Objective:To summarize the genotype and clinical characteristics of chylomicron retention disease (CMRD) caused by secretion associated Ras related GTPase 1B (SAR1B) gene variations.Methods:Clinical data and genetic testing results of 2 children with CMRD treated at Children′s Hospital of Fudan University and Jiangxi Provincial Children′s Hospital from May 2022 to July 2023 were summarized. To provide an overview of the clinical and genetic characteristics of CMRD caused by SAR1B gene variations, all of the literature was searched and reviewed from China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, China VIP database, China Biology Medicine disc and PubMed database (up to January 2024) with "chylomicron retention disease" "Anderson disease" or "Anderson syndrome" as the search terms. All relevant literatures were reviewed to summarize the clinical and genetic features of CMRD caused by SAR1B gene variations.Results:One 11-year-old boy and one 4-month-old girl with CMRD. Both patients had lipid malabsorption, failure to thrive, decreased cholesterol, elevated transaminase and creatine kinase, and Vitamin E deficiency, with homozygous variations (c.224A>G) and compound heterozygous variations (c.224A>G and c.554G>T) in SAR1B gene, respectively. Case 1 was followed up for over a month, and he still occasionally experienced lower limb muscle pain. Case 2 was followed up for more than a year, and her had caught up to normal levels. Both patients had no other significant discomfort. Literature search retrieved 0 Chinese literature and 22 English literatures. In addition to the 2 cases reported in this study, a total of 51 patients were identified as CMRD caused by SAR1B gene variations. Twenty-one types of SAR1B variants 10 missense, 4 nonsense, 3 frameshift, 1 in-frame deletion, 1 splice, 1 gross deletion, and 1 gross insertion-deletion were found among the 51 CMRD cases. Among all the patients, 49 cases had lipid malabsorption (43 cases had diarrhea or fatty diarrhea, 17 cases had vomiting, and 12 cases had abdominal distension), 45 cases had lipid soluble Vitamin deficiency (43 cases had Vitamin E deficiency, 10 cases had Vitamin A deficiency, 9 case had Vitamin D deficiency, and 5 cases had Vitamin K deficiency), 35 cases had failure to thrive, 32 cases had liver involvement (32 cases had elevated transaminases, 5 cases had fatty liver, and 3 cases had hepatomegaly), 29 cases had white small intestinal mucosa under endoscopy, and 17 cases had elevated creatine kinase, 14 cases had neuropathy, 5 cases had ocular lesions, 2 cases had acanthocytosis, 1 case had decreased cardiac ejection fraction, and 1 case was symptom-free.Conclusions:Early infancy failure to thrive and lipid malabsorption are common issues for CMRD patients. The laboratory tests are characterized by hypocholesterolemia with or without fat-soluble Vitamin deficiency, elevated liver enzymes and (or) creatine kinase. Currently, missense variations are frequent among the primarily homozygous SAR1B genotypes that have been described.

Immunotherapy has revolutionized the landscape of cancer treatment. However, single immunotherapy only works well in a small subset of patients. Combined immunotherapy with antitumor synergism holds considerable potential to boost the therapeutic outcome. Nevertheless, the synergistic, additive or antagonistic antitumor effects of combined immunotherapies have been rarely explored. Herein, we established a novel combined cancer treatment modality by synergizing p21-activated kinase 4 (PAK4) silencing with immunogenic phototherapy in engineered extracellular vesicles (EVs) that were fabricated by coating M1 macrophage-derived EVs on the surface of the nano-complex cores assembled with siRNA against PAK4 and a photoactivatable polyethyleneimine. The engineered EVs induced potent PAK4 silencing and robust immunogenic phototherapy, thus contributing to effective antitumor effects in vitro and in vivo. Moreover, the antitumor synergism of the combined treatment was quantitatively determined by the CompuSyn method. The combination index (CI) and isobologram results confirmed that there was an antitumor synergism for the combined treatment. Furthermore, the dose reduction index (DRI) showed favorable dose reduction, revealing lower toxicity and higher biocompatibility of the engineered EVs. Collectively, the study presents a synergistically potentiated cancer treatment modality by combining PAK4 silencing with immunogenic phototherapy in engineered EVs, which is promising for boosting the therapeutic outcome of cancer immunotherapy.

ObjectiveTo investigate the clinical and genetic features of patients with glycogen storage disease type Ⅸa (GSD Ⅸa), and to improve the clinical understanding of the disease. MethodsA retrospective analysis was performed for the clinical data of 20 patients who were hospitalized and genetically diagnosed with GSD Ⅸa in Children’s Hospital of Fudan University from January 2015 to December 2018, and their clinical and genetic features were summarized. ResultsAll 20 patients with GSD Ⅸa were male, with a median age of 2.5 years at the time of confirmed diagnosis. All patients had hepatomegaly and elevated aminotransferases; of all patients, there were 5 patients (250%) with growth retardation, 19 (95.0%) with fasting hypoglycemia, 14 (70.0%) with hyperlactatemia, 9 (45.0%) with hypertriglyceridemia, and 5 (25.0%) with hypercholesterolemia. Fasting blood ketone was measured for 8 patients and all of these patients had an increase in blood ketone; all patients had normal uric acid, and 5 patients (25.0%) had positive urine ketone. Liver biopsy was performed for 18 patients, among whom 15 had mild to moderate liver fibrosis. A total of 16 mutations were detected in the PHKA2 gene, among which 5 were known pathogenic mutations and 11 were novel mutations, and most of the mutations were detected in the c.3614 locus. All patients were treated with uncooked cornstarch, and most patients achieved an improvement in clinical manifestations. ConclusionGSD Ⅸa is more common in male patients. This disease should be considered for patients with hepatomegaly, elevated aminotransferases, growth retardation, fasting hypoglycemia, elevated fasting blood ketone, and normal uric acid. Liver biopsy may help with the diagnosis of this disease, and clinical biochemical parameters and gene detection can be used to confirm diagnosis and classification. Most patients have mild clinical manifestations, while some patients may have liver fibrosis, and treatment with uncooked cornstarch can improve the condition of this disease.

【Objective】 To study the effects of platelets donation frequency on iron, copper, zinc content and superoxide dismutase(SOD) activity in plasma of blood donors. 【Methods】 128 apheresis platelet donors from August 25, 2020 to August 25, 2021 in our center were divided into 4 groups according to the frequency of platelet donation: first-time donors(n=30) were enrolled as group 1, and donors with 2 to 7 donations(n=23), 8 to 14 donations(n=29), 15 to 24 donations(n=46) within the previous period were group 2, group 3 and group 4. All these donors were males, with the average age of 42 ± 8.3, and had not donated whole blood in the past two years. Inductively coupled plasma mass spectrometry(ICP-MS) was used to detect the content of copper, iron and zinc in plasma of different groups of platelet donors. The SOD activity was detected by WST colorimetric kit. All data were statistically analyzed by SPSS 19.0 software. 【Results】 Significant differences in the content of iron and copper, but no in zinc, were noticed in donors of different groups(P<0.05). Multiple comparison showed that first-time blood donors presented significantly higher iron content but significantly lower copper content than those of donors with 15 to 24 blood donations per year(P<0.05), and no significant difference was found in iron and copper content among other groups(P>0.05). There was no significant difference in zinc content between every two groups(P>0.05). The SOD inhibition rate of blood donors in different groups was not significantly different. 【Conclusion】 The content of plasma iron, copper, and zinc and the SOD activity were not significantly affected if platelet donations were less than 15 times within a year. For those donated platelets more than 15 times within a year, the content of iron was found to decrease and copper to increase. It is suggested that platelet donations more than 15 times is correlated with the content of iron and copper in plasma of blood donors. Therefore, the proportion of iron-rich food should be appropriately increased in the daily diet for high-frequency(≥15 times per year) apheresis platelet donors after blood donation.

OBJECTIVETo explore the clinical characteristics of cataract surgery after radial keratotomy (RK) and appropriate calculation of intraocular lens (IOL) power.

METHODSEight patients with cataract (12 eyes) after RK were treated in our hospital from March, 2010 to June, 2013. The visual acuity, keratometric power and length of the ocular axis were examined before the operation. For each patient, 3 groups of corneal curvature values were measured using a automatic keratometer (TOPCON-KR8800) and the minimal K value was selected. Myopic or hyperopic posterior chamber IOL (-1.00 to -2.00 D) were selected based on automatic calculations with SRK-T. Phacoemulsification and IOL implantation were then performed, and the patients were followed up for visual acuity and refractive statuses at 3 months after the operation.

RESULTSAll the 12 operated eyes showed improved visual acuity after the operation. The uncorrected visual acuity reached 0.8 to 1.0 in 6 eyes and 0.4 to 0.6+ in the other 6, with a corrected visual acuity ranging from 0.6 to 1.0. The refractive status after operations was nearly emmetropic (+0.75 to -1.00 D) in 6 eyes and myopic in the other 6 (-1.00 to -2.50 D).

CONCLUSIONSPhacoemulsification and IOL implantation is feasible in cataract patients with previous RK. Selecting the minimal K values for central corneal curvature and calculation of the IOL power using the SRK T equation with a reservation of -1.00 to -2.00 D can better ensure the safety of the procedure and avoid the occurrence of hyperopia >+3.00D.

Cataract Extraction ; Cornea ; Humans ; Hyperopia ; Keratotomy, Radial ; Lens Implantation, Intraocular ; Lenses, Intraocular ; Myopia ; Phacoemulsification ; Visual Acuity

Objective To explore the clinical characteristics of cataract surgery after radial keratotomy (RK) and appropriate calculation of intraocular lens (IOL) power. Methods Eight patients with cataract (12 eyes) after RK were treated in our hospital from March, 2010 to June, 2013. The visual acuity, keratometric power and length of the ocular axis were examined before the operation. For each patient, 3 groups of corneal curvature values were measured using a automatic keratometer (TOPCON-KR8800) and the minimal K value was selected. Myopic or hyperopic posterior chamber IOL (-1.00 to-2.00 D) were selected based on automatic calculations with SRK-T. Phacoemulsification and IOL implantation were then performed, and the patients were followed up for visual acuity and refractive statuses at 3 months after the operation. Results All the 12 operated eyes showed improved visual acuity after the operation. The uncorrected visual acuity reached 0.8 to 1.0 in 6 eyes and 0.4 to 0.6+ in the other 6, with a corrected visual acuity ranging from 0.6 to 1.0. The refractive status after operations was nearly emmetropic (+0.75 to-1.00 D) in 6 eyes and myopic in the other 6 (-1.00 to-2.50 D). Conclusions Phacoemulsification and IOL implantation is feasible in cataract patients with previous RK. Selecting the minimal K values for central corneal curvature and calculation of the IOL power using the SRK T equation with a reservation of-1.00 to-2.00 D can better ensure the safety of the procedure and avoid the occurrence of hyperopia>+3.00D.

Objective To explore the clinical characteristics of cataract surgery after radial keratotomy (RK) and appropriate calculation of intraocular lens (IOL) power. Methods Eight patients with cataract (12 eyes) after RK were treated in our hospital from March, 2010 to June, 2013. The visual acuity, keratometric power and length of the ocular axis were examined before the operation. For each patient, 3 groups of corneal curvature values were measured using a automatic keratometer (TOPCON-KR8800) and the minimal K value was selected. Myopic or hyperopic posterior chamber IOL (-1.00 to-2.00 D) were selected based on automatic calculations with SRK-T. Phacoemulsification and IOL implantation were then performed, and the patients were followed up for visual acuity and refractive statuses at 3 months after the operation. Results All the 12 operated eyes showed improved visual acuity after the operation. The uncorrected visual acuity reached 0.8 to 1.0 in 6 eyes and 0.4 to 0.6+ in the other 6, with a corrected visual acuity ranging from 0.6 to 1.0. The refractive status after operations was nearly emmetropic (+0.75 to-1.00 D) in 6 eyes and myopic in the other 6 (-1.00 to-2.50 D). Conclusions Phacoemulsification and IOL implantation is feasible in cataract patients with previous RK. Selecting the minimal K values for central corneal curvature and calculation of the IOL power using the SRK T equation with a reservation of-1.00 to-2.00 D can better ensure the safety of the procedure and avoid the occurrence of hyperopia>+3.00D.

Objective The present study was designed to investigate the risk factors affecting bleeding during percutaneous nephrolithotomy. Methods The records of 218 patients with percutaneous nephrolithotomy procedure by a single surgeon were retrospectively reviewed.The mean age was 48 years ( range,19 -70).One hundred and forty six patients had staghore stones,and 7 patients had previous open or percutaneous nephrolithotomy histories.Forty-one patients had concomitant diabetes mellitus,and 89 cases had hypertension.The following factors including age,sex,BMI,diabetes status,hypertension status,stone type,calix of puncture,previous open or percutaneous nephrolithotomy history,number of accesses,size of accesses,operative time,and surgeon experience were analyzed.Univariate analysis and multivariate step regression analysis were used for statistical assessment. Results 207 procedures were successfully performed,and 11 patients failed because of difficulty to establish the accesses.Single-tract was used in 176 cases and multiple-tract was used in 31 cases.163 cases were performed via a 18 F access and 44 cases via a 24 F access.The mean operative time was 78.4 min.The overall blood transfusion rate was 7.7％,and stone type ( P =0.034),diabetes ( P =0.030),number of accesses ( P =0.019 ),size of accesses ( P =0.008) and operative time (P =0.001 ) were the risk factors affecting blood transfusion requirement.The average hemoglobin (Hb) drop after percutaneous nephrolithotomy procedures was 11.2 g/L,and stone type ( P ＜ 0.001 ),diabetes ( P =0.015 ),number of accesses ( P =0.016),size of accesses ( P ＜ 0.001 ) and operative time ( P ＜ 0.001 ) were the risk factors affecting Hb drop.The following covariates including Hb drop:age,sex,BMI,previous open or percutaneous nephrolithotomy history,hypertension status,calix of puncture and surgeon experience were not risk factors affecting blood transfusion requirement and Hb drop.Multivariate stepwise regression analysis showed that diabetes ( OR =1.75 ),stone type ( OR =1.92),number of accesses ( OR =2.45 ),size of accesses ( OR =1.32) and operative time ( OR =1.66) significantly increased risk of bleeding. Conclusions Stone type,diabetes,number of accesses,size of accesses and operative time were the risk factors affecting blood loss during percutaneous nephrolithotomy.

Objective To study the expression of enhancer of zeste homolog 2 (EZH2) gene in transitional cell carcinoma (TCC) of the bladder celt lines, carcinoma tissues and normal bladder tis-sues and to evaluate the roles of EZH2 in the development and progression of bladder carcinoma. Methods RT-PCR, Western-blot and immunocytochemistry were used to analyze the expression of EZH2 of the bladder cell lines (T24, EJ, MGH-U1, BIU-87). The prostate cancer cell line PC-3M was used as an EZH2-positive cell line. EZH2 gene expressions in 45 cases of bladder carcinoma and 12 cases of normal bladder mueosa were detected by RT-PCR. Of cancer cases, 31 were superficial tumors and 14 were invasive tumors; 13 were G1, 21 were G2 and 11 were G3. Results EZH2 was detected in the 4 TCC cell lines. The EZH2 expression rate of TCC (82.2%) was significantly higher than that of normal bladder tissues (8.3%, P<0.05). The expression rate in superficial tumors was 74.2% and in invasive tumors was 100.0%, but there was no significant difference (P>0.05). The expression rates increased with tumor cell grade increase, but there was no significant difference (P> 0.05). Conclusions EZH2 could play an important role in the development and progression of blad-der carcinoma. It could be used as a potential gene therapy target of bladder cancer.

Objective To study the epidemic factors of hemorrhagic fever with renal syndrome (HFRS) in an area in Tianjin in 1997—2005. Methods The descriptive statistical analysis was used to describe the status of HFRS. The Hantavirus(HV) carrier in the mice was investigated and the data of the meteorological, agricultural and population were collected. Rank sum tests were employed to analyze the epidemic of the disease. Results The epidemic of HFRS in the investigated area started from 1997 with annually increasing, the peak was seen in 2002, then it was dropping down. There were 105 cases in total with 4 cases died. The cases were found all over the district, including 11 towns and 70 villages. The cumulative incidence rate was 2.90/100 000, the mortality rate was 0.11/100 000, and the case fatality rate was 3.81%. The seasonal difference was found in this study. The incidences in April and May were highest, accounted for 44.76% of the total cases. The cases in the 30-year-old group accounted for one third of the total occurrence, the ratio of male to female was 3.57∶1. The incidence was highest in the farmers, accounted for 26.67%, in the transient population it accounted for 54.29%. There was a consistency between the index of HV carrier and the epidemic trend. A positive correction was seen between the average temperature and the disease incidence rate (rs=0.746, P=0.021), a negative correction was seen between the precipitation and the incidence rate (rs=-0.695, P=0.038) and between the crop area and the incidence rate (rs=-0.167, P=0.532). Conclusion The investigated area is the epidemic area where HFRS is caused by Seoulvirus(SEOV), the primitive host is Rattusnorvegicus. The main epidemic factors include the transient population massively moved into the area since the mid 1990s, the change of the predominant mice in this area, destruction of the habitats of the mice, the rats migration, the increase of the index of HV and the transformation project of houses and the farmland destruction.