[Molecular genetic characteristics of a family which coinheritance of rare-88 C>G (HBB:c.-138 C>G) ß-thalassemia mutation with α-thalassemia and review of the literature].

The molecular genetic characteristics of a family with rare -88 C>G (HBB: c.-138 C>G) ß-thalassemia gene mutation were studied using cohort study. The cohort study was conducted from June to August 2022 by Prenatal Diagnosis Center of Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center. The phenotype and genotype were analyzed by hematological cytoanalyzer, automatic electrophoretic analysis system, and next-generation sequencing (NGS). And then, Sanger sequencing was used to verify the rare gene results. The results showed that the proband, her father, her uncle and her younger male cousin had discrete microcytosis (MCV 70.1 fl, 71.9 fl, 73.1 fl and 76.6 fl, respectively) and hypochromia (MCH 21.5 pg,22.0 pg,22.6 pg and 23.5 pg, respectively), elevated hemoglobin A2 level (5.3%, 5.4%, 5.4% and 5.5%, respectively), slightly elevated or normal fetal hemoglobin (Hb F), but no anemia. The proband was identified to have co-inherited ɑ-thalassemia (Hb Westmead gene heterozygous mutation, ɑwsɑ/ɑɑ) and ß-thalassemia with a rare -88 C>G (HBB: c.-138 C>G) heterozygous mutation (ß-88 C>G/ßN). Her mother had the same α-thalassemia as the proband. Her father, her uncle and her younger male cousin had the same rare -88 C>G heterozygous mutations as the proband. While her grandmother and younger brother were not carrier of thalassemia. In conclusion, 4 cases of rare -88 C>G(HBB:c.-138 C>G) heterozygous mutation had been detected in a Chinese family. Carriers of this beta-thalassemia are clinically asymptomatic. This study enriches the knowledge of the thalassemia mutation spectrum in Chinese people and provides valuable information for genetic counseling, prenatal diagnosis, and prevention of thalassemia, providing a scientific basis for improving the quality of birth population and preventing birth defects.

[Treatment and prognosis of multiple primary malignant neoplasms complicated with renal cell carcinoma].

OBJECTIVE: To investigate the treatment and prognosis of multiple primary malignant neoplasms (MPMN) complicated with renal cell carcinoma (RCC), and to make risk stratification. METHODS: A retrospective study of 27 cases of MPMN with RCC in two centers, including the different tumors of MPMN, specific treatment methods, and the interval between primary cancers. At the same time, the survival conditions, including recurrence, metastasis and survival, were followed up for statistical analysis. The interval between the two kinds of primary cancer within 6 months was simultaneous MPMNs, and more than 6 months was metachronous MPMNs. For simple risk stratification of cases, as long as one of the MPMNs had a stage Ⅲ or higher malignancy, which was defined as high risk. RESULTS: Among the 27 patients, 20 were male and 7 were female, with age at the time of diagnosis was 42-82 years, with an average age of (61.3±11.7) years. The age at the diagnosis of renal cancer was 43-87 years, with an average age of (66.0±11.3) years. There were 21 cases with duplex primary malignant neoplasms, 4 cases with triple primary malignant neoplasms, and 2 cases with quadruple primary malignant neoplasms. The interval between first cancer and second cancer was 0-360 months, with a median of 18 months. There were 17 cases of metachronous multiple primary malignant neoplasms and 10 cases of simultaneous multiple primary malignant neoplasms. The most common system of MPMN with comorbid RCC involved urologic system, digestive system and respiratory system. The most common locations of MPMN with comorbid RCC were bladder cancer, lung cancer and colon cancer. Follow-up time calcu- lated from the last cancer was 2-156 months, with a median of 32 months. And 14 cases survived and 13 cases died, with 11 cases being tumor related. Tumor stage was the risk factor of prognosis. Any kind of tumor stage in stage Ⅲ or above had a relatively poor prognosis. CONCLUSION: MPMN complicated with RCC is relatively rare. Standard treatment should be used for each cancer type during the treatment process. The prognosis mainly depends on the highest stage of each tumor. Simple risk stratification shows that the prognosis of the high-risk group is worse. This simple stratification method may be helpful to predict the prognosis.

[Bilateral papillary renal cell carcinoma following kidney transplantation: A case report].

With the continuous development of kidney transplantation technique, the survival time after kidney transplantation is gradually prolonged. Thus, the malignant tumor has been the important influencing factor on the long-term survival for kidney transplantation patients. Renal cell carcinoma is a relatively common tumor after kidney transplantation. Besides, clear cell renal cell carcinoma and papillary renal cell carcinoma are the relatively common pathological types for renal cell carcinoma following kidney transplantation. However, bilateral renal cell carcinoma following kidney transplantation is comparatively rare. In this article, we presented a case of bilateral papillary renal cell carcinoma, which occurred after kidney transplantation. And the diagnosis and treatment were introduced in detail. The patient was 37 years old, and he underwent kidney transplantation 13 years ago in our hospital, because of kidney failure. After kidney transplantation, he had regular medical check-up every year. In this year, his urological ultrasound results indicated bilateral renal tumors. And then, he received abdominal and pelvic computed tomography, and the result also showed bilateral renal tumors, which were likely to be malignant tumors. After adequate consultation, the patient chose surgical treatment. The patient received long-term immunosuppressive therapy, because of kidney transplantation. Considering this, the surgeon decided to choose a staging surgical treatment, in order to reduce the bad influence of one-stage surgery. Then, the patient first underwent retroperitoneal laparoscopic radical nephrectomy for right renal tumor in our hospital, and he had no complications after operation. The pathological results showed papillary renal cell carcinoma. He was discharged successfully. He underwent retroperitoneal laparoscopic radical nephrectomy for left renal tumor in our hospital one month later, and he had no complications after operation. The pathological results also showed papillary renal cell carcinoma. He was discharged successfully two days after surgery. In the 3-month follow-up, the patient was recovering well. To sum up, the incidence of bilateral renal cell carcinoma following kidney transplantation is relatively rare, and bilateral radical nephrectomy is effective and safe treatment. Above all, it is the patient's condition that determines the choice of staging surgery or simultaneous surgery.

[Clinical and imaging features of Chlamydia psittaci pneumonia: an analysis of 48 cases in China].

Objective: To explore the clinical characteristics, imaging findings, laboratory tests and treatment strategies for Chlamydia psittaci pneumonia. Methods: From January 1, 2019 to January 20, 2021, 48 cases of Psittacosis from 11 hospitals in China were diagnosed via metagenomic next-generation sequencing(mNGS). The data of all patients on occupational history, clinical manifestations, laboratory tests, chest computed tomography(CT)findings, treatment outcomes and prognosis were retrospectively analyzed. Results: Among the 48 patients, there were 29 males and 19 females, with a mean age of (57.1±10.3) years. Thirty patients had a confirmed history of exposure to poultry. The onset to admission interval was (6.5±3.2) days, and hospital stay was (12.4±4.8) days. Clinical manifestations included fever (100%, 48/48), relative bradycardia (71%, 34/48), cough (54.2%, 26/48), sputum (27.1%, 13/48), fatigue (16.7%, 8/48), headache and delirium (20.8%, 9/48), and gastrointestinal symptoms (16.7%, 8/48). Laboratory data showed that white blood cells were (8.0±3.8)×109/L, and the proportion of neutrophils increased in 44 patients. The level of C-reactive protein was (155.3±74.1)mg/L, and that of procalcitonin (PCT)in 59.5% of patients was more than 0.5 µg/L. Percentages of patients with increased lactate dehydrogenase and creatine kinase were 82.9% and 45.2%, respectively. Chest CT scans showed unilateral lung involvement in 34 cases(70.8%) and single lobe involvement in 27 cases(56.3%).The most common imaging change was consolidation, with 38 cases (79.2%) showing lobar consolidation. In terms of treatment, 25 patients were treated with fluoroquinolones alone, 6 patients with doxycycline alone, and 13 patients with combined treatment. The combined-treatment group and the doxycycline alone group were similar in the course of defervescence. The combined treatment group and the doxycycline alone group were both superior to the fluoroquinolones alone group. However, 11 patients were admitted to ICU, all of them received artificial ventilation, and 5 cases developed shock, and one died. Conclusions: Chlamydia psittaci pneumonia is an animal-derived infectious disease with unique features in clinical symptoms, laboratory tests and chest imaging. Appropriate treatment is able to significantly shorten the course of disease and improve the prognosis.

[Analysis of self-control trial results of narrow band imaging and white light in transurethral resection of bladder tumor].

OBJECTIVE: To investigate the effect of NBI assisted white light transurethral resection of bladder tumor (TURBT) in the treatment of bladder urothelial carcinoma and to summarize the experience of narrow band imaging (NBI) operation. METHODS: Patients with bladder urothelial carcinoma were selected, and TURBT was performed after anesthesia. First of all, the bladder tumor was found and resected under white light. Then we replaced with NBI, looked for suspicious lesions and resected them, The specimens excised under white light and NBI were collected separately. The number, location and pathological results of the lesions under white light were recorded, and the residual lesions under NBI were also recorded. To evaluate the effect of NBI, the ratio of residual bladder tumor was calculated. The cases were divided into three groups according to the time sequence. The clinical data of each group were collected and the learning curve of TURBT under NBI assisted white light was observed. RESULTS: A prospective study of 45 patients with bladder tumor from April 2018 to January 2020, including 32 males and 13 females, aged from 23 to 89 years, with an average age of 65.2 years. All the operations were successfully completed, without obvious complications after operation. Nine cases were single and 36 cases were multiple. The maximum diameter of the tumors was 0.5 to 4.0 cm, with an average of 2.2 cm. The histopathology of the resected tissue under white light was urothelial carcinoma, and 19 cases (42.2%) were pathologically positive by NBI resection. The 45 cases were divided into three groups according to the time sequence, 15 cases in each group. The true positive rate of NBI was 33.3%, 46.7% and 46.7%, respectively, and the false positive rate was 60.0%, 46.7% and 26.7%, respectively in the three groups. CONCLUSION: TURBT is an effective way to treat bladder urothelial cancer, NBI is an effective supplement of white light, which can increase the detection rate of bladder cancer and reduce post-operative recurrence. The NBI light source has a certain learning curve. With the increase of cases, the false-positive rate of NBI is gradually reduced. After the NBI operator has rich experience, the recognition degree of flat tumor is gradually improved under white light, and the residual rate of NBI is reduced after the removal under white light.

[Feasibility study of blood oxygen level-dependent magnetic resonance imaging in evaluating the response of metastatic lymph nodes of rabbit VX2 tumor to radiotherapy].

Objective: To investigate the feasibility of blood oxygen level-dependent magnetic resonance imaging (MRI) in evaluating the response of metastatic lymph nodes of rabbit VX2 tumor to radiotherapy. Methods: Twenty-eight healthy New Zealand white rabbits which were provided by the Laboratory Animal Center of Soochow University, male or female, 2 to 3 months, weighing 2 to 3 kg, were used to establish the animal model of VX2 tumor popliteal fossa metastatic lymph node, and then were divided into either the radiotherapy group (n=16) or the control group (n=12). The radiotherapy group received a 20 Gy radiotherapy per rabbit, the control group received sham radiotherapy. All rabbits underwent MRI scan on four time points, including before (0 day), 3rd, 7th and 14th days after radiotherapy. The two parameters of size and R(2*) value (s(-1)) of lymph node were measured. At each time point,two rabbits in each group were sacrificed randomly to resect lymph nodes for pathological examination, and two parameters of microvessel density (MVD, strip/HP) and apoptosis index (AI, %) were analyzed. The parameters among the four time points in each group or between the two groups were compared. The correlation of lymph node size and R(2*) value with MVD or AI was analyzed, respectively. Results: A significant size difference was neither between the two groups or among the each time points in each group (P>0.05). The R(2*) of lymph node in the radiotherapy group was (29.6±1.7),(36.8±2.6),(44.8±5.8) and (57.7±6.2) s(-1) at the time points of 0, 3, 7 and 14 days, respectively, showing a gradual increase trend; MVD was (52.3±2.5),(41.0±3.6),(34.0±3.6) and (22.7±2.5) strip/HP respectively, showing a decreasing trend; AI was 12.8%±0.5%,14.9%±0.6%,20.6%±0.5% and 27.5%±0.7% respectively, showing a gradual increase trend (all P<0.05). In the control group, both R(2*) value and AI among the four time points did not change statistically (all P>0.05), but MVD showed a gradual increase trend,(50.0±3.0),(53.0±1.7),(60.3±2.5) and (70.0±2.0) strip/HP, respectively, P<0.05. There were significant differences in R(2*) and MVD at 3, 7 and 14 days, in AI at 7 and 14 days between the two groups (all P<0.05). There was a linear correlation of R(2*) value, but not of size, with MVD and AI (r=-0.87 and 0.94, respectively). Conclusion: Blood oxygen level-dependent MRI can indirectly reflect the hypoxic status of metastatic lymph nodes after radiotherapy, and has potential value in evaluating the response of metastatic lymph nodes to radiotherapy.

[Single-center study of laparoscopic radical nephrectomy with Mayo 0-2 level inferior vena cava thrombectomy].

OBJECTIVE: To investigate the safety and feasibility of laparoscopic treatment for renal carcinoma with Mayo 0-2 level venous thrombosis. METHODS: From January 2015 to February 2018, 58 renal carcinoma cases with venous thrombus underwent laparoscopic radical nephrectomy with inferior vena cava thrombectomy in Department of Urology, Peking University Third Hospital, of which, 51 cases were male, and 7 female, aged 29-82 years. According to the Mayo grade classification, 20 cases were level 0, 20 cases were level 1, and 18 cases were level 2, with left side being 22 cases, and right side 36 cases. The patients except for those complicated with hemorrhagic diseases, cardiac and pulmonary insufficiency, or those who could not tolerate anesthesia and surgical contraindications, underwent the operation after comprehensive examinations. RESULTS: The 58 cases of renal tumor with venous tumor emboli were successfully completed with the surgeries, including 50 cases of totally laparoscopic surgery, 8 cases of laparoscopy surgery from convert to open (among the patients who were converted to open surgery, 7 were complicated with grade 2 tumor thrombus and 1 with grade 1 tumor thrombus). The main reasons for converting to open surgery were huge tumors (the largest of which was about 16 cm in diameter), severe adhesion and difficulty of separation. For different patients, different surgical methods and procedures were adopted according to the tumor direction and the different grade of tumor thrombus. Radical nephrectomy combined with vena cava tumor thrombus removal was performed in 55 cases and segmental resection of vena cava in 3 cases. The operation time was 132-557 min, and blood loss was 20-3 000 mL. Post-operative pathological types: 51 cases were clear cell carcinoma, 5 cases were type 2 of papillary carcinoma, 1 case was squamous cell carcinoma, and 1 case was chromophobe cell tumor. In the study, 47 cases were followed up for 1-36 months, and 4 cases died (the survival time was 5-15 months, with an average of 10.2 months). CONCLUSION: Laparoscopic radical nephrectomy with inferior vena cava thrombectomy is a reasonable choice for renal tumor with Mayo 0-2 level venous thrombosis. For different tumor directions and different grades of tumor thrombus, an appropriate operation plan can give the maxim benefit to the patients with skillful surgeons.

[The effect of ambient PM(10) on sperm quality in Wuhan].

Objective: To investigate the effect of exposure to particulate matter ≤10 µm in aerodynamic diameter (PM(10)) on sperm quality in different stages of sperm development. Methods: This cross-sectional study included 1 827 patients attending the reproductive medicine center in Renmin Hospital of Wuhan University during April 2013 to January 2015. Air pollution data from January 2013 to January 2015 was obtained from the database of Wuhan Municipal Environmental Protection Bureau. The generalized linear model was employed to assess the association between each exposure variables and sperm parameters for several exposure windows (0-9, 10-14, 15-69, 70-90, 0-90 days before sampling) . Results: The average levels of PM(10) was (116.2±71.6) µg/m(3) during the research period. Sperm volume was (75.4±49.1) ×10(6)/ml in sample population, (29.4±16.2) % in progressive motility and (51.8±21.6) % in total motility. Exposure to PM(10) was inversely associated with sperm concentration (ß:-0.319; 95%CI:-0.529,-0.046) during 70-90 lag days. PM(10) exposure during the 0-90 lag days was significantly associated with progressive motility (ß:-0.312; 95%CI:-0.527,-0.097) and total motility (ß:-0.347; 95%CI:-0.636,-0.059) after adjusted for age, education level, BMI, smoking, abstinence time, temperature, humidity and season. Conclusion: Exposure to PM(10) was associated with statistically significant decrements in sperm concentration and motility, and the adverse impact on sperm concentration was significantly in early phases of spermatogenesis.

[Radical nephrectomy and thrombectomy for Mayo clinic stage III tumor thrombus: a surgical technique and clinical experience].

OBJECTIVE: To evaluate the effectiveness and safety of radical nephrectomy and inferior vena cava thrombectomy in the treatment of patients with Mayo III tumor thrombus, and to introduce our experience and surgical technique. METHODS: The clinical data of 8 patients with Mayo III tumor thrombus from October 2014 to September 2016 were analyzed retrospectively. Of the 8 patients, 3 were male and 5 were female. The average age was (50.8±18.7) years (18 to 77 years). The average body mass index (BMI) was (22.7±4.4) kg/m2 (15.2 to 30.8 kg/m2). Imaging suggested the right renal tumor in all the 8 cases. The average tumor size was (7.9±2.5) cm. Open radical nephrectomy and inferior vena cava thrombectomy was conducted in 5 cases and laparoscopic surgery in 3 cases, and 1 case was converted to open surgery. RESULTS: All the 8 surgeries were completed successfully with no death case. The average surgery time was (370.3±101.6) min, ranging from 272-567 min. The average vena cava blocked time was (41.0±12.1) min, ranging from 17-55 min. The blood loss volume was (1 181.3±915.7) mL, ranging from 200-3 000 mL. During the operation, 5 cases were infused with suspended red blood cells, the amount of blood transfusion was 800-2 000 mL. 3 cases were infused of plasma with 400-1 000 mL. The average hospital stay was 9-23 d, with an average of (14.1±4.0) d. In the 8 patients, 4 cases underwent inferior vena cava wall resection because of invasion by tumor thrombus. Preoperative serum creatinine was 60-101 µmol/L, with an average of (76.4±15.3) µmol/L. Serum creatinine 1 week after the operation was 74-127 µmol/L, with an average of (100.8±21.1) µmol/L. Pathological diagnosis showed 6 cases of clear cell carcinoma, 1 case of papillary carcinoma type II, and 1 case of Ewing's sarcoma. Among the 8 patients, early postoperative complications occurred in 5 cases. Postoperative complications were graded as level II, according to the Clavien classifications. The 8 cases were followed up for 2 to 24 months with an average of 11.3 months. There was 1 patient who suffered from lung metastasis. CONCLUSION: Our initial clinical results show that radical nephrectomy and inferior vena cava thrombectomy is safe and effective for patients with Mayo III tumor thrombus. The wide extension of grade III vein tumor thrombus leads to the difficulty of operation technique. Sufficient preoperative preparation, rich operative experience and skills can improve the safety of operation.

[Feasibility of using blood oxygen level-dependent magnetic resonance imaging to evaluate renal fibrosis of ureteral obstruction of rabbits].

Objective: To investigate the feasibility of blood oxygen level-dependent MR (MR-BOLD) in assessing renal fibrosis of ureteral obstruction of rabbits. Methods: Forty healthy New Zealand rabbits were randomly divided into control group (n=8) and unilateral ureteral obstruction (UUO) group (n=32). The rabbits in the UUO group were subjected to unilateral ureteral obstruction of the left kidney.Coronal T(2) weighted imaging (T(2)WI) and axial BOLD examinations were performed before operation, 2, 4, 6 and 8 W after operation (each subgroup n=8). After the examinations, nephrectomy was performed for histologic evaluation.The T(2)(*) relaxation rate of the renal cortex (CR(2)(*)) , medulla (MR(2)(*)) and the same level of muscle(R(2)(*)(muscle)) were measured separately.The normalization of the cortex and medulla (sR(2)(*)), and the difference of sR(2)(*) between renal cortex and medulla before and post UUO (ΔsR(2)(*)) were calculated.The differences of sR(2)(*) (sCR(2)(*), sMR(2)(*), sCR(2)(*)(control), sMR(2)(*)(control)) at each time point between control and UUO group were compared by using independent sample t test.The LSD test was used to compare the sR(2)(*) in the control with that in the UUO group.The ΔsCR(2)(*) and ΔsMR(2)(*) values of the subgroups at UUO 2, 4, 6 and 8 W were compared by independent sample t test. Results: The sR(2)(*) values of UUO group were all lower than those of control group (all P<0.05), while sR(2)(*)(control) and sR(2)(*) in UUO group before operation were not significant different (P>0.05). The sCR(2)(*) values of UUO 2, 4, 6 and 8 W were 0.32±0.01, 0.37±0.01, 0.47±0.02 and 0.50±0.03.The sMR(2)(*) values were 0.39±0.02, 0.48±0.02, 0.58±0.04 and 0.65±0.05.There were significant differences of sCR(2)(*)(between) UUO 2 W and 6 W, UUO 2 W and 8 W, UUO 4 W and 6 W, UUO 4 W and 8 W (all P<0.01). There were significant differences of sMR(2)(*)(between) UUO 2 W and 6 W, UUO 2 W and 8 W, UUO 4 W and 8 W (all P<0.01). No significant difference was founded between sCR(2)(*) and sMR(2)(*) at each time point in control group (P>0.05). The ΔsCR(2)(*) values of UUO 2, 4, 6 and 8 W were 0.31±0.02, 0.20±0.02, 0.14±0.20, 0.09±0.04; the ΔsMR(2)(*) values were 0.51±0.05, 0.36±0.04, 0.28±0.05, 0.19±0.05. The ΔsCR(2)(*) values of UUO 2, 4 and 6 W were less than ΔsMR(2)(*) (P<0.05). There was no significant difference between ΔsCR(2)(*) and ΔsMR(2)(*) in UUO 8 W (P>0.05). Conclusions: The R(2)(*) change in medulla resulted from renal fibrosis is more significant than cortex.MR-BOLD can reflect the process of renal fibrosis.It's feasible and of great value to use renal MR-BOLD for the assessment of renal fibrosis induced by unilateral ureteral obstruction.

[Feasibility of susceptibility weighted imaging in the evaluation of renal fibrosis induced by unilateral ureteral obstruction in white rabbits].

Objective: To evaluate the feasibility of susceptibility weighted imaging (SWI) to reflect the progression of renal fibrosis (RF) induced by unilateral ureteral obstruction (UUO) in rabbits. Methods: Total of 32 New Zealand white rabbits (aged 4-5 months) were used to establish the UUO model (RF group) and were divided into 4 subgroups (including RF-2W group, RF-4W group , RF-6W group and RF-8W group) according to the duration of obstruction(2, 4, 6 and 8 weeks). Another 8 rabbits, underwent sham operation, were used as the control group (Sham group). T2 weighted imaging (T(2)WI) and SWI sequences were performed on the rabbits at 2, 4, 6 and 8 weeks after UUO, respectively. Rabbits were sacrificed and specimens were obtained after MR examination, then hematoxylin&eosin staining and Masson staining were performed to explore the renal tubular injury and interstitial fibrosis. The relationship between the relative signal-to-noise ratio(rSNR)measured on the SWI fusion maps and the degree of renal fibrosis was analyzed. Analysis of variance was used to compare the difference of rSNRs among 5 groups. Results: The rSNRs of the inner medulla gradually decreased over time, the rSNRs of Sham group, RF-2W group, RF-4W group, RF-6W group and RF-8W group was 2.29±0.18, 1.73±0.30, 1.67±0.08, 1.42±0.28, 1.12±0.15, respectively (F=25.876, P<0.01). In RF-2W group, the rSNRs of the outer medulla and cortex increased when compared with those in the Sham group, then they decreased gradually over time in the other groups (F=5.230, 7.621, both P<0.05). The pathological results demonstrated that the morphology of renal tubules in Sham group was normal and no apoptosis or necrosis was seen in the tubular epithelial cells. In the RF-2W group, the main pathological manifestations included renal tubules dilatation, tubular epithelial cell degeneration or necrosis and the infiltration of inflammatory cell. In Masson staining, lots of blue areas were present in the interstitial. As the obstruction time prolonged, the renal tubular collapse, inflammatory cells and fibroblasts increased significantly. Meanwhile blue area also increased significantly in Masson staining. Conclusion: SWI can be used as a noninvasive method to evaluate the pathological progression of fibrosis in the rabbit UUO model.

[The effects of exposure to ozone on sperm quality in Wuhan].

Objective: To evaluate the effects of exposure to ozone (O(3)) on sperm quality during different stages of spermatogenesis. Methods: All 1 780 subjects attending to the Reproductive Medicine Center in Renmin Hospital of Wuhan University were recruited from April, 4, 2013 to June, 30, 2015. The subjects were living in Wuhan more than 3 months before attending to the program, aged 20 to 40 years. Semen quality (sperm concentration and sperm count) were measured according to standardized protocols. Corresponding daily 8 hours average concentration of O(3), other polluted concentration, average temperature and relative humidity were collected in different time, including lag 0, 10, 70 and 90 d, and lag 0-9 d, lag 10-14 d, lag 70-90 d and lag 0-90 d. After controlling the age, BMI, education level and other confounders, generalized linear Model was used to investigate the association between O(3) and sperm quality during different stages of spermatogenesis. Results: Average daily concentration of O(3) during the study period was (114.20±74.88) µg/m(3) and the mean values of sperm concentration and count were (76.32±50.17) millions/ml and (164.77 ± 133.05) millions/sample, respectively. Exposure to O(3) was associated with decreasing sperm concentration and count. For every 1 µg/m(3) increase of O(3), the decrease of sperm concentration during lag 10, lag 0-9 and lag 10-14 days exposure windows were 0.040 (95%CI: 0.004-0.077) millions/ml, 0.081 (95% CI: 0.003-0.158) millions/ml and 0.059 (95% CI: 0.001-0.116) millions/ml, respectively. And the decrease of sperm count during lag 10, lag 0-9 days exposure windows were 0.105 (95%CI: 0.008-0.202) millions/sample and 0.221 (95% CI: 0.016-0.426) millions/sample. After stratification, in the ozone concentration

[Impact of atmospheric particulate matter at different period of gestation on low birth weight: a meta-analysis].

Objective: To analyze the influence of atmospheric particulate matters (PM(2.5) and PM(10)) on low-birth-weight (LBW) infants at different periods of gestation. Methods: We conducted a systematic literature search for 2 471 articles related to particulate matter and LBW published from January 1st 2000 to January 1st 2016 using the PubMed, Cochrane Library, Web of Science, Science Direct, Chinese Web of Knowledge, Wanfang and Weipu, and the keywords were" air pollution" , "adverse birth outcomes" , "adverse pregnancy outcomes" , "low birth weight/LBW" . According to criteria, 27 literatures were selected and included. Metafor package of the R 3.1.1 Software was used to check the heterogeneity and merge the effect value of the selected literatures, and sensitivity analysis and publication bias were detected and adjusted. Results: A total of 2 471 studies selected form the databases, 27 enrolled in this analysis according to the inclusion and exclusion criteria. Each 10 µg/m(3) increase in PM(2.5) was associated with combined OR values of 1st trimester, 2nd trimester, 3rd trimester and entire gestation at 1.02(95% CI: 0.87-1.19), 1.03 (95% CI: 0.91-1.16) , 1.07 (95%CI: 1.04-1.11) and 1.09 (95%CI: 1.04-1.15), respectively. And 10 µg/m(3) increase in PM(10) was associated with combined OR values of 1st trimester, 2nd trimester, 3rd trimester and entire gestation at 1.66 (95%CI: 1.06-2.61), 1.58 (95%CI:1.28-1.95) , 1.38 (95%CI: 1.23-1.56) and 1.04 (95%CI: 0.99-1.09), respectively. After adjusting the bias of publication, each 10 µg/m(3) increase in PM(2.5) was associated with the risk of low birth weight at 1.11 (95%CI: 1.02-1.21). Conclusion: This meta analysis supports an adverse impact of maternal exposure to particulate air pollution on low birth weight, varying in effects by exposure period.

Associations between matrix metalloproteinase gene polymorphisms and the development of cerebral infarction.

The aim of this study was to investigate the association between MMP3 rs3025058 and MMP9 rs3918242 polymorphisms and the development of ischemic stroke in a Chinese population. Between May 2013 and January 2015, 335 patients with ischemic stroke and 335 health control subjects were enrolled in this study. The MMP3 rs3025058 and MMP9 rs3918242 polymorphisms were analyzed using polymerase chain reaction coupled with restriction fragment length polymorphism. By multivariate logistic regression analysis, the CC genotype of MMP9 rs3918242 was shown to be associated with a significantly increased risk of ischemic stroke when compared with the TT genotype [OR (95%CI) = 5.47 (2.64-12.38)]. The TC+CC genotype of MMP9 rs3918242 was furthermore found to be associated with an elevated risk of ischemic stroke in higher BMI individuals [OR (95%CI) = 1.81 (1.03-3.22)]. The findings of this study suggest that the MMP9 rs3918242 polymorphism is associated with an elevated risk of ischemic stroke and that this gene polymorphism interacts with BMI in the risk of ischemic stroke.

[Acute impact of cold spells on mortality during 2001-2011 in Jiang'an district of Wuhan, China].

OBJECTIVE: To evaluate the association between cold spells and nonaccidental mortality from 2001 to 2011 in the Jiang'an District of Wuhan, China. METHODS: We collected mortality data for December 2001 to 2010 and January to March 2002 to 2011 in the study area. According to the International Classification of Diseases, we stratified the mortality data into three cause-specific categories: nonaccidental mortality, cardiovascular mortality, and respiratory mortality. We also obtained meteorological data (from the China Meteorological Administration) and ambient pollution data (from the Wuhan Environmental Monitoring Center) during the same periods. In the present study, a cold spell was defined as 5 or more consecutive days with daily average temperatures below the 5th percentile of daily mean temperatures (2.58 ℃) from January to December in 2001-2011. A distributed lag nonlinear model (DLNM) was applied to assess the acute effect of cold spells on daily nonaccidental mortality. RESULTS: During the study period, the total number of nonaccidental deaths was 17 119, including 9 403 (75.5%) among individuals aged over 65 years; 7 968 (46.5%) people died of cardiovascular disease. According to this definition, there were a total of 13 cold spell events and 111 days of duration in Wuhan during the study period. Study days were divided into three periods: non-cold spell days, 2008 cold spell days, and cold spell days in other years. Average daily mean temperatures of the above three periods were (8.2±4.5), (-0.7±1.4), and (0.8±1.2) ℃, respectively, corresponding to average daily deaths of 14.0±4.2, 18.2±4.5, and 14.9±4.9 for nonaccidental mortality. After adjusting for long-term trends, seasonal trends, weekdays, holidays, and relative humidity, analysis by the DLNM revealed that cold spells were associated with increased mortality risk, with a cumulative relative risk (RR) of 1.56 (95% CI: 1.36-1.79) at lag 0-27 days in 2008, higher than that in other years with 1.23 (95%CI: 1.08-1.41). Cold spells were not significantly associated with respiratory mortality and people under 65 years of age; however, during the 2008 cold spell RR increased to 1.96 (95% CI: 1.62-2.37) and 1.67 (95% CI: 1.43-1.95) for cardiovascular mortality and older adults (≥65 years old), respectively; both males and females had high mortality risk, with RRs of 1.60 (95%CI:1.33-1.92) and 1.50 (95% CI: 1.23-1.84), respectively. The association between cold spells and mortality remained nearly unchanged with and without adjustment for ambient pollutants (PM10, SO2, and NO2) in the DLNMs. CONCLUSION: In Wuhan, both the 2008 cold spell and cold spells in other years were significantly associated with increased nonaccidental mortality. People with cardiovascular disease and elderly adults may be more susceptible to the impact of cold spells on mortality.

Development of novel and polymorphic microsatellite DNA loci from Haliotis ovina.

Twelve microsatellite loci were developed from Haliotis ovina by the magnetic bead hybridization method. Genetic variability was assessed using 30 individuals from 3 wild populations. The number of alleles per locus ranged from 2 to 5, and the polymorphism information content ranged from 0.1228 to 0.6542. Observed and expected heterozygosities ranged from 0.0000 to 0.7778 and 0.1288 to 0.6310, respectively. These loci should provide useful information for genetic studies such as genetic diversity, pedigree analysis, construction of genetic linkage maps, and marker-assisted selection breeding in H. ovina.

[Clinical and prognostic analysis of opsoclonus-myoclonus-ataxia syndrome in children].

Objective: To summarize the clinical and prognostic features of children with opsoclonus-myoclonus-ataxia syndrome (OMAS). Methods: A total of 46 patients who met the diagnostic criteria of OMAS in the Department of Neurology, Beijing Children's Hospital from June 2015 to June 2023 were retrospectively analyzed. Centralized online consultations or telephone visits were conducted between June and August 2023. The data of the children during hospitalization and follow-up were collected, including clinical manifestations, assistant examination, treatment and prognosis. According to the presence or absence of tumor, the patients were divided into two groups. The chi-square test or Mann-Whitney U test was used to compare the differences between the two groups. Univariate Logistic regression was used to analyze the factors related to OMAS recurrence and prognosis. Results: There were 46 patients, with 25 males and the onset age of 1.5 (1.2, 2.4) years. Twenty-six (57%) patients were diagnosed with neuroblastoma during the course of the disease, and no patients were categorized into the high-risk group. A total of 36 patients (78%) were followed up for≥6 months, and all of them were treated with first-line therapy with glucocorticoids, gammaglobulin and (or) adrenocorticotrophic hormone. Among the 36 patients, 9 patients (25%) were treated with second-line therapy for ≥3 months, including rituximab or cyclophosphamide, and 17 patients (47%) received chemotherapy related to neuroblastoma. At the follow-up time of 4.2 (2.2, 5.5) years, 10 patients (28%) had relapsed of OMAS. The Mitchell and Pike OMS rating scale score at the final follow-up was 0.5 (0, 2.0). Seven patients (19%) were mildly cognitively behind their peers and 6 patients (17%) were severely behind. Only 1 patient had tumor recurrence during follow-up. The history of vaccination or infection before onset was more common in the non-tumor group than in the tumor group (55%(11/20) vs. 23%(6/26), χ²=4.95, P=0.026). Myoclonus occurred more frequently in the non-tumor group (40%(8/20) vs. 4%(1/26), χ²=7.23, P=0.007) as the onset symptom. Univariate Logistic regression analysis showed that the tumor group had less recurrence (OR=0.19 (0.04-0.93), P=0.041). The use of second-line therapy or chemotherapy within 6 months of the disease course had a better prognosis (OR=11.64 (1.27-106.72), P=0.030). Conclusions: OMAS in children mostly starts in early childhood, and about half are combined with neuroblastoma. Neuroblastoma in combination with OMAS usually has a low risk classification and good prognosis. When comparing patients with OMAS with and without tumors, the latter have a more common infection or vaccination triggers, and myoclonus, as the onset symptom, is more common. Early addition of second-line therapy is associated with better prognosis in OMAS.

[Clinical characteristics and short-term prognosis of 22 cases with SARS-CoV-2 infection associated acute encephalopathy].

Objective: To investigate the clinical features and short-term prognosis of patients with SARS-CoV-2 infection associated acute encephalopathy (AE). Methods: Retrospective cohort study. The clinical data, radiological features and short-term follow-up of 22 cases diagnosed with SARS-CoV-2 infection associated AE in the Department of Neurology, Beijing Children's Hospital from December 2022 to January 2023 were retrospectively analyzed. The patients were divided into cytokine storm group, excitotoxic brain damage group and unclassified encephalopathy group according to the the clinicopathological features and the imaging features. The clinical characteristics of each group were analyzed descriptively. Patients were divided into good prognosis group (≤2 scores) and poor prognosis group (>2 scores) based on the modified Rankin scale (mRS) score of the last follow-up. Fisher exact test or Mann-Whitney U test was used to compare the two groups. Results: A total of 22 cases (12 females, 10 males) were included. The age of onset was 3.3 (1.7, 8.6) years. There were 11 cases (50%) with abnormal medical history, and 4 cases with abnormal family history. All the enrolled patients had fever as the initial clinical symptom, and 21 cases (95%) developed neurological symptoms within 24 hours after fever. The onset of neurological symptoms included convulsions (17 cases) and disturbance of consciousness (5 cases). There were 22 cases of encephalopathy, 20 cases of convulsions, 14 cases of speech disorders, 8 cases of involuntary movements and 3 cases of ataxia during the course of the disease. Clinical classification included 3 cases in the cytokine storm group, all with acute necrotizing encephalopathy (ANE); 9 cases in the excitotoxicity group, 8 cases with acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) and 1 case with hemiconvulsion-hemiplegia syndrome; and 10 cases of unclassified encephalopathy. Laboratory studies revealed elevated glutathione transaminase in 9 cases, elevated glutamic alanine transaminase in 4 cases, elevated blood glucose in 3 cases, and elevated D-dimer in 3 cases. Serum ferritin was elevated in 3 of 5 cases, serum and cerebrospinal fluid (CSF) neurofilament light chain protein was elevated in 5 of 9 cases, serum cytokines were elevated in 7 of 18 cases, and CSF cytokines were elevated in 7 of 8 cases. Cranial imaging abnormalities were noted in 18 cases, including bilateral symmetric lesions in 3 ANE cases and "bright tree appearance" in 8 AESD cases. All 22 cases received symptomatic treatment and immunotherapy (intravenous immunoglobulin or glucocorticosteroids), and 1 ANE patient received tocilizumab. The follow-up time was 50 (43, 53) d, and 10 patients had a good prognosis and 12 patients had a poor prognosis. No statistically significant differences were found between the two groups in terms of epidemiology, clinical manifestations, biochemical indices, and duration of illness to initiate immunotherapy (all P>0.05). Conclusions: SARS-CoV-2 infection is also a major cause of AE. AESD and ANE are the common AE syndromes. Therefore, it is crucial to identify AE patients with fever, convulsions, and impaired consciousness, and apply aggressive therapy as early as possible.

[Clinical characteristics and gene analysis of GRIN2B gene related neurological developmental disorders in children].

Objective: To analyse the clinical and gene characteristics of GRIN2B gene related neurological developmental disorders in children. Methods: The data of 11 children with GRIN2B gene related neurological developmental disorders from November 2016 to February 2021 were collected from Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health and analyzed retrospectively. The clinical features, electroencephalogram (EEG), brain imaging and gene testing results were summarized. Results: Among 11 children 6 were boys and 5 were girls. Two of them were diagnosed with developmental and epileptic encephalopathy. The ages of seizures onset were 3 months and 9 months, respectively. Seizure types included epileptic spasm, tonic seizures, tonic spasm and focal seizures, and 1 patient also had startle attacks. EEG showed interictal multifocal epileptiform discharges. Both of them were added with more than 2 anti-seizure drugs, which were partially effective but could not control. They had moderate to severe mental and motor retardation. The phenotype of 9 cases was developmental delay or intellectual disability without epilepsy, age of visit 1 year to 6 year and 4 months of whom 5 cases had severe developmental delay, 2 cases had moderate and 2 cases had mild delay. Multi-focal epileptiform discharges were observed in 3 cases, no abnormality was found in 3 cases, and the remaining 3 cases did not undergo EEG examination. Ten cases underwent brain magnetic resonance imaging (MRI), 6 cases had nonspecific abnormalities and 4 cases were normal. Nine GRIN2B gene heterozygous variants were detected by next-generation sequencing in these 11 patients, 8 cases had missense variants and 1 case had nonsense variant, all of which were de novo and 3 of which were novel. Missense variants were found in 10 patients, among them 6 cases had severe developmental delay, 3 cases had moderate and 1 case had mild developmental delay, but the patient with nonsense variant showed mild developmental delay without epilepsy. Conclusions: The phenotypes of GRIN2B gene related neurological developmental disorders in children are diverse, ranging from mild intellectual impairment without epilepsy to severe epileptic encephalopathy. Patients with epileptic phenotype usually have an onset age of infancy, and spasm and focal seizures are the most common seizure types. And the epiletice episodes are refractory. Most of the patients with missense variants had severe developmental delay.

[Molybdenum cofactor deficiency type B manifested as Leigh-like syndrome: a case report and literature review].

Objective: To explore the phenotypes and genotypes of molybdenum cofactor deficiency type B (MoCD-B) manifested as Leigh-like syndrome. Methods: The clinical data, laboratory tests, neuroimaging and gene results of one patient diagnosed as MoCD-B at Beijing Children's Hospital and Hebei Children's Hospital in December 2018 were collected. Related literature was searched and reviewed at Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure and PubMed (up to September 2020) by using terms "MOCS2" "molybdenum cofactor deficiency" "Leigh-like syndrome,MOCS2" "molybdenum cofactor deficiency, Leigh-like syndrome". The phenotypes and genotypes of MoCD-B were summarized. Results: A 7 months and 14 days old boy with the chief complaint of "cough for 6 days, abnormal posture for 4 days and fever for 2 days" was admitted to Hebei Children' Hospital on December 2018. His abnormal posture presented as opisthotonos accompanied with dysphagia, without seizures. His previous psychomotor development was described as normal. He was born at term after an uneventful pregnancy to non-consanguineous parents. Blood test showed a slightly increased lactic acid and a significantly decreased uric acid. Urine metabolism test showed an obviously increased xanthine and hypoxanthine. Brain magnetic resonance imaging showed hyperintense signal on T2 weighted image and fluid attenuated inversion recovery in bilateral globus pallidus and pedunculus cerebri. The patient was diagnosed with Leigh-like syndrome. No obvious improvement was achieved after cocktail therapy and symptomatic treatment. The whole exome sequencing showed that the patient carried a homozygous variant of MOCS2 gene, c.19G>T(p.Val7Phe), which was a previously reported pathogenic site in the literature and could cause MoCD-B. His parents carried a heterozygous variant respectively. A total of 41 MoCD-B cases with MOCS2 gene variants were collected through literature review and our study, among which 30 cases had full medical records. The onset ages of 23 (77%) cases were in neonate, manifesting with severe encephalopathy, including neonatal-onset intractable seizures, developmental delay, laboratory abnormalities included very low levels of serum and urinary uric acid, increased urinary levels of xanthine and hypoxanthine. Cranial imaging showed cerebral atrophy, cystic encephalomalacia, etc. The onset ages of 7 patients varied from 5 months to 23 years. Four cases had normal psychomotor development before disease onset. Neurological disorders appeared acutely or exacerbated after external triggers and all of them had basal ganglia involvement. Among the 30 cases, 3 cases had a relatively milder phenotype with the ability of brief communication and walking without or with support. Conclusions: Molybdenum cofactor deficiency is a rare disease. Most cases had severe phenotypes and poor outcomes, but some cases may have mild phenotype. MoCD-B caused by MOCS2 gene variants may manifest as Leigh-like syndrome with a normal psychomotor development before the trigger of infection strike. Hypouricemia, xanthinuria and hypoxanthinuria can be indicators of the disease. The presence of MOCS2 gene variants would confirm a final diagnosis.