This study aims to investigate the effect of Chaijin Jieyu Anshen Formula on the neuroinflammation of rats with insomnia complicated with depression through the regulation of triggering receptor expressed on myeloid cells 2(TREM2)/complement protein C1q signaling pathway. Rats were randomly divided into a normal group, a model group, a positive drug group, as well as a high, medium, and low-dose groups of Chaijin Jieyu Anshen Formula, with 10 rats in each group. Except for the normal group, the other groups were injected with p-chlorophenylalanine and exposed to chronic unpredictable mild stress to establish the rat model of insomnia complicated with depression. The sucrose preference experiment, open field experiment, and water maze test were performed to evaluate the depression in rats. Enzyme-linked immunosorbent assay was employed to detect serum 5-hydroxytryptamine(5-HT), dopamine(DA), and norepinephrine(NE) levels. Hematoxylin and eosin staining and Nissl staining were used to observe the damage in nucleus accumbens neurons. Western blot and immunofluorescence were performed to detect TREM2, C1q, postsynaptic density 95(PSD-95), and synaptophysin 1(SYN1) expressions in rat nucleus accumbens, respectively. Golgi-Cox staining was utilized to observe the synaptic spine density of nucleus accumbens neurons. The results show that, compared with the model group, Chaijin Jieyu Anshen Formula can significantly increase the sucrose preference as well as the distance and number of voluntary activities, shorten the immobility time in forced swimming test and the successful incubation period of positioning navigation, and prolong the stay time of space exploration in the target quadrant test. The serum 5-HT, DA, and NE contents in the model group are significantly lower than those in the normal group, with the above contents significantly increased after the intervention of Chaijin Jieyu Anshen Formula. In addition, Chaijin Jieyu Anshen Formula can alleviate pathological damages such as swelling and loose arrangement of tissue cells in the nucleus accumbens, while increasing the Nissl body numbers. Chaijin Jieyu Anshen Formula can improve synaptic damage in the nucleus accumbens and increase the synaptic spine density. Compared to the normal group, the expression of C1q protein was significantly higher in the model group, while the expression of TREM2 protein was significantly lower. Compared to the model group, the intervention with Chaijin Jieyu Anshen Formula significantly downregulated the expression of C1q protein and significantly upregulated the expression of TREM2. Compared with the model group, the PSD-95 and SYN1 fluorescence intensity is significantly increased in the groups receiving different doses of Chaijin Jieyu Anshen Formula. In summary, Chaijin Jieyu Anshen Formula can reduce the C1q protein expression, relieve the TREM2 inhibition, and promote the synapse-related proteins PSD-95 and SNY1 expression. Chaijin Jieyu Anshen Formula improves synaptic injury of the nucleus accumbens neurons, thereby treating insomnia complicated with depression.
Animals ; Male ; Rats ; Nucleus Accumbens/metabolism* ; Drugs, Chinese Herbal/administration & dosage* ; Depression/complications* ; Membrane Glycoproteins/genetics* ; Rats, Sprague-Dawley ; Sleep Initiation and Maintenance Disorders/complications* ; Neurons/metabolism* ; Receptors, Immunologic/genetics* ; Signal Transduction/drug effects* ; Synapses/metabolism*

The present study analyzed the potential biomarkers of chronic obstructive pulmonary disease(COPD) with lung-Qi deficiency syndrome by non-targeted metabolomics and explored the biological basis of this syndrome. Blood samples of 96 COPD patients with lung-Qi deficiency syndrome(COPD with lung-Qi deficiency syndrome group) and 106 healthy people(healthy control group) were collected, and the metabolic profiles of both groups were analyzed by ultra-high performance liquid chromatography-quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS). Multivariate statistical analysis and differential metabolite screening were carried out by using Progenesis QI and Simca-P. Metabolic pathways were constructed through the MetaboAnalyst. Seven potential biomarkers, such as L-cystathionine, protoporphyrinogen Ⅸ, and citalopram aldehyde, were identified. Compared with the results in the healthy control group, the content of citalopram aldehyde, N1-methyl-2-pyridone-5-carboxamide, and 11β,17β-dihydroxy-4-androsten-3-one was significantly up-regulated, while that of the other four compounds such as L-cystathionine, dihydrotestosterone, protoporphyrinogen Ⅸ, and D-urobilinogen was down-regulated. These potential biomarkers involved six metabolic pathways, including cysteine and methionine metabolism, porphyrin and chlorophyll metabolism, drug metabolism of cytochrome P450, steroid hormone biosynthesis, glycine, serine, and threonine metabolism, and nicotinate and nicotinamide meta-bolism. This study is expected to provide a certain scientific basis for the research on traditional Chinese medicine syndrome of COPD with lung-Qi deficiency syndrome from the molecular biology level.
Aldehydes ; Biomarkers ; Chromatography, High Pressure Liquid ; Citalopram ; Cystathionine ; Humans ; Lung ; Metabolomics/methods* ; Pulmonary Disease, Chronic Obstructive

Objective: Systematically summarize the research progress of clinical trials of gastric cancer oncology drugs and the overview of marketed drugs in China from 2012 to 2021, providing data and decision-making evidence for relevant departments. Methods: Based on the registration database of the drug clinical trial registration and information disclosure platform of Food and Drug Administration of China and the data query system of domestic and imported drugs, the information on gastric cancer drug clinical trials, investigational drugs and marketed drugs from January 1, 2012 to December 31, 2021 was analyzed, and the differences between Chinese and foreign enterprises in terms of trial scope, trial phase, treatment lines and drug type, effect and mechanism studies were compared. Results: A total of 114 drug clinical trials related to gastric tumor were registered in China from 2012 to 2021, accounting for 3.7% (114/3 041) of all anticancer drug clinical trials in the same period, the registration number showed a significant growth rate after 2016 and reached its peak with 32 trials in 2020. Among them, 85 (74.6%, 85/114) trials were initiated by Chinese pharmaceutical enterprise. Compared with foreign pharmaceutical enterprise, Chinese pharmaceutical enterprise had higher rates of phase I trials (35.3% vs 6.9%, P=0.001), but the rate of international multicenter trials (11.9% vs 67.9%, P<0.001) was relatively low. There were 76 different drugs involved in relevant clinical trials, of which 65 (85.5%) were targeted drugs. For targeted drugs, HER2 is the most common one (14 types), followed by PD-1 and multi-target VEGER. In the past ten years, 3 of 4 marketed drugs for gastric cancer treatment were domestic and included in the national medical insurance directory. Conclusions: From 2012 to 2021, China has made some progress in drug research and development for gastric carcinoma. However, compared with the serious disease burden, it is still insufficient. Targeted strengthening of research and development of investment in many aspects of gastric cancer drugs, such as new target discovery, matured target excavating, combination drug development and early line therapy promotion, is the key work in the future, especially for domestic companies.
China ; Gastrointestinal Agents/therapeutic use* ; Gastrointestinal Neoplasms ; Humans ; Pharmaceutical Preparations ; United States ; United States Food and Drug Administration

Background:Transcranial alternating current stimulation (tACS) offers a new approach for adult patients with major depressive disorder (MDD).The study is to evaluate the efficacy and safety of tACS treating MDD.Methods:This is an 8-week,double-blind,randomized,placebo-controlled study.Ninety-two drug-naive patients with MDD aged 18 to 65 years will receive 20 daily 40-min,77.5-Hz,15-mA sessions of active or sham tACS targeting the forehead and both mastoid areas on weekdays for 4 consecutive weeks (week 4),following a 4-week observation period (week 8).The primary outcome is the remission rate defined as the 17-item Hamilton depression rating scale (HDRS-17) score ≤7 at week 8.Secondary outcomes are the rates of response at weeks 4 and 8 and rate of remission at week 4 based on HDRS-17,the proportion of participants having improvement in the clinical global impression-improvement,the change in HDRS-17 score (range,0-52,with higher scores indicating more depression) over the study,and variations of brain imaging and neurocognition from baseline to week 4.Safety will be assessed by vital signs at weeks 4 and 8,and adverse events will be collected during the entire study.Discussion:The tACS applied in this trial may have treatment effects on MDD with minimal side effects.

Objective: To investigate the effect and mechanism of Mailuoning Compound for treatment of early steroid-induced osteonecrosis of femoral head (SONFH) in rats by obturator nerve block. Method: 24 rats were injected with endotoxin 10 μg·kg^-1 through tail vein. After 24 hours, prednisolone acetate 20 mg·kg^-1 was given by intraperitoneal injection, once every 24 hours for 3 consecutive days. After successful modeling, the rats were randomly divided into the model group (n=12), the treatment group (n=12) and the normal control group (n=6). In the treatment group, 2 mL·kg^-1 of Mailuoning compound was injected into the obturator nerve from the 4th day, 3 times a week for 8 weeks. The arterial blood was collected from rats on the first day of the 9th week after model building to detect the content of blood lipid; the femoral head was taken to prepare the paraffin section, and the pathological changes of femoral head was observed and the changes of empty bone lacuna rate, bone trabecular area and bone lacuna area were quantitatively analyzed; The changes of bone morphogenetic proteins(BMPs),transforming growth factor-β₁(TGF-β₁),vascular endothelial cell growth factor(VEGF),and Ⅷ factor related antigen(Ⅷ-R Ag) were quantitatively analyzed by immunohistochemical method. Result: In the model group, the bone trabeculae were sparse, thin, disorganized and broken; some of the bone cells were necrotic and the number of empty bone lacunae was increased. In the treatment group, the number of trabeculae was increased; the structure was clear, most of which was normal bone cells, with a few necrotic bone cells, and the number of empty bone lacunae was decreased obviously. The rate of empty bone lacuna and the area of bone lacuna in the treatment group were significantly lower than those in the model group (P<0.05);the positive area ratio of VEGF, BMPs, TGF-β₁ and the microvessel density of Ⅷ-R Ag in the treatment group were significantly higher than those in the model group (P<0.05), with significantly lower blood lipid contents (P<0.05). Conclusion: Mailuoning compound can improve the microcirculation state of femoral head, promote the formation of new bone and blood vessel in femoral head by regulating the expression of VEGF, BMPs, TGF-β₁, Ⅷ-R Ag and down-regulating blood lipid content, thus effectively controlling the development of early SONFH. This can provide a theoretical basis for the treatment of early SONFH.

Metabolomics is an omics subject which studies on the metabolic network of organism and the intrinsic metabolic change of entirety with the aim of clarifying the mechanism of medicinal effect and pathogenesis of disease, is similar to the whole concept theory of Chinese medicine. The mectabolomics technology helps to promote the modern process of traditional Chinese medicine. This article illustrated the application research on the concept of metabolomics, the syndrome of Chinese medicine, quality and components of traditional Chinese medicine, traditional Chinese medicine compounds and so on, explored the problems on the current research and the prospect meanwhile.

Objective To explore the feasibility of low-concentration contrast agent and low-dose technology for pulmonary angiography by comparing the image quality and radiation doses to the patient by different tube voltages and concentrations of contrast agents.Methods Totally 60 patients suspected with pulmonary embolism were divided into C, L1 and L2 groups, of which,Group C had the scanning parameters of 120 kV and 350 mgI/ml,Group L1 had the parameters as 100 kV and 350 mgI/ml and Group L2 had the parameters of 100 kV and 270 mgI/ml.The three groups had the tube voltage as 500 mA, the contrast agent dose as 25 ml,physiological saline dose as 40 ml and flow rate as 4.5 ml/s.SPSS 19.0 software was used to compare and analyze the CT values of pulmonary artery segment,superior vena cava and ascending aorta,main pulmonary artery noises,the image quality as well as the radiation doses of volume scanning. Results The three groups had the main pulmonary aortas and their branches display clearly to meet clinical requirements.When compared with Group C,Group L1 had higher CT values of the main pulmonary aorta and its branches,higher image noise while lower radiation dose (P<0.01);Group L2 had equivalent CT values of the main pulmonary aorta and its branches (P>0.05),higher image noise while lower radiation dose (P<0.01).When compared with Group L1,Group L2 had lower CT values of the main pulmonary aorta and its branches (P<0.01),and equivalent image noise and radiation dose (P>0.05).Conclusion Low-concentration contrast agent and low-dose technology gains feasibility and advantages when used in 320-slice CT pulmonary angiography.

OBJECTIVE: Cytokines produced by various cells are strong local mediators of inflammation. Interleukin-1beta (IL-1β) and C-reactive protein (CRP) play essential roles in the development and progression of diabetes mellitus (DM). Thus periodontal diseases could be related to DM via the same mediators of inflammation. To evaluate plasma and gingival crevicular fluid (GCF) levels of IL-1β and CRP in adolescents with DM to further investigate whether DM has an impact on the levels of inflammation factors at an early stage, and to analyze the risk of developing periodontal diseases in adolescents with DM. METHODS: A total of 121 adolescents aged from ten to sixteen years were enrolled, 41 adolescents diagnosed with diabetes mellitus were collected in the DM group, and 80 nondiabetic adolescents as the control group. The periodontal indices of each individual were recorded, including plaque index (PLI), modified bleeding index (mBI), probing depth (PD) and attachment loss (AL). GCF and intravenous blood samples were collected, and CRP and IL-1β levels were detected by enzyme-linked immunosorbent assay (ELISA). RESULTS: (1) PLI of DM group and control group were 1.23±0.05 and 0.95±0.04 separately, with significant difference (P=0.001). DM group and control group had mBI of 0.80±0.08 and 0.51±0.06 separately, with significant difference (P=0.003). Attachment loss was found in none of the subjects. PDs of DM group and control group were (2.37±0.51) mm and (2.31±0.05) mm separately, and there was no significant difference. (2) CRP in GCF was only detectable in partial of the individuals, with a detectable rate of 22.9% (11/48) in total. The detectable rate of CRP in GCF was significantly higher in DM group (38.5%) than that in control group (4.5%, P=0.006). The plasma level of CRP in DM group [0.23 (0.15, 1.89) mg/L] was higher than that in control group [0.19 (0.12, 4.18) mg/L], but without significance (P=0.776). (3) The plasma levels of IL-1β in DM group and control group were (14.11±0.57) ng/L and (14.71±0.50) ng/L separately, but there was no significance (P=0.456). GCF levels of IL-1β in DM group and control group were (12.91±1.95) μg/L and (17.68±3.07) μg/L, without significant difference (P=0.185). CONCLUSION Periodontitis was not observed in adolescents with DM at an early stage. However, the rising levels of periodontal indices and CRP in GCF, might indicate that adolescents with DM have a higher risk of developing periodontal diseases in the future.
Adolescent ; C-Reactive Protein/analysis* ; Dental Plaque Index ; Diabetes Mellitus, Type 2 ; Disease Progression ; Enzyme-Linked Immunosorbent Assay ; Female ; Gingival Crevicular Fluid/chemistry* ; Humans ; Interleukin-1beta/analysis* ; Male ; Periodontal Diseases ; Periodontal Index ; Periodontitis ; Plasma

Objective To study the difference effects of enriching blood function of different medicinal parts in Angelica on the hemolytic blood deficiency in rats.Methods Wistar rats were randomly divided into 6 groups:blank group,model group,positive control group,Angelica group,Angelica body group,Angelica tail group.The hemolytic blood deficiency rats was established by acetyl phenylhydrazine hydrochloride.Rats in normal and model groups were orally administered with saline,while rats in positive control group were orally treated with Lvjiaobuxue granule at the dose of 3.60 g · kg-1.Water decoction of Angelica,Angelica body and Angelica tail groups were orally at the dose of 10.8g · kg-1.All the drugs were administered to rats for consecutive 12 d.The contents of red blood cell (RBC),hematocrit (HCT),hemoglobin (HGB),platelet (PLT),mean corpuscular volume (MCV),mean corpuscular hemoglobin(MCH) and mean corpuscular hemoglobin concentration(MCHC) were detected by hematology analyzer.While liver index (LI),thymus index (TI),spleen index (SI),reticulocyte (RC),and marrow karyocyte were calculated.After collecting thighbone,marrow cell cycle was detected by flow cytometry method flow cytometry.Results With the treatment of Angelica and Angelica body water decoction,the whole blood contents of RBC,HGB,HCT,PLT,MCHC were (6.05 ±0.22),(6.12 ±0.12) 1012/L;(155.80 ±4.89)％,(154.40 ±5.19)％;(53.79±1.88),(53.27 ± 1.57) g · L-1;(68.21 ± 5.63),(67.53 ± 5.11) 1010/L;(289.70 ± 3.94),(289.91 ± 8.41)g · L-1,respectively in each group,which were obviously higher than that of model group (P ＜ 0.05,P ＜ 0.01).The contents of MCH,MCV in Angelica and Angelica body groups were (25.75 ± 0.44),(25.23 ± 1.09) pg;(88.88 ± 1.67),(87.01 ±2.72) fl,which were lower than that of model group(all P ＜0.05).After used by Angelica tail,the contents of RBC,HGB,HCT were (5.69 ± 0.40) 1012/L,(123.10 ± 3.70) ％,(51.41 ± 2.03) g · L-1,which were higher than that of model group (all P ＜ 0.05).Conclusion Angelica and Angelica body,in which has same enrichment blood effect has effect of enriching blood on the hemolytic blood deficiency rats,and Angelic tail has weaker effect of enriching blood.

Objective To observe the visual outcomes of big-bubble deep anterior lamellar keratoplasty (DALK) for the treatment of keratoconus using a femtosecond laser.Methods A total of 30 patients (50 affected eyes) with keratoconus were enrolled in the study by the self control observation method.All the patients were treated with femtosecond laser assisted DALK by large bubble method,and the curative effect was observed.Results All the 30 patients underwent the surgery successfully.In the early time after the surgery,the corneal grafts were transparent,the corneal physiological thickness was restored,and the grafts fitted the implant bed elastic layer well.The uncorrected visual acuity and the best corrected visual acuity on day 7,1 month,6 months and 1 year after surgery were higher than those before surgery (all P ＜ 0.05),but there was no significant difference between above time points (all P ＞ 0.05).The corneal curvature and corneal astigmatism were significantly decreased after surgery,the thickness of the thinnest cornea was significantly increased after surgery (all P ＜0.05),but there was no significant difference between the different time points after surgery (all P ＞ 0.05).The endothelial cell density before surgery and 1 year after surgery was (2989.34 ±294.52) · mm-2 and (2821.19 ±325.51) · mm-2,while loss rate of endothelial cell was (5.62 ± 0.56)％,but there was no significant difference between different time points after surgery (all P ＞ 0.05).There were no complications during the surgery,but wound dehiscence occurred in 1 eye,loose suture in 1 eye,and stromal rejection in 1 eye,and there was no other complication after surgery.Conclusion It is safe and effective of femtosecond-laser assisted DALK by a big-bubble method to treat keratoconus,and it is a good choice for patients with advanced keratoconus.