Objective To preliminarily describe the current situation of chronic disease drug continuity between community hospitals and the Affiliated Hospital of Qingdao University in the medical alliance,to explore the key points for further improving the connection between upper and lower-level hospitals in the medical alliance,and to improve the drug supply guarantee and the ability of pharmaceutical services of primary medical institutions.Methods The nine community hospitals within the medical alliance centered on the Affiliated Hospital of Qingdao University were taken as the research subjects to investigate the medication continuity between the community hospitals and the core hospital in terms of cardiovascular diseases,diabetes,and respiratory system diseases before and after the medical alliance.Results Before the integration of medical alliances,the drug linkage rate for cardiovascular diseases,diabetes,and respiratory system diseases in community hospitals and core hospitals was relatively low.After the integration of medical alliances,the average drug linkage rate for the three chronic diseases significantly increased,all exceeding 60%.At the same time,the drug catalog in community hospitals was streamlined,reducing the phenomenon of one drug having multiple specifications.There is a significant difference in the number of drug varieties provided by different community hospitals for the three chronic diseases.Conclusion The medical alliance with the Affiliated Hospital of Qingdao University as the core promotes the up-down linkage of drug treatment in community hospitals,simplifies the drug catalog of primary medical structure,and facilitates the treatment and prescription of chronic patients.

Objective To preliminarily describe the current situation of chronic disease drug continuity between community hospitals and the Affiliated Hospital of Qingdao University in the medical alliance,to explore the key points for further improving the connection between upper and lower-level hospitals in the medical alliance,and to improve the drug supply guarantee and the ability of pharmaceutical services of primary medical institutions.Methods The nine community hospitals within the medical alliance centered on the Affiliated Hospital of Qingdao University were taken as the research subjects to investigate the medication continuity between the community hospitals and the core hospital in terms of cardiovascular diseases,diabetes,and respiratory system diseases before and after the medical alliance.Results Before the integration of medical alliances,the drug linkage rate for cardiovascular diseases,diabetes,and respiratory system diseases in community hospitals and core hospitals was relatively low.After the integration of medical alliances,the average drug linkage rate for the three chronic diseases significantly increased,all exceeding 60%.At the same time,the drug catalog in community hospitals was streamlined,reducing the phenomenon of one drug having multiple specifications.There is a significant difference in the number of drug varieties provided by different community hospitals for the three chronic diseases.Conclusion The medical alliance with the Affiliated Hospital of Qingdao University as the core promotes the up-down linkage of drug treatment in community hospitals,simplifies the drug catalog of primary medical structure,and facilitates the treatment and prescription of chronic patients.

Objective:To understand the clinical features of granulomatous hepatitis (GH) induced by intravesical instillation with Bacille Calmette-Guérin vaccine (BCG).Methods:Case reports of GH which was confirmed by liver biopsy and induced by intravesical BCG therapy were collected by searching PubMed and Elsevier databases as of December 2021. The following information of patients including general information, intravesical BCG situations (dose, times of instillation, traumatic catheterization occurrence), GH occurrence (onset time, clinical manifestations, laboratory tests and liver biopsy results), other adverse reactions, treatments, and outcomes were extracted and analyzed descriptively.Results:A total of 23 patients, who were all male, were entered in the analysis, aged from 34 to 80 years with a median age of 66 years. The primary diseases were bladder cancer in 22 patients and ureteral carcinoma in 1 patient. The times of instillation until GH occurred were recorded in 19 patients. Of them, 2 patients had instillation once and the time was 16 at most. Ten patients had traumatic catheterization during the last instillation, including hematuria in 7 patients, pain in 2 patients, and difficulty in urethral intubation in 1 patient. Time from the last instillation to the onset of GH was from 3 h to 440 days (≤7 days in 18 patients, 10, 14, 21, 180, and 440 days in 1 patient respectively) with a median time of 3 days. Among the 23 patients, 21 had fever, 12 had jaundice, 9 had hepatomegaly, 7 had fatigue, 5 had anorexia, 2 had weight loss, and 1 had night sweats; 12 manifested as GH alone and 11 had concomitant adverse reactions. Abnormal liver function appeared in 22 patients, mainly including elevated alkaline phosphatase and elevated aspartate aminotransferase (each in 17 patients). Mycobacterium bovis identification/culture results were recorded in 20 patients and 7 were positive. Liver biopsies showed noncaseating granuloma of epithelioid in 10 patients, noncaseating granuloma in 7 patients, epithelioid granuloma in 4 patients, and hepatic granuloma without details in 2 patients. After discontinuation of BCG instillations and treatments with anti-tuberculosis agents and/or corticosteroids, 22 patients were improved and 1 patient died of BCG sepsis and multiple organ failure.Conclusions:GH usually occurs within 1 week after intravesical instillation with BCG and mainly manifests as fever, jaundice, hepatomegaly, and abnormal liver function, which may be accompanied by other adverse reactions related to BCG instillation. Liver biopsy can help the diagnosis. The prognosis is good after combination therapy with anti-tuberculosis agents and corticosteroids, but death may occur in severe cases.

Objective:To summarize the clinical phenotype of patients with developmental and epileptic encephalopathy 85 caused by SMC1A gene truncating variation.Methods:The clinical data of 4 patients with epileptic encephalopathy caused by SMC1A gene truncating variation from August 2016 to June 2020 were analyzed retrospectively. Related literatures up to October 2021 with the key words "SMC1A" "Developmental and epileptic encephalopathy 85" "SMC1A, epilepsy" and "SMC1A, truncating" in PubMed, CNKI, and Wanfang databases were searched. Relevant literature was summarized and reviewed.Results:These 4 patients were all female. The onset age of seizure were all in the infantile period. They were admitted to the hospital at 3, 2, 11 and 18 months respectively. Focal seizures occurred in all 4 patients, while 1 of them experienced infantile spasm. The characteristic of cluster was observed in all of them with an interval of 14 days to 5.0 months. The seizures were all refractory to different kinds of anti-seizure medications. All 4 patients had severe developmental retardation with microcephaly (head circumference<-2 s). The interictal electroencephalogram (EEG) was characterized by diffuse slow wave. The 4 SMC1A gene variants were p.Gly655fs, p.Glu811fs, p.Arg412fs and p.Ile143fs, all of which were de novo frameshift variation after parental validation. There were another 17 cases with SMC1A gene truncating variation reported in 6 English articles and 1 Chinese article. Among these 21 patients, who were all female, the onset of seizures occurred between 0.5 and 18.0 months of age. Seventeen cases (81%) had the characteristics of cluster attacks, and the intervals of attack cycles were different. Seizure types included generalized tonic-clonic seizure (12 cases (57%)), focal seizure (11 cases(52%)), myoclonic(4 cases(19%)), spasm (4 cases(19%)), atypical absence (3 cases(14%)), tonic seizure (2 cases (10%)), and atonia (1 case(5%)). In addition, 4 cases (19%) had status epilepsy. All patients had moderate to severe mental retardation. Microcephaly was found in all patients. Among 18 cases,EEG in 8 cases had diffuse slow wave background. Brain magnetic resonance imaging (MRI) was normal in 13 cases (62%). Other MRI changes included cerebellar atrophy (3 cases), thin corpus callosum (3 cases), and lateral ventricular enlargement (2 cases). Twenty patients did not respond well to antiepileptic drugs. Conclusions:The clinical phenotypes of patients with epilepsy encephalopathy 85 caused by SMC1A gene truncating variation are characterized by female, early-onset, clustering of seizures, development delay and microcephaly. Diffuse slow waves are shown in interictal EEG in partial. Response to treatment and prognosis are poor.

Objective:To understand the clinical features of granulomatous hepatitis (GH) induced by intravesical instillation with Bacille Calmette-Guérin vaccine (BCG).Methods:Case reports of GH which was confirmed by liver biopsy and induced by intravesical BCG therapy were collected by searching PubMed and Elsevier databases as of December 2021. The following information of patients including general information, intravesical BCG situations (dose, times of instillation, traumatic catheterization occurrence), GH occurrence (onset time, clinical manifestations, laboratory tests and liver biopsy results), other adverse reactions, treatments, and outcomes were extracted and analyzed descriptively.Results:A total of 23 patients, who were all male, were entered in the analysis, aged from 34 to 80 years with a median age of 66 years. The primary diseases were bladder cancer in 22 patients and ureteral carcinoma in 1 patient. The times of instillation until GH occurred were recorded in 19 patients. Of them, 2 patients had instillation once and the time was 16 at most. Ten patients had traumatic catheterization during the last instillation, including hematuria in 7 patients, pain in 2 patients, and difficulty in urethral intubation in 1 patient. Time from the last instillation to the onset of GH was from 3 h to 440 days (≤7 days in 18 patients, 10, 14, 21, 180, and 440 days in 1 patient respectively) with a median time of 3 days. Among the 23 patients, 21 had fever, 12 had jaundice, 9 had hepatomegaly, 7 had fatigue, 5 had anorexia, 2 had weight loss, and 1 had night sweats; 12 manifested as GH alone and 11 had concomitant adverse reactions. Abnormal liver function appeared in 22 patients, mainly including elevated alkaline phosphatase and elevated aspartate aminotransferase (each in 17 patients). Mycobacterium bovis identification/culture results were recorded in 20 patients and 7 were positive. Liver biopsies showed noncaseating granuloma of epithelioid in 10 patients, noncaseating granuloma in 7 patients, epithelioid granuloma in 4 patients, and hepatic granuloma without details in 2 patients. After discontinuation of BCG instillations and treatments with anti-tuberculosis agents and/or corticosteroids, 22 patients were improved and 1 patient died of BCG sepsis and multiple organ failure.Conclusions:GH usually occurs within 1 week after intravesical instillation with BCG and mainly manifests as fever, jaundice, hepatomegaly, and abnormal liver function, which may be accompanied by other adverse reactions related to BCG instillation. Liver biopsy can help the diagnosis. The prognosis is good after combination therapy with anti-tuberculosis agents and corticosteroids, but death may occur in severe cases.

Objective: To investigate the efficacy and safety of ketogenic diet (KD) and antiepileptic drugs(AEDs) in the children with drug refractory Dravet syndrome (DS). Methods: Thirty-two cases of drug refractory DS were enrolled into the Department of Neurology, Shenzhen Children′s Hospital Affiliated to Shantou University Medical School from July 2016 to December 2017, and they were divided into 2 groups: KD group and AEDs group (16 cases for each group), respectively.KD was added to as an additional therapy for KD group, and oral AEDs were administered only in AEDs group.In KD group, oral AEDs were not adjusted for the first 3 months.AEDs could be adjusted within a limited range in 2 groups after 3 months.The clinical efficacy, improvement of cognitive function, retention rate and side effects were observed and compared after 3, 6, 12 months of treatment.The average monthly seizure frequency within 3 months before enrollment was recorded as the baseline.The clinical efficacy was assessed by comparing the seizure frequency of each observation period with the baseline. Results: In KD group, after 3, 6, 12 months′ follow-up, KD the-rapy was maintained in 15, 14, 12 patients.The number of patients whose seizure reduction over 50% was 10, 12, 11 cases, respectively.The number of patients whose seizure reduction over 90% was 7, 9, 10 cases, respectively.The number of patients who were seizure free was 3, 6, 8 cases, respectively.In AEDs group, after 3, 6, 12 months′ therapy, the number of patients whose seizure reduction over 50% was 6, 7, 8 cases, respectively, the number of patients whose seizure reduction over 90% was 3, 3, 4 cases, respectively.The number of patients who were seizure-free was 2, 1, 2 cases, respectively.There was a significant difference in the seizure reduction between 2 groups after 6, 12 months (P<0.05). Furthermore, the incidence of status epilepticus (SE) was significantly reduced in KD group, and non-fever related status epilepticus (NFSE) was preferentially improved.There was a significant difference in the incidence of SE between before and after treatment in the KD group (P<0.05). After 12 months, there was a significant difference in the incidence of SE between 2 groups (P<0.05). After 6, 12 months of treatment, the patients in KD group had significant improvements in adaption, gross motor and language quotients by Gesell Developmental Scale compared to the AEDs group (all P<0.05). Eleven of 12 children who adhered to the therapy for 1 year in KD group had improvement of developmental quotient ≥ 1 grade, however, 7 cases of 16 children in AEDs group had this improvement.The incidence of adverse effect in the KD group and the AEDs group was 37.5%(6/16 cases) and 56.3%(9/16 cases), respectively, and the difference was not significant (P>0.05). Conclusions KD can not only reduce seizure frequency and relieve SE, but also improve the cognitive function of drug refractory DS.The adverse reaction ratio of KD does not increase significantly compared to AEDs.Therefore, KD is effective and safe therapy for children with drug-resistant DS.

AIM: To evaluate the effects of interfer ?-2b (IFN ?-2b ) on atherosclerosis(AS).METHODS: Thirty normal male rabbits were randomly divided into five groups:normal control group(NC group, n= 6), atherosclerosis group(AS group, n =6),virus (herpesvirus Ⅰ,HSV-Ⅰ)infected atherosclerosis group(V group, n= 6), interferon (interferon ?-2b) intervented atherosclerosis group (IFN-Ⅰgroup, n= 6),interferon intervented and virus infected atherosclerosis group (IFN-Ⅱ group, n= 6). Serum lipids were measured and the thoracic aortas were sampled for histopathological, immunohistochemical and in situ hybridization study. RESULTS: The aorta atherosclerosis areas of NC, IFN-Ⅰ and IFN-Ⅱ groups were lower than that of AS group significantly, respectively, and the area of AS group was lower than that of V group ( P