[Clinical characteristics of children with MT-TK gene m.8344A>G variation].

Objective: To summarize the clinical characteristics of children carrying the m.8344A>G variant of MT-TK gene. Methods: A case series study was conducted to retrospectively collect data of 22 children with mitochondrial disease caused by MT-TK gene m.8344A>G variation who were treated at the Department of Neurology of Beijing Children's Hospital of Capital Medical University from January 2012 to January 2024. Their clinical data, laboratory tests, muscle pathology, genetic testing, and the follow-up results were analyzed. Pearson correlation analysis was used for correlation analysis. Results: Among the 22 children, there were 13 boys and 9 girls. The age of onset was 5.00 (2.75, 9.00) years. Fifteen children had myoclonic epilepsy with ragged-red fibers (MERRF), 3 had Leigh syndrome (LS), and 4 had LS-MERRF overlap syndrome (LS-MERRF). Myoclonus presented and worsened progressively in all 15 MERRF children, with 10 as the initial symptom and 5 developing progressively during the disease course. Myoclonus was predominantly focal, worsening with fine motor tasks or stress. Electroencephalogram monitoring in the 15 MERRF children revealed myoclonic seizures in 10 children, with 6 classified as myoclonic epilepsy, and 4 as subcortical myoclonus. Two children had generalized myoclonic seizures, and 1 each had absence seizures and generalized seizures. Twelve children had cerebellar ataxia, 10 children exhibited exercise intolerance, and 8 children had muscle weakness. Magnetic resonance imaging (MRI) revealed periventricular white matter involvement in 1 child and bilateral hippocampal involvement in 1 child, likely due to frequent seizures. All 3 children with LS exhibited developmental regressions, accompanied with 2 symptoms include cerebellar ataxia, muscle weakness, and dysphagia. The clinical manifestations of 4 LS-MERRF overlap children presented with combined features of MERRF and LS. Cranial MRI in the 7 LS and LS-MERRF children showed brainstem involvement (all affecting the midbrain) in 6 children and basal ganglia involvement in 4 children. Among the 22 children, 12 had m.8344A>G variant levels >90%, 3 had >80%-90%, 4 had >70%-80%, and 3 had >60%-70%. Higher variant level correlated with the LS phenotype and earlier onset age (r=0.47, -0.50; P=0.018 and 0.029, respectively). Sanger sequencing in 19 mothers revealed m.8344A>G variations in 18, with 4 showing exercise intolerance. Follow-up of 13 children on antimyoclonic treatment showed>75% reduction in seizures with levetiracetam monotherapy in 2 children, with combination therapy required in others. Most achieved >50% seizures reduction within 2 years, but the effectiveness declined with disease progression. Conclusions: The m.8344A>G variant is rare, with MERRF being the most common phenotype, while LS and LS-MERRF are less common. Children with higher ratio of the m.8344A>G variant are more likely to present LS phenotype. Myoclonus, primarily focal, is a key feature, with levetiracetam as the first-line treatment and benzodiazepines recommended for refractory cases.

[Long-term hypomethylating agents in patients with myelodysplastic syndromes: a multi-center retrospective study].

Objective: To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) . Methods: A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results: Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype (P=0.02, OR=0.39, 95%CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation (P=0.02, OR=0.22, 95%CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95%CI 21.14-30.19) months. HMA response (P=0.036, HR=0.47, 95%CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype (P=0.024, HR=2.14, 95%CI 1.10-4.15) , leukemia transformation (P<0.001, HR=2.839, 95%CI 1.64-4.92) , and TP53 mutation (P=0.012, HR=2.19, 95%CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion: Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

[Analysis and summary of clinical characteristics of 289 patients with paroxysmal nocturnal hemoglobinuria in Zhejiang Province].

Objective: To further improve the understanding of paroxysmal nocturnal hemoglobinuria (PNH), we retrospectively analyzed and summarized the clinical characteristics, treatment status, and survival status of patients with PNH in Zhejiang Province. Methods: This study included 289 patients with PNH who visited 20 hospitals in Zhejiang Province. Their clinical characteristics, comorbidity, laboratory test results, and medications were analyzed and summarized. Results: Among the 289 patients with PNH, 148 males and 141 females, with a median onset age of 45 (16-87) years and a peak onset age of 20-49 years (57.8% ). The median lactic dehydrogenase (LDH) level was 1 142 (604-1 925) U/L. Classified by type, 70.9% (166/234) were classical, 24.4% (57/234) were PNH/bone marrow failure (BMF), and 4.7% (11/234) were subclinical. The main clinical manifestations included fatigue or weakness (80.8%, 235/289), dizziness (73.4%, 212/289), darkened urine color (66.2%, 179/272), and jaundice (46.2%, 126/270). Common comorbidities were hemoglobinuria (58.7% ), renal dysfunction (17.6% ), and thrombosis (15.0% ). Moreover, 82.3% of the patients received glucocorticoid therapy, 70.9% required blood transfusion, 30.7% used immunosuppressive agents, 13.8% received anticoagulant therapy, and 6.3% received allogeneic hematopoietic stem cell transplantation. The 10-year overall survival (OS) rate was 84.4% (95% CI 78.0% -91.3% ) . Conclusion: Patients with PNH are more common in young and middle-aged people, with a similar incidence rate between men and women. Common clinical manifestations include fatigue, hemoglobinuria, jaundice, renal dysfunction, and recurrent thrombosis. The 10-year OS of this group is similar to reports from other centers in China.

[Ultrasonic convex array probe applied to increase success rate of external cephalic version without anesthesia].

Objective: To explore the feasibility of using ultrasonic convex array probe compressing abdominal wall to increase success rate of external cephalic version (ECV) without anesthesia in full-term and near-term pregnancy. Methods: Totally 190 singleton and non-cephalic presentation pregnant women in 36-39+4 weeks of gestation performed ECV from April 2019 to August 2023 in the First Affiliated Hospital of Nanjing Medical University were analyzed. According to whether use the ultrasound probe compressing fetal breech or not, the pregnant women were divided into two groups: 81 cases in the probe-compressing group (including primipara 61 cases and multipara 20 cases) and 109 cases in the non-probe-compressing group(including primipara 72 cases and multipara 37 cases). Clinical data, ECV related factors and complications were analyzed and compared between the two groups. Results: (1) The overall success rate of ECV was 64.2% (122/190). There was no significant difference in the success rate of ECV between probe-compressing group and non-probe-compressing group [69.1% (56/81) vs 60.6% (66/109), χ2=1.490, P=0.222]. The total vaginal delivery rate after successful ECV was 81.1% (99/122), while 71.1% (54/76) in primipara and 97.8% (45/46) in multipara, respectively. (2) Compare to the non-probe-compressing group, the success rate of ECV in primipara was significantly higher in the probe-compressing group [45.8% (33/72) vs 70.5% (43/61)], but the gestational age was shorter and the height was higher in the probe-compressing group (all P<0.05). The success rate of ECV of multipara in the probe-compressing group (65.0%, 13/20) was lower than that in the non-probe-compressing group (89.2%, 33/37), but there was no significant difference between the two groups (P>0.05). (3) Multivariate logistic regression analysis showed that abdominal wall compressed by ultrasound probe (OR=2.601, 95%CI: 1.113-6.075; P=0.027) and amniotic fluid index (AFI; OR=1.010, 95%CI: 1.001-1.020; P=0.028) were positive factors for the successful rate of ECV in primipara pregnant women. (4) The main complication of ECV was transient fetal heart rate reduction (8.9%,17/190), the incidence in the probe-compressing group was significantly higher than that in the non-probe-compressing group [14.8% (12/81) vs 4.6% (5/109); χ2=5.967, P=0.015]. No statistical differences were found in rates of complications between the ECV successful and unsuccessful pregnant women, and between probe-compressing and non-probe-compressing groups (all P>0.05). No adverse maternal and neonatal outcomes related to ECV were observed. Conclusions: The ultrasonic convex array probe compressing could significantly improve the success rate of ECV in primipara without increasing the incidence of adverse maternal and fetal outcomes. The success rate of ECV in primipara is influenced by AFI and operation mode.

[Clinical effects of superficial temporal artery lobulated perforator flaps in repairing skin and soft tissue defects after temporal tumor resection].

Objective: To explore the feasibility and clinical effects of using superficial temporal artery lobulated perforator flaps in repairing skin and soft tissue defects after tumor resection in the temporal region. Methods: A retrospective observational study method was used. From March 2017 to October 2022, ten patients with temporal skin tumors were admitted to the Affiliated Hospital of Zunyi Medical University, including six women and four men, with age ranging from 42 to 87 years. Among them, three patients had squamous cell carcinoma and seven patients had basal cell carcinoma, with disease duration ranging from 6 months to 5 years. All temporal tumors underwent expanded resection, leaving wound areas of 5.4 cm×4.2 cm to 7.0 cm×4.0 cm after tumor resection. Superficial temporal artery frontal branch flaps with areas of 5.5 cm×1.2 cm to 7.0 cm×1.5 cm, superficial temporal artery descending branch flaps with areas of 4.2 cm×3.5 cm to 5.0 cm×4.0 cm, and superficial temporal artery parietal branch flaps with areas of 4.2 cm×1.0 cm to 5.0 cm×1.0 cm were designed to repair the wounds and reconstruct the hairline. The donor areas of the flaps were closed and sutured directly. The survival of the flaps was observed on 3 to 5 days after surgery, and the healing of wounds on the donor and recipient sites was observed when the stitches were removed on 5 to 7 days after surgery. During follow-up after surgery, the appearance of the temporal area, scar hyperplasia, hairline reconstruction, and tumor recurrence were observed in the temporal region on the affected side. Results: All the flaps survived well on 3 to 5 days after surgery, and all the donor and recipient site wounds healed well on 5 to 7 days after surgery. During follow-up of 3 to 6 months after surgery, the surgical incisions were concealed; the flaps were not swollen, with a consistent color to the surrounding skin; there were no obvious hypertrophic scars; the reconstructed hairline on the affected side was not significantly different from that of the healthy side; there was no tumor recurrence in the local area. Conclusions: For large areas of skin and soft tissue defects in the temporal region, the use of superficial temporal artery lobulated perforator flaps can repair the wounds in different regions and suture the donor sites in the primary stage simultaneously. The surgical operation is simple, and the facial appearance conforms to the aesthetic requirement after surgery with no tumor recurrence in the local area but a good repair effect. This method is particularly suitable for repairing large areas of skin and soft tissue defects in the temporal region in elderly patients.

[Mitochondrial pyruvate carrier deficiency: 3 cases report and literature review].

Objective: To analyze the clinical and genetic features of patients with mitochondrial pyruvate carrier deficiency (MPYCD). Methods: This was a case series research. The clinical data, genetic characteristics, and glutamine treatment efficacy of 3 patients diagnosed with MPYCD at the Department of Neurology, Beijing Children's Hospital, Capital Medical University and Department of Pediatrics, Guizhou Provincial People's Hospital, from August 2019 to June 2023 were retrospectively collected. A literature search with "MPC1 gene" "MPC2 gene and" "mitochondrial pyruvate carrier deficiency" as keywords was conducted at the Wanfang Data Knowledge Service Platform, China National Knowledge Infrastructure (CNKI) and PubMed (up to June 2023). Clinical and genetic characteristics of patients with MPYCD were summarized. Results: Case 1 was a 3 years and 11 months old boy, while case 2 was a 4 years and 10 months old boy and case 3 was an 8 years and 9 months old girl. Case 2 and case 3 were siblings from one consanguineous family. All 3 patients presented with general developmental delay, growth failure and elevated serum lactate. Cranial magnetic resonance imaging (MRI) showed subtle bilateral symmetrical T2 signal hyperintensity in basal ganglia and thalamus in case 1, but normal in case 2 and 3. Trio-WES revealed case 1 harboring compound heterozygous missense variants c.208G>A (p.Ala70Thr) and c.290G>A (p.Arg97Gln) in MPC1 gene, while case 2 and 3 revealed a homozygous variant c.290G>A (p.Arg97Gln) in the same gene. All 3 cases were diagnosecl as MPYCD. Clinical symptoms including motor ability, cognition and activity endurance were improved in these 3 patients after taking glutamine for 2 years. A total of 5 articles published in English were reviewed, and no Chinese literature was found. Including these 3 cases, 15 cases were enrolled for analysis. Eleven patients carried MPC1 gene variants and 4 cases carried MPC2 gene variants. Except for 3 cases died during prenatal period, 9 of 12 enrolled born cases were onset before 6 months old. The most common clinical symptoms were mental and motor general developmental delay, microcephaly, growth failure and hypotonia. All patients had elevated blood lactate and pyruvate, but the ratio of lactate/pyruvate was normal. Seven patients performed cranial MRI, 3 exhibited non-specific changes, 2 showed bilateral symmetrical T2 signal hyperintensity in basal ganglia and thalamus, and 3 were normal. A total of 5 MPC1 gene missense variants and 2 MPC2 gene variants were identified in 15 cases. Conclusions: Onset age of patients with MPYCD is usually within 6 months. The main clinical characteristics are developmental delay, microcephaly and growth failure, accompanied by increased serum lactate and pyruvate. Glutamine supplement could lead to clinical improvements.

[Reliability and validity of the Chinese version of adverse childhood experiences international questionnaire in parents of preschool children].

OBJECTIVE: To test the reliability and validity of the Chinese version of adverse childhood experiences international questionnaire (ACE-IQ) in Chinese parents of preschool children. METHODS: The parents of preschool children in 6 kindergartens in Tongzhou District of Beijing were selected by stratified random cluster sampling, and the Chinese version of ACE-IQ after translation and adaptation was used for survey online. The collected data were randomly divided into two parts. One part of the data (n=602) was used for exploratory factor analysis (EFA), to screen items and evaluate structural validity, and then form the final Chinese version of ACE-IQ. The other part of the data (n=700) was used for confirmatory factor analysis (CFA), criterion validity analysis and reliability analysis. At the same time, experts investigation method was used to evaluate the content validity of the final Chinese version of ACE-IQ. RESULTS: After deleting four items of collective violence, the Chinese version of ACE-IQ with twenty-five items indicated good structural, criterion and content validity. Analysis results showed that the Chinese version of ACE-IQ presented a seven-factor model dimension, namely emotional neglect, physical neglect, family dysfunction, family violence, emotional and physical abuse, sexual abuse and violence outside the home, and the total score of the binary version of ACE-IQ Chinese version was positively correlated with the total score of childhood trauma questionaire-28 item short form (CTQ-SF, r=0.354, P < 0.001) and the center for epidemiological studies depression scale (CES-D, r=0.313, P < 0.001) respectively. Results from five experts showed that the item-level content validity index (I-CVI) of 25 items was between 0.80 and 1.00, and the average of all I-CVIs on the scale (S-CVI/Ave) of the scale was 0.984. At the same time, the internal consistency (Cronbach's α coefficient) of the whole scale was 0.818, and the split-half reliability (Spearman-Brown coefficient) was 0.621, which demonstrated good reliability. CONCLUSION: This study has formed a Chinese version of ACE-IQ with 25 items and 7 dimensions, which has good reliability and validity among the parents of preschool children in China. It can be used as an evaluation instrument for measuring the minimum threshold of the adverse childhood experiences in the parents of preschool children in the cultural background of China.

[Comparative study of unilateral biportal endoscopy and coaxial large channel endoscopy for lumbar spinal stenosis].

Objective: To compare the efficacy of unilateral biportal endoscopy (UBE) and coaxial large channel endoscopy for lumbar spinal stenosis. Methods: A total of 176 patients with lumbar spinal stenosis treated in Tianjin Hospital from March 2015 to October 2021 were included in this study. Of the patients, 110 cases were treated with UBE, including 52 males and 58 females, with a mean age of (75.1±10.4) years; while 66 cases were treated with coaxial large channel endoscopy, including 31 males and 35 females, with an average age of (77.2±13.1) years. The visual analogue scale (VAS) score of pain and Oswestry disability index (ODI) were compared before and after surgery between the two groups, with the improvement rate calculated. The operation time, intraoperative blood loss, perioperative conditions and complications were compared. The operation efficacy was evaluated according to MacNab scale and was compared between the two groups. Results: There was no significant differences in age, gender, disease course, VAS of pain, ODI and index levels between the two groups before operation (all P>0.05). The operation time and postoperative drainage in UBE group and coaxial large channel endoscopy group were comparable [(60.1±12.4)min, (62.5±13.2)min and (103.8±20.7)ml, (98.5±22.1)ml, respectively, both P>0.05]. After the operation, the VAS score of low back pain, VAS score of leg pain and ODI of the two groups were all lower than those before operation, and decreased continuously during follow-up; and under the repeated measures analysis of variance, significant differences were found between different time points (all P<0.05), no significant difference was found between the two groups (all P>0.05), nor interaction between groups and time points was detected (all P>0.05). The patients were followed-up for (18.0±4.2) months (6 to 30 months). There was no significant difference in VAS and ODI improvement rates and excellent rate of efficacy between the two groups at the last follow-up (all P>0.05). Conclusions: Both UBE and coaxial large channel endoscopy can provide excellent results for lumbar spinal stenosis. UBE has sufficient decompression and is convenient to explore and remove the herniated disc.

Potential cerebrovascular protective functions of lycium barbarum polysaccharide in alleviating hyperglycemia-aggravated cerebral ischemia/reperfusion injury in hyperglycemic rats.

OBJECTIVE: Lycium barbarum polysaccharide (LBP) is the efficient primary compound of Lycium barbarum and has been shown to alleviate hyperglycemia-aggravated cerebral ischemia/reperfusion (I/R) injury. However, the cerebrovascular changes related to diabetes mellitus (DM) and the potential cerebrovascular protective effects of LBP are still unknown. This study aimed to explore the cerebrovascular protective functions of LBP on cerebral I/R injury in diabetic rats and its potential mechanisms. MATERIALS AND METHODS: Sprague Dawley (SD) rats were separated into three groups: the normoglycemic (NG), diabetic hyperglycemic (HG), and HG + LBP (50 mg/kg) treatment groups. A 30 min transient middle cerebral artery occlusion (tMCAO) with 24 h reperfusion was established. The neurological deficits, cerebral water content, infarct volume, and cerebrovascular permeability were assessed to evaluate the extent of cerebral injury. Histopathological alterations were assessed by hematoxylin and eosin, Nissl, immunohistochemical, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling staining. A transmission electron microscope was used to detect ultrastructural alterations, and a western blot was used to examine protein expression. RESULTS: The HG rats exhibited a significant increase in neurological deficits, cerebral water content, infarct volume, cerebrovascular permeability, neural cell death, and apoptosis compared with the NG rats, and the LBP treatment alleviated these effects. Cerebrovascular structure analysis showed that the cross-sectional area (CSA) and wall thickness were remarkably altered in the HG rats compared with the NG rats. The LBP treatment protected the cerebrovascular structure and vasoreactivity by decreasing the wall thickness and increasing the CSA, α-smooth muscle actin, and endothelial nitric oxide synthase expression of cerebral vessels. CONCLUSIONS: The intake of LBP benefits the cerebrovascular structure and vasoreactivity in diabetic rats. Our research provides a possible new strategy for treating stroke in patients with DM.

[Early onset epileptic encephalopathy caused by mitochondrial arginyl-tRNA synthetase gene deficiency: report of two cases and literature review].

Objective: To summarize the clinical features of two early onset epileptic encephalopathy (EOEE) patients with arginyl-tRNA synthetase (RARS2) gene variations and to review related literature. Methods: The clinical data and genetic features of two pontocerebellar hypoplasia type 6 (PCH6) patients with RARS2 variation diagnosed by the Department of Neurology, Beijing Children's Hospital from January 2017 to December 2018 were analyzed retrospectively. A literature search with "RARS2" "pontocerebellar hypoplasia type 6" and "early onset epileptic encephalopathy" as key words was conducted at China national knowledge infrastructure (CNKI), Wanfang Data Knowledge Service Platform and PubMed (up to May 2020), literature about RARS2 gene variation patients and their complete clinical data were chosen and reviewed. Results: The onset age of the two cases (1 male, 1 female) were 2 months and 29 days respectively and the early onset symptom of them was epileptic encephalopathy. The main symptoms included seizures, development delay, microcephaly and lactic acidosis. In addition to these symptoms, the female also had dyspnea, hypoglycemia and metabolic acidosis after birth. Brain magnetic resonance imaging (MRI) of the two patients were normal at first. Follow up at four-month (case 1) and eight-month (case 2) MRI showed atrophy of cerebral and cerebellar, but the pons was not affected. All four heterozygous variations in RARS2 gene revealed by whole-exome sequencing (p.Arg560His and p.Arg6His from case 1, p.Arg254Trp and p.Phe5Ser from case 2) were novel. No eligible reports were found in Chinese journals, while 17 reports were found in English literature. Excluded cases with incomplete data together with these two cases, a total of 34 patients from 20 families were found. All patients had developmental delay while 94% (32/34) patients showed the initial symptoms within 3 months, 93% (28/30) patients were diagnosed as epilepsy, 89% (25/28) patients had progressively microcephaly and 52% (16/31) cases did not show the pons atrophy on brain MRI. Twenty of 28 cases (71%) were refractory epilepsy. There were 31 types of gene variations and most of them were missense variations (21/31, 68%). Conclusions: The majority of PCH6 cases caused by RARS2 gene variation show the initial symptoms within 3 months, characterized by EOEE, most of them are refractory epilepsy, accompanied by developmental delay, microcephaly and increased lactic acid. Brain MRI indicates progressive cerebral or pontocerebellar atrophy.

[Efficacy and safety of oral pyrotinib in HER2 positive metastatic breast cancer: real-world practice].

OBJECTIVE: Pyrotinib, a novel irreversible pan-ErbB receptor tyrosine kinase inhibitor, showed promising antitumor activity and acceptable tolerability in phase II and phase III randomized clinical trials. We assessed the activity and safety of oral pyrotinib for human epidermal growth factor receptor 2 (HER2) positive metastatic breast cancer patients in the real world. METHODS: We retrospectively analyzed 72 HER2 positive metastatic breast cancer (MBC) patients who received oral pyrotinib based regimens at Beijing Cancer Hospital and other four hospitals (Peking University First Hospital, China-Japan Friendship Hospital, General Hospital of PLA, Peking University Third Hospital) from August 2018 to September 2019. Progression free survival (PFS), objective response rate (ORR), adverse events (AE) of pyrotinib were investigated. RESULTS: Seventy-two patients with HER2 positive MBC were enrolled. The median age of the patients was 55 years (range: 32-79 years). Sixty-nine (95.8%) patients had received anti-HER2 treatment in the metastatic and/or (neo) adjuvant settings; 61 (84.7%) patients had received anti-HER2 treatments in the metastatic setting in terms of trastuzumab 56 (77.8%) patients, lapatinib 36 (50.0%) patients, and T-DM1 4 (5.6%) patients. Among these 72 patients who received oral pyrotinib based regimens, 62 (86.1%) patients received pyrotinib (±trastuzumab) in combination with chemotherapy, 6 (8.3%) patients received pyrotinib (± trastuzumab) in combination with endocrine therapy and 4 (5.6%) patients received pyrotinib (±trastuzumab). Sixty-five (90.3%) patients received 400 mg pyrotinib once daily as initial dose, and 7 (9.7%) patients received 320 mg. OBJECTIVE response and safety to pyrotinib based therapy were evaluable in all the 72 patients. One (1.4%) patient achieved complete response (CR), 18 (25.0%) patients achieved partial response (PR), 41 (56.9%) patients had stable disease (SD), and 12 (16.7%) patients had progressive disease (PD). The ORR (CR+PR) was 26.4% and the median PFS was 7.6 months (95%CI: 5.5-9.7 months). Among the 36 patients with prior lapatinib therapy, the median PFS was 7.9 months (95%CI: 4.1-11.7 months). Among the 15 patients with brain metastasis, the median PFS was 6.0 months (95%CI: 2.2-9.8 months). The main toxicities related to pyrotinib were diarrhea in 57 (79.2%) cases, and 48 (66.7%) cases with grade 1-2 as well as 9 (12.5%) cases with grade 3. CONCLUSION: Pyrotinib based therapy is an effective treatment for patients with HER2 positive MBC, including patients with lapatinib treatment failure and brain metastasis, and the toxicities can be tolerated.

[Effects of dexmedetomidine on cerebral oxygen saturation and postoperative revival period in elderly patients with ovarian cancer].

Objective: To observe the effects of dexmedetomidine on cerebral oxygen saturation and postoperative recovery in elderly patients with ovarian cancer. Methods: Sixty elderly patients with ovarian cancer were randomly divided into two groups. Both groups were given total intravenous anesthesia. Patients in group D were given a loading dosage of dexmedetomidine 0.5 µg/kg, followed by continuous infusion 0.2 µg·kg(-1)·h(-1) until 30 minutes before the end of operation. Group C were given normal saline at the same time. The cerebral oxygen saturation was observed and recorded before anaesthesia (T0), an hour after operation (T1), the end of operation (T2) and 30 min after tracheal extubation (T3). The time of extubation and adverse reactions such as restlessness, shivering and respiratory inhibition were observed in both groups. Results: There was no significant difference in cerebral oxygen saturation between the two groups at different time points (P>0.05), and the degree of restlessness and its incidence in group D were lower than those in group C, and the adverse reactions such as shivering were lower (P<0.05). Conclusion: Dexmedetomidine has no obvious effect on cerebral oxygen saturation in elderly patients with ovarian cancer. It can effectively prevent and reduce postoperative restlessness, does not affect recovery time, and has fewer adverse reactions.

[The role of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving adjuvant chemotherapy].

Objectives: To investigate the efficacy and safety of prophylactic use of pegylated recombinant human granulocyte colony-stimulating factor(PEG-rhG-CSF) in breast cancer receiving docetaxel as adjuvant chemotherapy. Methods: A total of 58 patients with breast cancer receiving adjuvant chemotherapy with docetaxel were included between January 2014 to October 2017. Prophylactic use of PEG-rhG-CSF was administered.Patients were further divided into two groups according to the frequency of PEG-rhG-CSF use: frequent use group (≥3 cycles) and non-frequent use group (<3 cycles). Results: There were significant differences in the incidence rates of grade 3/4 neutropenia between the prophylactic group and non-prophylactic group in cycle 1-3(P<0.05). Less febrile neutropenia (FN) was also noted in the prophylactic group compared with the non-prophylactic group in cycle 1 and cycle 3 (P<0.05). Grade 3/4 neutropenia and FN were less in the frequent use of group compared with the non-frequent use group(P<0.001). The most common side effects of PEG-rhG-CSF included fatigue (10.2%), bone joint pain(50.8%), and 2 patients (3.4%) refused further treatment because of bone joint pain. Conclusions: PEG-rhG-CSF should be prophylactically used for preventing neutropenia and febrile neutropenia in breast cancer patients receiving adjuvant chemotherapy with docetaxel regimen.

[Clinical application of oxycodone combined with dexmedetomidine in percutaneous ultrasound-guided radiofrequency ablation of hepatocellular carcinomas].

Objective: To explore the effects of oxycodone combined with dexmedetomidine in percutaneous ultrasound-guided radiofrequency ablation of hepatocellular carcinomas. Methods: Sixty patients who underwent percutaneous ultrasound-guided radiofrequency ablation of hepatocellular carcinomas were randomly divided into fentanyl group (group A) and oxycodone group( group B), with 30 patients in each group. Patients in group A were injected with fentanyl (2 µg/kg), and patients in group B were injected with oxycodone (0.2 mg/kg). All the patients were injected with dexmedetomidine, with a loading dose of 0.5 µg/kg for 10 minutes and a continuous infusion rate of 0.2 µg·kg(-1)·h(-1) until the end of the operation. The changes of heart rate (HR), mean arterial pressure (MAP), pulse oxygen saturation (SPO(2)) and bispectral index (BIS) were monitored at different time points: time when patients entering the operating room (T0), the beginning of operation (T1), 10 minutes after operation (T2), the end of operation (T3), 15 minutes after the end of operation (T4). The incidence of side effects (nausea and vomiting, respiratory depression and body movements) was assessed. The visual analogue scale (VAS) scores were also recorded at T0, T3 and an hour postoperatively. Results: Five patients of Group A had the body movements during the operation, and it was improved after injecting with fentanyl 2 µg/kg. Compared with T0, HR in two groups decreased significantly at T2 (P<0.05). At each time point, the difference of MAP, HR, SPO(2) and BIS was not statistically significant in two groups. The incidence of Nausea and vomiting, body movements was lower in group B than that in group A(P<0.05). The VAS scores were lower in group B than that in group A at T3 and an hour postoperatively (P<0.05). Conclusion: The combination of oxycodone and dexmedetomidine can be used safely and effectively in percutaneous ultrasound-guided radiofrequency ablation of hepatocellular carcinomas, and it shows more effective analgesia and less side-effects.

[A preliminary study on the outcome of lower-risk myelodysplastic syndrome by low-dose decitabine].

Objective: To assess the efficiency and safety of low-dose decitabine in patients with lower-risk myelodysplastic syndrome (MDS) to couple with the clinical significance of MDS-related gene mutations. Methods: This study was done in 4 institutions in Zhejiang Province. A total of 62 newly diagnosed patients with lower-risk MDS were assigned to two groups of decitabine (12 mg·m(-2)·d(-1) for 5 consecutive days) and best supportive care (BSC) . Their bone marrow samples were subject to examinations of MDS-related 15 gene mutations. The primary endpoints were the proportion of patients who achieved overall response (ORR) after at least two cycles and progression-free survival (PFS) , and their relevances to the gene mutations. Results: Of 62 enrolled patients, and 51 cases were included in the final analysis. 16 of 24 patients (66.7%) in decitabine group achieved ORR versus 8 of 27 (29.6%) in BSC group (χ(2)=6.996, P=0.008) ; PFS prolongation of decitabine versus BSC was statistically significant (not reached vs 13.7 months, P=0.037) . Among 51 patients, at least one gene mutation was identified in 20 patients (39.2%) , including 4 single SF3B1 mutation. PFS in cases with gene mutations (not including single SF3B1 mutation) was significantly shorter than of no gene mutation (9.2 months vs 18.5 months, P=0.008) , but not for ORR (37.5% vs 58.1%, P=0.181) . Among 16 patients with mutated genes, ORR in decitabine and BSC groups were 75% (6/8) and 0 (0/8) , respectively. The most adverse events in decitabine group were grade 3 to 4 neutropenia (45.8%) and grade 3 to 4 infections (33.3%) . Conclusion: This preliminary study showed that low-dose decitabine produced promising results with an acceptable safety in lower-risk MDS patients, especially for those with mutated genes. Further study targeting poor prognostic lower-risk MDS patients should be warranted.

[Predictive and prognostic value of monitoring lymphocyte subsets in peripheral blood before and after chemotherapy in patients with metastatic breast cancer].

OBJECTIVE: To detect the proportion of lymphocyte subsets in peripheral blood of the advanced breast cancer patients before and after chemotherapy with docetaxel and thiotepa, as well as the association between the proportion of peripheral blood lymphocyte subsets with the response rate and prognosis. METHODS: The proportions of lymphocyte subsets (CD3+ T cell, CD3+/CD4+ T cell, CD3+/CD8+ T cell, CD3-/CD16+56+ NK cell, CD3+/CD16+56+ T cell, CD19+ B cell, CD4+/CD25+ T cell, CD8+/CD28- T cell, CD8+/CD28+ T cell) in the peripheral blood of 86 patients were analyzed with flowcytometry before and after chemotherapy. The result was analyzed in combination with clinicopathological data. RESULTS: The proportion of regulatory T cells (Treg) after chemotherapy in the disease control patients decreased significantly compared with that of the progressive patients (P=0.034). The difference of the proportions of Treg before and after chemotherapy affected significantly the overall survival (OS). The OS of the patients with decreased proportion of Treg was significantly longer than that of the patients with increased proportion of Treg, which was 23.5 and 9.4 months respectively (P<0.05). CONCLUSION: The patients with decreased proportion of Treg after chemotherapy had higher response rate and better survival benefit.

Body color development and genetic analysis of hybrid transparent crucian carp (Carassius auratus).

The aim of this study was to investigate the genetic mechanism of the transparent trait in transparent crucian carp. We observed body color development in transparent crucian carp larvae and analyzed heredity of color in hybrids produced with red crucian carp, ornamental carp, and red purse carp. The results showed that the body color of the newly hatched larvae matured into the adult pattern at approximately 54 days post-hatching. Two inter-species reciprocal crosses between transparent crucian carp and red crucian carp, and self-cross F1 of transparent crucian carp and self-cross F1 of red marking transparent crucian carp were conducted, and results indicated that the transparent-scaled trait is dominant over the normal-scaled trait. Furthermore, the transparent trait is a quantitative trait. All offspring in the four inter-genera reciprocal crosses of transparent crucian carp with ornamental carp and red purse carp were hybrids of common carp and crucian carp, and had a relatively low survival rate of 10-20%. Moreover, the transparent-scaled trait was observed to be dominant over the normal-scaled trait in the hybrid fish. In conclusion, our results suggest that the genetic mechanism underlying the color of goldfish is complex and requires further investigation.