ObjectiveTo study the mechanism of compound Xishu granules （CXG） in inhibiting the proliferation of hepatocellular carcinoma cells by regulating ferroptosis. MethodsThe transplanted tumor model of human Huh7 was established with nude mice and the successfully modeled mice were randomized into model， Fufang Banmao （0.21 g·kg^-1）， low-dose （1.87 g·kg^-1） CXG， medium-dose （3.74 g·kg^-1） CXG， and high-dose （7.49 g·kg^-1） CXG groups. Mice were administrated with drinking water or CXG for 28 days， and the body weight and tumor volume were measured every 4 days. Hematoxylin-eosin staining was employed to observe the histopathological changes of tumors. The cell-counting kit-8 （CCK-8） was used to examine the survival rate of Huh7 cells treated with different concentrations （0， 31.25， 62.5， 125， 250， 500， 1 000 mg·L^-1） of CXG for 24 h and 48 h. CA-AM， DCFH-DA， and C11-BODIPY^581/591 fluorescent probes were used to determine the intracellular levels of ferrous ion （Fe²⁺）， reactive oxygen species （ROS）， and lipid peroxide （LPO）， respectively. The colorimetric method was employed to measure the levels of glutathione （GSH） and superoxide dismutase （SOD）. Western blot was employed to determine the protein levels of glutathione peroxidase 4 （GPX4）， transferrin receptor 1 （TFR1）， and ferritin heavy chain 1 （FTH1）， respectively. ResultsIn the animal experiment， compared with the model group， the drug treatment groups showed reductions in the tumor volume from day 12 （P<0.01）. After treatment， the Fufang Banmao and low-， medium-， and high-dose CXG groups had lower tumor volume， relative tumor volume， and tumor weight than the model group （P<0.05）， with tumor inhibition rates of 48.99%， 79.93%， 91.38%， and 97.36%， respectively. Moreover， the CXG groups had lower tumor volume and relative tumor volume （P<0.05 in all the three dose groups） and lower tumor weight （P<0.05 in medium-dose and high-dose groups） than the Fufang Banmao group. Compared with the model group， the drug treatment groups showed reduced number of tumor cells， necrotic foci with karyopyknosis， nuclear fragmentation， and nucleolysis， and the high-dose CXG group showed an increase in the proportion of interstitial fibroblasts. In the cell experiment， compared with the blank group， CXG reduced the survival rate of Huh7 cells in a dose-dependent manner after incubation for 24 h and 48 h （P<0.05）. Compared with the blank group， the RSL3 group and the low-， medium-， and high-dose CXG groups showed a decrease in the relative fluorescence intensity of CA-AM and increases in the fluorescence intensity of DCFH-DA and fluorescence ratio of C11-BODIPY^581/591， which indicated elevations in the levels of Fe²⁺ （P<0.01）， ROS （P<0.05）， and LPO （P<0.01）， respectively. Compared with the blank group， the RSL3 and low-， medium-， and high-dose CXG groups showed lowered levels of GSH and SOD （P<0.05）. In addition， the RSL3 group and the medium- and high-dose CXG groups showed down-regulated expression of GPX4 and FTH1 （P<0.05）， and the low- and high-dose CXG groups presented up-regulated expression of TFR1 （P<0.05）. ConclusionCXG suppresses the proliferation of hepatocellular carcinoma cells by inducing ferroptosis via downregulating the GSH-GPX4 signaling axis and increasing intracellular Fe²⁺and LPO levels.

Restless legs syndrome （RLS） is a common neurological sensory-motor disorder， and the diagnosis of RLS mainly rely on the subjective clinical symptoms described by the patient， with a lack of specific auxiliary examinations or biomarkers. The diagnosis of this disease is still challenging for atypical cases. Various other diseases may have similar clinical symptoms as RLS， such as leg discomfort， leg pain and abnormal leg movement. This article summarizes the RLS mimics that might be confused with RLS symptoms， including the neurogenic， vascular， and musculoskeletal factors that might cause leg discomfort and pain， as well as the differential diagnosis of sleep-related movement disorders with symptoms overlapped with RLS， so as to help clinicians recognize RLS phenotype and provide a reference for the diagnosis of diseases that might be confused with RLS.

AIM:To analyze the efficacy of modified pterygium resection combined with conjunctival autograft transplantation(CAT)in the treatment of pterygium.METHODS: A total of 140 patients(154 eyes)with pterygium treated in the ophthalmology department of our hospital from January 2018 to January 2021 were selected and grouped according to random number table method. In the observation group, 70 cases(76 eyes)were treated with modified pterygium excision combined with CAT, and improved iris restorer was used during the operation. In the control group, 70 patients(78 eyes)were treated with conventional pterygium excision combined with CAT, during which traditional iris restorer was used. Follow up for 1a, the postoperative vision, subjective symptoms, conjunctival signs(conjunctival congestion and chemosis), corneal epithelial healing, postoperative complications and recurrence rate were compared between the two groups.RESULTS: Compared with pre-operation, vision of the two groups decreased significantly on 1, 3 and 5d after operation(P<0.05), while there was no statistically significant difference between the groups(P>0.05). Compared with 1d after operation, the scores on subjective symptoms, conjunctival hyperemia and edema in the two groups decreased significantly on 3, 5 and 14d after operation(P<0.05), and those scores of the observation group on 3, 5 and 14d after operation were significantly lower than those of control group(P<0.05).The corneal fluorescein staining(FL)scores of the observation group on 3, 5 and 14d after operation were significantly lower than those of the control group(P<0.05). The proportion of repair time of corneal epithelial defect ≤5d in the observation group was significantly higher than that in the control group(P<0.05). The incidence rates of conjunctival granuloma, symblepharon, and the recurrence rate in the observation group were significantly lower than those in the control group(P<0.05).CONCLUSION: Modified pterygium resection combined with CAT is effective in the treatment of pterygium, which can alleviate postoperative irritative symptoms, conjunctival congestion and edema, and it is more conducive to postoperative corneal epithelial reconstruction, reduction of postoperative complications and recurrence rate.

Gene editing technology has been a hotspot in the field of biotechnology. CRISPR/Cas systems are efficient gene editing tools because of its specificity, simplicity and flexibility, these features enabled the rapid application of CRISPR/Cas systems in a variety of organisms. Moreover, the combination of transcriptional activator with dead Cas protein can achieve specific regulation of gene expression at the transcription level, which has made important contributions to the development of biotechnology in medical and agriculture. Overexpression of foreign genes is a common method to verify gene function and regulation. However, due to the limitation of vector capacity, it is difficult to achieve overexpression of multiple genes. CRISPR/Cas9 activation system can regulate the expression of multiple genes under the guidance of different guide RNAs to verify gene functions at the regulatory level. This review summarizes the composition of the CRISPR/Cas9 activation system and different activation strategies, and summarizes solutions for excessive activation. It may facilitate the application of CRISPR/Cas9 activation system in genetic improvement of cotton and herbicide resistance research.
Biotechnology ; CRISPR-Cas Systems/genetics* ; Gene Editing ; Phenotype ; RNA, Guide, Kinetoplastida/metabolism*

Early distinction of bipolar disorder (BD) from major depressive disorder (MDD) is difficult since no tools are available to estimate the risk of BD. In this study, we aimed to develop and validate a model of oxidative stress injury for predicting BD. Data were collected from 1252 BD and 1359 MDD patients, including 64 MDD patients identified as converting to BD from 2009 through 2018. 30 variables from a randomly-selected subsample of 1827 (70%) patients were used to develop the model, including age, sex, oxidative stress markers (uric acid, bilirubin, albumin, and prealbumin), sex hormones, cytokines, thyroid and liver function, and glycolipid metabolism. Univariate analyses and the Least Absolute Shrinkage and Selection Operator were applied for data dimension reduction and variable selection. Multivariable logistic regression was used to construct a model for predicting bipolar disorder by oxidative stress biomarkers (BIOS) on a nomogram. Internal validation was assessed in the remaining 784 patients (30%), and independent external validation was done with data from 3797 matched patients from five other hospitals in China. 10 predictors, mainly oxidative stress markers, were shown on the nomogram. The BIOS model showed good discrimination in the training sample, with an AUC of 75.1% (95% CI: 72.9%-77.3%), sensitivity of 0.66, and specificity of 0.73. The discrimination was good both in internal validation (AUC 72.1%, 68.6%-75.6%) and external validation (AUC 65.7%, 63.9%-67.5%). In this study, we developed a nomogram centered on oxidative stress injury, which could help in the individualized prediction of BD. For better real-world practice, a set of measurements, especially on oxidative stress markers, should be emphasized using big data in psychiatry.
Biomarkers/metabolism* ; Bipolar Disorder/metabolism* ; Depressive Disorder, Major/diagnosis* ; Early Diagnosis ; Humans ; Oxidative Stress

Classic hypothalamic-pituitary-end-organ feedback loops – the hypothalamic-pituitary-adrenal axis (HPAA), hypothalamic-pituitary-thyroidal axis (HPTA), and hypothalamic-pituitary-gonadal axis (HPGA) – are associated with the neuroendocrine and immune systems in major depressive disorder (MDD). Female patients with MDD present with evident neuroendocrine and immunological changes. Glucocorticoid, thyroid hormone, and reproductive steroid levels fluctuate with menstrual cycles, which might lead to glucocorticoid receptor resistance, impairment of triiodothyronine conversion, and sex hormone secretion disorders. In this review, we summarize the independent and interactive functions of these three axes in female MDD patients. The similar molecular structure of steroids implies an interrelationship between the hypothalamic-pituitary-end-organ axes and the competitive inhibitory effects at the receptor level, especially when considering the HPAA and HPGA.

Objective: Several COVID-19 patients have overlapping comorbidities. The independent role of each component contributing to the risk of COVID-19 is unknown, and how some non-cardiometabolic comorbidities affect the risk of COVID-19 remains unclear. Methods: A retrospective follow-up design was adopted. A total of 1,160 laboratory-confirmed patients were enrolled from nine provinces in China. Data on comorbidities were obtained from the patients' medical records. Multivariable logistic regression models were used to estimate the odds ratio ( Results: Overall, 158 (13.6%) patients were diagnosed with severe illness and 32 (2.7%) had unfavorable outcomes. Hypertension (2.87, 1.30-6.32), type 2 diabetes (T2DM) (3.57, 2.32-5.49), cardiovascular disease (CVD) (3.78, 1.81-7.89), fatty liver disease (7.53, 1.96-28.96), hyperlipidemia (2.15, 1.26-3.67), other lung diseases (6.00, 3.01-11.96), and electrolyte imbalance (10.40, 3.00-26.10) were independently linked to increased odds of being severely ill. T2DM (6.07, 2.89-12.75), CVD (8.47, 6.03-11.89), and electrolyte imbalance (19.44, 11.47-32.96) were also strong predictors of unfavorable outcomes. Women with comorbidities were more likely to have severe disease on admission (5.46, 3.25-9.19), while men with comorbidities were more likely to have unfavorable treatment outcomes (6.58, 1.46-29.64) within two weeks. Conclusion Besides hypertension, diabetes, and CVD, fatty liver disease, hyperlipidemia, other lung diseases, and electrolyte imbalance were independent risk factors for COVID-19 severity and poor treatment outcome. Women with comorbidities were more likely to have severe disease, while men with comorbidities were more likely to have unfavorable treatment outcomes.
Adult ; Aged ; COVID-19/virology* ; China/epidemiology* ; Comorbidity ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Severity of Illness Index ; Treatment Outcome

Neuroimmune system may be involved in the pathological process of bipolar disorder (BD), but the essential association is not fully understood. Accumulating evidence has shown that BD involves the activation of immune cells and the release of inflammatory substances in the central nerve system (CNS). Meanwhile, neuroimmune responses also interact with other hypothesis of the etiology of BD that are widely recognized, such as neurotransmitter systems, neuroendocrine systems, neurotrophic factors, and oxidative stress. Simultaneously, related genes and immune changes in peripheral blood vary with it. Overall, neuroimmunity may play an important role in the pathogenesis of BD, and the inflammatory cytokines, especially interleukin-6 and tumor necrosis factor-alpha, have potential value for the clinical diagnosis and prognosis of BD, as well as predicting the therapeutic effects of drugs. Large-scale studies are needed to extend the evidence on neuroimmunity in BD, and to examine its clinical value for applications such as early prediction and treatment.

Somnambulism is defined as a state of dissociated consciousness triggered by impaired arousal, which results in partial wakefulness and partial sleep. No effective therapy or medication has been available for treating children with somnambulism. Herein we present a case in a 4.5-year-old girl, who presented with somnambulism associated with separation anxiety disorder every night in a week. The girl received formal assessment and appropriate interventions, and the symptoms disappeared within a week. The treatment was carried out in 5 stages: diagnosis of the disease, establishment of trust, information collection, supervision, and individualized psychotherapy. Although dreams in childhood can be difficult to interpret, close observation of the behaviors in sleepwalking, as a special form of dream, in addition to the more precise description by the guardians, still provides useful clues to understand those dreams. For children with somnambulism, early intervention with psychotherapy can significantly decrease the false revival of the unconscious desires, and thus may serve as a treatment option other than medications.
Child ; Child, Preschool ; Female ; Humans ; Psychoanalytic Therapy ; Sleep ; Somnambulism ; therapy

OBJECTIVE: To characterize the traits of neuropsychological functioning deficits in patients with attention-deficit/ hyperactivity disorder (ADHD) with comorbid disruptive, impulse-control, and conduct disorders (DICCD). METHODS: Twenty out-patients with ADHD, 20 with ADHD with comorbid DICCD, and 20 with DICCD, all aged 6-16 years, were enrolled in this study, with 20 healthy subjects matched for age, gender and IQ serving as the healthy controls. The patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Revision (DSM-5). All the subjects were assessed with Golden Stroop test and emotional Stroop test to evaluate their response inhibition and emotional responding. RESULTS: In Golden Stroop test, the interference scores (IGs) of errors and reaction time both differed significantly among the groups ( < 0.05), and were the highest in patients with ADHD only. In emotional Stroop test, the mean reaction time (MRT) showed significant differences among the groups ( < 0.05); the MRT of positive- congruent trials in ADHD with comorbid DICCD group was shorter than that in ADHD group but longer than that in group DICCD; the MRT in the 3 case groups were all longer than that in the control group. The MRT of both positive-incongruent trials and negative-congruent trials in ADHD with comorbid DICCD group and DICCD group was shorter than that in ADHD group but longer than that in the control group. The MRT of negative- incongruent trials in DICCD group was shorter than that in ADHD group and ADHD with comorbid DICCD group but longer than that in the control group. CONCLUSIONS The response inhibition deficit and abnormal emotional responding are the core symptoms of ADHD. Bias emotional stimuli may render response inhibitory dysfunction in patients with DICCD with callous-unemotional traits of emotional responding disorder, especially in dealing with negative emotional trials, while the comorbidity of ADHD and DICCD tends to have the emotional response trait of DICCD.
Adolescent ; Attention Deficit Disorder with Hyperactivity ; diagnosis ; physiopathology ; Attention Deficit and Disruptive Behavior Disorders ; diagnosis ; physiopathology ; Case-Control Studies ; Child ; Comorbidity ; Diagnostic and Statistical Manual of Mental Disorders ; Emotions ; Humans ; Reaction Time ; Stroop Test