[Analysis of the clinical characteristics and therapeutic effect of refractory juvenile dermatomyositis to tofacitinib].

Objective: To elucidate the clinical features of patients with refractory juvenile dermatomyositis (JDM), and to explore the efficacy and safety of tofacitinib in the treatment of refractory JDM. Methods: A total of 75 JDM patients admitted to the Department of Rheumatology and Immunology in Shenzhen Children's Hospital from January 2012 to January 2021 were retrospectively analyzed, and to analyze the clinical manifestations, efficacy and safety of tofacitinib in the treatment of refractory JDM. Patients were divided into refractory group with using of glucocorticoids in combination with two or more anti-rheumatic drugs for treatment, and the presence of disease activity or steroid dependence after a one-year follow-up. The non-refractory group is defined as clinical symptoms disappeared, laboratory indicators were normal, and clinical remission was achieved after initial treatment, and the clinical manifestations and laboratory indexes of the two groups were compared. The Mann-Whitney U test, Fisher's precision probability test was used for intergroup comparison. Binary Logistic multivariate regression analysis was used to identify risk factors for refractory JDM. Results: Among the 75 children with JDM, 41 were males and 34 were females with a age of onset of 5.3 (2.3, 7.8) years. The refractory group consisted of 27 cases with a age of onset of 4.4 (1.5, 6.8) years, while the non-refractory group consisted of 48 cases with a age of onset of 5.9 (2.5, 8.0) years. Compared with 48 cases in the non-refractory group, the proportion of interstitial lesions and calcinosis in the refractory group was higher than that in the non-refractory group (6 cases (22%) vs. 2 cases (4%), 8 cases (30%) vs. 4 cases (8%), both P<0.05). Binary Logistic regression analysis showed that observation group were more likely to be associated with to interstitial lung disease (OR=6.57, 95%CI 1.22-35.31, P=0.028) and calcinosis (OR=4.63, 95%CI 1.24-17.25, P=0.022). Among the 27 patients in the refractory group, 22 cases were treated with tofacitinib, after treatment with tofacitinib, 15 of 19 cases (86%) children with rashes showed improvement, and 6 cases (27%) with myositis evaluation table score less than 48 score both were improved, 3 of 6 cases (27%) had calcinosis were relieved, and 2 cases (9%) had glucocorticoid-dependence children were successfully weaned off. During the tofacitinib treatment, there was no increase in recurrent infection, blood lipids, liver enzymes, and creatinine were all normal in the 22 cases. Conclusions: Children with JDM with calcinosis and interstitial lung disease are more likely to develop refractory JDM. Tofacitinib is safe and effective for refractory JDM.

[Effect of enterostomy on analgesic pattern in patients with advanced digestive tract cancer].

Objective: To explore the effect of enterostomy on analgesic pattern in advanced digestive tract cancer. Methods: A retrospective cohort study was carried out, which was approved by the Ethics Committee of the Sixth Affiliated Hospital of Sun Yat-sen University (E2018026). Inclusion criteria were as follows: (1)age and gender were not limited; (2) all the gastrointestinal malignancies were confirmed histologically, and local recurrence or metastasis were confirmed by CT or MR; (3) numerical rating scale (NRS) ≥4 points, opioid analgesic drugs were required; (4) informed consents were signed by patients of their own. Exclusion criteria were as follows: (1) malignancies of early stage; (2) suspicious adverse mental states which might lead to poor administration compliance; (3) hypersensitivity or allergic reactions to opioids. Clinical data of patients with advanced gastrointestinal cancer receiving comprehensive treatment at the Medical Oncology Department of the Sixth Affiliated Hospital of Sun Yat-sen University from September 2016 to April 2017 were retrospectively collected. The patients were divided into the stoma group and the non-stoma group. The clinical findings of two groups were analyzed, including age, sex, ostomy status, pain location, presence or absence of intestinal obstruction, pain characteristics, selection of opioid analgesic agents, treatment of side effects of analgesics. Pain was assessed using brief pain inventory(BPI) table and NRS score. Strong opioids were prescribed for patients of NRS ≥4. Patients who were intolerant to opioids required opioid titration. The titration drugs included oral or IV morphine and oxycodone. After achievement of adequate pain control, long-acting opioids were administered, which included sustained-release morphine tablets, controlled release oxycodone and transdermal fentanyl. Criteria for pain relief included NRS≤3, breakthrough pain <3 times/day and duration of adequate pain control >3 days. The χ(2) test and the Wilcoxon signed rank sum test (nonparametric test) were used to analyze the clinical features of patients in the stoma and non-stomach groups. In order to find the factors associated with maintenance therapy and the use of laxatives, the variables were compared as well as in multivariate analysis with multiple regression models. For all the statistical tests, a value of P<0.05 in a two-tailed test was established as the alpha significance level. Result: A total of 123 patients were enrolled in this study, including 79 males (64.2%) and 44 females (35.8%) with a median age of 51 years. Fifty-two patients were in stoma group, including 30 (24.4%) of ileostomy and 22 (17.9%) of colostomy, and 71 patients were in non-stoma group. Pain of 40 (76.9%) patients in stoma group located in abdomenopelvic site while the pain of 44 (62.0%) patients in non-stoma group located in other sites. Compared with non-stoma group, cases in stoma group complained more abdominopelvic pain (73% vs. 62.0%, P<0.001).The median NRS pain score before treatment in the stoma group and the non-stoma group was 5.7 and 5.6, respectively, without statistically significant difference (P=0.741). After analgesic management, the above scores reduced to 2.1 and 2.3, respectively, without statistically significant difference as well (P=0.092). Analgesic treatment was effective in 111 cases (90.2%), including 49 cases (94.2%) in the stoma group, and 62 cases (87.3%) in the non-stoma group, and there was no statistically significant difference between the two groups (P=0.202). There was more application of fentanyl transdermal patch [34.6%(18/52) vs. 9.8%(7/71)] in the stoma group, while more application of lactulose laxative [78.9%(56/71) vs. 61.5%(32/52)](χ(2)=10.023, P=0.002) in the non-stoma group. Multivariate analysis revealed that ostomy (OR=0.290, 95%CI: 0.102-0.824, P=0.009) and pain site (OR=5.691, 95%CI:1.709-18.948, P=0.005) were independent factors affecting the choice of the first line opioid sustained release agent. Of the 123 patients with maintaining analgesia, 98 had available data of laxative use, of whom 46 used laxatives to prevent or treat constipation, and the proportion of laxatives in stoma group (21.2%, 11/52) was significantly lower than that in non-stoma group (49.3%, 35/71) (χ(2)=6.957, P=0.008). Multivariate analysis of the application of laxative use showed that age (OR=0.281, 95% CI: 0.123-0.684, P=0.010) and ostomy (OR=2.621, 95% CI: 1.033-6.687, P=0.045) were independent factors affecting the use of lactulose laxatives. Conclusions: Enterostomy may affect the analgesic pattern in advanced digestive tract cancer. Patients with stoma are more likely to use fentanyl transdermal patches and younger patients with stoma do not need prophylactic use of laxatives.

Tooth dimensions of Southern Chinese.

Teeth in casts of a random sample from the Hong Kong Oral Health Survey of 12-year-old children (n=459; 295 boys and 164 girls) were measured in the mesiodistal, buccolingual, and clinical crown height dimensions. Sexual dimorphism was evident in all tooth types in nearly all tooth dimensions, with the exception of the mesiodistal dimension of mandibular central incisors. The Chinese male tooth dimensions were larger than in females in nearly all characters. The measurements were compared with other human groups. Results showed that the Southern Chinese had larger tooth dimensions than the Japanese and than the White Americans. Hence it is important to have data concerning a relevant human group for purposes of clinical diagnosis and planning of treatment. These data may also be useful in forensic dentistry.

PCR assessment of HSV-1 corneal infection in animals treated with rose bengal and lissamine green B.

PURPOSE: In vivo, the ophthalmic dye rose bengal displays profound antiviral effects against herpes simplex virus (HSV)-1, thus limiting its utility in diagnosis of epithelial keratitis when used before viral culture is performed. In contrast, lissamine green B does not possess significant antiviral activity in vivo. To determine whether polymerase chain reaction (PCR) could successfully detect HSV-1 DNA in ocular samples that have been exposed to ophthalmic dyes, animal models were used to observe the presence of infectious HSV-1 and viral DNA in eyes treated with rose bengal or lissamine green B. METHODS: Animals were bilaterally infected with HSV-1 strain H129, and at daily intervals up to 16 days post infection (dpi) rose bengal or lissamine green B was instilled in the left eyes. The right eyes were not treated with dyes. Swabs of the dye-treated and untreated eyes were assayed by PCR for viral infectivity by culture and the presence of DNA specific for a fragment of the HSV-1 DNA polymerase gene. RESULTS: A statistically equivalent number of samples from lissamine green B-treated and untreated eyes were positive by both viral culture and PCR. In contrast, rose bengal significantly decreased the infectious virus present in ocular secretions. A total of 44% and 78% of the rose bengal-treated and untreated eye samples, respectively, were positive by culture from 1 through 16 dpi. PCR was more sensitive than culture for detection of HSV-1 in rose bengal-treated eyes, in that 74% of rose bengal-treated samples were positive by PCR compared with 44% that were positive by culture during the 16-day period studied. It was also noted that both rose bengal and lissamine green B treatments slightly prolonged the period during which viral DNA was detectable in ocular secretions by PCR, possibly because the singlet oxygen produced by these photoreactive dyes compromised ocular cellular, humoral, and nonspecific immune factors allowing viral DNA to persist for slightly longer periods. CONCLUSIONS: PCR can successfully detect HSV-1 DNA in ocular samples that are culture negative and contain rose bengal or lissamine green B. Visualization of ocular epithelial defects with lissamine green B does not interfere with detection of infectious virus or HSV-1 DNA.

Comparative analyses of the latency-associated transcript promoters from herpes simplex virus type 1 strains H129, +GC and KOS-63.

We have analyzed the activity of a specific portion of the latency-associated transcript (LAT) promoter of three strains of herpes simplex virus type 1 (HSV-1) in neuronal and non-neuronal cell types. Restriction fragments containing the LAT promoter sequences and the 5'-end of the LATs were isolated from HSV-1 strains H129, +GC and KOS-63, sequenced and cloned into a chloramphenicol transferase (CAT) plasmid vector. These vectors were separately assayed for CAT production in human (SknSH) and mouse (C-1300) neuroblastoma cell lines and a human continuous cell line (HeLa). Strain KOS-63 contained a C to T base substitution within the LAT promoter binding factor element upstream of the cAMP response element binding sequence. In replicate experiments, in which the construct DNA was used for transfection, the CAT constructs from strains H129 and +GC functioned equally well in all three cell lines. In contrast, the strain KOS-63 CAT construct functioned significantly better in HeLa cells than in neuroblastoma cell lines and better than the identical CAT constructs from strains H129 and +GC. In addition, the construct from strain KOS-63 functioned less well in the human neuroblastoma cell line than in HeLa or C-1300 neuroblastoma cells. When LAT expression was examined directly in vivo by in situ hybridization, strain KOS-63 produced slightly less LAT RNA than strain H129 within trigeminal ganglionic neurons of latently infected rabbits. However, utilizing competitive gel-shift assays, DNA fragments containing the LAT promoter binding element from all three strains bound equivalent amounts of HeLa cell nuclear proteins. Together, these results suggest that the activity expressed by the strain KOS-63 LAT promoter in vivo and in vitro may relate to positive or negative effects of DNA binding proteins on LAT transcription, and that these effects are cell-type dependent.

Enhancement by benzodiazepines of the inhibitory effect of adenosine on skeletal neuromuscular transmission.

1. Interactions of benzodiazepines with adenosine on the neuromuscular transmission were studied in mouse diaphragm preparations. 2. In tubocurarine (0.6-0.8 microM)-partially paralyzed preparations, diazepam (35 microM) and Ro 5-4864 (3-30 microM), a peripheral type benzodiazepine receptor agonist, potentiated the inhibitory effect of adenosine on indirect twitch responses. 3. The central type receptor agonist, clonazepam did not affect the inhibitory effect of adenosine. 4. The peripheral benzodiazepine receptor antagonist, PK11195 (1-10 microM) attenuated the adenosine inhibition and antagonized the potentiation by Ro 5-4864. 5. Ro 5-4864 failed to enhance further the inhibitory effect of adenosine in the presence of dipyridamole, an adenosine uptake inhibitor that also potentiated adenosine inhibition. 6. Neither Ro 5-4864 nor PK 11195 affected the inhibition produced by a stable adenosine analogue, 2-chloroadenosine, which is not a substrate for the adenosine uptake system. 7. Ro 5-4864 did not affect endplate potentials (e.p.ps) in the absence of adenosine, but reduced the amplitude of e.p.ps in the presence of adenosine without affecting miniature e.p.ps. 8. It is suggested that benzodiazepines potentiate the adenosine-effected presynaptic inhibition of neuromuscular transmission by an inhibition of adenosine uptake through activation of peripheral type benzodiazepine receptors.

An improved rapid method for purification of herpes simplex virus DNA using cesium trifluoroacetate.

A method for purification of herpes simplex virus DNA from cell culture is described which yields highly purified viral DNA within 8 h. The method involves the freezing and thawing of virus-infected cells followed by isopycnic centrifugation of the lysate supernatant in cesium trifluoroacetate. It was found that this method recovered DNA from most of the cell-associated virus particles in such sufficient purity that the DNA was digestible with restriction enzymes and could be used to transfect cells without the need for additional purification steps. Purification of viral DNA from cells that were not subjected to freezing and thawing was less efficient due to the amount of viral DNA that remained cell-associated.

beta-Eudesmol as an antidote for intoxication from organophosphorus anticholinesterase agents.

beta-Eudesmol, a sesquiterpenol present in Chinese herbs, improved the tetanic contraction impaired by diisopropylfluorophosphate in isolated mouse diaphragm preparations by an inhibition of the regenerative acetylcholine release. The antagonism was enhanced when a small concentration of obidoxime was present. Neither enzyme reactivation nor curare-like action was evident. beta-Eudesmol (300 mg/kg, i.p.) elevated the LD50 of diisopropylfluorophosphate (s.c.) in control mice from 4.2 to 6.4 mg/kg and in mice pretreated with atropine from 7.8 to 10.6 mg/kg. In mice pretreated with atropine and obidoxime, beta-eudesmol showed a greater synergistic effect, increasing the LD50 from 281 to more than 800 mg/kg. beta-Eudesmol also markedly alleviated diisopropylfluorophosphate-induced muscle fasciculation, tremor and convulsion and prolonged the time to death. It is proposed that beta-eudesmol may be added to the standard antidotal regimen (atropine plus obidoxime) for treating organophosphate intoxication.

Chinese herb constituent beta-eudesmol alleviated the electroshock seizures in mice and electrographic seizures in rat hippocampal slices.

We have found that beta-eudesmol, a sesquiterpenol constituent of Chinese herb antagonized organophosphate-induced lethal toxicity by reversing the neuromuscular failure and reducing the occurrence of convulsions. Its possible antiepileptic action was further explored in electroshock seizure mice in vivo and in high potassium treated rat hippocampal slices in vitro. At a dose with little effect on the motor activity, beta-eudesmol prevented the convulsions and lethality induced by maximal electroshock but not those by pentylenetetrazol or picrotoxin. At subeffective doses, beta-eudesmol and phenytoin showed additive effect in preventing electroshock seizures. Extracellular recording of field potentials in CA1 pyramidal layer of hippocampal slices showed that beta-eudesmol reduced the high potassium (8.5 microM)-induced electrographic seizure activity. The potential of beta-eudesmol to serve as an antiepileptic or a conjuvant in phenytoin therapy is suggested.

The dental caries status and dental treatment patterns of 12-year-old children in Hong Kong.

A randomly selected sample of 662 12-year-old Hong Kong children, 529 of whom were Southern Chinese and 133 non-Chinese, was clinically examined for dental caries. The DMFT values were 2.76 and 1.66 for the Chinese and non-Chinese children, respectively. The D component for the Chinese children was 2.12, while for the non-Chinese children it was only 0.45. Approximately 24.0% of the Chinese children had attended the dentist because they were in pain. Only 3.8% of the Chinese children had sought orthodontic or preventive treatment, compared with 24.0% of the non-Chinese children. Although these findings indicate the caries experience to be well below the FDI/WHO global goal for the year 2000, there is a great need to increase the level of dental awareness among Chinese children.

Oral hygiene and toothbrushing habits of 12-year-old children in Hong Kong.

Randomly selected groups of 486 Southern Chinese and 129 non-Chinese 12-yr-old Hong Kong children were examined for calculus and oral debris. The non-Chinese children had less plaque and calculus than the Chinese children (P less than 0.001). The girls had lower plaque scores than the boys in both ethnic groups. The higher frequency of toothbrushing by the girls possibly reflects their greater awareness of personal appearance. There is a need to increase the standard of oral hygiene and the level of dental awareness amongst Chinese children living in Hong Kong.

The ectrodactyly-ectodermal dysplasia-clefting syndrome: a literature review and case report.

Ectrodactyly, atypical anhidrotic ectodermal dysplasia, and cleft lip and palate are the principal manifestations of ectrodactyly-ectodermal dysplasia-clefting syndrome. Intraorally, the common manifestations of the syndrome are hypodontia, enamel hypoplasia, and generalized microdontia. In addition, the patient may suffer from xerostomia and have a deeply fissured tongue. The oral mucosa appears, in some patients, to have an increased susceptibility to candidiasis. This case report describes a patient who exhibits many of the manifestations of the syndrome and explains ways in which many of the anomalies of the dentition can be esthetically and functionally corrected.

Secular trends in stature and weight in southern Chinese children in Hong Kong.

As part of a mixed cross-sectional and longitudinal survey of Hong Kong children which commenced in 1982, 1048 children (539 boys and 509 girls) with a mean age of 12 years 7 months were measured for standing height and weight. Positive secular trends had occurred in the past two decades when the results of this study were compared with those of Chang and his co-workers who performed a survey in 1961-63. At 12 years old, boys were 6.7 cm taller and 5.7 kg heavier, while girls were 4.2 cm taller and 2.9 kg heavier than subjects in 1961-63.

Tooth-size discrepancies among different occlusion groups of southern Chinese children.

The purpose of this study was to compare Bolton anterior and overall ratios among different occlusion groups of southern Chinese children. Fifty plaster casts with Class I occlusion, 30 with Class II occlusion, and 30 with Class III occlusion were selected from a random sample of 1247 12-year-old southern Chinese children in early permanent dentition in Hong Kong. For the anterior ratio, a statistically significant difference was found between the Bolton standard and the Class III occlusion group. For the overall ratio, statistically significant differences were found between the Bolton standard and the Class II occlusion group, and between the Class II and the Class III occlusion groups. Thus specific standards are required for Class II and Class III cases from the southern Chinese population.

Oral and craniofacial morphology of a patient with Larsen syndrome.

A case is reported of a 15 years old Chinese female with Larsen syndrome exhibiting many characteristic facial and skeletal features plus hitherto unreported orofacial anomalies including delayed dental development; hypodontia affecting all the permanent canines, second and third molars, maxillary lateral incisors and second premolars; morphological anomalies of the maxillary first premolars and molars; a class 3 skeletal pattern and reduced upper facial height. Cephalometric radiographs showed the skull bones to have an appearance similar to that of osteopetrosis.

Cloning and restriction endonuclease mapping of herpes simplex virus type-1 strains H129 and +GC.

EcoRI fragments of herpes simplex virus I (HSV-1) strains H129 and +GC were cloned and the EcoRI and BglII restriction enzyme sites were mapped. Comparison of these enzyme sites with the sequence of HSV-1 strain 17syn+ demonstrated that all EcoRI sites were identical. For H129, the BglII sites were also found to match strain 17syn+ BglII sites. With one exception, the BglII sites in strain +GC also aligned with the strain 17syn+ sequence. The one exception was a missing BglII site from strain +GC located between bases 25,149 and 25,154 in the EcoRI D fragment within the viral deoxyribonuclease gene (UL12). The BglII site represents the first difference to be mapped within HSV-1 strains H129 and +GC which have unique pathobiological properties in animal models of acute and reactivated infections.