The methodological framework for interventional clinical research of Chinese medicine （CM） under the research mode of syndrome dominating disease provides a set of technical principles and methods to design， evaluate， and implement of this kind. It consists of three main parts including general principles， research points and key design elements， with a total of 25 items. This methodological framework proposes implementing requirements and recommendations in a variety of aspects， including basic norms to be followed in relevant studies， perspectives for selecting research topics， as well as the technological details on study population （P）， intervention （I） and comparison（C）， outcome measurement （O）， time frame （T） of treatment and follow-up， sample orientation （prospective versus retrospective）， study design （S） format and type. To provide practical guidance for future studies， this article clearly explains each items of the methodological framework through some supportive cases.

Abstract: It is well-known that crystal form of a drug is a key factor impacting the physicochemical properties of the drug, which in turn affects its in vivo efficacy, safety and stability. The study on crystal forms of solid-state drugs is crucial for drug quality control, selection of production process and evaluation of clinical efficacy. The combination of chemometric and analytical techniques exhibited its great ability to analyze a large amount of multidimensional data, providing the possibility for quantification of trace amount of crystals (< 1%). Meanwhile, using the process analytical technology (PAT) to monitor the crystal content real-time during prescription preparation process can further realize the control on formulation quality and serve as a core technology to support the patent protection of crystalline forms. In this review, the combined application of crystal analytical techniques and chemometric methods for the quantitative analysis of trace crystals were summarized, aiming to provide guidance for the manufacturing of pharmaceutical preparations and their quality control.

OBJECTIVE To observe the changes of cardiac function,local inflammation level and macrophage M2 polarization in mice with acute myocardial infarction(AMI after electroacupuncture preconditioning at the Neiguan point,and to explore the possible mechanisms from the perspective of regulating the DNA-PK/Rictor/Myc signaling pathway.METHODS Male C57BL/6J mice were randomly divided into sham group,model group and electroacupuncture group,with 10 mice in each group.The electroacupuncture group received bilateral electroacupuncture interventions at the Neiguan points,sparse-dense wave,2/15 Hz,1 mA,20 min/time,once a day for 3 consecutive days,and AMI models were performed 0.5 h after the electroacupuncture interventions.The myocardial ischemia model was prepared by ligating the left anterior descending branch.Echocardiography was used to detect cardiac ejection frac-tion(EF and fractional shortening(FS to evaluate cardiac function;HE and TUNEL staining were used to observe the pathological morphology of myocardium and apoptosis of cardiomyocytes,and immunohistochemistry and ELISA were used to detect IL-1β,TNF-α and NLRP3 in infarcted myocardium and peripheral blood to evaluate the level of inflammation;flow cytometry was used to detect cardiac macrophage polarization status,and Western blot method to detect the protein expression levels of DNA-PK,p-DNA-PK,Rictor and Myc in infarcted myocardium.RESULTS Compared with the sham group,the model group showed significantly lower EF and FS(P<0.000 1,significant inflammatory cell infiltration,significantly higher cardiomyocyte apoptotic index(P<0.001,up-regulated expression of IL-1β,NLRP3 and TNF-α in the myocardium and serum(P<0.01,P<0.001,a significant increase in the percentage of macrophages(P<0.001,a decrease in the percentage of cardiac M2-type macrophages(P<0.000 1,and a significant decrease in the expression levels of p-DNA-PK,Rictor and Myc proteins in myocardium(P<0.05,P<0.000 1.Compared with the model group,EF and FS were significantly higher in the electroacupuncture group(P<0.000 1,inflammatory cell infiltration was re-duced,cardiomyocyte apoptotic index was decreased(P<0.01,and the expression of IL-1β,NLRP3 and TNF-α was down-regula-ted in myocardium and serum(P<0.05,P<0.01,P<0.001;the macrophage percentage was decreased(P<0.05,cardiac M2-type macrophage percentage was increased(P<0.01,and p-DNA-PK,Rictor and Myc protein expression was enhanced in myocardium(P<0.05,P<0.01,P<0.000 1.CONCLUSION Electroacupuncture preconditioning may promote macrophage M2 polarization,attenuate local inflammation,and reduce cardiomyocyte apoptosis by modulating the DNA-PK/Rictor/Myc signaling pathway,thus im-proving cardiac function and achieving myocardial protective effects.

【Objective】 To investigate the current state of infant responsive caregiving and to analyze its correlation with caregiver parenting confidence, in order to provide theoretical basis for improving the level of responsive care for infants and young children. 【Methods】 A cross-sectional survey was conducted from October 2022 to February 2023 to select 1 028 infants and young children under 3 years old who underwent health examinations in the Department of Child Healthcare. Participants completed a general data questionnaire, the Karitane Parenting Confidence Scale, and the Infant Responsive Caregiving Scale. Hierarchical multiple linear regression analysis was used to investigate the related influencing factors of infant responsive care and to analyze the relationship between caregiver parenting confidence and responsive caregiving. 【Results】 The level of responsive caregiving was found to be associated with various factors such as infant age(χ²=21.196), mode of pregnancy(Z=-2.072), history of pregnancy protection during pregnancy(Z=-4.713), history of pregnancy complications (Z=-4.504), gestational week at birth(χ²=41.358), small for term infants(Z=-3.497), neonatal intracranial hemorrhage(Z=-5.425), neonatal hyperbilirubinemia(Z=-2.184), maternal education level(χ²=9.419), family income(χ²=11.211) as well as type of family (χ²=15.360)(P < 0.05). Additionally, a significant correlation was observed between parenting confidence and responsive caregiving(r=0.421,P<0.001). Hierarchical multiple linear regression analysis revealed that caregiver parenting confidence had a significant positive effect on the level of responsive caregiving (B=0.623, P<0.05), even after controlling for the effect of demographic factors. 【Conclusion】 The level of infant responsive caregiving is influenced by caregiver parenting confidence, and increasing caregiver parenting confidence can effectively improve the quality of responsive caregiving for infants and young children.

AIM: To analyze changes in the ocular surface parameters of keratoconus after long-term wearing of rigid gas permeable contact lens(RGPCL).METHODS:Prospective case study. A total of 113 keratoconus patients(213 eyes)fitted with RGPCL in the optometry center of Gansu Provincial Hospital from January 2018 to January 2022 were included. They were divided into three groups according to the severity of keratoconus, including 42 cases(80 eyes)in mild keratoconus group, 54 cases(102 eyes)in moderate keratoconus group and 17 cases(31 eyes)in severe keratoconus group. Furthermore, the non-invasive tear break-up time(NIBUT), non-invasive tear meniscus height(NITMH), red eye index, lipid layer thickness, fluorescent corneal staining, meibomian gland secretory function, Schirmer I test and ocular surface disease index(OSDI)scores were observed by Keratograph analyzer before and after wearing RGPCL for 1 wk, 1, 3, 6, 12 mo, respectively.RESULTS: There were no statistical significance in the age, NIBUT, NITMH, lipid layer thickness, meibomian gland secretory function and Schirmer I test among the three groups(P>0.05), while there were statistical significance in the sphere, cylinder, spherical equivalent, best corrected visual acuity(BCVA), non-contact intraocular pressure(IOPNCT), anterior, posterior corneal surface Kmax, corneal surface thickness at the thinnest point, eye redness index, fluorescent corneal staining, and OSDI(P<0.05). In the mild keratoconus group, NIBUT had statistical differences at 3, 6 and 12 mo after wearing RGPCL(P<0.05), NITMH had statistical differences in 6 and 12 mo(P<0.05), the eye redness index, fluorescent corneal staining and OSDI scores had statistical differences in 1 wk and 1 mo(P<0.05), and lipid layer thickness and meibomian gland secretory function had statistical differences in 12 mo(P<0.05). In the moderate keratoconus group, there were statistical differences in NIBUT at 6 and 12 mo after wearing lenses(P<0.05); there were statistical differences in the NITMH, lipid layer thickness and meibomian secretory function at 12 mo after wearing lens(P<0.05); there were statistical differences in the eye redness index at 1 wk, 1 and 3 mo after wearing RGPCL(P<0.05); there were statistical differences in the fluorescent corneal staining at 1 wk after wearing RGPCL(P<0.05); there were statistical differences in the OSDI at 1 wk and 1 mo after wearing RGPCL(P<0.05). In the severe keratoconus group, there were statistical differences in the NIBUT, NITMH and eye redness index at 1 wk, 1, 3, 6 and 12 mo after wearing RGPCL(P<0.05); there were statistical differences in the lipid layer thickness at 6,12 mo after wearing RGPCL(P<0.05); there were statistical differences in the fluorescent corneal staining and OSDI scores at 1 wk, 6 and 12 mo after wearing RGPCL(P<0.05); there were statistical differences in the meibomian secretory function at 6 and 12 mo after wearing RGPCL(P<0.05); and there were statistical differences in the Schirmer I test at 12 mo after wearing RGPCL(P<0.05).CONCLUSION: Long-term wearing of RGPCL can affect the ocular surface microcirculation in keratoconus patients, thus making differences in patients subjective. However, it has no significant impact on the visual quality of patients. Therefore, long-term wearing of RGPCL is safely to control the progression of keratoconus.

Vascular dementia (VaD) is the second commonest type of dementia which lacks of efficient treatments currently. Neuroinflammation as a prominent pathological feature of VaD, is highly involved in the development of VaD. In order to verify the therapeutic potential of PDE1 inhibitors against VaD, the anti-neuroinflammation, memory and cognitive improvement were evaluated in vitro and in vivo by a potent and selective PDE1 inhibitor 4a. Also, the mechanism of 4a in ameliorating neuroinflammation and VaD was systematically explored. Furthermore, to optimize the drug-like properties of 4a, especially for metabolic stability, 15 derivatives were designed and synthesized. As a result, candidate 5f, with a potent IC₅₀ value of 4.5 nmol/L against PDE1C, high selectivity over PDEs, and remarkable metabolic stability, efficiently ameliorated neuron degeneration, cognition and memory impairment in VaD mice model by suppressing NF-κB transcription regulation and activating cAMP/CREB axis. These results further identified PDE1 inhibition could serve as a new therapeutic strategy for treatment of VaD.

Objective : To systematically evaluate the adherence to antiretroviral therapy among HIV/AIDS patients in China, so as to provided evidence-based insights into improving the efficacy of antiretroviral therapy. Methods: Publications pertaining to the adherence to antiretroviral therapy among HIV/AIDS patients in China were retrieved in CNKI, Wanfang Data, VIP, PubMed, and Cochrane Library from 2012 to 2022. A meta-analysis was performed using the software Stata 16.0. Sensitivity analysis was performed with the leave-one-out method, and the publication bias was evaluated using funnel plot and Begg's test. Results: A total of 1 171 publications were screened, and 33 publications were included in the final analysis, which covered 11 218 subjects in 19 study areas and included 18 high-quality publications and 15 medium-quality publications. Meta-analysis showed that the pooled adherence to antiretroviral therapy was 86.57% (95%CI: 86.01%-87.12%, P<0.05) among HIV/AIDS patients, and subgroup analysis showed high adherence among HIV/AIDS patients in eastern China (92.13%, 95%CI: 91.45%-92.82%). Sensitivity analysis showed the robustness of the meta-analysis results, and no publication bias was detected as revealed by the funnel plot and Begg's test (P>0.05). Conclusions The adherence to antiretroviral therapy is 86.01% to 87.12% among HIV/AIDS patients in China. Intensified health education and follow-up management is required among HIV/AIDS patients in China.

Objective To observe the role of tumor necrosis factor-α (TNF-α) and platelet-derived growth factor-B (PDGF-B) in kiwi fruit essence-mediated protection of radiation-induced lung injury (RILI) in rats. Methods 96 male healthy Sprague-Dawley rats were divided into normal control group, model group, and kiwi fruit essence treatment group(60 and 240 mg/kg) by the random number table method, with 24 animals in each group. The whole lungs underwent 6 MV X-ray irradiation (18 Gy) to induce RILI animal models in rats of the latter three groups. On the next day after irradiation, rats in the latter two groups were intragastrically administrated with 60 or 240 mg/kg kiwi fruit essence, once a day. The rats in the normal control and model groups were treated with 9 g/L sodium chloride solution. Eight rats in the latter three groups were randomly sacrificed on days 14, 28, and 56, while normal control rats were sacrificed on day 56 as the overall control. Blood samples were collected and separated. Serum concentrations of TNF-α and PDGF-B were detected using ELISA. The lung tissues were isolated for HE and Masson staining to evaluate alveolitis and pulmonary fibrosis (PF). The hydroxyproline (HYP) content in lung tissues was detected. The mRNA and protein expression of pulmonary TNF-α and PDGF-B were determined by quantitative real-time PCR and immunohistochemistry. Results Compared with the model group, treatment with 60 and 240 mg/kg kiwi fruit essence group significantly reduced alveolitis on days 14 and 28 as well as PF lesions on days 28 and 56. Compared with the normal control group, HYP content in the lung tissue of the model group increased on day 28 and day 56, while TNF-α and PDGF-B levels in the serum and lung tissues increased at each time point. Compared with the model group during the same period, 60 and 240 mg/kg kiwi fruit essence element treatment group reported the diminished levels of serum and pulmonary TNF-α on day 14 and day 28. Consistently, the lung tissue HYP content and serum and pulmonary PDGF-B levels on day 28 and day 56 were reduced. In addition, the above indicators in the 240 mg/kg kiwi fruit essence treatment group were lower than those for the 60 mg/kg kiwi fruit essence treatment group. Conclusion Kiwi fruit essence can alleviate RILI in rats, which is related to the down-regulation of TNF-α expression at the early stage and decreased PDGF-B level at the middle and late stages.
Animals ; Male ; Rats ; Fruit/metabolism* ; Lung/radiation effects* ; Lung Injury/prevention & control* ; Oils, Volatile ; Proto-Oncogene Proteins c-sis/metabolism* ; Pulmonary Fibrosis ; Rats, Sprague-Dawley ; Tumor Necrosis Factor-alpha/metabolism* ; Actinidia/chemistry*

Objective? To investigate the status of cancer-induced fatigue in patients with primary liver cancer (PLC) and its influencing factors. Methods? A total of 149 postoperative PLC patients undergoing surgical treatment during October 2015 to September 2017 in the Second Affiliated Hospital of Harbin Medical University were recruited by convenience sampling method. The general data questionnaire, Cancer-Related Fatigue Scale (CFS) and Social Support Rating Scale (SSRS) were used to investigate the patients. A total of 149 questionnaires were sent out and 120 valid questionnaires were collected. Results? The CFS score of the 120 postoperative PLC patients was (48.13±5.33). The difference in CFS scores of PLC patients with different education level, monthly income, medical expenses payment, duration of the disease, cognition of disease, chemotherapy and social support was statistically significant (P＜0.05). Multivariate linear regression analysis showed that the influencing factors of cancer-related fatigue in patients with PLC were medical expenses payment, duration of disease, cognition of disease, adjuvant chemotherapy and social support (P＜ 0.05). Conclusions? Cancer-related fatigue is a common problem in PLC patients and is affected by many factors. Clinicians need to combine with the actual situation of patients to develop more targeted individualized programs to alleviate the patient fatigue, improve patient social support, and further improve the quality of life of patients.

Objective To analyze the characteristics of early cognitive impairment in leukoaraiosis (LA) patients and fractional anisotropy (FA) changes by diffusion tensor imaging (DTI) in various regions of interest (ROIs), and explore the relationship between FA values and cognitive impairment. Methods A total of 38 chronic ischemic LA patients, admitted to our hospital from August 2015 to August 2016, and 20 healthy elderly controls were chosen in our study. Comprehensive assessment of cognitive functions, and MRI and DTI examinations were performed in subjects from these two groups. The cognitive functions, and FA values in ROIs were compared between the two groups;the FA values in ROIs of mild, moderate, and severe ischemic LA patients were compared. The correlations between FA values in ROIs and cognitive functions in LA patients were analyzed. Results As compared with the healthy control group, the patient group had significantly lower Mimi Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) scores, statistically longer time of Stroop test C, lower scores of verbal fluency test (VFT), digit span (DS)-inverted sequence, word similarity test in Chinese Revision of Wechsler Intelligence Scale for Children (WISC-CR), auditory verbal learning test (AVLT), clock drawing test and block testing, and significantly longer time of Trail Marking Test A (TMTA) and Stroop test B (P<0.05), suggesting that the overall cognitive function, executive function, memory, visual-spatial ability, information processing capability of LA patients decreased greatly. Significantly decreased FA values in bilateral anterior horn of lateral ventricle, left superior frontal gyrus, left inferior frontal gyrus, bilateral frontal orbital gyrus, right deep temporal lobe, right cingulate gyrus, and genu of corpus callosum in the LA patient group were noted as compared with those in the control group (P<0.05). In mild, moderate and severe LA patients, the FA values of these ROIs decreased in turn, with statistically significant differences (P<0.05). In the LA patient group, correlation analysis showed that the scores of auditory verbal learning test were positively correlated with FA values in the brain regions of left anterior horn of lateral ventricle, bilateral frontal orbital gyrus, deep white of right temporal lobe, right cingulate gyrus, and genu of corpus callosum (P<0.05), and negatively correlated with FA values in left inferior frontal gyrus (P<0.05); the scores of trail making test A were negatively related with FA values in right anterior horn of lateral ventricle (P<0.05); the Stroop test B scores were negatively correlated with FA values in deep white matter of the right temporal lobe (P<0.05); the Stroop test C scores were negatively related with FA values in left orbital frontal cortex, deep white of right temporal lobe, right cingulate gyrus, and genu of corpus callosu (P<0.05); and the block testing scores were positively related with FA values in left frontal orbital gyrus, right temporal lobe deep, and genu of corpus callosu (P<0.05). Conclusions The early cognitive impairment and decreased FA values are noted in LA patients. FA values are related to cognitive impairment. DTI contributes to diagnose early cognitive impairment in LA patients.