[Analysis of clinical phenotype and gene mutation characteristics of MYH9-related disorder].

Objective: To investigate the clinical phenotype and gene mutation characteristics of MYH9-related disorder (MYH9-RD). Methods: The clinical data of 66 patients with MYH9-RD in the First Affiliated Hospital of Soochow University from January 2010 to December 2022 were retrospectively analyzed. According to the bleeding symptom, the patients were divided into bleeding and non-bleeding group, and according to the mutation sites, the patients were divided into non-muscle myosin heavy chain ⅡA head region (MD) and tail region (TD) mutation group. Statistical analysis was made to explore the clinical features in different groups such as platelet counts, bleeding, renal function, cataracts and hearing as well as MYH9 gene mutations. Results: A total of 66 MYH9-RD patients were included, with 28 males and 38 females, diagnosis age of 1-63(26±2) years. And 41% (27/66) of the patients had no family history. All patients presented with macrothrombocytopenia and normal platelet aggregation(10/10), 92% (54/59) of the patients had visible blue inclusion bodies in neutrophils, 30% (20/66) had bleeding symptoms, 45% (22/49) had proteinuria or glomerulonephropathy, 20% (8/41) had bilateral hearing impairment, and 10% (4/42) had bilateral cataracts. 18 mutation sites were identified in total, including 15 missense, 1 splicing and 2 termination mutations. Among them, p.Asp1424Asn, p.Arg1933* and p.Arg702His/Cys mutations were identified in 56% (29/52) of the patients, and p.Ser96Leu, Arg1165Cys and p.Glu1841Lys mutations were recurrent mutations, while p.Ala44Thr, p.Asp1447Ala and c.3838-2A>G mutations were novel mutations. The average platelet count of patients in bleeding group was (19±3)×109/L, which was significantly less than (36±3)×109/L in non-bleeding group (P<0.001). Compared with TD mutation group, patients of MD mutation group were presented with lower platelet count and higher risk of bleeding, as well as more severe clinical presentations including renal and hearing impairment and cataracts (all P<0.05). Conclusion: Mutations of p.Asp1424Asn, p.Arg1933* and p.Arg702His/Cys in MYH9 gene are hotspot mutations for MYH9-RD patients, Compared with TD mutation group, patients of MD mutation group were presented with lower platelet count and higher risk of bleeding, as well as more severe clinical presentations including renal and hearing impairment and cataracts.

[A combined regimen based on bortezomib and glucocorticoids for 6 patients with recurrent/refractory immune thrombotic thrombocytopenic purpura].

Objective: To observe the efficacy and adverse reactions of a combination therapy regimen based on bortezomib and glucocorticoids in recurrent/refractory immune thrombocytopenic purpura (iTTP) . Methods: Six patients with recurrent/refractory TTP were included and treated with a glucocorticoid and two courses of bortezomib-based regimen. The clinical remission status of patients, changes in ADAMTS13 activity/ADAMTS13 inhibitor, and the occurrence of treatment-related adverse reactions were observed. Results: Of the 6 patients, 2 were males and 4 were females, with a median age of 21.5 (18-68) years. Refractory TTP was found in 1 case and recurrent TTP in 5 cases. Glucocorticoids were administered with reference to prednisone at 1 mg·kg(-1)·d(-1), and gradually reduced in dosage after achieving clinical remission. Bortezomib is subcutaneously administered at 1.3 mg/m(2) on days 1, 4, 8, and 11 with a 28-day treatment course consisting of 2 courses. Six patients achieved clinical remission after receiving bortezomib as the main treatment. ADMATS13 activity returned to normal in all patients with TTP after treatment, and the ADAMTS13 inhibitor turned negative. Thrombocytopenia is the most common adverse reaction after treatment, with other adverse reactions, including peripheral neuritis and abdominal pain, but ultimately all patients returned to normal. In a median follow-up of 26 (9-41) months, 5 patients maintained sustained remission, and 1 patient relapsed after 16 months of bortezomib treatment. Conclusion: Combination therapy of bortezomib and glucocorticoids has a satisfactory therapeutic effect and controllable adverse reactions for recurrent/refractory iTTP.

[Methylated SDC2 testing in stool DNA for early screening of colorectal cancer in Shipai Town, Dongguan City].

Objective: To explore the utility of stool-based DNA test of methylated SDC2 (mSDC2) for colorectal cancer (CRC) screening in residents of Shipai Town, Dongguan City. Methods: This was a cross-sectional study. Using a cluster sampling method, residents of 18 villages in Shipai Town, Dongguan City were screened for CRC from May 2021 to February 2022. In this study, mSDC2 testing was employed as a preliminary screening method. Colonoscopy examination was recommended for individuals identified as high-risk based on the positive mSDC2 tests. The final screening results, including the rate of positive mSDC2 tests, the rate of colonoscopy compliance, the rate of lesions detection, and the cost-effectiveness of screening, were analyzed to explore the benefits of this screening strategy. Results: A total of 10 708 residents were enrolled and completed mSDC2 testing, giving a participation rate of 54.99% (10 708/19 474) and a pass rate of 97.87% (10 708/10 941). These individuals included 4 713 men (44.01%) and 5 995 women (55.99%) with a mean age of (54.52±9.64) years. The participants were allocated to four age groups (40-49, 50-59, 60-69, and 70-74 years), comprising 35.21%(3770/10 708), 36.25% (3882/10 708), 18.84% (2017/10 708), and 9.70% (1039/10 708) of all participants, respectively. mSDC2 testing was positive in 821/10 708 (7.67%) participants, 521 of whom underwent colonoscopy, resulting in a compliance rate of 63.46% (521/821). After eliminating of 8 individuals without pathology results, data from 513 individuals were finally analyzed. Colonoscopy detection rate differed significantly between age groups (χ2=23.155, P<0.001),ranging from a low of 60.74% in the 40-49 year age group to a high of 86.11% in the 70-74 year age group. Colonoscopies resulted in the diagnosis of 25 (4.87%) CRCs, 192 (37.43%) advanced adenomas, 67 (13.06%) early adenomas, 15 (2.92%) serrated polyps, and 86 (16.76%) non- adenomatous polyps. The 25 CRCs were Stage 0 in 14 (56.0%) individuals, stage I in 4 (16.0%), and Stage II in 7(28.0%). Thus, 18 of the detected CRCs were at an early stage. The early detection rate of CRCs and advanced adenomas was 96.77% (210/217). The rate of mSDC2 testing for all intestinal lesions was 75.05% (385/513). In particular, the financial benefit of this screening was 32.64 million yuan, and the benefit-cost ratio was 6.0. Conclusion: Screening for CRCs using stool-based mSDC2 testing combined with colonoscopy has a high lesion detection rate and a high cost-effectiveness ratio. This is a CRC screening strategy that deserves to be promoted in China.

[Clinical diagnosis and treatment of hereditary thrombocytopenia and purpura: a report of five cases and literature review].

Objective: To report the clinical manifestations and laboratory features of five patients with congenital thrombotic thrombocytopenic purpura (cTTP) and explore its standardized clinical diagnosis and treatment along with a review of literature. Methods: Clinical data of patients, such as age of onset, disease manifestation, personal history, family history, and misdiagnosed disease, were collected. Treatment outcomes, therapeutic effects of plasma infusion, and organ function evaluation were observed. The relationship among the clinical manifestations, treatment outcomes, and ADAMTS13 gene mutation of patients with cTTP was analyzed. Additionally, detection of ADAMTS13 activity and analysis of ADAMTS13 gene mutation were explored. Results: The age of onset of cTTP was either in childhood or adulthood except in one case, which was at the age of 1. The primary manifestations were obvious thrombocytopenia, anemia, and different degrees of nervous system involvement. Most of the patients were initially suspected of having immune thrombocytopenia. Acute cTTP was induced by pregnancy and infection in two and one case, respectively. ADAMTS13 gene mutation was detected in all cases, and there was an inherent relationship between the mutation site, clinical manifestations, and degree of organ injury. Therapeutic or prophylactic plasma transfusion was effective for treating cTTP. Conclusions: The clinical manifestations of cTTP vary among individuals, resulting in frequent misdiagnosis that delays treatment. ADAMTS13 activity detection in plasma and ADAMTS13 gene mutation analysis are important bases to diagnose cTTP. Prophylactic plasma transfusion is vital to prevent the onset of the disease.

[Combined endoscopic and microsurgical resection of pineal region meningiomas by modified Poppen approach].

To retrospectively analyze the clinical data of patients with pineal region meningioma. All the patients underwent combined endoscopic and microsurgical procedure by modified Poppen approach (double-scopic technique) between January 2018 and March 2021 in the Department of Neurosurgery of the First Affiliated Hospital of Soochow University. A total tumor resection was achieved in all the patients without deaths. All the pineal region meningiomas were pathologically confirmed. During the follow-up period, none of the 10 patients experienced tumor progression, and 4 of patients were treated by radiotherapy after surgery. The external ventricular drainage was performed in 8 cases intraoperatively, and no case underwent the ventriculoperitoneal shunt during the follow-up period. The clinical symptoms of 9 cases were improved,1 case had no improvement, and no patients presented deteriorated symptoms. Combined endoscopic and microsurgical surgery resection of pineal region meningiomas by modified Poppen approach helped the surgeons directly observe the cerebral deep vein systems in pineal region with endoscope and significantly enhance the total resection rate of pineal region meningiomas, thereby decreasing the damage of cerebral deep vein systems in pineal region and reducing the incidence of surgical complications.

[Clinical diagnosis and treatment analysis of 553 cases of acoustic neuroma in a single center].

Objective: To explore the relationship between microsurgery and prognosis of acoustic neuroma. Methods: A total of 553 acoustic neuroma surgical cases admitted to the First Affiliated Hospital of Soochow University from January 1, 1986 to September 30, 2016, were collected retrospectively. They were divided into 1986-1995 group, 1996-2005 group, and 2006-2016 group. The general information, tumor size, preoperative hospital stay, total hospital stay, operation time, intraoperative blood transfusion, use of neuroelectrophysiological monitoring, internal auditory canal wall grinding, tumor resection degree, postoperative facial nerve function rating (House-Brackmann grading), discharge status, and quality of life assessment KPS of patients were statistically analyzed. Results: Compared with the 1986-1995 group and the 1996-2005 group, the average age of patients in the 2006-2016 group ((52.9±13.3) years) was larger but the overall tumor volume ((3.7±0.8) cm) was smaller, and preoperative hospital stay ((4.9±1.9) days), the total hospital stay ((19.4±6.4) days) was significantly reduced, the operation time ((4.6±1.0) hours) was shortened, the intraoperative blood transfusion rate (18.5%) was significantly reduced, the intraoperative neuroelectrophysiological monitoring utilization rate (8.9%), and the internal auditory canal rate (12.7%) was higher. While increasing the tumor total resection and near total resection rate (89.2%), it further improved the postoperative facial nerve function retention rate (71.5%), and significantly increased the discharge cure rate (88.5%) (P<0.05). At the same time, the postoperative quality of life assessment good rate (KPS≥60 points) and excellent rate (KPS≥80 points) of the patients in the 2006-2016 group increased significantly, reaching 94.2% and 45.8% (P<0.05). Conclusion: The maturity of microsurgery techniques and the use of intraoperative neuroelectrophysiological monitoring can shorten the treatment cycle of patients with acoustic neuroma, increase the tumor resection rate and postoperative facial nerve function retention rate, and effectively improve the quality of life of patients after surgery.

[Prevalence of pediatric hypertension during three separate visits based on one center cross-sectional study].

From November to December 2019, a cross-sectional study including 1 243 children aged 8~13 years was conducted in one primary school in Huantai County, and 1 238 children with complete data were finally included. A total of 1 238, 146, and 83 children were included in the first, second and third visit of the follow-up, respectively. With the follow-up visits increasing, the systolic blood pressure (SBP) and diastolic blood pressure (DBP) levels of the 83 children who were followed up across all three different visits decreased significantly across three different visits (both Pfor trend<0.05). The prevalence of elevated blood pressure across the three visits was 11.8%, 6.8% and 4.0% (Pfor trend<0.001); the prevalence of elevated SBP was 11.4%, 6.5%, and 4.0% (Pfor trend<0.001); the prevalence of elevated DBP was 1.1%, 1.0%, and 0.4%, respectively (Pfor trend>0.05).

[Analysis of prognosis and risk factors of 730 patients with anterior communicating aneurysm].

Objective: To investigate the prognosis and risk factors of patients with anterior communicating aneurysm treated by aneurysm clipping or interventional embolization. Methods: The clinical data of 730 patients with anterior communicating aneurysm who underwent aneurysm clipping or interventional embolization in the department of neurosurgery, the first affiliated hospital of Soochow University from January 1999 to December 2018 were retrospectively analyzed. The prognosis of patients in the clipping group from 1999 to 2008 and the clipping group from 2009 to 2018, the clipping group from 2009 to 2018 and the interventional group from 2009 to 2018 were compared respectively, and the risk factors affecting the prognosis of patients were statistically analyzed. Results: The rate of poor prognosis was 32.7% in the clipping group from 1999 to 2008, 21.3% in the clipping group from 2009 to 2018, and the rate of intraoperative aneurysm rupture and postoperative cerebral infarction was lower in the clipping group from 2009 to 2018 (P<0.05). There was no significant statistical difference in the prognosis between the clipping group and the interventional group from 2009 to 2018 (P>0.05). The results of multivariate analysis showed that preoperative Hunt-Hess grade, postoperative cerebral infarction and postoperative hemorrhage were the risk factors affecting the prognosis of patients (P<0.05). Conclusion: The prognosis of patients treated by clipping from 2009 to 2018 was significantly improved compared with that from 1999 to 2008. There was no significant difference in the prognosis between the clipping group and the interventional group from 2009 to 2018. Preoperative Hunt-Hess grading, postoperative cerebral infarction and postoperative hemorrhage were independent risk factors affecting the prognosis.

Effect of heat stress on mitogen-activated protein kinases in the hypothalamic-pituitary-gonadal axis of developing Wenchang chicks.

The regulatory roles of mitogen-activated protein kinase (MAPK) signaling pathways on the hypothalamic-pituitary-gonadal axis (HPG axis) of Wenchang chicks under heat stress (HS) were investigated. Additionally, the crosstalk between these signaling pathways was explored. Immunohistochemical experiments and Western blotting were employed to quantify extracellular regulated protein kinases (ERK), c-Jun N-terminal kinases (JNK), and p38MAPK (P38). In female chicks, hypothalamic ERKs were upregulated in Weeks 1 and 2 in the HS group compared with the control group (CK), while JNK and p38 were downregulated (P < 0.05). Pituitary MAPKs were all downregulated in the HS group compared with the CK group in Week 3, but p38 was upregulated in Week 4 (P < 0.01). In the HS group, ovarian MAPKs were all upregulated compared with the CK group during Week 5, whereas ERK was downregulated in Week 6 (P < 0.01). In contrast to the patterns of MAPK expression in female chicks in the HS and CK groups, ERK in male chicks showed a completely opposite pattern in Weeks 1, 2, and 5, while p38 and JNK were downregulated in both female and male chicks under HS during Weeks 2 and 3. In the HS group, pituitary and testis MAPKs showed a pattern opposite to that observed in female chicks under HS in Week 5; MAPKs were all downregulated (P < 0.05). Thus, there are gender differences in the MAPK signaling pathways in the HPG axis in chicks, and these pathways showed plasticity. Early HS can enhance chick growth and development as well as promote developing in the MAPK signaling pathways in the HPG axis. However, after heated brooding was discontinued in chicks, long-term HS obstructed chick development and caused tissue and function injury to the HPG axis.

Effects of ranolazine on cardiac function in rats with heart failure.

OBJECTIVE: To investigate the effects of ranolazine on the cardiac function and myocardial apoptosis in rats with heart failure and its possible mechanisms. MATERIALS AND METHODS: Thirty Wistar rats were randomly divided into sham operation (negative control; NC), chronic heart failure (CHF), and ranolazine groups. Suprarenal abdominal aortic coarctation was used to induce CHF in rats. Five weeks later, rats in the ranolazine group received ranolazine (50 mg/kg) daily, whereas those in the CHF group received normal saline. After 4 weeks, changes in hemodynamic parameters, cardiac structure and pathology, myocardial apoptosis, and protein expression were assessed. RESULTS: The left ventricular end-diastolic pressure (LVEDP) significantly increased in the CHF group; whereas the maximal rate of left ventricular pressure rise and fall (±dp/dtmax) decreased, compared to those in the NC group. Ranolazine significantly reduced LVEDP and increased ±dp/dtmax (p<0.01), compared to those in the CHF group. Severe impairment of cardiomyocytes was observed in the CHF group with evident inflammation; however, ranolazine reversed these deficits. Rats in the CHF group exhibited an increase in TUNEL-positive cells, which was inhibited by ranolazine, where the apoptotic index significantly decreased in ranolazine-treated rats (p<0.01). Also, ranolazine downregulated caspase-9 expression and upregulated pAKT and Bcl-2 expression in rat cardiomyocytes. Moreover, ranolazine significantly inhibited myocardial apoptosis and caspase-9 expression, promoted AKT phosphorylation, and upregulated pAKT and Bcl-2 expression in vitro, compared to those in the control group (p<0.001). LY294002 inhibited ranolazine-induced suppression of myocardial apoptosis (p<0.001). CONCLUSIONS: Ranolazine improved cardiac function and inhibited myocardial apoptosis in rats with CHF, which could be attributed to the regulation of AKT phosphorylation.

[Clinical observation of desmopressin in the treatment of 15 patients with DDAVP].

Objective: To assess the significance of DDAVP use in the diagnosis and treatment of VWD. Methods: An analysis of 15 VWD cases who referred to Hematology Division of First affiliated Hospital of Soochow University and treated with DDAVP from March 2016 to August 2018 was conducted. Efficacy and treatment response of DDAVP were monitored by observations of changes in factor Ⅷ procoagulant (FⅧ∶C) and von Willebrand Factor (VWF) related indicators before and 2 h after DDAVP injection. Results: Of 15 cases with VWD, 7 males and 8 females with a median age of 23 (6-46) years, 7 of 9 type I VWD patients achieved complete response (CR) , 1 type 2A VWD case CR, 5 type 3 VWD ones no response (NR) . The VWF multimer analysis in 5 patients combined with other plasma VWF values were in accordance with the known diagnosis. Conclusions: DDAVP was effective in most type 1 patients, and ineffective in some type 2 and almost all type 3 cases. It was helpful for diagnosis and subsequent treatment planning.

[The diagnostic value of PLASMIC score in the discrimination between thrombotic thrombocytopenic purpura and disseminated intravascular coagulation].

Objective: PLASMIC score was evaluated its value in differential diagnosis between the patients with thrombotic thrombocytopenic purpura (TTP) and those with disseminated intravascular coagulation (DIC) . Method: Twenty-four patients with TTP and 41 cases with DIC were retrospectively analyzed in this study. The platelet count, average red blood cell volume, indirect bilirubin, creatinine and prothrombin time international normalised ratio were collected, and then PLASMIC scores were calculated. Results: According to the risk classification of PLASMIC score, three (12.5%) TTP patients had moderate risk, and the rest 21 (87.5%) cases had high risk. In DIC patients, 92.7% cases were in low risk group, 4.9% at moderate risk, and only one case had high risk. Of these 65 patients, the sensitivity and the specificity to TTP of the high risk of the scoring system were 87.5% and 97.6%, respectively. Conclusion: The patients with high risk of PLASMIC score correlated well with clinical TTP diagnosis. The scoring system showed to be an excellent diagnostic model to distinguish TTP patients from those with DIC.

[Development of keratophakia and new research advances in lenticule transplantation].

In the 1980s, a new treatment of aphakia and keratoconus with keratophakia thrived because of its simple, effective and reversible characteristics. However, due to the limited cornea resources and the unpredictability of long-term treatment effects, epikeratophakia has not been widely accepted. Refractive lenticule extraction is a type of corneal refractive surgery with minimal invasiveness, accuracy and good refractive stability and has got great clinical attention and promotion. The removed refractive stromal lenticules as good graft materials can be applied for treatment of keratoconus and hyperopia based on the epikeratophakia principle. This review describes the history and development of keratophakia and the basic research and clinical effect of refractive lenticule transplantation. (Chin J Ophthalmol, 2018, 54: 792-796).

[A phase â ¢ multi-center clinical trial on safety and efficacy of a domestic plasma derived factor â ¨ for the treatment of patients with hemophilia B].

Objective: To evaluate the efficacy and safety of a domestic human plasma derived coagulation Factor Ⅸ concentrate (pd-FⅨ) in patients with hemophilia B. Methods: The study was a multicenter, open-label and single-arm study. The efficacy of pd-F Ⅸ was evaluated by objective performance criteria. The doses of pd-FⅨ were calculated according to the bleeding symptom and disease severity. The infusion efficiency of pd-FⅨ and improvement of bleeding symptoms were measured at 30 minutes and (24±4) h after the first infusion, respectively. Adverse events were recorded. Viral infection and FⅨ inhibitor were detected 90 d after the first infusion. Results: All 36 subjects with hemophilia B were enrolled in the study. The median age of these patients was 31 years old and the median injection doses were 4 (1-17) times. The hemostatic effect of 27/36 (75.00%) and 9/36 (25.00%) acute bleeding events were rated as "excellent" and "better" , respectively. The recovery rate was 111.92% (65.55%-194.28%) at 30 minutes after infusion of FⅨ. There was no adverse event related to FⅨ. No reactivation of HBV, HCV or HIV and FⅨ inhibitor was detected at 90-104 d after the first FⅨ infusion. Conclusion: This domestically made human plasma derived FⅨ concentrate is safe and effective in the treatment of acute bleeding in patients with hemophilia B. Clinical trial registration: China food and Durg Administration, 2016L08027.

Correction to: Molecular characterization of Blastocystis sp. in captive wild animals in Qinling Mountains.

There were errors in Fig. 1 of the originally published article. Correct fig. 1 is presented here.

[α1-antitrypsin Pittsburg mutations: report of two cases in the same family].

Objective: To analyze the clinical and laboratory abnormalities of two patients with α1-antitrypsin (α1-AT) Pittsburgh in a family and review the literatures. Methods: Both plasma clotting time and factor activities were performed using clotting or substrate methods. Platelet aggregation was evaluated using an optical aggregometer. The serum protein electrophoresis was performed on Sebia HYDRASYS by using Agarose gel. The exons of α1-AT were amplified by using polymerase chain reaction (PCR) and then sequenced and compared with NCBI GenBank records. Results: The proband had several ruptures of corpus luteum and bleeding after operation, while her daughter had no bleeding history. Both of them showed prolonged coagulation tests which could not be corrected by mixing with the normal plasma. They also showed low levels of plasma coagulation factors, undetected protein C and S activity and abnormal bands of α1-globulin. The results of gene sequencing demonstrated that they were heterozygous for g.T17132G (p.Met358Arg) mutation of α1-antitrypsin gene (NG_008290.1) . Conclusions: Comparing with the data of previously reported cases, our results confirmed the obvious abnormality of coagulation test and the discrepancy of bleeding tendency of α1-antitrypsin Pittsburgh patients, and suggested that the rupture of corpus luteum would be a specific characteristic in women of child-bearing age.