[Clinical characteristics and prognosis of 8 cases of severe infant botulism].

Objective: To summarize the clinical characteristics and prognosis of severe infant botulism and evaluate the therapeutic effect of botulinum antitoxin in the pediatric intensive care unit (PICU). Methods: The clinical data of 8 cases diagnosed with infantile botulism were retrospectively analyzed in the PICU of Beijing Children's Hospital from October 2019 to August 2023. Data of basic demographic information, clinical manifestations, laboratory tests, treatment and prognosis of each child were collected and analyzed using descriptive statistical methods. Results: Eight laboratory-confirmed cases of infant botulism were included in this study, all of which were male infants with an age of 6.0 (3.3,6.8) months. Three of the children were from Inner Mongolia Autonomous Region, 2 of them were from Hebei, and the other 3 were from Beijing, Shandong and Xinjiang Uyghur Autonomous Region, respectively. All the patients were previously healthy. In 4 of these cases, the possible cause was the ingestion of either honey and its products or sealed pickled food by the mother or child before the onset of the disease. The first symptom was poor milk intake (4 cases), followed by shallow shortness of breath (7 cases), limb weakness (7 cases) and so on. The typical signs were bilateral dilated pupils (8 cases) and decreased limb muscle strength (8 cases). The main subtype was type B (7 cases), and only 1 case was classified as type A. Six of the children were treated with antitoxin therapy for a duration of 24 (19, 49) d. Seven of them had invasive mechanical ventilation. All the patients survived upon discharge with a follow-up period of 29 d to 3 years and 8 months. Six patients had fully recovered, and 2 recently discharged patients were gradually recovering. Conclusions: For infants with suspected contact or ingestion of botulinum and presented with bilateral pupillary paralysis, muscle weakness and clear consciousness, the stool should be collected for diagnostic testing using a mouse bioassay as soon as possible. Type B was the most common type. The antitoxin treatment was effectiveness and the prognosis was well.

Comparison of PFNA and DHS in the treatment of sarcopenia with Seinsheimer type V subtrochanteric fracture.

OBJECTIVE: We aimed at comparing the curative effect of proximal femoral nail antirotation (PFNA) and dynamic hip screw (DHS) in the treatment of Seinsheimer type V (type V) subtrochanteric fractures with sarcopenia. PATIENTS AND METHODS: A retrospective analysis was performed on 59 patients with type V subtrochanteric fractures complicated with sarcopenia admitted to the Department of Orthopedics of the affiliated Jiangning Hospital with Nanjing Medical University from January 2016 to December 2021. Sarcopenia was diagnosed based on grip strength and skeletal muscle index (SMI). According to different surgical methods, they were divided into PFNA group (32 cases) and DHS group (27 cases). The age, gender, time from injury to operation, SMI value, incision length, operation time, intraoperative blood loss, fluoroscopy times, perioperative blood transfusion, lower limb full weight-bearing time, visual analogue scale (VAS) for pain at 3 months after operation and at the last follow-up, Harris score as well as postoperative complications were compared between the two groups. RESULTS: There were no significant differences in age, gender, time from injury to operation, and SMI between the two groups. The length of surgical incision, blood loss and blood transfusion in the PFNA group were less than those in the DHS group; however, the number of intraoperative fluoroscopies was more than that in the DHS group. The PFNA group had earlier full weight-bearing time, lower VAS score and higher Harris score at 3 months after operation, while there was no statistically significant difference in VAS score and Harris score between the two groups at the last follow-up. The incidence of complications in the PFNA group was lower than that in the DHS group, and the difference was statistically significant. CONCLUSIONS: Both PFNA and DHS are effective methods for the treatment of type V subtrochanteric fractures complicated with sarcopenia. Strikingly, PFNA is preferred because of its short surgical incision, less blood loss, faster recovery, and lower incidence of complications.

[Effectiveness and safety of nimodipine in preventing cerebral vasospasm after subarachnoid hemorrhage in children].

Objective: To evaluate the effect of prophylactic nimodipine in vasospasm prevention and outcome improvement in children with subarachnoid hemorrhage (SAH). Methods: A prospective, randomized controlled clinical trial which enrolled children with SAH who were admitted to pediatric intensive care unit (PICU) of Beijing Children's Hospital from January 2015 to October 2018 was conducted. A total of 43 patients were randomly divided into nimodipine group (24 patients) and control group (19 patients) according to random number table. Transcranial Doppler (TCD) was used to dynamically monitor blood flow velocity and spectrum monography of bilateral middle cerebral artery (MCA) for vasospasm evaluation. Pediatric cerebral performance category (PCPC) scale was used to evaluate patients' brain function on 28(th) day after discharge. Data were analyzed by t test, Mann-Whitney U test, χ(2) test. Results: Except heart rate ((157±26) vs. (137±34) beats/min, t=2.079, P=0.045), no significant differences existed between the two groups in basic demographic characteristics, primary diseases, and clinical manifestations (all P>0.05). The peak velocities of bilateral MCA on the 5(th) day after admission were significantly lower in nimodipine group (left MCA (136±34) vs. (158±23) cm/s, t=-2.890, P=0.006; right MCA (129±34) vs. (176±27) cm/s, t=-3.717, P=0.001). Likewise, a lower peak velocity of left MCA was observed on the 7(th) day after admission in nimodipine group ((127±45) vs. (152±13) cm/s, t=-2.903, P=0.007), but no significant difference existed in that of right MCA ((131±48) vs. (150±22) cm/s, t=-1.760, P=0.090). Eleven patients suffered from vasospasm, 25% (6/24) in nimodipine group and 26% (5/19) in control group (χ(2)=0.010, P=1.000), within whom 8 patients had complete remission after continuing nimodipine treatment, one died in hospital and the other two's vasospasm still existed at the time of discharge. No significant differences were found between the two groups in mean length of hospitalization, proportion of mechanical ventilation, Glasgow coma scale at discharge, survival rate at discharge or survival rate on 28(t)h day after discharge (all P>0.05). However, nimodipine group had a higher proportion of favorable PCPC brain function (92% (22/24) vs. 63% (12/19), χ(2)=5.208, P=0.030). No side effects such as hypotension, rash or injection site erythema were observed. Conclusion: Prophylactic nimodipine cannot reduce vasospasm incidence in children with SAH but may improve short-term brain function, without any significant safety issues.

[Clinical and genetic characteristics of congenital myasthenia syndrome with episodic apnea caused by CHAT gene mutation: a report of 2 cases].

Objective: To investigate the clinical and genetic features of congenital myasthenia syndrome with episodic apnea (CMS-EA) caused by gene mutation of choline acetyltransferase (CHAT) Methods: The clinical data of 2 patients with congenital myasthenia syndrome were collected, and both were diagnosed from 2013 to 2015 in Beijing Children's Hospital, Capital Medical University. The clinical features and gene mutation characteristics were analyzed, and the patients were followed-up for therapeutic efficacy. Results: The two patients (case 1 and case 2) had the onset soon after birth and at 3 months after birth respectively. The two patients were admitted to the PICU due to dyspnea, cyanotic episodes that required intubation. The patients had repeated apnea and became ventilator dependent. Case 1 died due to refusal of any treatment. Case 2 had a tracheotomy, and gradually weaned from ventilator after using pyridostigmine. The hospitalization of case 2 lasted 162 days. Case 2 was followed up to the age of 3 years and 4 months, and was extubated and was maintained on oral neostigmine but still had fluctuating ptosis and minor physical and mental retardation. Both cases were negative for anti-AChR, anti-acetylcholinesterase, anti-MuSK antibodies. Neostigmine test was negative in case 1 and suspiciously positive in case 2. Low-frequency repetitive nerve stimulation testing of case 2 was negative. Cranial MRI scans of both cases showed brain atrophy-like change. Genetic testing showed compound heterozygous deletions (exon 4, 5, 6) and pathogenic variant c.914T>C (p.I305T) in CHAT in case 1, compound heterozygous variants c.1007T>C (p.I336T) and c.64C>T (p.Q22X) in CHAT in case 2. To our knowledge, compound heterozygous deletions (exon 4, 5, 6) and p.Q22X were novel, previously unreported variants. Conclusion: CMS-EA usually presents at birth or in the neonatal period with hypotonia, ptosis, dysphagia due to severe bulbar weakness, and respiratory insufficiency with cyanosis and apnea. Early treatment with pyridostigmine is helpful to the improvement of clinical symptoms and prognosis.

Effects of low-dose epinephrine on perioperative hemostasis and inflammatory reaction in major surgical operations: a randomized clinical trial.

Essentials Blood loss and immune reaction are closely related to morbidity and recovery after surgery. We studied the effect of epinephrine plus tranexamic acid on blood loss and immune reaction. Epinephrine plus tranexamic acid reduced postoperative total blood loss and immune reaction. Epinephrine plus tranexamic acid did not increase the incidence of complications. SUMMARY: Background Hemostasis, thrombosis and surgical stress-induced immune reactions are important for perioperative morbidity and recovery after major surgical operations. Objectives To evaluate the effects of combined administration of low-dose epinephrine (LDEPI) and tranexamic acid (TXA) on perioperative blood loss, thromboembolic complications and inflammatory responses in patients undergoing total hip arthroplasty (THA). Patients/Methods Patients scheduled for THA (n = 195) were randomized into three interventions: intravenous LDEPI plus TXA (group IV); topical diluted epinephrine plus TXA (group TP); and TXA alone as control (group CT). The primary outcome was perioperative blood loss on postoperative day (POD) 1. Secondary outcomes included perioperative blood loss on POD 3, intraoperative blood loss, volume of drainage, transfusion values, coagulation and fibrinolysis parameters, inflammatory cytokine levels, cases of thrombosis, intravenous fluid on the operation day, and length of hospital stay. Results The mean calculated amounts of total blood loss in groups IV, TP and CT were 631.2 mL, 760.5 mL, and 825.6 mL, respectively, on POD 1; treatment effects (differences) were 194.4 mL (95% confidence interval [CI] 146.7-242.0) and 65.0 mL (95% CI 17.4-112.7). Groups IV and TP had lower levels of proinflammatory cytokines (tumor necrosis factor-α and interleukin [IL]-1ß) and higher levels of the anti-inflammatory cytokine IL-10, and showed faster development of coagulation and fibrinolysis (without change in peak levels), than group CT early postoperation. No differences were observed in transfusion, thromboembolic and other outcomes among the groups. Conclusion The combined administration of LDEPI and TXA was more effective in reducing perioperative blood loss and alleviating the inflammatory response than TXA alone, without increasing the incidence of thromboembolic and other complications.

Influence of dexmedetomidine to cognitive function during recovery period for children with general anesthesia.

OBJECTIVE: We studied the influence of Dexmedetomidine on cognitive function in children during the recovery period of general anesthesia. PATIENTS AND METHODS: Ninety-three children who underwent general anesthesia were selected and randomly divided into (1) the control group, (2) the dexmedetomidine group, and (3) the dezocine group. Fentanyl, propofol, and rocuronium were used in all patients to induce anesthesia, while sevoflurane inhalation and propofol were used to maintain anesthesia. In the control group, 20 ml NS were infused intravenously 10 min before anesthetic induction. In the dexmedetomidine group, 1.0 µg/kg dexmedetomidine in 20 ml was infused for 10 min. In the dezocine group, 0.1 mg/kg dezocine in 20 ml was infused for 10 min. Mean arterial blood pressure, average heart rate, and average oxygen saturation (SaO2) were compared at the following time points: end of surgery (T0), before extubation (T1), during extubation (T2), and 30 min after extubation (T3). The VAS scale, Ramsay sedation score, delirium grading scale and occurrence of adverse reactions at 30 min after extubation were recorded. The occurrence of postoperative cognitive dysfunction (POCD) and the expression of serum neuron-specific enolase (NSE) and IL-6 at postoperative days 1 and 7 were recorded. RESULTS: Comparing mean arterial blood pressure, average heart rate, and average oxygen saturation (SaO2) at the different time points in the dexmedetomidine group, there were no statistically significant differences (p>0.05). The difference in the occurrence of adverse reactions in the different groups was statistically significant (p<0.05). The occurrence of postoperative cognitive dysfunction (POCD) at postoperative day 1 was significantly higher in the control group than the other two groups (p<0.05), and on the postoperative day 7th, the differences were not statistically significant (p>0.05). Regarding the expression of neuron-specific enolase (NSE) and IL-6, the levels were the highest in the control group, followed by the dezocine group (p<0.05). CONCLUSIONS: The dexmedetomidine is safer than dezocine in aspects of hemodynamics, sedation, analgesia, degree of delirium, occurrence of adverse reactions, and postoperative cognitive dysfunction (POCD). The improvement in the occurrence of postoperative cognitive dysfunction (POCD) is related to the levels of serum neuron-specific enolase (NSE) and IL-6.

[Current situation of enteral nutrition interruptions in sepsis children in pediatric intensive care unit].

OBJECTIVE: To analyze the interruptions of enteral nutrition (EN) and it's relationship to prognosis in children with sepsis in pediatric intensive care unit (PICU). METHOD: Daily EN intake and reasons for EN interruptions were prospectively observed and recorded in children with sepsis who were admitted to our PICU from November 2012 to April 2013. Clinical prognosis was compared between children with and without EN interruptions by t, rank-sum and χ(2) tests. RESULT: Totally 60 consecutive children were included, 42 males, median age 9.67 (5.36, 37.0) months; 50 children suffered from EN interruptions, while 10 children did not. Median time to EN initiation was 2.59 (1.53, 3.67) h; EN was interrupted in 83% (50/60) of children, for a total of 108 times and 696 h, the most common reasons were fibrobronchoscopy and radiologic procedures, 27 and 29 times respectively. Children spent 0.04 (0.02, 0.08) of their total observation period without EN nutrition due to EN interruptions, and was not correlated with pediatric critically ill score (r=0.12, P=0.38). Children with EN interruptions suffered from longer PICU duration ((12±7) vs. (7±4) d, t=2.18, P=0.03), but there was no significant difference in the 28(th) hospital day's mortality between these two groups (6 cases vs. 1 case, χ(2)=0.00, P=1.00). CONCLUSION: EN is frequently interrupted due to procedures needed fasting, EN intolerance and other reasons in children with sepsis. EN interruptions may have something to do with prolonged PICU length of stay, but the relationship needs to be examined in future studies.

Hsp90 modulates the stability of MLKL and is required for TNF-induced necroptosis.

The pseudokinase mixed lineage kinase domain-like protein (MLKL) is a key component of tumor necrosis factor (TNF)-induced necroptosis and plays a crucial role in necroptosis execution. However, the mechanisms that control MLKL activity are not completely understood. Here, we identify the molecular chaperone Hsp90 as a novel MLKL-interacting protein. We show that Hsp90 associates with MLKL and is required for MLKL stability. Moreover, we find that Hsp90 also regulates the stability of the upstream RIP3 kinase. Interference with Hsp90 function with the 17AAG inhibitor destabilizes MLKL and RIP3, resulting in their degradation by the proteasome pathway. Furthermore, we find that Hsp90 is required for TNF-stimulated necrosome assembly. Disruption of Hsp90 function prevents necrosome formation and strongly reduces MLKL phosphorylation and inhibits TNF-induced necroptosis. Consistent with a positive role of Hsp90 in necroptosis, coexpression of Hsp90 increases MLKL oligomerization and plasma membrane translocation and enhances MLKL-mediated necroptosis. Our findings demonstrate that an efficient necrotic response requires a functional Hsp90.

Polymorphisms associated with egg number at 300 days of age in chickens.

We looked for variations that could be associated with chicken egg number at 300 days of age (EN300) in seven genes of the hypothalamic-pituitary-gonadal axis, including gonadotrophin-releasing hormone-I (GnRH-I), GnRH receptor (GnRHR), neuropeptide Y (NPY), dopamine D2 receptor (DRD2), vasoactive intestinal polypeptide (VIP), VIP receptor-1 (VIPR-1), prolactin (PRL), and the QTL region between 87 and 105 cM of the Z chromosome. Ten mutations in the seven genes were chosen to do marker-trait association analyses in a population comprising 1310 chickens, which were obtained from a company located in Guangdong Province of China. The C1704887T of VIPR-1 was found to have a highly significant association with EN300. The T5841629C of DRD2 and the C1715301T of VIPR-1 were significantly associated with EN300. A highly significant association was also found between the C1704887T-C1715301T haplotypes of VIPR-1 and EN300. H1H3 had the highest EN300. Four PCR-RFLP variations in the candidate QTL region were selected to investigate their genetic effects on EN300. The haplotypes of T32742468C-G32742603A in this region showed a highly significant association with EN300. Bioinformatics analyses showed that both T32742468C and G32742603A were located in intron 1 of the SH3-domain GRB2-like 2 (SH3GL2) gene. We conclude that five SNPs, including C1704887T and C1715301T of VIPR-1, T5841629C of DRD2, and T32742468C and G32742603A of SH3GL2, would be useful as markers for breeding to increase chicken EN300.

Basic radiobiological investigations of fast neutrons.

The radiobiological properties of a cyclotron-produced 43-MeV (p----Be) fast-neutron beam relative to gamma rays have been investigated using Chinese hamster V79 cells in culture. As expected, the relative biological effectiveness (RBE) of this neutron beam for cell killing was shown to increase as dose decreased, and the effectiveness per unit dose was slightly less compared to a 25-MeV (d----Be) neutron beam. By tracing single cells that formed microcolonies after irradiation, we found cell proliferation kinetics to be retarded to a greater extent by fast neutrons than by gamma irradiation. Following either neutron or gamma irradiation, a fraction of the irradiated cells failed to divide in the first postirradiation division and another fraction could produce as many as four generations of progeny before proliferation stopped. The properties of these cells presumed to be destined for death suggest that more than one mechanism and/or multistep process underlies the radiation-induced proliferative death. The fast-neutron beam was also found to be more effective quantitatively than gamma rays in producing DNA double-strand breaks (DSBs, measured by nondenaturing filter elution), and G1-phase chromosome fragments (measured by the premature chromosome condensation technique). However, the reverse was observed for DNA single-strand breaks (SSBs, measured by alkaline filter elution or hydroxylapatite uncoiling). Interestingly, both fast neutrons and gamma rays produced a large component of SSBs and DSBs with a fast-rejoining time constant of about 2-5 min, which appears to be independent of dose. The latter results could not resolve the possibility of lengthening the repair-time constant by increasing radiation dose within the range that is reflected by the shoulder of the survival curve, and consequently did not support the idea of repair saturation as a mechanism for the presence of the shoulder. The RBE for the hypoxanthine phosphoribosyl transferase mutation frequency per survivor at the 10% survival level was estimated to be 2.5, a value that is comparable to the RBE (2.1) for cell killing at the same survival level. Although most of the above-mentioned findings are compatible qualitatively with the relatively high-LET (linear energy transfer) nature associated with the fast-neutron beam, the significance of the action attributable to the mixture of LET could not be delineated in these experiments. Further, the biological significance of DSBs and chromosome aberration and the molecular mechanisms responsible for the repair and expression of these damaging processes remain to be elucidated.

Germ cell comparative Drosophila mutagenesis: sensitivity and mutation pattern in chemically treated stem cells.

Mutagenesis studies on Drosophila oogonial cells with methylnitrosourea, dimethylnitrosamine, and diethylnitrosamine revealed unexpectedly high rates of sex-linked recessive lethals relative to other male and female germ cell stages. Indeed, the oogonial mutation rates with chemicals are higher than with massive X-ray or neutron exposures of oogonia. Analysis of the distribution of lethals per treated female suggests most of the mutations recovered are of independent origin, with very small levels of clustering of identical mutations. In the male stem cell population (spermatogonia) on the other hand, the distribution of lethals is primarily nonrandom and highly clustered. The nature of the mutational endpoint and the different pattern of germ cell development in the two sexes are the probable causes of this difference. The oogonial sensitivity to chemical mutagens may have important bearing on strategies for assessing human hazard.