Objective To investigate the distribution of abnormal karyotypes and their associations with clinical manifestations of the infertile patients in southern Sichuan Province.Methods A total of 4 157 infertile patients who attended the Reproductive Medicine Center of our hospital from July 2018 to June 2021 were included.The chromosome karyotype in peripheral blood was detected by G-banding,and their semen analysis results,uterine development and other clinical data were collected.Results Among the 4 157 patients,chromosomal polymorphisms were found in 239 cases(5.75％),and abnormal karyotypes wee found 137 cases(3.30％).The abnormal karyotypes included 57 cases(41.61％)of sex chromosome aneuploidy,6 cases(4.38％)of Robertsonian transloca-tions,32 cases(23.36％)of balanced translocations,21 cases(15.33％)of chromosomal inversions,9 cases(6.57％)of mosai-cism,8 cases(5.84％)of marker chromosomes,3 cases(2.19％)of sex reversal and 1 case(0.73％)of sex chromosome deletion.In male patients with abnormal karyotypes,91.58％showed abnormal semen parameters,while in those with polymorphic karyotypes,55％had abnormal semen parameters.The patients with Turner syndrome had significantly smaller uterine dimensions(longitudinal,transverse,and anteroposterior)compared to the normal control group(P＜0.01).Conclusion Chromosomal abnormalities should be the important cause of infertility.Conducting karyotype analysis combining with clinical manifestations is crucial examination for the di-agnosis and reproductive guidance of infertile patients.

OBJECTIVE: To provide prenatal diagnosis, pedigree analysis and genetic counseling for a pregnant woman who had given birth to a child featuring global developmental delay. METHODS: A pregnant woman who underwent prenatal diagnosis at the Affiliated Hospital of Southwest Medical University in August 2021 was selected as the study subject. Peripheral blood samples were collected from the woman, her husband and child, in addition with amniotic fluid sample during mid-pregnancy. Genetic variants were detected by G-banded karyotyping analysis and copy number variation sequencing (CNV-seq). Pathogenicity of the variant was predicted based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). Candidate variant was traced in the pedigree to assess the recurrence risk. RESULTS: The karyotypes of the pregnant woman, her fetus, and affected child were 46,XX,ins(18)(p11.2q21q22), 46,X?,rec(18)dup(18)(q21q22)ins(18)(p11.2q21q22)mat and 46,XY,rec(18)del(18)(q21q22)ins(18)(p11.2q21q22)mat, respectively. Her husband was found to have a normal karyotype. CNV-seq has revealed a 19.73 Mb duplication at 18q21.2-q22.3 in the fetus and a 19.77 Mb deletion at 18q21.2-q22.3 in her child. The duplication and deletion fragments were identical to the insertional fragment in the pregnant woman. Based on the ACMG guidelines, the duplication and deletion fragments were both predicted to be pathogenic. CONCLUSION The intrachromosomal insertion of 18q21.2-q22.3 carried by the pregnant woman had probably given rise to the 18q21.2-q22.3 duplication and deletion in the two offspring. Above finding has provided a basis for genetic counseling for this pedigree.
Child ; Female ; Humans ; Pregnancy ; DNA Copy Number Variations ; East Asian People ; Pedigree ; Prenatal Diagnosis/methods* ; Chromosomes, Human, Pair 18/genetics* ; Male ; Fetus ; INDEL Mutation

Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

Objective:To evaluate the efficacy and safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of pseudomyxoma peritonei (PMP).Methods:In this descriptive case series study, we retrospective analyzed the records of PMP patients treated with CRS and HIPEC between January 2013 and June 2023 at Affiliated Cancer Hospital and Institute of Guangzhou Medical University. The inclusion criteria were as follows: (1) Aged 18 to 75 years and nonpregnant women. (2) Histologically confirmed diagnosis of pseudomyxoma peritonei. (3) Karnofsky Performance Scale (KPS)>70. (4) The functions of major organs such as the heart, liver, lungs, and kidneys can tolerate major surgery for long periods of time. (5) No evidence of extra-abdominal metastasis. Patients with extensive intra-abdominal adhesions or severe infectious diseases were excluded. The main outcomes were overall survival (OS) and postoperative major complications. The postoperative major complications were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (version 5.0). We used the peritoneal cancer index (PCI) score to quantitatively assess the peritoneal metastases and the completeness of cytoreduction (CCR) score at the end of surgery (CCR-0 and CCR-1 considered to be complete CRS).Results:A total of the 186 PMP patients with a median age of 56 (interquartile range extremes (IQRE), 48-64) years were included, 65 (34.9%) males and 121 (65.1%) females. The median peritoneal cancer index (PCI) score was 28 (20-34). Appendiceal origin accounted for 91.4%. Histological types were low grade in 99 patients (53.2%), high grade in 57 patients (30.6%), and 55 patients (29.6%) received complete cytoreduction (CCR-0/1). The median operative duration was 300 (211-430) minutes for all patients. Treatment-related 30-day mortality was 2.7%; 90-day mortality 4.3%; reoperation 1.6%; and severe morbidity 43.0%. Within the entire series, anemia(27.4%), electrolyte disturbance(11.6%), and hypoalbuminemia(7.5%) were the most frequent major complications (grade 3-4). The incidences of gastrointestinal anastomotic leakage, abdominal bleeding, and abdominal infection were 2.2%, 2.2%, and 4.3%, respectively. After a median follow-up of 38.1 (95%CI:31.2-45.1) months, the 5-year OS was 50.3% (95%CI: 40.7%-59.9%) with a median survival time of 66.1 (95%CI: 43.1-89.1) months. The survival analysis showed that patients with pathological low grade, low PCI, and low CCR score had better survival with statistically significant differences (all P<0.05). Further stratified into complete and incomplete CRS subgroups, the 5-year OS of the CCR-0 and CCR-1 subgroups was 88.9% (95%CI: 68.3%-100.0%) and 77.6% (95%CI: 62.7%-92.5%), respectively; and 42.0% (95%CI: 29.5%-54.5%) in the CCR-2/3 subgroup. Conclusions:CRS and HIPEC may result in a long-term survival benefit for PMP patients with acceptable perioperative morbidity and mortality. This strategy, when complete CRS is possible, could significantly prolong survival for strictly selected patients at experienced centers.

Objective:To understand the reliability and validity of quality of life instruments for cancer patients-brain neoplasm [QLICP-BN (V1.0)], a self-developed quality of life scale for cancer patients.Methods:The quality of life of 112 patients with brain neoplasms in Yunnan Cancer Hospital from March 2012 to November 2013 was measured. The general data questionnaire and QLICP-BN (V1.0) were used for data collection. The reliability, validity and responsiveness of the scale were tested, and then the metric characteristics of the scale were evaluated.Results:The split-half reliability of the total score of the scale was 0.95, the Cronbach αcoefficient was 0.92, and the test-retest correlation coefficient rwas 0.78. After extracting common factors by the principal component method and rotating with the maximum variance, the specific module obtained three principal components, and the cumulative variance contribution rate was 64.18%. The score of specific module was 75.30±17.44 before treatment and 78.91±12.20 after treatment ( t=-2.481, P=0.015). The total score of scale before treatment was 65.26±12.29, and that after treatment was 69.62±10.41, with a statistically significant difference ( t=-4.492, P<0.001). The total responsiveness of the scale was 0.456, showing moderate responsiveness. Conclusion:QLICP-BN (V1.0) has good reliability, validity and a certain degree of responsiveness. It can be used as a measurement tool for the quality of life of patients with brain neoplasms in China.

Objective:To present briefly introductions and evaluations on the constructs, psychometric properties (reliability, validity, reactivity etc.) and applications of the system of Quality of Life Instruments for Cancer Patients QLICP(V1.0) including 12 kinds of scales for patients with head and neck cancer, brain cancer, lung cancer, breast cancer, esophageal cancer, gastric cancer, colorectal cancer, liver cancer, cervical cancer, ovarian cancer, leukemia and lymphoma.Methods:Based on our measuring data from relevant patients at hospitals, the constructs, characteristics and psychometrics of the system above were analyzed and presented. Internal consistency reliability for each domain and the overall scale was assessed using Cronbach's alpha coefficient, and test-retest reliability through calculating the Pearson correlation coefficient between the first and second assessments. The criterion-related validity was evaluated by correlating corresponding domains of two instruments. Responsiveness was assessed through comparing the mean difference between the pre-treatment and post-treatments with standardized response mean (SRM). The use agreements and literature reviews of this system were used to understand the applications of 12 kinds measurement scales.Results:The quality of life scales for 12 kinds of cancer patients of the system QLICP(V1.0) have good construct( 5 domains, 11-15 facets), reliability, validity and a certain degree of responsiveness. The internal consistency reliability Cronbach's α coefficients for the overall scale of QLICP in different cancers was from 0.67 to 0.92, and the test-retest reliability (correlation coefficient) was from 0.61 to 0.99. The criterion-related validity (correlation coefficient) was for the overall scale of QLICP in different cancers was from 0.28 to 0.89, and the responsiveness SRM was from 0.25 to 1.28. And also they were widely used in clinical practice and relevant studies for the corresponding cancers.Conclusion:The system QLICP(V1.0) is of outstanding characteristics with all psychometrics meeting requirements and better construct (clear hierarchical structure with items→ facets→ domains→ overall ), and can be used widely in clinical practice further.

Objective: To compare the differences and similarities among the system of quality of life instruments for cancer patients (QLICP) V1.0, the quality of life questionnaire (QLQ) from European Organization for Research and Treatment of Cancer (EORTC) and Functional Assessment of Cancer Therapy (FACT) from Center on Outcomes, Research and Education (CORE) of America. Methods: Based on literatures and our measuring data from patients at hospitals, the constructs, characteristics and psychometrics of the systems above were analyzed and compared. Internal consistency reliability was assessed using Cronbach α coefficient for each domain, and test-retest reliability through calculating the Pearson correlation coefficient r between the first and second assessments as well as intra-class correlation (ICC). Construct validity was evaluated by Pearson correlation coefficient r (item-domains correlations) and factor analysis. The criterion-related validity was evaluated by correlating corresponding domains of two instruments. Responsiveness was assessed through comparing the mean difference between the pre-treatment and post-treatment with standardized response mean (SRM). Results: The instruments of three systems were of different outstanding characteristics with all psychometrics meeting requirements. Measurements for 12 types of cancers showed that the internal consistency reliability Cronbach α coefficient for the overall scale of QLICP (V1.0) was 0.67-0.92, and for FACT was 0.79-0.98. The test-retest reliability (r or ICC) for the overall scale of QLICP (V1.0) was 0.61-0.99, and for FACT was 0.60-0.98. The SRM for the overall scale of QLICP (V1.0) was 0.25-1.28, and for FACT was 0.11-0.83. However, the QLICP was of better construct (clear hierarchical structure with items→facets→domains→overall) and Chinese culture. Conclusion The instruments of three systems can be used as the instruments to assess quality of life for patients with cancer with selections basing on different settings.

Limb girdle muscular dystrophy (LGMD) is characterized by progressive proximal muscle weakness with high genetic heterogeneity.LGMD is the fourth prevalent form of muscular dystrophies in the adult neurology department.Since most patients are juvenile-or adult-onset and present as limb muscle weakness,it would be easily misdiagnosed as myositis or metabolic myopathies.The final diagnosis depends on muscle immunohistochemical staining,Western blotting and genetic screening.In China,LGMD2B and LGMD2A are the most prevalent forms,accounting for 74.3％ in overall LGMD.Patients with LGMD2B usually have onset age between 19-27 years old.LGMD2B patients present as asymptomatic hyper creatine kinase emia (CK) at the early stage,and later develop to typical proximal muscle weakness with bilateral calf atrophy and extremely high serum CK.The onset age of LGMD2A patients is between 7-18 years old.LGMD2A patients presented as proximal muscle weakness with or without bilateral scapular winging and Achilles tendon contractures.Serum CK can be moderately or highly elevated.Current therapies are mainly supportive and the effective treatment is insufficient.The ongoing global elinical history study and gene therapy bring us new hope for treating LGMD in the coming future.

Objective To summarize the clinical features,natural history and causes of death of mitochondrial encephalomyopathy,lactic acidosis and stroke-like episodes (MELAS).Methods We retrospectively evaluated the clinical findings of 64 patients diagnosed as MELAS more than 3 years (death cases excluded) in Huashan Hospital from January 2005 to March 2017 and analyzed the natural course and the causes of death of the disease.Results Among 64 patients,the male-to-female ratio was 1.3 ∶ 1.Median onset age was 20.5 (16.8) years.The peak of incidence age was from 14 to 22 years.The most common features of MELAS in acute phase were seizures (48/64,75.0％),headache (41/64,64.1％),blurred vision (37/64,57.8％),nausea and vomiting (27/64,42.1％),fever (25/64,39.1％),mental and behavioral disorder (24/64,37.5％).Lactate dehydrogenase (31/60,51.6％),resting blood lactic acid (43/58,74.1％) and cerebral spinal fluid lactic acid (9/9) were elevated.Abnormal findings in electroencephalogram (36/40,90.0％),electrocardiogram (37/47,78.7％),electromyography (25/41,61.0％) were detected.In this cohort,20 patients (20/64,31.3％) with MELAS were dead.A Kaplan-Meier survival curve showed the estimated overall median survival time was 12 years.The median survival time of the group onset before sex maturity (≤ 14 years) was 8 years and that in the group onset after sex maturity (＞ 14 years) was 21 years.The causes of death were cardiogenic incidence (4/20,20.0％),pulmonary infection (4/20,20.0％),lactic acidosis (2/20,10.0％) and status epilepticus (2/20,10.0％).Conclusions MELAS is usually presented in young people associated with high mortality rate.The leading causes of death are cardiogenic,pulmonary infection and lactic acidosis.

Objective To evaluate the safety and efficacy of botulinum toxin type A for injection in the treatment of post-stroke upper limb spasticity (dosage was 200 U,or 240 U if combined with thumb spasticity).Methods The study was a multi-center,stratified block randomized,double-blind,placebocontrolled trial.All the qualificd subjects were from 15 clinical centers from September 2014 to February 2016.They were randomized (2∶1) to injections of botulinum toxin type A made in China (200-240 U;n =118) or placebo (n =60) in pivotal phase after informed consent signed.The study was divided into two stages.The pivotal trial phase included a one-week screening,12-week double-blind treatment,followed by an expanded phase which included six-week open-label treatment.The tone of the wrist,finger,thumb flexors was assessed at baseline and at weeks 0,1,4,6,8,12,16 and 18 using Modified Ashworth Scale (MAS),disability in activities of daily living was rated using the Disability Assessment Scale and impaction on pain,muscle tone and deformity was assessed using the Global Assessment Scale.The primary endpoint was the score difference between botulinum toxin type A and placebo groups in the tone of the wrist flexor using MAS at six weeks compared to baseline.Results Muscle tone MAS score in the wrist flexor of botulinum toxin type A and placebo groups at six weeks changed-1.00 (-2.00,-1.00) and 0.00 (-0.50,0.00) respectively from baseline.Botulinum toxin type A was significantly superior to placebo for the primary endpoint (Z =6.618,P ＜ 0.01).The safety measurement showed 10 subjects who received botulinum toxin type A had 13 adverse reactions,with an incidence of 8.47％ (10/118),and three subjects who received placebo had three adverse reactions,with an incidence of 5.00％ (3/60) during the pivotal trial phase.All adverse reactions were mild to moderate,none serious.There was no significant difference in adverse reactions incidence between the botulinum toxin type A and the placebo groups.During the expanded phase three subjects had four adverse reactions and the incidence was 1.95％.All adverse reactions were mild,none serious.Conclusion Botulinum toxin type A was found to be safe and efficacious for the treatment of post-stroke upper limb spasticity.Clinical Trial Registration:China Drug Trials,CTR20131191