Through a compound induction method, combined with neurobehavioral, macroscopic characterization and objective pathological evaluation indicators, a murine depression model of liver depression transforming into fire syndrome was constructed and confirmed. The model was constructed using a combination of sleep deprivation, light exposure, and alternate-day food deprivation. Evaluation was conducted at three levels: face validity, constructs validity, and predictive validity. The establishment of the liver depression transforming into fire syndrome depression model was further validated through the counterproof of traditional Chinese medicine formulas. In terms of face validity, compared to the control group, mice in the model group exhibited typical depressive symptoms in neurobehavioral assessments; the general observation of the model group mice reveals disheveled and lackluster fur, along with delayed and easily agitated responses. Additionally, there is a substantial increase in water consumption. In the sleep phase detection of mouse, the model group showed a significant increase in the proportion of time spent in the wake phase during sleep, accompanied by a significant decrease in the proportions of time spent in both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep phases. There are significant differences in physiological indicators such as average blood flow velocity, blood flow rate, tongue, urine, and claw color (r values) in the internal carotid artery. Structural validity demonstrated that levels of 5-hydroxytryptamine (5-HT), dopamine (DA), and γ-aminobutyric acid (GABA) in the hippocampus of model mice decreased significantly, while acetylcholine (ACh), tryptophan (Try), and glutamic acid (Glu) levels increased significantly. Treatment with Danzhi Xiaoyao San led to varying degrees of restoration in the aforementioned neurotransmitters. In terms of predictive validity, the antidepressant paroxetine effectively ameliorated depressive behaviors in the model mice, and the classic formula Danzhi Xiaoyao San demonstrated varying degrees of improvement in depression-related indicators. In conclusion, this study has established a novel animal model of liver-stagnation with the fire depression, thereby expanding the repertoire of traditional Chinese medicine depression models. This development contributes to the diversification of melancholic syndrome models in Chinese medicine, offering a broader spectrum of options for scientific exploration, efficacy evaluation, and drug screening in the future prevention and treatment of depression with traditional Chinese medicine. Animal experiments were conducted with the approval and supervision of the Animal Ethics Committee of Jiangxi University of Traditional Chinese Medicine (ethics number: 20230313040).

Objective To compare the clinical efficacy of ligament advanced reinforcement system(LARS)and autoge-nous hamstring tendon plus high-strength suture in arthroscopic reconstruction of posterior cruciate ligament(PCL).Methods A total of 96 patients with simple PCL injury treated with arthroscopic posterior cruciate ligament reconstructive surgery admit-ted to our hospital between August 2019 and December 2021 were selected for complete follow-up.There were 78 males and 18 females,40 cases of left leg and 56 cases of right leg,the aged from 20 to 56 years old with an average of(32.50±8.68)years old.The transplants were divided into two groups:LARS group(52 cases)and autogenous hamstring tendon plus high-strength suture group(44 cases).In the LARS group,there were 42 males and 10 females;with an average age of(31.84±8.62)years old;body mass index(BMI)was(24.73±2.29)kg·m-2;7 mm LARS was used to reconstruct PCL.In the autologous tendon group,there were 36 males and 8 females,with an average age of(33.06±8.99)years old,BMI was(23.52±2.16)kg·m-2,and the PCL was reconstructed with four strands of hamstring tendons and three pieces of Ethibond suture.All patients underwent functional rehabilitation guided exercise and were followed up regularly after surgery to objectively evaluate the stability of the knee joint by KT-1000 measurement of knee relaxation,and subjective evaluation of knee function by Lysholm score,Tegner score,and International Knee Documentation Council(IKDC)score.Data from preoperative,3,6,and 12 month follow-up were collected and analyzed by SPSS software to compare postoperative recovery and ligament relaxation between the two groups of patients.Results Ninety-six patients were followed up for 12 months.KT-1000 measurement of knee joint in autoge-nous tendon group and LARS group before operation[(10.73±1.46)points vs(10.55±1.53)points],6 months after operation[(3.02±0.75)points vs(2.35±0.60)points],12 months after operation[(3.77±1.76)points vs(2.44±0.60)points].There was significant difference between the two groups at 6 and 12 months after operation(P＜0.05),but there was no significant dif-ference between the two groups at 3 months after operation(P＞0.05).In the autogenous tendon group and LARS group,before operation and 12 months after operation,total Lysholm score[(40.6±16.8),(91.25±6.35)points vs(51.92±18.52),(92.35±5.30)points],Tegner score[(1.8±0.7),(5.8±0.6)points vs(1.7±0.8)、(5.7±0.7)points]and total IKDC score[(54.50±6.33),(83.90±3.93)points vs(54.40±4.24),(83.62±3.64)points],the differences were statistically significant(P＜0.05),indicating that the knee function of the two groups was improved after surgery.At 3 and 6 months after operation in the autoge-nous tendon group and LARS group,the total Lysholm score[(65.86±11.54),(74.60±6.46)points vs(73.46±6.42),(86.73±4.62)points],Tegner score[(2.5±0.6),(3.5±0.5)points vs(4.3±0.7),(5.0±1.4)points],the total scores of IKDC[(55.78±2.68),(70.62±4.74)points vs(65.31±4.60),(79.71±2.93)points].The difference between two groups was statistically sig-nificant(P＜0.05).The results showed that the function of the knee joint in the LARS group was better than that the autologous tendon group.However,at 12 months after the operation,there was no significant difference in the score of knee joint function between the two groups(P＞0.05).The results showed that the stability of LARS group was better than that of autologous tendon group.Conclusion Both the autogenous hamstring tendon plus high-strength suture and LARS reconstruction can significantly improve the knee function and stability,with satisfactory postoperative results.Howervr the LARS provides superior postopera-tive stability.

Aim To explore the effect and mechanism of the artesunate(ART)on hepatocellular carcinoma(HCC).Methods The cell lines MHCC-97H and HCC-LM3 were used to be detected.MTT and clone formation were used to determine the cell proliferation;Wound healing was used to detect the cell migration;Transwell was used to test the cell invasion.Flow-cy-tometry was used to detect cell apoptosis and cell cy-cle.RNA-seq and qRT-PCR was used to detect the genes expression.Results The proliferation,migra-tion and invasion of treated cells were obviously inhibi-ted(P＜0.01).Moreover,the apoptosis rate in-creased significantly,so did the proportion of G2/M cells.Transcriptomic analysis identified GADD45A as a potential target of ART through RNA-sequencing da-ta,and suggested that ART might induce apoptosis and cell cycle arrest through regulating the expression of GADD45A.In addition,the results of mechanism studies and signaling analysis suggested that GADD45A had interaction with its upstream gene NACC1(nucle-us accumbens associated 1).Moreover,after ART treatment,the expressions of GADD45A and NACC1 were changed significantly.Conclusion ART may be a potential drug to resist HCC by affecting the expres-sion of GADD45A and its upstream gene NACC1,which provides a new drug,a new direction and a new method for the clinical treatment of HCC.

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ² test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.
Colectomy ; Colonic Neoplasms/surgery* ; Female ; Humans ; Laparoscopy ; Male ; Prognosis ; Propensity Score ; Retrospective Studies ; Robotic Surgical Procedures ; Treatment Outcome

Multidrug resistance of tumors has been a severe obstacle to the success of cancer chemotherapy. The study wants to investigate the reversal effects of imperatorin (IMP) on doxorubicin (DOX) resistance in K562/DOX leukemia cells, A2780/Taxol cells and in NOD/SCID mice, to explore the possible molecular mechanisms. K562/ DOX and A2780/Taxol cells were treated with various concentrations of DOX and Taol with or without different concentrations of IMP, respectively. K562/DOX xenograft model was used to assess anti-tumor effect of IMP combined with DOX. MTT assay, Rhodamine 123 efflux assay, RT-PCR, and Western blot analysis were determined in vivo and in vitro. Results showed that IMP significantly enhanced the cytotoxicity of DOX and Taxol toward corresponding resistance cells. In vivo results illustrated both the tumor volume and tumor weight were significantly decreased after 2-week treatment with IMP combined with DOX compared to the DOX alone group. Western blotting and RT-PCR analyses indicated that IMP downregulated the expression of P-gp in K562/DOX xenograft tumors in NOD/SCID mice. We also evaluated glycolysis and glutamine metabolism in K562/DOX cells by measuring glucose consumption and lactate production. The results revealed that IMP could significantly reduce the glucose consumption and lactate production of K562/DOX cells. Furthermore, IMP could also remarkably repress the glutamine consumption, α-KG and ATP production of K562/DOX cells. Thus, IMP may sensitize K562/DOX cells to DOX and enhance the antitumor effect of DOX in K562/DOX xenograft tumors in NOD/SCID mice. IMP may be an adjuvant therapy to mitigate the multidrug resistance in leukemia chemotherapy.

The present study explored the effect of co-amorphous technology in improving the dissolution rate and stability of silybin based on the puerarin-silybin co-amorphous system prepared by the spray-drying method. Solid-state characterization was carried out by powder X-ray diffraction(PXRD), polarizing microscopy(PLM), Fourier transform infrared spectroscopy(FT-IR), differential scanning calorimetry(DSC), etc. Saturated powder dissolution, intrinsic dissolution rate, moisture absorption, and stability were further investigated. The results showed that puerarin and silybin formed a co-amorphous system at a single glass transition temperature which was higher than that of any crude drug. The intrinsic dissolution rate and supersaturated powder dissolution of silybin in the co-amorphous system were higher than those of the crude drug and amorphous system. The co-amorphous system kept stable for as long as three months under the condition of 40 ℃, 75% relative humidity, which was longer than that of the single amorphous silybin. Therefore, the co-amorphous technology could significantly improve the dissolution and stability of silybin.
Calorimetry, Differential Scanning ; Desiccation ; Drug Compounding/methods* ; Drug Stability ; Silybin ; Solubility ; Spectroscopy, Fourier Transform Infrared ; Technology ; X-Ray Diffraction

Objective:To analyze the patterns of antibacterial agents in Chinese children surveyed by the China multi-center monitoring network for the application of antibacterial agents in children and neonates in 2019 by using World Health Organization (WHO) Access, Watch, Reserve and Not-recommended (AWaRe) and typical anatomical/therapeutic/chemical (ATC) in this study.Methods:The cross-sectional method was adopted.A multi-center cross-sectional survey was conducted on one day from September to December 2019.The information of all inpatients taking antibiotics was uploaded to the network-based data collection system (https: //garpec-31.mobilemd.cn/login.aspx? relogin=true). This study covered 13 hospitals from 10 provinces and cities in China.All hospitalized children in the Respiratory Department, Infectious Disease Department, General Surgery Department, Pediatric Intensive Care Units, Neonatal Intensive Care Units and Neonatology joined in this survey.The clinically used antibacterial agents were classified by AWaRe and ATC, and the AWaRe and ATC distributions of antibacterial agents prescribed for Chinese children and neonates were described.Results:Of the 2 644 antibiotic prescriptions included from 13 hospitals, 2 134 (80.71%) were for children and 510 (19.29%) were for neonates.Of all antibiotic prescriptions, there were 368 (13.92%) Access antibiotics prescriptions, 1 973 (74.62%) Watch prescriptions, 60 (2.27%) Reserve prescriptions and 243 (9.19%) Not-recommended prescriptions.The top-five antibiotics prescribed for children and neonates were third-generation cephalosporins (1 056, 39.94%), macrolides (492, 18.61%), carbapenems (275, 10.40%), beta lactam-beta lactamase inhibitors (246, 9.30%), and second-generation cephalosporins (136, 5.14%). The use ratios of Access, Watch, Reserve and Not-recommended antibiotics in each center ranged from 0 to 30.00%, 36.67% to 97.20%, 0 to 17.02% and 0 to 33.33%, respectively.In 1 360 antibiotic prescriptions for children and neonates with pneumonia, there were 152 (11.18%) Access antibiotics, 1 051 (77.28%) Watch antibiotics, 37 (2.72%) Reserve antibiotics, and 120 (8.82%) Not-recommended antibiotics.The top-five antibiotics prescribed for children with pneumonia were third-generation cephalosporins (522, 38.38%), macrolides (388, 28.53%), beta lactam-beta lactamase inhibitors (141, 10.37%), carbapenems (117, 8.6%) and penicillins (49, 3.60%).Conclusions:Watch antibiotics and broad spectrum antibiotics such as third-generation cephalosporins and macrolides prone to induce resistance are the main antibacterial agents used in Chinese children and neonates with pneumonia.Broad-spectrum antibiotics may be overused in Chinese children and neonates.

According to the taste analysis of Pudilan Xiaoyan Oral Liquid, the unpleasant taste of the oral liquid is mainly caused by the inherent taste of Chinese medicine and the taste introduced in the preparation process, which leads to its unpopularity among children. Therefore, aiming at the special children patient group, Xiaoer Pudilan Xiaoyan Syrup was developed via technology optimization and dosage form improvement to improve the unpleasant taste and enhance the medication compliance among children. Based on the material properties of Pudilan Xiaoyan Oral Liquid and Xiaoer Pudilan Xiaoyan Syrup extracts, the authors compared the properties(pH, density, turbidity, viscosity, chromaticity, particle size), taste, content of five quality markers and in vivo pharmacokinetic characteristics of these two preparations, to evaluate the suitability of Xiaoer Pudilan Xiaoyan Syrup. The results showed that compared with those of Pudilan Xiaoyan Oral Liquid, the pH, density, turbidity, viscosity and chromaticity of Xiaoer Pudilan Xiaoyan Syrup were significantly changed, and the unpleasant taste was reduced by 26%; the transfer rate of the main active ingredients chicoric acid was increased, while the transfer rate of baicalin had small difference from that of the oral liquid. In addition, pharmacokinetics revealed that the total absorption amount of baicalin in vivo was higher, and the time to peak T_(max) of baicalin and oroxindin in the syrup and the mean residence time MRT_(last )of corynoline in vivo were significantly prolonged. The absorption degree of Xiaoer Pudilan Xiaoyan Syrup and Pudilan Xiaoyan Oral Liquid in the body was the same: baicalin>oroxindin>corynoline. The new dosage form process was simpler than that of the original dosage form, safe, environmentally friendly, reasonable and feasible, meeting the mass production demand. This provided a basis for the reasonable and scientific optimization of Xiaoer Pudilan Xiaoyan Syrup, and also laid a foundation for its further safe and rational use, so as to expand the clinical application in children.
Child ; Humans ; Drugs, Chinese Herbal ; Glucuronates

Taking Pudilan Xiaoyan Oral Liquid as a demonstration, the effective delivery of quality markers in alcohol precipitation of Chinese medicine oral liquid preparations was studied. With the transfer rates of adenosine, corynoline, cichoric acid, baicalin, and wogonin as evaluation indexes, the effect of the density of concentrate before alcoholic precipitation, volume fraction of ethanol, stirring speed, temperature of concentrated solution, stirring time, alcohol concentration, alcohol precipitation time, alcoholic precipitation temperature, alcohol addition rate, and the pH of concentrate on the alcohol precipitation process was investigated by Plackett-Burman trial design, thus obtaining the key factors that influenced the alcohol precipitation process. The key factors were further optimized by Box-Behnken design to determine the optimal alcohol precipitation conditions. When the density of concentrate before alcoholic precipitation was 1.12 g·mL~(-1), the pH of concentrate was 6.86, and the alcohol concentration was 50.00%, the transfer rates of baicalin and wogonin were 91.86% and 87.78%, respectively. When the density of concentrate before alcoholic precipitation was 1.13 g·mL~(-1), the concentration of alcohol was 74.50%, and the alcoholic precipitation temperature was 17.0 ℃, the transfer rates of adenosine, corynoline, and cichoric acid were 85.95%, 71.62% and 83.19%, respectively. The method of optimizing alcohol precipitation techniques and determining the parameters of Pudilan Xiaoyan Oral Liquid by response surface methodology is reasonable and feasible, which provides guidance and experience for the effective delivery of quality markers in Chinese medicine oral liquid preparations.
Drugs, Chinese Herbal ; Ethanol ; Adenosine ; Chemical Precipitation

OBJECTIVE: To reveal the neuroprotective effect and the underlying mechanisms of a mixture of the main components of Panax notoginseng saponins (TSPN) on cerebral ischemia-reperfusion injury and oxygen-glucose deprivation/reoxygenation (OGD/R) of cultured cortical neurons. METHODS: The neuroprotective effect of TSPN was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, flow cytometry and live/dead cell assays. The morphology of dendrites was detected by immunofluorescence. Middle cerebral artery occlusion (MCAO) was developed in rats as a model of cerebral ischemia-reperfusion. The neuroprotective effect of TSPN was evaluated by neurological scoring, tail suspension test, 2,3,5-triphenyltetrazolium chloride (TTC) and Nissl stainings. Western blot analysis, immunohistochemistry and immunofluorescence were used to measure the changes in the Akt/mammalian target of rapamycin (mTOR) signaling pathway. RESULTS: MTT showed that TSPN (50, 25 and 12.5 µ g/mL) protected cortical neurons after OGD/R treatment (P<0.01 or P<0.05). Flow cytometry and live/dead cell assays indicated that 25 µ g/mL TSPN decreased neuronal apoptosis (P<0.05), and immunofluorescence showed that 25 µ g/mL TSPN restored the dendritic morphology of damaged neurons (P<0.05). Moreover, 12.5 µ g/mL TSPN downregulated the expression of Beclin-1, Cleaved-caspase 3 and LC3B-II/LC3B-I, and upregulated the levels of phosphorylated (p)-Akt and p-mTOR (P<0.01 or P<0.05). In the MCAO model, 50 µ g/mL TSPN improved defective neurological behavior and reduced infarct volume (P<0.05). Moreover, the expression of Beclin-1 and LC3B in cerebral ischemic penumbra was downregulated after 50 µ g/mL TSPN treatment, whereas the p-mTOR level was upregulated (P<0.05 or P<0.01). CONCLUSION TSPN promoted neuronal survival and protected dendrite integrity after OGD/R and had a potential therapeutic effect by alleviating neurological deficits and reversing neuronal loss. TSPN promoted p-mTOR and inhibited Beclin-1 to alleviate ischemic damage, which may be the mechanism that underlies the neuroprotective activity of TSPN.
Animals ; Beclin-1 ; Brain Ischemia/metabolism* ; Glucose ; Infarction, Middle Cerebral Artery/drug therapy* ; Mammals/metabolism* ; Neuroprotection ; Neuroprotective Agents/therapeutic use* ; Oxygen ; Panax notoginseng ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats ; Reperfusion Injury/metabolism* ; Saponins/therapeutic use* ; TOR Serine-Threonine Kinases/metabolism*