OBJECTIVE To provide a detailed report and interpretation of the method and results for determining the weights of the technical indicators from the “multi-dimensional and multi-criteria comprehensive evaluation index system （first edition）” stated in Guideline for Multi-dimensional and Multi-criteria Comprehensive Evaluation of Chinese Patent Medicine. METHODS Normalization calculations were performed on the comprehensive weight values calculated by the analytic hierarchy process and expert weighting method to obtain the objective weights of the indicators. RESULTS The weight results of the six primary dimensions in the current comprehensive evaluation indicator system of Chinese patent medicine showed effectiveness dimension＞ safety dimension＞standard dimension＞application dimension＞scientific dimension＞economic dimension， with weight values of 0.281 0， 0.268 5， 0.195 8， 0.107 3， 0.096 1 and 0.051 3 respectively， consistent with the results of most researches currently. CONCLUSIONS The process of weight determination in this indicator system is scientifically reasonable， with clear methods and clear interpretations， and is worthy of further optimization and widespread application.

In order to develop a more effective drug for dry eye disease, the preparation of lifitegrast eye drops was carried out, and the safety and efficacy of lifitegrast eye drops in vitro and in vivo were investigated. First the method for the determination of lifitegrast content was established, and then the composition and preparation process of the preparation were determined by literature review and single factor experiment. Finally, the safety of lifitegrast eye drops was evaluated by Draize eye irritation test and HE staining, and the therapeutic efficacy was evaluated by Schirmer test and ELISA test. The results showed that the final prescription of lifitegrast eye drops consisted of 5% lifitegrast, 0.4% sodium chloride, 0.3%−0.4% anhydrous disodium hydrogen phosphate, 0.3% sodium thiosulfate pentahydrate and 0.3% sodium hydroxide. The appearance of lifitegrast eye drops was transparent and slightly brownish yellow solution, the pH was7.75±0.05, the osmotic pressure was in the range of 200−330 mOsmol/kg and it had good stability at 60℃ for 3 months. There was no significant difference in irritation study compared with normal saline. Schirmer test showed that tear secretion was increased and the expression of inflammatory factors IL-6, IL-1β and TNF-α in tears were significantly decreased after treatment with lifitegrast eye drops and compared to the commercially available emulsion cyclosporine eye drops, it takes effect faster. The above results indicate that lifitegrast eye drops are simple to prepare and stable, which is a better choice for the rapid treatment of dry eye disease.

Objective To analyze the influence of medication compliance of chronic type 2 diabetes management patients on disease control in two communities in Kunming.Methods A total of 138 patients with type 2 diabetes who were included in chronic disease management in Guandu and Xiaobanqiao communities of Kunming were selected from December 2021 to September 2022.Basic information collection and HbAlc and other related tests were improved.A questionnaire survey of 8-item Morisliy medication adherence scale(MMAS-8)was conducted to analyze the levels of HbAlc and other indexes of three groups with high(group A),medium(group B),and low(group C)adherence,and to conduct statistical analysis.Results Group A accounted for 22.5%,group B for 44.9%,and group C for 32.6%.There were significance differences in urinary albumin creatinine ratio(UACR),HbA1c and blood creatinine among the three groups(P<0.05).The levels of UACR,HbAlc and serum creatinine in group A were lower than those in group B and group C,and there was a negative correlation between UACR,HbAlc and serum creatinine and medication compliance rate(P<0.05).Conclusion In the Guandu Community and Xiaobanqiao community of Kunming,only 22.5%of patients with chronic type 2 diabetes had high medication compliance.The higher the compliance,the lower the level of UACR,HbAlc and serum creatinine,there is a correlation between the two,suggesting that medication compliance should be regarded as one of the key points in the management of chronic diabetes mellitus in the community,and the intervention of patients'medication compliance should be strengthened.

Dexmedetomidine,which is an α2 adrenergic receptor agonist with sedative,analgesic,anxiolytic and anti-sympathetic effects,has become a widely used drug in clinical anesthesia and intensive care unit(ICU).Compared with other drugs in the department of anesthesiology,dexmedetomidine has no obvious respiratory depression and no obvious hemodynamic changes,and can significantly reduce the dosage of sedative and analgesic drugs when combined with other anesthetics.In clinical applications,dexmedetomidine has been found to induce a sedative response that is associated with rapid arousal.Dexmedetomidine is traditionally thought to act through α2 adrenergic receptors to lower blood pressure,dilate blood vessels and lower heart rate,but it is unclear how it affects neural circuits in the brain.In recent years,there has been an increasing number of studies on the mechanism of action of dexmedetomidine,which has confirmed that the ventrolateral preoptic nucleus(VLPO),locus coeruleus(LC)and ventral tegmental area(VTA)of the hypothalamus are involved in the sedation mediated by dexmedetomidine,the dorsal root ganglion(DRG)and superior cervical ganglion(SCG)are involved in dexmedetomidine-mediated analgesia,and the hypothalamic preoptic area(PO)and hypothalamic paraventricular nucleus(PVN)are involved in the changes in body temperature and water-electrolyte balance mediated by dexmedetomidine,providing a new direction for understanding the mechanism of dexmedetomidine in the central nervous system.

Acute respiratory distress syndrome(ARDS)is a severe critical respiratory disease characterized by refractory hypoxemia,which is caused by intrapulmonary and extrapulmonary factors.It has a rapid onset,and high morbidity and mortality.With the global prevalence and mutation of respiratory viruses,the diagnosis and treatment of ARDS have become more complicated,requiring exploration into the molecular mechanisms and effective therapeutic methods of the occurrence and development of ARDS in clinical practice.Researchers have found that the pathogenesis of ARDS involves the interaction of multiple factors,including imbalances in inflammatory responses and redox reactions,dysregulation of endothelial cells,disruption of alveolar-capillary barrier and abnormalities in coagulation function.Although advancements in molecular biology techniques such as genomics and proteomics have provided new insights into the pathogenesis of ARDS,there is still a lack of early diagnostic biomarker and effective drugs targeted for ARDS.At present,more comprehensive and in-depth basic and clinical research is still needed.Increasing evidence suggests that transient receptor potential vanilloid-1(TRPV1),also known as the capsaicin receptor,plays a crucial role in respiratory system diseases.TRPV1 is widely distributed in the upper respiratory tract,airway smooth muscle,alveoli and pulmonary blood vessels,participating in mediating airway dilation and constriction,cough reflex,and release of inflammatory mediators related to inflammation and pain,as well as sensing and transmitting various biological signals related to temperature,chemical substances and mechanical stress stimuli in the respiratory system.The widespread distribution and diverse physiological functions of TRPV1 make it a research hotspot in the occurrence and development of respiratory system diseases such as pneumonia,pulmonary edema,cough,asthma and acute lung injury.This article reviews the correlation and molecular mechanisms between ARDS caused by sepsis,traumatic brain injury and respiratory viruses with TRPV1,aiming to summarize the positive effects of regulating TRPV1 expression on the pathogenesis of ARDS and provide reference for strengthening early diagnosis and effective intervention measures for ARDS.

Objective To evaluate the risk of bias and reporting quality in randomized controlled trials(RCTs)of the Chinese medicine injection for acute cerebral infarction in the last five years.Methods RCTs literature on Chinese medicine injection in the treatment of acute cerebral infarction was systematically searched in CNKI,Wanfang Data,VIP,China Biology Medicine Database(CBM),PubMed,Embase and Cochrane Library from April 20,2018 to April 20,2023.The risk of bias and reporting quality of included RCTs were evaluated using the Cochrane Risk of Bias Tool(ROB 1.0)and CONSORT-CHM Formulas 2017,respectively.Results A total of 4 301 articles were retrieved,and 408 RCTs were included according to inclusion and exclusion criteria.The ROB evaluation results showed that the the majority of studies were rated as having an unclear risk of bias due to the lack of reporting on allocation concealment,blind method,trial registration information,and funding sources.The evaluation results of CONSORT-CHM Formulas 2017 showed that the number of reported papers of 17 items was greater than or equal to 50%,and the number of reported papers of 25 items was less than 10%,and most of the RCTs did not show the characteristics of TCM syndrome differentiation and treatment.Conclusion The quality of Chinese medicine injection in the treatment of acute cerebral infarction RCTs is generally low.It is recommended that researchers refer to the methodology design of RCTs and international reporting standards,improve the trial design,standardize the trial report,and highlight the characteristics of TCM syndrome differentiation and treatment.

ObjectiveTo investigate the identification of kidney Yang deficiency syndrome of patients with osteoporosis（OP）， and to form the clinical syndrome identification rules of traditional Chinese medicine（TCM）. MethodBasic information， etiology， clinical symptoms and other characteristics of 982 OP patients were included， and statistical tests were used to screen the variables associated with kidney Yang deficiency syndrome. Taking the decision tree as the base model， bootstrap aggregation algorithm（Bagging algorithm） was utilized to establish the classification model of kidney Yang deficiency syndrome in OP， generating numerous rules and removing redundancy. Combining least absolute shrinkage and selection operator（LASSO） regression to screen key rules and integrate them to construct an identification model， achieving the identification of kidney Yang deficiency syndrome in OP patients. ResultEighteen key identification rules were screened out， and of these， where 11 rules with regression coefficients>0 correlated positively with the kidney Yang deficiency syndrome， the rule with the highest coefficient was chilliness（present）&feverish sensation over the palm and sole（absent）. The other 7 rules with regression coefficients<0 correlated negatively with the syndrome， the rule with the lowest coefficient was reddish tongue（present）&diarrhea（absent）&deficiency of endowment（absent）. According to the regression coefficients of each key rule， variables with importance>0.2 were ranked as chilliness， reddish tongue， feverish sensation over the palm and sole， cold limbs， clear urine， diarrhea， deficiency of endowment， prolonged illness. The results of the partial dependence analysis of the identification model showed that compared to OP patients without chilliness， those with chilliness（present） had a 0.266 8 higher probability of being identified as having kidney Yang deficiency syndrome， indicating that this variable had the highest impact on identification of the syndrome. Similarly， compared to OP patients without reddish tongue， those with reddish tongue had a 0.141 9 lower probability of being identified as having kidney Yang deficiency syndrome， indicating that this variable had the highest impact on identifying non-kidney Yang deficiency syndrome. The accuracy， sensitivity， specificity and area under receiver operating characteristic curve（AUC） of the established kidney Yang deficiency syndrome identification model in the test set were 0.865 9， 0.853 7， 0.872 0 and 0.931 5， respectively. ConclusionA precise identification model of OP kidney Yang deficiency syndrome is conducted basing on the rule ensemble method of Bagging combining LASSO regression， and the screened key rules can explain the identification process of kidney Yang deficiency syndrome. In this research， according to the regression coefficients of rules， the importance and partial dependence of variables， combined with the thinking of TCM， the influence of patient characteristics on the identification of syndromes is described， so as to reveal the primary and secondary syndromes of identification and assist the clinical identification of kidney Yang deficiency syndrome.

A growing number of studies have identified sex differences in response to general anesthesia; however, the underlying neural mechanisms are unclear. The medial preoptic area (MPA), an important sexually dimorphic structure and a critical hub for regulating consciousness transition, is enriched with estrogen receptor alpha (ERα), particularly in neuronal clusters that participate in regulating sleep. We found that male mice were more sensitive to sevoflurane. Pharmacological inhibition of ERα in the MPA abolished the sex differences in sevoflurane anesthesia, in particular by extending the induction time and facilitating emergence in males but not in females. Suppression of ERα in vitro inhibited GABAergic and glutamatergic neurons of the MPA in males but not in females. Furthermore, ERα knockdown in GABAergic neurons of the male MPA was sufficient to eliminate sex differences during sevoflurane anesthesia. Collectively, MPA ERα positively regulates the activity of MPA GABAergic neurons in males but not in females, which contributes to the sex difference of mice in sevoflurane anesthesia.
Anesthesia ; Animals ; Estrogen Receptor alpha/metabolism* ; Female ; Male ; Mice ; Preoptic Area ; Sevoflurane/pharmacology* ; Sex Characteristics

Post-traumatic stress disorder(PTSD) caused by various natural disasters and man-made events has gradually become the highlight of neuroscientists. Sleep disorders after PTSD can impair the effect of treatment and affect the patient's prognosis. In addition, treatment for sleep problems can be effective in improving outcomes for people with PTSD, which indicates that it is significant to pay attention to sleep disorders after PTSD. However, current studies have focused more on the incidence of PTSD and severity of related symptoms after a traumatic event, and less on the occurrence and mechanism of sleep disorders after PTSD. A number of articles on stress and sleep disorders published in recent years provide reliable clues to understand the probable mechanisms of sleep disorders after PTSD. After summarizing the latest research results, this article finds that the occurrence of sleep disorder after PTSD may be related to the changes of connectivity between insula, hippocampus and medial-prefrontal cortex. Apart from that, decline in the mean phase difference of slow spindles in PTSD patients may reflect pathological changes in the thalamic cortical circuit, which may contribute to the objective diagnosis of PTSD and the development of sleep-focused interventions. This paper provides a systematic review of changes in sleep characteristics and possible neural circuitry mechanisms after PTSD from clinical and basic perspectives, which may provide potential directions for future researches on the pathological mechanism of sleep disorders after PTSD and screening novel intervention targets.

The lateral hypothalamic area (LHA) plays a pivotal role in regulating consciousness transition, in which orexinergic neurons, GABAergic neurons, and melanin-concentrating hormone neurons are involved. Glutamatergic neurons have a large population in the LHA, but their anesthesia-related effect has not been explored. Here, we found that genetic ablation of LHA glutamatergic neurons shortened the induction time and prolonged the recovery time of isoflurane anesthesia in mice. In contrast, chemogenetic activation of LHA glutamatergic neurons increased the time to anesthesia and decreased the time to recovery. Optogenetic activation of LHA glutamatergic neurons during the maintenance of anesthesia reduced the burst suppression pattern of the electroencephalogram (EEG) and shifted EEG features to an arousal pattern. Photostimulation of LHA glutamatergic projections to the lateral habenula (LHb) also facilitated the emergence from anesthesia and the transition of anesthesia depth to a lighter level. Collectively, LHA glutamatergic neurons and their projections to the LHb regulate anesthetic potency and EEG features.