scores in the high-age group were significantly lower than that in the common elderly group( P<0.001). There were no statistically significant differences in tumor location, degree of differentiation, pathological type, T stage, and N stage between the two groups(all P>0.05). The overall postoperative complication rate in the high-age group was significantly higher than that in the common elderly group(38.2% vs.24.7%, P=0.036); the medical complications were significantly increased in the high-age group(21.8% vs.10.9%, P=0.022), whereas the surgical complications did not increase significantly(25.5% vs.17.1%, P=0.135). Multivariate analysis revealed that the number of comorbidities ≥2( HR=2.502, 95% CI: 1.275-4.911, P=0.008), preoperative NRS 2002 scores ≥5( HR=2.714, 95% CI1.294-5.693, P=0.008), and preoperative ADL scores<100( HR=2.012, 95% CI1.010-4.009, P=0.047)were independent risk factors for medical complications.Additionally, ASA grade ≥ 3( HR=2.586, 95% CI: 1.444-4.632, P=0.001)and proximal or distal gastrectomy( HR=2.397, 95% CI: 1.237-4.574, P=0.009)were independent risk factors for surgical complications. Conclusions:The occurrence of postoperative medical complications in very elderly patients with gastric cancer undergoing radical surgery has increased, while the rate of surgical complications has not increased.Moreover, advanced age itself is not an independent risk factor for postoperative complications.More attention should be paid to medical complications, and the management of commodities and nutritional support should be strengthened during the perioperative period.

Objective:This study aimed to analyze the infection status of viral viruria within one year after kidney transplantation, its impact on renal allograft function, and associated risk factors.Methods:A retrospective case-control study was conducted, involving 370 patients who underwent allogeneic kidney transplantation at Renji Hospital, Shanghai Jiao Tong University School of Medicine, from January 1, 2020 to December 31, 2021. Urinary viral loads of BK virus (BKV), JC virus (JCV), cytomegalovirus (CMV), and Epstein-Barr virus (EBV) were detected using PCR fluorescent probe assays. Patients were categorized into infection and non-infection groups. Glomerular filtration rate (GFR) and tacrolimus trough concentration was measured during infections, and clinical data were collected. Univariate analysis was performed to identify risk factors for viral viruria.Results:The 1-year patient survival rate and graft survival rate were both 98.6%. The incidence rates of viral viruria were as follows: JCV (42.7%), BKV (29.7%), CMV (11.6%), and EBV (2.9%), with statistically significant differences among viruses ( P<0.001). Single viral infection accounted for 48% of cases, while co-infections were predominantly BKV+JCV (9%). JCV infection rates remained consistently high throughout the year (22.4%-28.9%), whereas BKV infections peaked at 3 months postoperatively (20.5%). Co-infection with low-load JCV (>2 000 copies/ml) and CMV (>6 000 copies/ml) led to a significant decline in GFR at 6 months post-transplantation [median difference: 16.7 ml/(min×1.73 m2), P=0.019]. Univariate analysis revealed that elevated tacrolimus trough concentration was independent risk factor for BKV (4.90 vs. 4.30 ng/ml, Z=4.29, P<0.001) and JCV infections (5.30 vs. 4.80 ng/ml, Z=4.25, P<0.001). Conclusion:High incidences of JCV and BKV infections were observed post-kidney transplantation. Co-infection with low-load JCV and CMV accelerates renal function impairment, highlighting the critical role of tacrolimus concentration management in reducing viral infection risks.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Purpose/Significance To explore the feasibility of applying blockchain technology to the current healthcare system of hos-pitals,and to achieve the purpose of protecting patients'privacy to the greatest extent possible at a lower cost.Method/Process 505 questionnaires are randomly distributed and collected from people of different age groups in Beijing,Tianjin,Shanghai and Shenzhen who have a certain degree of understanding of blockchain technology,and the results are analyzed.Result/Conclusion Different age groups are highly concerned about personal privacy and privacy protection,and are willing to accept blockchain as an emerging technology.There is a greater demand and acceptance for the application of blockchain technology in the primary health care systems.

Objective To analyze the occurrence and predictive factors of early death(ED)in elderly(≥60 years old)patients with newly diagnosed acute promyelocytic leukemia(APL)induced by single-agent arsenic trioxide(ATO).Methods The clinical da-ta of 71 consecutive elderly APL patients and 456 consecutive young APL patients were collected.Ten clinical and laboratory parameters,which could be obtained rapidly by clinicians were selected.Chi-square test and Logistic regression analysis were used for statistical a-nalysis.Results The ED rate in elderly patients(22.5％,16/71)was higher than that in young patients(15.1％,69/456),but the difference was not statistically significant(P=0.115).The incidence of infection-related ED(8.5％)and thrombosis-related ED(2.3％)in elderly patients was significantly higher than that in young patients(2.0％and 0.3％,respectively),and the difference was statistically significant(P＜0.01).Peripheral white blood cell count＞10 × 109/L and male were independent risk factors for ED in both the elderly and young patients.And hypoalbuminemia(P＜0.001)and plasma fibrinogen＜1g/L(P=0.001)were still independent risk factors for ED only in young patients.Conclusion When induced by single-agent ATO,the elderly APL patients were significantly different from the young patients in terms of clinical features,incidence and risk factors of ED.Therefore age-stratified study on ED in APL is necessary.