[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.

[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.

[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.

[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).

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.

[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).

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

Blastocystis is one common protist inhabiting in gastrointestinal tracts of animals and humans. Examining the subtypes has important implications for assessing the zoonotic potential of Blastocystis and intestinal health of hosts. In the present study, a total of 497 fecal samples collected from 37 wild animal species in Qinling Mountains were investigated for the presence and subtypes of Blastocystis. Of them, 200 (40.2%) were positive for Blastocystis and 13 subtypes were found, including eight known subtypes (STs1-3, 5, 10, 12-14) and five possible novel subtypes (temporarily named as STs18-22), with ST10 as the predominate subtype and the subtype ST5 was detected in an ostrich for the first time. These findings indicated the wide distribution and specific subtype characteristics of Blastocystis in wild animals of Qinling Mountains.

[Influence of wearing long wavelength filter glasses on refractive development of children's hyperopia].

Objective: To investigate the effect of wearing long wavelength filter glasses on refractive development of children's hyperopia. Methods: Case control study. Seventeen 5-7 years' old children with high hyperopia from optometry clinic of Eye and ENT Hospital Affiliated to Fudan University were enrolled in this research. The experiment design was self-control between right and left eye, 3 children were lost during two years' period of observation, all the children's hyperopic refraction were more than +6.00 D, cycloplegic by 1% atropine. All the children were required to wear long wavelength filter glasses for 6 hours after waking up, the rest of the time with the conventional glasses. Refraction, axis and red/green match point were tested before the intervention and 3, 6, 12, 18, 24 months, after the intervention. Results: After two years' intervention, hyperopia decreased, eye axis increased, the best corrected visual acuity increased both in experimental eyes and control eyes, but there were no statistically significant difference between the two groups at each time point. All children were with normal color vision, compared to the long-wavelength light, the hyperopic eyes were more sensitive to middle-wavelength light, no significant difference was found between two groups, red/green match points were 42.802±1.216 and 42.889±1.560 respectively. After wearing long wavelength filter, red/green match point were significant decreased in the experimental group in 6 months and 12 months time points (6 months: 0.995±0. 543 vs. 0.104±0.143, t=3.04, P=0.005, 12 months: 1.096±0.392 vs. 0.17±0.248, t=2.725, P=0.008). The experiment eyes were more sensitive to long-wavelength light than the control eyes. But in later time, there was no significant difference between two groups. Conclusion: Wearing long wavelength filter glasses two years has no effect on refractive development on children with high hyperopia, but it can cause short-term chromatic adaptation, making hyperopic eyes more sensitive to the long-wavelength light. (Chin J Ophthalmol, 2017, 53: 33-38).

Serum mannose-binding lectin levels after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Mannose-binding lectin (MBL) is a key molecule of complement system, which is activated after aneurysmal subarachnoid hemorrhage (aSAH). We investigated the association of serum MBL levels with injury severity and clinical outcomes among aSAH patients. MATERIALS AND METHODS: Serum MBL levels were determined in 132 aSAH patients and 132 controls. We assessed the association of serum MBL levels with 6-month mortality and unfavorable outcome (Glasgow Outcome Scale score, 1-3) and injury severity reflected by World Federation of Neurological Surgeons (WFNS) scores and modified Fisher scores. Factors found significant on univariate analysis were further tested on a multivariate model. Meantime, the prognostic predictive values were evaluated using a receiver operating curves analysis. RESULTS: Serum MBL levels were significantly higher in patients than in controls. Serum MBL levels were independently associated with WFNS scores and modified Fisher scores. MBL was identified as an independent prognostic predictor for 6-month mortality and unfavorable outcome. Moreover, its predictive value was similar to those of WFNS scores and modified Fisher scores. CONCLUSIONS: Elevated serum MBL concentrations are associated with injury severity and long-term poor prognosis after aSAH.

Multilocus genotyping of Giardia duodenalis and Enterocytozoon bieneusi in dairy and native beef (Qinchuan) calves in Shaanxi province, northwestern China.

Giardia duodenalis and Enterocytozoon bieneusi are two common protozoa that parasitize the intestinal epithelium of animals and humans. Calves have been identified as important reservoirs of these two pathogens, but limited data is available for these two pathogens in calves in China. In the present study, the prevalence and assemblages/genotypes of both parasites in calves of dairy and native beef (Qinchuan) cattle in Shaanxi province, northwestern China, were analyzed using multilocus genotyping (MLST). Of 371 fecal samples collected from calves (including 198 dairy calves and 173 Qinchuan calves), the respective overall prevalence of G. duodenalis and E. bieneusi was 18.87 (70 of 371) and 19.68 % (73 of 371). Both the zoonotic G. duodenalis assemblage A and animal adapted assemblage E were found in dairy and Qinchuan calves. Seventeen, eight, five, and two G. duodenalis subtypes were detected at the triose phosphate isomerase (tpi), ß-giardin (bg), glutamate dehydrogenase (gdh), and small subunit ribosomal RNA (SSU-rRNA) loci, with five and two novel subtypes detected at the tpi and bg loci, forming 25 multiple genotypes (MLGs) (15 and 11 in dairy and Qinchuan calves, respectively). Of 73 samples that were positive for E. bieneusi at the ribosomal RNA internal transcribed spacer (ITS) locus, five ITS genotypes were found, including three known zoonotic genotypes (I, J, CHN1) and two novel genotypes (CSX1 and CSX2). MLST analysis of three microsatellite loci (MS1, MS3, MS7) and one minisatellite locus (MS4) detected six, two, two, and two genotypes at the MS1, MS3, MS4, and MS7 loci, respectively, forming ten MLGs (seven and four in dairy and Qinchuan calves, respectively). These results indicate complex population structures of G. duodenalis and E. bieneusi in calves in Shaanxi province and the zoonotic potential of these two pathogens in calves in this province.

[Microsurgery treatment of midline deep brain lesions (clinical analysis of 25 cases)].

Objective: To explore experience and methods in the microsurgical treatment of midline deep brain lesions. Methods: The clinical data of patients with midline deep brain lesions were retrospectively analyzed. The clinical manifestation, imaging findings, lesion locations, surgical procedures, pathological diagnosis and follow-up results were summarized and analyzed. All the lesions were located deeply in the brain midline: corpus callosum (n=1), thalamus and basal ganglia (n=6), lateral ventricle (n=4), the third ventricle (n=2), pineal region (n=8), brainstem and fourth ventricle region (n=4). Results: Symptoms of 25 cases improved to varying degrees after operation and all the lesions got gross total removal without perioperative death. Followed by necessary adjuvant radiotherapy and/or chemotherapy, there were no recurrence during the follow-up period. Conclusions: Suitable surgical approaches should be individually chosen according to lesion location, the surrounding neural and vascular anatomy, blood supply, the patient's medical condition and the operator's experience. Localization of minor lesions can be assisted by neuronavigation system. In addition to try to determine the border of the lesion during operation, we emphasize the protection of the surrounding vital neural structures and deep veins. Finally, adjuvant radiotherapy and/or chemotherapy based on histology should be adopted to prevent recurrence.

[The application and mechanism analysis of postoperative intracranial pressure monitoring in giant meningioma(clinical analysis of 7 cases)].

OBJECTIVE: To investigate varying patterns of intracranial pressure(ICP)after giant meningioma resection and analyze the causes of the variation of ICP in different postoperative phases. METHODS: Clinical data, surgical approachs and the ICP monitoring data of 7 patients with giant meningioma in different positions who were admitted to the First Affiliated Hospital of Soochow University from October 2013 to July 2014 and received microsurgical resection via different approachs were analysed retrospectively. The tumour locations were in convexity(n=1), olfactory groove(n=1), sphenoidal ridge(n=2), parasagittal(n=1), falx(n=1), petroclival(n=1) and resected via longitudinal fissure approach, subfrontal approach, extensive pterional approach, subtemporal approach. ICP monitoring probe was placed subdurally and average monitoring time was 9 days. Dehydrating agent was administered in all cases postoperatively. RESULTS: Tumors were totally resected (Simpson Grade Ⅰ or Ⅱ ) in all patients. The increase of ICP was observed on the 3(rd) day, peaked on the 4(th) day and reduced to normal on the 5(th)-7(th) day. Decompressive craniectomy and tracheotomy were performed in one case due to consciousness deterioration, severe brain edema and continuous ICP augment on the third day after operation. All the patients recovered well except for the cerebrospinal fluid rhinorrhea occurring in one case postoperatively, whose symptom ameliorated significantly after conservative treatment. CONCLUSION: ICP monitoring exerts an important role on the postoperative management of giant meningioma. Simultaneously, The summary of vast ICP monitoring data concerning to giant meningioma provides the evidence and experience for protecting neurological function via abundant preoperative preparations, reasonable operative approach, careful postoperative management.

Possible involvement of cathepsin B/D and caspase-3 in deferoxamine-related neuroprotection of early brain injury after subarachnoid haemorrhage in rats.

AIMS: Deferoxamine (DFX) has recently been shown to have a neuroprotective effect in animal models of subarachnoid haemorrhage (SAH). However, the precise mechanisms underlying these effects remain unclear. Our previous studies found that iron overload in lysosomes leads to lysosomal membrane damage and rupture, and then induces cell apoptosis in the oxidative stress conditions in vitro. We therefore analysed the time-course of the two of major lysosomal cathepsins (cathepsin B/D) and caspase-3 expression in brain and evaluated how DFX might affect these proteins and the parameters concerning early brain injury (EBI) after SAH. METHODS: We investigated the time-course of cathepsin B/D and caspase-3 expression in the cortex after SAH in rats. Furthermore, we assessed the effect of DFX on regulation of cathepsin B/D and caspase-3 and EBI following SAH. All SAH animals were subjected to a single injection of autologous blood into the prechiasmatic cistern. Protein concentrations were measured using Western blot analysis and immunohistochemistry. The extent of brain oedema was measured using the wet/dry method. Blood-brain barrier (BBB) permeability was assessed using IgG extravasation. Cortical apoptosis was examined using terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling (TUNEL). RESULTS: Cathepsin B/D and caspase-3 were up-regulated in the cortices of affected rats after SAH. Levels of both peaked at 48-h post-SAH. After intraperitoneal DFX administration, the elevated expression of cathepsin B/D and caspase-3 was down-regulated in the cortex 48 h after blood injection. In the DFX-treated group, early brain damage events, such as brain oedema, BBB impairment, cortical apoptosis, and alterations in clinical behaviour were significantly ameliorated relative to vehicle-treated SAH rats. CONCLUSIONS: These results suggest that the lysosomal membrane may be damaged after SAH, which leads to the release of proteases (cathepsin B/D) and activates the apoptotic pathway. Iron overload may be one key mechanism underlying SAH-induced oxidative stress and DFX may protect the lysosomal membrane, inhibit the release of cathepsin B/D, and ameliorate EBI by suppressing iron overload in the acute phase of SAH.

Treatment for early ultralow rectal cancer: pull-through intersphincteric stapled transection and anastomosis (PISTA) versus low anterior resection.

BACKGROUND: The aim of this study was to compare the functional and oncologic results of pull-through intersphincteric stapled transection and anastomosis (PISTA) with low anterior resection (LAR) in the treatment for early ultralow rectal cancer. METHODS: A total of 278 patients with early ultralow rectal cancer were retrospectively included and analyzed, with 136 in the PISTA group and 142 in the LAR group. RESULTS: Gender, age, tumor diameter, distance from the dentate line to the inferior margin of the tumor, tumor stage, length of operation and postoperative complications were comparable in the two groups. Compared with the LAR group, the PISTA group had a more accurate distal transection site, a lower daily fecal frequency (6 (5-7) vs. 8 (7-9), p < 0.001) and a lower Wexner incontinence score (13 (10-14) vs. 14 (13-16), p < 0.001) 3 months after ileostomy reversal, and a higher rate of satisfactory fecal continence (97.1 % vs. 90.8 %, p = 0.043). The follow-up period of the PISTA group was similar to that of the LAR group (56 (30-81) months vs. 54 (30-80) months, p = 0.982). The PISTA group was associated with a lower local recurrence rate (2.2 % vs. 11.3 %, p = 0.003). Kaplan-Meier analysis also showed that the PISTA group was associated with longer overall survival (p = 0.018) and longer local recurrence-free survival (p = 0.004) than the LAR group, while distant metastasis-free survival (p = 0.896) was comparable in the two groups. Multivariate analysis identified lymph node metastasis (p < 0.001) and operation (PISTA vs. LAR, p = 0.031) as independent predictive factors for local recurrence-free survival. CONCLUSIONS: PISTA is a technically simple, oncologically safe and functionally favorable procedure for the treatment for early ultralow rectal cancer.

[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.

[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.

[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.

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.