Objective:To analyze the clinical phenotypes and genetic features of a child with developmental and epileptic encephalopathy due to compound heterozygous variants in the ALG14 gene, and to improve clinicians′ understanding of the ALG14 gene and its associated disorders. Methods:Clinical data of a child with developmental and epileptic encephalopathy caused by ALG14 gene variants, who visited Linyi People′s Hospital on September 9, 2019, were collected and followed up. Whole exome sequencing (WES) and Sanger sequencing were applied to genetically detect the child and her parents, SWISS-MODEL software was used to perform 3D modeling of proteins for the screened ALG14 gene variants, and the literature was reviewed to summarize the clinical phenotypes and genetic characteristics of patients associated with ALG14 gene. Results:The proband, a 17-year-old female, presented with focal seizures and generalized tonic-clonic seizures, generalized developmental delay, cranial magnetic resonance imaging showing no significant abnormalities, and video-electroencephalogram showing widespread low-amplitude fast rhythms. The WES results showed that the affected child carried compound heterozygous variants c.243A>G (p.Ile81Met) and c.103delG(p.Glu35SerfsTer7) (NM_144988) in the ALG14 gene, and Sanger sequencing validation showed that they were derived from her father and mother with normal clinical phenotype, respectively, and the above loci had not been reported domestically or internationally. 3D modeling revealed that the p.Ile81Met variant resulted in a change in the coding amino acid at position 81, and alteration of the stability and hydrophobicity of the protein, which may affect the protein function; the p.Glu35SerfsTer7 variant resulted in early truncation of the peptide chain, loss of a large number of amino acid fragments, and significant alteration of the protein structure. According to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, p.Ile81Met was a variant of undetermined clinical significance (PM2+PM3+PP3), and p.Glu35SerfsTer7 was a likely pathogenic variant (PVS1+PM2+PP3). A total of 5 papers were retrieved reporting 13 cases related to ALG14 gene variants (including the present case), 4 cases with pure heterozygous variants, 9 with compound heterozygous variants, involving 11 variant types, all inherited from the parents, of which 9 being missense variants, 1 being shifted code variant, and 1 being intronic deletion variant. The main clinical phenotypes included epileptic seizure (11/13), hypotonia (10/13), craniofacial malformations (8/13), growth disorders (3/13), and behavioral abnormalities (2/13). Conclusions:This article reports the first case of ALG14 gene related developmental and epileptic encephalopathy in a child at home and abroad, characterized by focal seizures, generalized tonic-clonic seizures, and global developmental delay. The compound heterozygous variants c.243A>G (p.Ile81Met) and c.103delG(p.Glu35SerfsTer7) may be the genetic cause of this child, enriching the clinical phenotype and variation spectrum related to this gene.

Objective To explore the core theories and medication characteristics of traditional Chinese medicine in the treatment of Sj?gren syndrome(SS).Methods Search for relevant literatures on the treatment of SS with traditional Chinese medicine published in CNKI,Wanfang Data Knowledge Service Platform,VIP,and SinoMed from the establishment of the database to September 30,2022,screen the prescriptions for the treatment of SS with traditional Chinese medicine and conduct data mining.Results A total of 137 prescriptions were finally selected,involving 186 Chinese medicines.Among them,yin-nourishing medicines,interior heat-clearing medicines and qi-tonifying medicines were used most frequently,and Maidong,Shengdihuang,Baishao ranked among the top 3 in terms of usage frequency.The four qi of Chinese medicines were mainly based on the cold,and the five flavors were based on the sweet flavors.The channel tropism were based on lung meridian and liver meridian.Entropy clustering analysis finally obtained four new prescriptions.Conclusion The treatment of SS is based on nourishing yin for moistening dryness,invigorating spleen and replenishing qi,removing toxicity substance and resolving macula,and dredging channels.At the same time,it emphasizes the application of concepts such as sour and sweet transform into yin,body fluids and blood share the same source,and seeking yin from yang.

Objective To explore the core theories and medication characteristics of traditional Chinese medicine in the treatment of Sj?gren syndrome(SS).Methods Search for relevant literatures on the treatment of SS with traditional Chinese medicine published in CNKI,Wanfang Data Knowledge Service Platform,VIP,and SinoMed from the establishment of the database to September 30,2022,screen the prescriptions for the treatment of SS with traditional Chinese medicine and conduct data mining.Results A total of 137 prescriptions were finally selected,involving 186 Chinese medicines.Among them,yin-nourishing medicines,interior heat-clearing medicines and qi-tonifying medicines were used most frequently,and Maidong,Shengdihuang,Baishao ranked among the top 3 in terms of usage frequency.The four qi of Chinese medicines were mainly based on the cold,and the five flavors were based on the sweet flavors.The channel tropism were based on lung meridian and liver meridian.Entropy clustering analysis finally obtained four new prescriptions.Conclusion The treatment of SS is based on nourishing yin for moistening dryness,invigorating spleen and replenishing qi,removing toxicity substance and resolving macula,and dredging channels.At the same time,it emphasizes the application of concepts such as sour and sweet transform into yin,body fluids and blood share the same source,and seeking yin from yang.

Objective:To analyze the clinical phenotypes and genetic features of a child with developmental and epileptic encephalopathy due to compound heterozygous variants in the ALG14 gene, and to improve clinicians′ understanding of the ALG14 gene and its associated disorders. Methods:Clinical data of a child with developmental and epileptic encephalopathy caused by ALG14 gene variants, who visited Linyi People′s Hospital on September 9, 2019, were collected and followed up. Whole exome sequencing (WES) and Sanger sequencing were applied to genetically detect the child and her parents, SWISS-MODEL software was used to perform 3D modeling of proteins for the screened ALG14 gene variants, and the literature was reviewed to summarize the clinical phenotypes and genetic characteristics of patients associated with ALG14 gene. Results:The proband, a 17-year-old female, presented with focal seizures and generalized tonic-clonic seizures, generalized developmental delay, cranial magnetic resonance imaging showing no significant abnormalities, and video-electroencephalogram showing widespread low-amplitude fast rhythms. The WES results showed that the affected child carried compound heterozygous variants c.243A>G (p.Ile81Met) and c.103delG(p.Glu35SerfsTer7) (NM_144988) in the ALG14 gene, and Sanger sequencing validation showed that they were derived from her father and mother with normal clinical phenotype, respectively, and the above loci had not been reported domestically or internationally. 3D modeling revealed that the p.Ile81Met variant resulted in a change in the coding amino acid at position 81, and alteration of the stability and hydrophobicity of the protein, which may affect the protein function; the p.Glu35SerfsTer7 variant resulted in early truncation of the peptide chain, loss of a large number of amino acid fragments, and significant alteration of the protein structure. According to the American College of Medical Genetics and Genomics and the Association for Molecular Pathology, p.Ile81Met was a variant of undetermined clinical significance (PM2+PM3+PP3), and p.Glu35SerfsTer7 was a likely pathogenic variant (PVS1+PM2+PP3). A total of 5 papers were retrieved reporting 13 cases related to ALG14 gene variants (including the present case), 4 cases with pure heterozygous variants, 9 with compound heterozygous variants, involving 11 variant types, all inherited from the parents, of which 9 being missense variants, 1 being shifted code variant, and 1 being intronic deletion variant. The main clinical phenotypes included epileptic seizure (11/13), hypotonia (10/13), craniofacial malformations (8/13), growth disorders (3/13), and behavioral abnormalities (2/13). Conclusions:This article reports the first case of ALG14 gene related developmental and epileptic encephalopathy in a child at home and abroad, characterized by focal seizures, generalized tonic-clonic seizures, and global developmental delay. The compound heterozygous variants c.243A>G (p.Ile81Met) and c.103delG(p.Glu35SerfsTer7) may be the genetic cause of this child, enriching the clinical phenotype and variation spectrum related to this gene.

Background::Human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) can profoundly affect the mental health of the people living with HIV (PLWH), with higher rates of anxiety, depression, and sleep disturbances. The disparities in neuropsychological problems evaluated by physicians and self-assessed by patients are still unknown.Methods::A total of 5000 PLWH and 500 physicians from 167 hospitals were enrolled in this cross-sectional study from September 2022 to February 2023. 4-Item Patient Health Questionnaire (PHQ-4) was used for the evaluation of depressive issues and anxiety issues by PLWH. Each physician assessed 10 PLWH under their care for the presence of depressive or anxiety issues. The primary outcomes of this study are the concordance rates on the depressive issues and anxiety issues evaluation between physicians and PLWH. The Cohen’s kappa test was used to assess the agreement between physicians and PLWH.Results::The concordance rate for the evaluation of depressive issues is 73.84% (95% confidence interval [CI]: 72.60-75.04%), and it is significantly different from the expected rate of 80% ( P <0.001). Similarly, the concordance rate for the evaluation of anxiety issues is 71.74% (95% CI: 70.47-72.97%), which is significantly different from the expected rate of 80% as per the null hypothesis ( P <0.001). The overestimation rate by physicians on depressive issues is 12.20% (95% CI: 11.32-13.14%), and for anxiety issues is 12.76% (95% CI: 11.86-13.71%). The mismatch rate for depressive issues is 26.16% (95% CI: 24.96-27.40%), and for anxiety issues is 28.26% (95% CI: 27.02-29.53%). The underestimation rate by physicians on depressive issues is 13.96% (95% CI: 13.03-14.95%), and for anxiety issues is 15.50% (95% CI: 14.52-16.53%). For the treatment regiments, PLWH sustained on innovative treatment regimen (IR) related to a lower prevalence of depressive issues (odds ratio [OR] = 0.71, 95% CI: 0.59-0.87, P = 0.003) and a lower prevalence of anxiety issues (OR = 0.63, 95% CI: 0.52-0.76, P <0.001). PLWH switch from conventional treatment regimen (CR) to IR also related to a lower prevalence of depressive issues (OR = 0.79, 95% CI: 0.64-0.98) and a lower prevalence of anxiety issues (OR = 0.81, 95% CI: 0.67-0.99). Conclusion::Nearly one in three PLWH had their condition misjudged by their physicians. The findings underscore the need for improved communication and standardized assessment protocols in the care of PLWH, especially during the acute phase of HIV infection.

Objective:To explore the clinical and genetic characteristics of five children with epilepsies due to variants of SCN8A gene. Methods:Clinical data of five children (four males and one female) admitted to Linyi People′s Hospital due to hereditary epilepsies between August 2015 and August 2022 were collected. Whole exome sequencing was carried out for these children, and candidate variants were verified by Sanger sequencing.Results:All of the five children were found to harbor variants of the SCN8A gene. Case 1, who had benign familial infantile epilepsy, inherited a known pathogenic c. 4840A>G variant from his father with similar symptoms. Cases 2 to 4 had presented with intermediate epilepsy. Among these, case 2 has harbored a de novo c. 3967G>A variant which was rated as pathogenic (PS1+ PS2+ PM1+ PM2_Supporting+ PP3) based on the guidelines from the American College of Medical Genetics and Genomics. Cases 3 and 4 were found to respectively harbor a de novo c. 415A>T and a c. 4697C>T variant, which were both rated as likely pathogenic (PS2+ PM1+ PM2_Supporting+ PP3). Case 5, who had early-onset infantile epileptic encephalopathy transformed into Lennox Gastaut-like syndrome, has harbored a de novo c. 5615G>A variant, which was known to be pathogenic. The children had their age of onset ranging from 2 to 14 months, and all had focal seizures and generalized tonic clonic seizures. Four children (cases 1, 2, 3 and 5) had cluster seizures, four (cases 1 to 4) had become seizure-free after single or dual treatment and showed normal growth and development, whilst case 5 was drug-resistant and showed severe developmental retardation. Conclusion:The five children had new features such as cluster seizures, occasional benign seizures in adulthood, and intermediate epilepsy which are prone to relapse after discontinuation of medication, which may be attributed to the pathogenic variants of the SCN8A gene.

Objective:To summarize the clinical and genetic characteristics of children with epilepsy associated with SCN2A gene variations. Methods:A retrospective study was performed. Eleven children with epilepsy admitted to Department of Pediatric Neurology, Linyi People's Hospital from January 2017 to December 2022 were included; all of them had pathogenic SCN2A gene mutation. Genetic results and clinical data as epileptic seizure type/frequency, intelligence and motor development of these 11 children were collected. Epilepsy-related variations and pathogenesis of SCN2A gene were analyzed, and their correlations with clinical phenotypes in these children were analyzed. Results:Among the 11 patients, 6 had self-limited epilepsy (4 with variation in the intracellular domain and 2 in the transmembrane domain), 1 had febrile convulsion accompanied by childhood absent epilepsy (with variation in the intracellular domain), and 4 had developmental epileptic encephalopathy (2 with variation in the extracellular domain and 2 with variation in the transmembrane domain). SCN2A gene was missense mutation in these 11 children, and the mutation site in 6 children was not reported before. Various forms of video EEG discharge were noted, and 1 child with self-limited epilepsy showed transient multifocal epileptic discharge during frequent seizures. Oxcarbazepine and topiramate were effective for self-limiting epilepsy, and lamotrigine was effective in 1 child with late-onset epileptic encephalopathy. Eleven patients were followed up for (66±32) months; the age ranged from 8 months to 11 years and 6 months at the last follow-up; 10 patients had seizure remission and 1 had uncontrolled seizure. Conclusions:Besides self-limited epilepsy and developmental epileptic encephalopathy, SCN2A gene mutations are also associated with febrile convulsion and childhood absent epilepsy. Phenotypic differences are highly correlated with mutation locations; developmental epileptic encephalopathy associated variants are mostly located in extracellular domains, while self-limited epileptic variants are mostly located in intracellular domains.

Objective:To explore the efficacy of a flat ground exoskeleton robot in improving the walking ability of stroke survivors.Methods:Fifty-eight stroke survivors with mobility difficulties were randomly divided into a robot group ( n=29) and a control group ( n=29). In addition to routine rehabilitation, the control group received conventional walking training, while the robot group underwent exoskeleton robot-assisted gait training. The 30-minute training sessions were held twice a day, 5 days per week for 5 weeks. Before as well as after 2 and 4 weeks of treatment, everyone′s walking ability was tested using the 6-minute walk test (6MWT) and functional ambulation scale (FAC). General lower limb motor function was quantified using the Fugl-Meyer Lower Extremity assessment (FMA-LE). Moreover, gait analysis was conducted before and after 4 weeks of treatment. Results:After 2 and 4 weeks of treatment, the average 6MWT times of both groups were significantly better than before the treatment, with the improvement of the robot group significantly greater than that of the control group after 2 weeks. After 2 and 4 weeks the average FMA-LE and FAC scores of both groups had improved significantly compared with before treatment. After 4 weeks the stride frequency and gait cycle of both groups had improved significantly.Conclusions:Exoskeleton robot-assisted gait training can improve walking ability and lower limb motor function of stroke survivors about as well as conventional walking training.

Objective:To investigate the safety and effectiveness of Willis covered stent in patients having carotid artery rupture during transnasal endoscopic pituitary tumor resection.Methods:A retrospective analysis was performed. Six patients having carotid artery rupture during transnasal endoscopic pituitary tumor resection admitted to the 3 hospitals from May 2016 to December 2019 were chosen; their clinical data were collected. The surgical processes and complications were concluded, and the prognoses were evaluated by modified Rankin scale (mRS).Results:One patient was treated with intraoperative simple tamponade compression for hemostasis, and died for massive intracranial hemorrhage 2 weeks after surgery. Five patients were occluded by Willis covered stents; the occluded success rate was 100% but ophthalmic arteries were blocked in all. During the perioperative period, diabetes insipidus occurred in one patient and incomplete oculomotor paralysis occurred in one patient; 5 patients were followed up for 3-12 months: MRI indicated subtotal resection of tumor in 4 patients and total resection in one patient, no new bleeding or ischemic stroke events occurred in these 5 patients, and the prognosis was good.Conclusion:Willis covered stent is safe and effective in patients having carotid artery rupture during transnasal endoscopic pituitary tumor resection.

Severe and critically ill patients with coronavirus disease 2019 (COVID-19) were usually with underlying diseases, which led to the problems of complicated drug use, potential drug-drug interactions and medication errors in special patients. Based on ( 6), and -19: , we summarized the experience in the use of antiviral drugs, corticosteroids, vascular active drugs, antibacterial, probiotics, nutrition support schemes in severe and critically ill COVID-19 patients. It is also suggested to focus on medication management for evaluation of drug efficacy and duration of treatment, prevention and treatment of adverse drug reactions, identification of potential drug-drug interactions, individualized medication monitoring based on biosafety protection, and medication administration for special patients.
Adrenal Cortex Hormones ; adverse effects ; therapeutic use ; Anti-Bacterial Agents ; therapeutic use ; Antiviral Agents ; adverse effects ; therapeutic use ; Betacoronavirus ; isolation & purification ; Coronavirus Infections ; drug therapy ; Critical Illness ; Drug Therapy ; Humans ; Nutritional Support ; Pandemics ; Pneumonia, Viral ; drug therapy ; Probiotics ; administration & dosage