AIM: To explore the intervention effect of Dahuangtang pellets (DHT) on diabetic nephropathy (DN) based on the AMP-activated protein kinase/mammalian target of rapamycin/unc-51-like kinase 1 (AMPK/mTOR/ULK1) signaling pathway. METHODS: Eight mice were randomly assigned to the model group, the dapagliflozin group, and the DHT (high, medium, and low dosage) group out of a total of 40 C57BL/KSJ-db/db (hereafter referred to as db/db) mice; another 10 C57BL/KSJ-db/dm mice were used as the normal group, saline was provided to the normal and model groups, and the mice in the treatment group received the appropriate medications. The medications were given for 10 consecutive weeks, once per day, to the mice in the treatment group. At weeks 0, 4, 8, and 10 of administration, fasting blood glucose (FBG) was assessed by drawing blood at a predetermined time from the tail vein; Urine samples were taken at 0, 5, and 10 weeks after treatment to evaluate the levels of albumin and creatinine, and the urinary albumin-creatinine ratio (ACR) was computed. After 10 weeks, mice in each group were assayed for 24 h total urine protein, serum creatinine (Scr), urea nitrogen (BUN) levels; Western blotting analysis was conducted to detect the expression of p-AMPK, p-mTOR, and p-ULK1, as well as the expression of autophagy related proteins homolog of yeast Atg6 (Beclin-1), autophagy-related proteins microtubule-associated protein 1 light chain 3 (LC3), P62 in renal tissue; Immunohistochemistry was used to measure the expression of podocyte lacunar membrane proteins (Nephrin, Podocin) in renal tissues; The pathological morphology of renal tissue was observed by light microscopy and transmission electron microscopy. RESULTS: Compared with the model group, FBG, ACR, and 24 h total urine protein were reduced in the dapagliflozin group and DHT groups of mice, and there was no statistically significant difference in Scr and BUN; In renal tissues, there is increased expression of p-AMPK and p-ULK1, decreased expression of p-mTOR, increased expression of LC3II / LC3I and Beclin-1, and decreased expression of P62 (P<0.01, P< 0.05); differentially upregulated in glomeruli are the podocyte lacunar membrane proteins Nephrin and Podocin (P<0.01, P<0.05); renal pathologic damage was reduced to varying degrees; transmission electron microscopy showed an increase in the number of autophagic vesicles and autophagic lysosomes. CONCLUSION: DHT can delay the development of DN by regulating the AMPK / mTOR / ULK1 signaling pathway, enhancing podocyte autophagy, and protecting glomeruli.

Objective To investigate potential causative associations between immunophenotype traits and cervical cancer by using two-sample Mendelian randomization(MR)analysis.Methods The genetic instrumental variables(IVs)of 731 immunophenotypes of peripheral blood were obtained from the GWAS Catalog database.The GWAS summary data of cervical cancer were obtained from FinnGen database.The inverse-variance weighted(IVW),weighted mode,weighted median,and MR Egger methods were used for evaluations.The sensitivity analysis and reverse Mendelian randomization analysis were conducted to eliminate bias and reverse causality.The MR Steiger directionality test was further used to ascertain the reverse causal relationship between immune cells and cervical cancer.Results A total of 71 immune cell subtypes associated with cervical cancer were identified,of which 31 had a strong association.The majority of the B cell panel was protective factors for cervical cancer.B-cell activating factor receptor(BAFF-R)was the most frequently expressed molecule in this analysis.It is expressed on several B cell subtypes.The CD20 on IgD+CD38+B cell(OR=1.887,95%CI:1.078-3.306,P=0.026)is the risk factor for cervical cancer.In cDC panels,the CD123 expression on plasmacytoid dendritic cell(OR=2.48,95%CI:1.229-5.003,P=0.011),CD123 expression on CD62L+plasmacytoid dendritic cell(OR=2.5,95%CI:1.231-5.077,P=0.011),CD80 expression on plasmacytoid dendritic cell(OR=2.62,95%CI:1.244-5.515,P=0.011),and CD80 expression on CD62L+plasmacytoid dendritic cell(OR=2.641,95%CI:1.246-5.596,P=0.011)were positively associated with the incidence of cervical cancer.All gynecological cancers in this study have no statistically significant effect on immune cells,according to reverse MR analysis.Conclusion This study emphasized the genetically predicted causality between immune cells and cervical cancer.In clinical practice,it is important to pay attention to the screening of peripheral blood immune cells for patients with cervical cancer.

Objective To compare the cost-utility of tislelizumab and sorafenib in the first-line treatment of advanced unresectable hepatocellular carcinoma,and to provide a reference for the selection of treatment regimens from the perspective of pharmacoeconomics.Methods A partitioned survival model was used to simulate the survival status of patients using tislelizumab or sorafenib within 10 years,and the cost and health output were calculated respectively to obtain the incremental cost-utility ratio(ICUR).The 3 times China's per capita gross domestic product(GDP)in 2022 was taken as the threshold for willingness to pay(WTP).Results During the simulation period,the ICER of tislelizumab versus sorafenib was 280 691.4 yuan/quality-adjusted life year(QALY),which was significantly higher than that of the sorafenib group,which had obvious economic performance.Univariate sensitivity analysis showed that the incidence of grade 3 or above adverse reactions in the tislelizumab group,the cost of tislelizumab,and the incidence of grade 3 or higher adverse reactions in the sorafenib group were important factors affecting ICUR.Probabilistic sensitivity analysis showed that tislelizumab had a significant cost-utility advantage when WTP was 3 times GDP,with an economic probability of 81.4％,and the results were robust.Conclusion For the first-line treatment of advanced unresectable hepatocellular carcinoma,tislelizumab has a significant cost-utility advantage over sorafenib.

Digital intelligence technologies, including artificial intelligence, big data, surgical navigation, surgical robots, and virtual reality, have been widely used in basic and clinical research in trauma and orthopedics. In order to provide trauma orthopedists with a quick overview of the current application of these technologies, this paper elaborates on the orthopedic workflow of fracture open reduction and internal fixation, on the aspects of recognition and classification of fracture X-ray images, fracture fragment segmentation based on thin-slice CT images, virtual fracture reduction, 3D fracture line heatmaps, design of an anatomical locking plate, intelligent navigation and orthopedic surgical robots, fracture reduction robots, and surgical process visualization.

Objective:To investigate the prospective association of sleep duration with the development of chronic obstructive pulmonary disease (COPD) in adults in Suzhou.Methods:The study used the data of 53 269 participants aged 30-79 years recruited in the baseline survey from 2004 to 2008 and the follow-up until December 31, 2017 of China Kadoorie Biobank (CKB) conducted in Wuzhong District, Suzhou. After excluding participants with airflow limitation, self-reported chronic bronchitis/emphysema/coronary heart disease history at the baseline survey and abnormal or incomplete data, a total of 45 336 participants were included in the final analysis. The association between daily sleep duration and the risk for developing COPD was analyzed by using a Cox proportional hazard regression model, and the hazard ratio ( HR) values and their 95% CI were calculated. The analysis was stratified by age, gender and lifestyle factors, and cross-analysis was conducted according to smoking status and daily sleep duration. Results:The median follow-up time was 11.12 years, with a total of 515 COPD diagnoses in the follow-up. After adjusting for potential confounders, multifactorial Cox proportional hazard regression analysis showed that daily sleep duration ≥10 hours was associated with higher risk for developing COPD ( HR=1.42, 95% CI: 1.03-1.97). The cross analysis showed that excessive daily sleep duration increased the risk for COPD in smokers ( HR=2.49, 95% CI: 1.35-4.59, interaction P<0.001). Conclusion:Longer daily sleep duration (≥10 hours) might increase the risk for COPD in adults in Suzhou, especially in smokers.

Objective:To investigate the association between sleep status and the risk for coronary heart disease in adults in Suzhou.Methods:Using the baseline and follow up information of 53 269 local residents aged 30-79 years in China Kadoorie Biobank conducted in Wuzhong District, Suzhou, 51 929 subjects were included in this study after excluding those reporting coronary heart disease, stroke and cancer at the baseline survey. A Cox proportional hazards regression model was used to analyze the association of healthy sleep score (0-3 points) and sleep factors (snoring, insomnia, long sleep duration and nap) with the risk for coronary heart disease.Results:The median follow-up time was 11.12 years, and 1 304 individuals were diagnosed with coronary heart disease during the follow-up. After adjusting for potential confounders, occasional snoring ( HR=1.20, 95% CI: 1.04-1.38), usual snoring ( HR=1.17, 95% CI: 1.02-1.33), insomnia disorder ( HR=1.41, 95% CI: 1.12-1.78), daytime dysfunction ( HR=1.56, 95% CI: 1.20-2.03) and perennial nap ( HR=1.37, 95% CI: 1.19-1.59) were associated with increased risk of coronary heart disease. Compared with those with sleep score of 0 - 1 (low sleep quality), the people with sleep score of 3 had reduced risk of coronary heart disease by 26% ( HR=0.74, 95% CI: 0.63-0.87). Stratified analysis showed that the association of healthy sleep score 3 with risk of coronary heart disease was stronger in low physically active individuals (interaction P<0.05). Conclusions:Snoring, insomnia disorders, daytime dysfunction, and perennial napping were all associated with increased risk for coronary heart disease, and keep healthy sleep mode might reduce the risk for coronary heart disease in adults.

The study established a mouse itch model induced by acute opioid and non-opioid pruritogens. The effects and mechanism of partial opioid agonist thienorphine on acute scratching behavior caused by opioid and non-opioid pruritogens was demonstrated. The noninvasive scratching behavior analysis system was established to test scratching behavior induced by morphine, bombesin, 5-hydroxytryptamine (5-HT) or chloroquine in C57 BL/6J mice. The effect of thienorphine (0.75, 1.5, 3 mg·kg^-1) on acute itch caused by above pruritogens were studied. The expression of protein kinase C δ (PKC δ) in mouse spinal cord was detected by Western blot after pruritogens addition with or without thienorphine pretreatment. All operations in the experiment were approved by the Institutional Animal Care and Use Committee of the Academy of Military Medical Sciences (IACUC-2021-017W). The scratching behavior increased significantly under morphine (1 nmol, i.t), bombesin (0.3 nmol, i.t), 5-HT (5 nmol, i.d) or chloroquine (20 nmol, i.d) treatment, respectively. Thienorphine (1.5 mg·kg^-1) significantly inhibited the scratching behavior induced by the morphine, bombesin, 5-HT and chloroquine. Thienorphine significantly reversed the changes in PKC δ protein expression induced by morphine or 5-HT. In conclusion, the partial opioid agonist thienorphine could inhibit scratching behavior induced by opioid and non-opioid pruritogens. It might reverse PKC δ through different pathways to inhibit opioids and non-opioids induced scratching behavior, which provided a new idea for exploring and treating itch.

OBJECTIVE To screen and quantitatively analyze differential quality markers （Q-Marker） in Zingiber officinale mixed and triturated with Schisandra chinensis （ZMTS） before and after processing. METHODS HPLC fingerprints of before processing [Z. officinale complicated with S. chinensis （ZWS）] and after processing （ZMTS） （10 batches each） were established. The differences of Q-Markers before and after processing were screened by the chemical pattern recognition method and Q-Marker “five principles”， and the contents were determined. RESULTS A total of 14 common peaks were identified in the fingerprints of ZWS， 22 common peaks were identified in the fingerprints of ZMTS， and 8 components were identified. Differential Q-Marker were screened by chemical pattern recognition and Q-Marker “five principles”， i. e. 6-gingerol， schisandrol A schisandrol B， 8-gingerol， 10-gingerol， schisandrin A， schisandrin B， schizandrin C. The average contents of the 8 differential Q-Markers in ZMTS were 229.46， 244.48， 39.96， 44.12， 61.17， 47.82， 100.11 and 9.70 μg/g， respectively. The average contents of the 4 differential Q-Markers （6-gingerol， schisandrol A， schisandrol B， 8-gingerol） in ZWS were 112.58， 19.01， 26.74 and 5.98 μg/g， respectively. CONCLUSIONS In this study， the differential Q-Markers before and after ZMTS processing are screened. The contents of the Q-Markers in ZMTS after processing are higher than those before processing.

Mesenchymal stem cells have emerged as a promising cell therapy for anti-tumor research due to their homing properties,low immunogenicity,anti-angiogenic activity,anti-inflammatory properties,and paracrine effects.Paclitaxel has been clinically used for over thirty years in the treatment of various tumors such as ovarian cancer,lung cancer,and breast cancer.However,the broad-spectrum anti-tumor properties of paclitaxel are not possessed by the aforementioned cell therapies.Moreover,its adverse reactions,including peripheral neuropathy,bone marrow suppression,and gastrointestinal reactions,have long plagued cancer patients.In recent years,many studies have focused on combining cell therapy with chemotherapy to achieve better treatment outcomes,giving rise to a new drug delivery system that utilizes mesenchymal stem cells as carriers for delivering chemotherapeutic drugs.This review summarizes the research progress in MSC-based drug delivery systems for paclitaxel.

Objective To investigate effects of calycosin(CA)on cigarette smoke(CS)induced airway epithelial cell damage in mice and the sirtuin 3/superoxide dismutase 2(SIRT3/SOD2)signaling pathway in mice.Methods A total of 90 mice were randomly separated into the control group,the cigarette smoke(CS)group,the CA low-dose treatment group(CA-L group),the CA high-dose treatment group(CA-H group)and the CA high-dose treatment plus SIRT3 inhibitor 3-TYP group(CA-H+3-TYP group),with 18 mice in each group.Tidal volume(TV)and peak expiratory flow rate(PEF)of lung function were detected by whole body plethysmography system.Serum levels of inflammatory factors[interleukin(IL)-6,tumor necrosis factor(TNF)-α]and oxidative stress indicators[reactive oxygen species(ROS),SOD]were detected by enzyme-linked immunosorbent assay(ELISA).The injury of airway epithelial cells in lung tissue was observed by HE staining.The expression levels of barrier related proteins(OCLN and ZO-1)in airway epithelial cells were detected by immunohistochemistry.Immunoblotting was applied to detect the expression of SIRT3/SOD2 signaling pathway related proteins.Results Compared with the control group,levels of TV,PEF,MAN and SOD and the expression levels of OCLN,ZO-1,SIRT3 and SOD2 were decreased in the CS group,while the levels of MLI,IL-6,TNF-α and ROS were increased(P＜0.05).Compared with the control group,the lung tissue structure was significantly damaged,the alveolar enlargement was obvious,the surrounding alveolar was accompanied by inflammatory cell infiltration,and the airway epithelial cells were obviously shed in the CS group.Different doses of CA alleviated lung tissue destruction,improved alveolar structure,reduced inflammatory cell infiltration,reduced airway epithelial cell shedding,increased levels of TV,PEF,MAN,SOD and OCLN,ZO-1,SIRT3 and SOD2,and decreased levels of MLI,IL-6,TNF-α and ROS.The effect of high dose CA was more significant than that of low dose CA(P＜0.05).SIRT3/SOD2 signaling pathway inhibitor 3-TYP partially reversed the ameliorative effect of CA on CS induced airway epithelial cell injury in mice.Conclusion CA can ameliorate CS induced airway epithelial cell damage in mice,and its mechanism is related to the activation of the SIRT3/SOD2 signaling pathway.