Effects of acute-phase monotherapy and combination therapy on quality of life in patients with depressive disorders / 四川精神卫生

BackgroundThe treatment of patients with depressive disorders is short of targeted outcome assessment. As a secondary outcome that is guided by patient values， quality of life is thus of relatively high evaluative value. In China， there exists a lack of large sample prospective cohort studies evaluating the effect of different treatment protocols on quality of life in patients with acute depressive disorder. ObjectiveTo explore the effects of monotherapy and combination therapy on the quality of life of patients with depressive disorder in acute phase， so as to provide references for optimizing the outcome of treatment for such patients. MethodsA prospective follow-up cohort study from August 24， 2020 to November 29， 2021 was conducted， including 1 330 patients from 22 hospitals across 18 cities in China. All these patients met the diagnostic criteria for depressive episodes， recurrent depressive disorder from the Diagnostic and Statistical Manual of Mental Disorders， fifth edition （DSM-5）. Patients were divided into monotherapy group （n=969） and combination therapy group （n=361） according to the acute phase treatment protocol. At baseline， the end of the first half month as well as the 1st， 2nd， 3rd， 6th， 9th and 12th months of treatment， patients were assessed with Inventory of Depressive Symptomatology Self-report （IDS-SR30）， Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form （Q-LES-Q-SF）， Concise Health Risk Tracking Scale （CHRT） and Siehan Disability Scale （SDS）. Frequency， Intensity， and Burden of Side Effects Rating （FIBSER） was adopted for assessment at each visit time point of treatment. Spearman correlation analysis was adopted to examine the correlation of quality of life with suicide risk， adverse reactions and impaired social functioning among patients. ResultsAt the end of three months of treatment， the Q-LES-Q-SF score of monotherapy group was higher than that of combination therapy group， and the difference was statistically significant （Z=2.008， P<0.05）. The time effects of both treatment protocols possessed statistical significance （F=111.393， P<0.01）. At the end of three months of treatment， the Q-LES-Q-SF score was negatively correlated with CHRT and SDS scores， respectively， in both monotherapy group and combination treatment group （r=-0.660， -0.712， -0.634， -0.718， P<0.01）. ConclusionBoth monotherapy and combination therapy can facilitate the improvement of the life quality of patients with acute depressive disorder， but monotherapy may achieve better than the combination therapy in this aspect. ［Funded by The National Key Research and Development Program of China "Research on the Prevention and Control of Major Chronic Non-communicable Diseases" （number， 2017YFC1311101）］

Psychological distress of patients with retinal detachment and its related factors / 现代临床护理

Objective To evaluate the psychological distress of patients with retinal detachment and analyze its causes and related factors. Method We adopted a general information questionnaire and psychological distress thermometer (DT) to do a cross-sectional survey among patients undergoing retinal detachment reduction surgery between February 2016 and May 2017 in West China Hospital in Sichuan Province. Results The average score of psychological pain in the patients with retinal detachment was 4.3 ±2.0. Significant psychological distress was observed in 83 cases, which accounted for 67.5% (DT score was greater than 4). The top 5 factors for the psychological distress caused by the retinal detachment were edema, physical activity restricted, worry, bathing/dressing, and sleep problem. Multivariate linear regression analysis showed that age, sports, time of retinal detachment and combination of chronic diseases had an effect on psychological pain score (all P＜0.05). Conclusions The psychological distress of patients treated in retinal detachment reduction surgery is severe, and the physical problems are the main causes of psychological distress. In order to effectively prevent the emergence of psychological problems, psychological intervention measures should be taken in patients at young age, long time of retinal detachment, doing sports, and combination with other chronic diseases.

Valproic Acid Combined With Postcardiac Arrest Hypothermic-Targeted Temperature Management Prevents Delayed Seizures and Improves Survival in a Rat Cardiac Arrest Model.

OBJECTIVES: High-dose valproic acid in combination with hypothermic-targeted temperature management has been reported to synergistically improve neurologic outcomes after cardiac arrest. This study investigated the potential synergistic mechanisms. DESIGN: Prospective, randomized, experimental study. SETTING: University research institution. SUBJECTS: Male Long Evans rats. INTERVENTION: Rats resuscitated from asphyxial cardiac arrest were randomized to one of the three groups: normothermic-targeted temperature management (37°C ± 1°C), hypothermic-targeted temperature management (33° ± 1° × 24 hr + placebo infusion), hypothermic-targeted temperature management plus high-dose valproic acid (300 mg/kg IV × 1 initiated 5 min post return of spontaneous circulation and infused over 20 min) (hypothermic-targeted temperature management + valproic acid). MEASUREMENTS AND MAIN RESULTS: Seventy-two-hour survival was significantly greater with hypothermic-targeted temperature management + valproic acid, compared to hypothermic-targeted temperature management and normothermic-targeted temperature management (p < 0.05). Survival with good neurologic function, neurodegeneration, expression of HSP70, phosphorylation of Akt and Erk1/2 were not significantly different between hypothermic-targeted temperature management and hypothermic-targeted temperature management + valproic acid. The prevalence of seizures during the first 72-hour postcardiac arrest was significantly lower with hypothermic-targeted temperature management + valproic acid compared to hypothermic-targeted temperature management and normothermic-targeted temperature management (p = 0.01). CONCLUSIONS: High-dose valproic acid combined with hypothermic-targeted temperature management prevents postcardiac arrest seizures and improves survival. It remains to be determined if the mechanism of seizure prevention is through the antiepileptic effect of valproic acid or direct neuroprotection. Overall, the combination of high-dose valproic acid and hypothermic-targeted temperature management remains a promising strategy to improve cardiac arrest outcomes.

Combined intra- and post-cardiac arrest hypothermic-targeted temperature management in a rat model of asphyxial cardiac arrest improves survival and neurologic outcome compared to either strategy alone.

AIM: Post-cardiac arrest hypothermic-targeted temperature management (HTTM) improves outcomes in preclinical cardiac arrest studies. However, inadequate understanding of the mechanisms and therapeutic windows remains a barrier to optimization. We tested the hypothesis that combined intra- and post-cardiac arrest HTTM provides a synergistic outcome benefit compared to either strategy alone. METHODS: Rats subjected to 8-min asphyxial cardiac arrest were block randomized to 4 treatment groups (n=12/group): NTTM) normothermic-targeted temperature management; 1-24 HTTM) HTTM initiated 1h post-ROSC and maintained for 24h; Intra-1 HTTM) HTTM initiated at CPR onset and maintained for 1h; and Intra-24 HTTM) HTTM initiated at CPR onset and maintained for 24h. HTTM was induced by nasopharyngeal cooling and maintained using an automated temperature regulation system. Target temperature range was 36.5-37.5°C for NTTM and 32.0-34.0°C for HTTM. Post-arrest neurologic function score (NFS) was measured daily, and rats surviving 72h were euthanized for histological analysis of neurodegeneration. RESULTS: Target brain temperature was achieved 7.8±3.3min after initiating intra-arrest cooling. The survival rate was 42%, 50%, 50%, and 92% in the NTTM, 1-24 HTTM, Intra-1 HTTM, and Intra-24 HTTM groups, respectively (p<0.05, Intra-24 group vs. all other groups). The rate of survival with good neurologic function (NFS≥450) was 33% in the Intra-24 HTTM group vs. 0% in all other groups (mid p<0.05). Hippocampal CA1 sector neurodegeneration was significantly reduced in the Intra-24 HTTM group compared to all other groups (p<0.05). CONCLUSION: Combined intra- and post-cardiac arrest HTTM has greater outcome benefits than either strategy alone.

Optimization of the Formulation of Dimemorfan Phosphate Tablets by Orthogonal Test / 中国药房

OBJECTIVE:To optimize the formulation of Dimemorfan phosphate tablets. METHODS:Using 60 min dissolution rate of dimemorfan phosphate as index,L9(34) orthogonal test was used to optimize the amount of starch,microcrystalline cellu-lose,croscarmellose sodium and concentration of HPMC E5 solution. The friability,hardness,60 min dissolution rate and main component were detected. The similarity of dissolution curves of Dimemorfan phosphate tablets was compared with that of imported tablets in 0.1 mol/L hydrochloric acid,pH 6.8 phosphate buffer,water and pH 4.0 acetate buffer. RESULTS:The optimized formu-lation of Dimemorfan phosphate tablet(1 000 tablets)was composed of dimemorfan phosphate 10 g,starch 60 g,microcrystalline cellulose 40 g,10% HPMC E5 solution and croscarmellose sodium 25 g. The friability,hardness,60 min dissolution rate and main component of 3 batches of Dimemorfan phosphate tablets prepared by optimized prescription were 0.42%-0.58%,9.8-10.5 kg,94.89%-96.21% and 99.21%-99.52%,respectively. In 4 dissolution mediums,similar factors f2 of dissolution curves between prepared tablets and imported tablets were above 50. CONCLUSIONS:Dimemorfan phosphate tablets were prepared successfully. The optimized formulation is rational. The dissolution behavior of prepared tablets is similar to that of imported tablets in vitro.

New methods for cloning large gene clusters based on CRISPR/cas9 / 生物工程学报

Cloning of large genomic sequences is an enabling technology in synthetic biology. To obtain large gene fragments, traditional cloning methods are faced with various defects, for instance, random library cloning relies always on high-throughput screening. It is difficult to get gene fragments more than 10 kb by PCR amplification. Assembly of small fragments is labor intensive with high mutation rates. It is difficult to find suitable cleavage sites on the fragment ends by restriction endonuclease. Recently genome-wide editing creates a new high-performance large fragments cloning methods. For example, CRISPR/cas9 system can identify and cut 20 bp nucleic acid sequences recognition sites used to obtain any desired gene fragments; if combined with Gibson or transformation associated recombination (TAR) assembly technology, these methods can efficiently clone large fragments. This article introduces large fragments cloning technology by classification, then proposes the choice criteria of methods for cloning gene fragments of different sizes.

Function of lamins in the mechanism of cell aging / 中国病理生理杂志

Cell aging,the fundamental unit of biological decay,is responsible for senile disease. With the development of research,the mechanism of cell aging has been investigated in molecular level. Two hypotheses have emerged to explain the reason that lamins contribute to cell aging,one is the mechanical stress hypothesis,the other is the gene expression hypothesis. The latter proposes that mutations in A-type lamins lead to abnormal tissue-specific gene regulation. In recent years,the molecular mechanisms of lamins causing cell aging primarily include gene mutation,Zmpste24 mutation,CAAX mutation and other mutations. These mutations in the gene that encode nuclear lamins cause nuclear lamina damage directly and result in cell aging,which have been associated with several degenerative disorders.