AIM: To investigate the clinical effect and side-effects of paroxetine in the treatment of generalized anxiety (GA). 　METHODS: Ninety patients who met Chinese classification and diagnostic criteria of mental disorders, 2nd Rev Ed (CCMD-2-R) criteria for GA were randomly divided into paroxetine group of 30 patients (M 12, F 18; age 40 a±s 13 a) which was treated with paroxetine 20-40 mg, po, qd or bid, benzodiazepines group of 30 patients (M 13, F 17; age 37 a±13 a) among them, 16 patients were treated with alprazolam 0.4-0.8 mg, po, bid or tid, 14 patients were treated with clonazepam 1-2 mg, po, bid or tid and placebo group of 30 patients (M 11, F 19; age 37 a±13 a) which was treated with placebo 1 tablet, tid for 12 wk. Effects were evaluated with Hamailton anxiety scale (HAMA), self-rating anxiety scale (SAS), clinical global impression scales (CGI) and treatment emergent symptoms scale (TESS), before and after the wk 2,4,8,12 of treatment.　RESULTS: The excellent response rates of paroxetine group and benzodiazepines group were 90 % and 50 % (P<0.01). The side-effects of paroxetine group were dry mouth, constipation, nausea, but those were less than that of benzodiazepines group. 　CONCLUSION: The study suggests that paroxetine is an effective drug for the long treatment of GA and the side-effect is less.

AIM: To compare the effects between topiramate and slow-release sodium valproate in treating refractory epilepsy. 　METHODS: Topiramate group of 39 patients (M 21, F 18; age 28 a± s 20 a) was compared with sodium valproate group of 41 patients (M 22, F 19; age 27 a±17 a) in antiepileptic effect of refractory epilepsy. Adult's and children's dosages of topiramate were increased gradually about 200 mg*d-1 and 4 mg*kg*d-1 respectively during about 2 mo, po, bid, for 6 mo as a course. Adult's dosage of slow-release sodium valproate was 0.5-1 g*d-1, and children's was increased gradually to total dosage: 15-30 mg*kg*d-1, po, qd or bid (morning or morning and noon), for 6 mo as a course. Effects were analysed between these two drugs after treatment 4 and 6 mo.　RESULTS： Simple and complex partial seizures with or without secondary generalized seizure, in topiramate group were much more improved than these in sodium valproate group 6 mo after treatment. Four patients of topiramate group appeared temporary adverse reactions of central nervous system, such as tiredness, sleepiness and distraction, but one patient of sodium valproate group had severer decreased function of bone marrow.　CONCLUSION: Topiramate is one of effective antiepileptic drugs and superior to slow-release sodium valproate. There are the apparent absence of any effects of topiramate on the bone marrow and on indexes of liver and kidney.

Objective:To investigate characteristics of fever and drug-induced liver injury (DILI) in inpatients with severe drug eruptions.Methods:A retrospective analysis was carried out on clinical data collected from 63 inpatients with severe drug eruptions from June 2007 to June 2020, and their characteristics of fever and DILI were investigated. Two-independent-sample t test or Kruskal-Wallis H test was used for intergroup comparison of measurement data, and intergroup comparison of enumeration data was performed using chi-square test or Fisher′s exact test. Results:Among the 63 patients with severe drug eruptions, 54 developed fever; low, moderate and high/ultra-high fever all occurred in about one third of the patients; of 17 patients with high/ultra-high fever, 16 sufferred from Stevens-Johnson syndrome (SJS) , toxic epidermal necrolysis (TEN) or drug hypersensitivity syndrome (DHS) ; 45 had irregular fever; fever duration ranged from 1 to 14 days in 51 patients; there were no significant differences in the fever grade or duration among the patients with different clinical types of drug eruptions ( P = 0.303, 0.719, respectively) ; rashes occurred earlier than or at the same time as fever in 92.59% of the patients. DILI occurred in 11 patients, 8 of whom had hepatocellular injury at admission, including 5 with DHS, 2 with SJS and 1 with TEN; 6 patients were accompanied by low, moderate or high fever, with the fever duration being 7.33 ± 4.97 days, and they all had grade 1 liver injury; liver function retesting at discharge showed complete recovery in 5 patients, improvement in 1, as well as conversion from hepatocellular injury to mixed liver injury in 1, and 1 patient did not undergo the liver function retesting due to against-medical-advice discharge. The other 3 patients had cholestatic liver injury, all of whom were diagnosed with DHS and accompanied by high or ultra-high fever, wtih the fever duration being 8.33 ± 3.51 days, and 1 patient had grade 4 liver injury (acute liver failure) ; liver function was improved in all the 3 patients at discharge. Conclusions:Patients with severe drug eruptions are prone to be accompanied by various types of fever, irregular fever is more common, fever usually lasts 2 weeks, and rashes often occur earlier than or at the same time as fever. DILI can occur in patients with severe drug eruptions, and is usually accompanied by fever; hepatocellular injury is more common, and prone to be improved rapidly; cholestatic liver injury is characterized by severe clinical symptoms and a long disease course, and most frequently occurs in patients with DHS.

BACKGROUND:Overweight or obesity is the most significant risk factors for knee osteoarthritis.Time-restricted diet shows an effective effect in preventing overweight or obesity.Whether infrapatellar fat pad,an important component of the knee joint,is affected by time-restricted diet and thus influences knee osteoarthritis remains unclear. OBJECTIVE:To employ a high-fat diet-induced rat model to investigate the effect of weight loss by time-restricted diet on infrapatellar fat pad,thereby providing evidence for early prevention and treatment of obesity-related knee osteoarthritis. METHODS:Fifteen male Sprague-Dawley rats were randomly divided into three groups(n=5 per group).Rats in the control group were allowed to eat at will for 24 hours and were fed the defined control diet(12%fat);rats in the high-fat diet group were allowed to eat at will for 24 hours and were fed the high-fat diet(45%fat);and rats in the high-fat diet with time-restricted diet group were fed the high-fat diet only from 9:00(2 hours after the light)to 17:00(2 hours before the dark).After 8 weeks of feeding,mDixon-Quant sequence was used to assess proton density fat fraction in the infrapatellar fat pad and subcutaneous adipose tissue in the right inguinal region.ELISA was used to quantify differences adipokine.Sirius red staining was used to evaluate changes in fibrosis of the infrapatellar fat pad.The expressions of uncoupling protein-1 in the infrapatellar fat pad and subcutaneous adipose tissue in the right inguinal region as well as leptin,adiponectin and tumor necrosis factor-α in the infrapatellar fat pad were detected by immunohistochemistry staining. RESULTS AND CONCLUSION:After 8 weeks of feeding,compared with the high-fat diet group,the body mass of rats in the control group(P=0.036)and the high-fat diet with time-restricted diet group(P=0.003)was significantly reduced.The proton density fat fraction in the infrapatellar fat pad in the high-fat diet group was significantly higher than that in the control group(P<0.001)and the high-fat diet with time-restricted diet group(P=0.004),while there was no significant difference in the proton density fat fraction of the subcutaneous adipose tissue among the three groups.The serum leptin levels of rats in the high-fat diet group were significantly higher than those in the control group(P=0.030)and the high-fat diet with time-restricted diet group(P=0.018).Compared with the high-fat diet group,the infrapatellar fat pad fibrosis characterized by Sirius red staining in the control group(P<0.001)and the time-restricted diet group(P=0.003)was significantly decreased.The expression of leptin in IFP of the high-fat diet group was significantly higher than that of the control group(P<0.001)and the high-fat diet with time-restricted diet group(P<0.001).The expression of adiponectin in the infrapatellar fat pad of the high-fat diet group was significantly lower than that of the control group(P=0.004)and the high-fat diet with time-restricted feeding group(P=0.048).However,there was no positive expression of uncoupling protein-1 in the infrapatellar fat pad and subcutaneous adipose tissue of all the three groups,and no positive expression of tumor necrosis factor-α in the infrapatellar fat pad.To conclude,time-restricted diet could retard the fibrosis of the infrapatellar fat pad,reduce the proton density fat fraction of the infrapatellar fat pad,and affect the level of adipokine in serum and infrapatellar fat pad.Time-restricted diet may become a simple and effective option for the treatment and prevention of obesity-related knee osteoarthritis.

OBJECTIVETo study the clinicopathologic features, differential diagnosis and prognosis of primary bone anaplastic large cell lymphoma(ALCL).

METHODSTwelve patients diagnosed with primary bone ALCL were retrospectively reviewed. The clinicopathologic features, immunohistochemic findings and results of in situ hybridization for EB virus were analyzed.

RESULTSOf the 12 patients, the male-to-female was 7: 5 with a median age of 17.5 years (range from 9 to 64 years). Bone pain was the presenting symptom in all patients. Radiographic examination demonstrated solitary osteolytic lesion in 8 patients and multiple lesions in the rest 4 patients. Spine (7 cases) was the most common site to be involved, followed by ilium (5 cases), sacrum (2 cases), humerus (1 case) and collarbone (1 case). Ten patients were available with the follow-up data including 5 ALK-positive and 5 ALK-negative patients, and the follow-up time was 2 to 47 months. Interestingly, the 3 dead patients were ALK-negative whereas 5 of 7 ALK-positive patients achieved remission.

CONCLUSIONSPrimary bone ALCL is a rare type of non-Hodgkin lymphoma and it more frequently involves the axial skeleton. Boys and young males are more commonly affected. Patients usually present at an early stage and have a relatively favorable prognosis. Expression of ALK protein may be associated with a favorable prognosis in primary bone ALCL.

Activin Receptors, Type I ; Adolescent ; Adult ; Alkaline Phosphatase ; Bone Diseases ; etiology ; Bone Neoplasms ; diagnostic imaging ; enzymology ; mortality ; Child ; Female ; Humans ; Lymphoma, Large-Cell, Anaplastic ; diagnostic imaging ; enzymology ; mortality ; Male ; Middle Aged ; Pain ; etiology ; Prognosis ; Radiography ; Receptor Protein-Tyrosine Kinases ; Retrospective Studies ; Young Adult

Objective:To investigate the effect of time-restricted feeding (TRF) on bone marrow fat of proximal femur in obese rats induced by high-fat diet (HFD) using proton density fat fraction (PDFF).Methods:Totally 30 male Sprague-Dawley rats were stratified and randomly sampled into 6 subgroups according to body weight, with 5 rats each. Then 2 subgroups were combined into one group, and there were totally 3 groups. The rats in the control group were fed with normal diet, and the rats could eat as much as they wanted for 24 h; the rats in the HFD group were fed with high-fat diet, and the rats could eat as much as they wanted for 24 h; the rats in the HFD+TRF group were fed with high-fat diet only between 9 AM (2 h after light) and 17 PM. One subgroup of rats from each group was examined with MRI on the femur on day 28 of the experiment, and the other subgroup from each group was examined on day 56 to measure the bone marrow PDFF of proximal femur based on mDixon-Quant quantitative sequence images. The rats were executed at the end of the scanning period, and blood samples were collected to measure serum levels of leptin. One-way ANOVA or Kruskal-Wallis H test was used to compare the differences in body weight, PDFF, and serum levels of leptin among 3 groups. The LSD- t test was used for multiple comparisons. Results:On day 28 of the experiment, the differences in body weight, PDFF, and serum leptin among the 3 groups of rats were not statistically significant ( P>0.05). On day 56, the bone marrow PDFF of proximal femur of the rats in the control group, HFD group, and HFD+TRF group were (7.2±1.4)%, (9.7±2.4)%, and (11.2±3.6)%, respectively. The differences in body weight, PDFF, and serum levels of leptin among the 3 groups of rats were statistically significant ( F=6.95, P=0.010, F=5.98, P=0.007, F=4.54, P=0.034). The results of multiple comparisons showed that the body weight in the HFD group was higher than those in the control group (LSD- t=52.96, P=0.036) and the HFD+TRF group (LSD- t=82.74, P=0.003). The values of bone marrow PDFF of proximal femur in the HFD+TRF group was higher than that in the control group (LSD- t=4.01, P=0.012). The serum levels of leptin in the HFD group were higher than those in the control group (LSD- t=1.45, P=0.030) and the HFD+TRF group (LSD- t=1.62, P=0.018). Conclusion:TRF induces an increase in the values of bone marrow PDFF of proximal femur in conjunction with weight loss in obese rats induced by HFD, and the increase in bone marrow fat may be related to the decrease in serum leptin.

SARS-CoV-2 Omicron variant (B.1.1.529) was first discovered in South Africa in November 2021 and has since become a mainstream strain worldwide. Omicron variant was defined as the fifth "variant of concern (VOC)" by World Health Organization on November 26, 2021. This paper illustrates the mutation trends of Omicron variants in terms of SARS-CoV-2 genome and protein structure as well as nucleic acid site mutations and amino acid site mutations, describes the features of Omicron mutation sites in terms of lineage comparison among the VOCs and Omicron sublineages, and further highlights the influences of Omicron site mutations from the aspects of immune escape, virulence and transmission ability. Moreover, this paper also reviews the development of direct antiviral agents, antibodies and vaccines, aiming to provide reference for further investigation.

Zika virus belongs to the family Flaviviridae, genus Flavivirus and is mainly transmitted to humans by Aedes. The outbreak of Zika virus infection in South America in 2015 raised worldwide health concern due to the increasing incidence of microcephaly, Guillain-Barre syndrome and myelitis, although most of the patients were asymptomatic. Here, to further understand and elucidate the pathogenic mechanism of Zika virus infection-associated myelitis, this review summarized the latest advance in biological characteristics, transmission and treatment of Zika virus infection as well as the related case reports and possible mechanisms.

Objective To analyze the differences in the expressions of the total and phosphorylated proteins in human colon cancer HCT116 cells after the knockout (KO) of retinoic acid-induced protein 16 (RAI16) and explore the possible mechanism and related signaling pathways affecting its protein function in HCT116 cells. Methods HCT116 KO and WT cell proteins were collected and extracted, and the protein extraction efficiency was detected via a sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) experiment. After protein digestion, the peptides were labeled with TMT and analyzed via mass spectrometry. We used bioinformatics methods to analyze the identified differential proteins and differentially phosphorylated proteins by using GO, KEGG, and STRING databases. Results The results of SDS-PAGE showed no evident protein degradation. In addition, some key bands were significantly different between the experimental and control groups. A total of 147 up-regulated and 230 down-regulated differential proteins were screened in accordance with the conditions of Foldchange≥1.5 or Foldchange≤1/1.5 and P<0.05. Meanwhile, 106 up-regulated and 217 down-regulated phosphorylation sites were screened. GO enrichment analysis revealed that the differential proteins were mainly enriched in the composition of nucleoplasm, nucleus and cytoplasm, RNA binding, cadherin and chromatin, DNA repair, RNA splicing, and positive regulation of DNA as template transcription. The results of KEGG enrichment indicated that the differential proteins were mainly enriched in nucleocytoplasmic transport, spliceosomes, cell cycle, cell-cell tight junctions, viral carcinogenesis, microRNAs in cancer, etc. The protein interaction network mainly focused on DDX17, NCL, EEF2, CDK1, SSRP1, and SMARCC1. The statistical findings unveiled the up-regulated changes in the two omics of SKP1, ORC1, and BAD and the down-regulated changes in RBL1, RB1, CDK1, CDC6, MCM4, TFDP1, CHD4, and SNW1. Moreover, the phosphorylation differences were more significant than the protein differences. Conclusion RAI16 plays the possible crucial role in multiple biological functions and signaling pathways through key proteins, such as SKP1, ORC1, RB1, and CDK1, which affect the cell cycle and thereby the occurrence and development of cancer.