Objective Most patients with chronic insomnia depend on long-term medication， which may easily lead to a poor treatment outcome and adverse drug reactions， and transcranial alternating current stimulation （tACS）， as a noninvasive neuromodulation technique， can improve chronic insomnia. This study aims to investigate the clinical efficacy of tACS combined with pharmacotherapy in the treatment of chronic insomnia. Methods A total of 46 patients with chronic insomnia were enrolled and randomly divided into pharmacotherapy group with 20 patients and pharmacotherapy+tACS treatment group with 26 patients. The tACS electrodes were attached to the frontal region and the bilateral mastoids， with a frequency of 77.5 Hz and a current intensity of 15 mA， for 40 minutes each time， once a day for 10 consecutive days. The primary outcome measures were Pittsburgh Sleep Quality Index （PSQI） score and its improvement rate after 4 weeks， and the secondary outcome measures included the scores of Hamilton Depression Rating Scale （HAMD）， Hamilton Anxiety Rating Scale （HAMA）， Mini-Mental State Examination （MMSE）， and Montreal Cognitive Assessment （MoCA） and their improvement rates. Results Compared with the pharmacotherapy group， the pharmacotherapy+tACS treatment group had a significant reduction in PSQI score （P<0.05）， with an improvement rate of 37% and 21%， respectively， suggesting that the combined therapy had a better effect in improving sleep quality. The pharmacotherapy+tACS treatment group also had reductions in HAMA and HAMD scores， suggesting improvements in anxiety and depression symptoms， and there were no significant differences in MMSE and MoCA scores between the two groups. Conclusion Pharmacotherapy combined with tACS has a better effect than pharmacotherapy alone in improving sleep quality and anxiety and depression symptoms in patients with chronic insomnia， and therefore， it has good application prospects in clinical practice.

Objective To predict the core targets and action pathways of Hedysari Radix based on UPLC-MS/MS and network pharmacology methods,and to verify the results of network pharmacology by molecular docking and molecular dynamics techniques.This article aims to investigate immune regulation mechanism of effective components absorbed into blood from Hedysari Radix.Methods Qualitative quantification of effective components absorbed into blood from Hedysari Radix were operated by using UPLC-MS/MS technique.The corresponding targets of effective components absorbed into blood from Hedysari Radix were screened by TCMSP and HERB databases.Targets of immune-related disease were obtained through DisGeNET,OMIM,TTD,and MalaCards databases.The network of"components absorbed into blood from Hedysari Radix-immune-related diseases"was then constructed.GO and KEGG enrichment analysis and mapped the PPI network were performed.Molecular docking and molecular dynamics techniques were applied for validation.Results A total of 8 prototype components absorbed into blood,synergistically acting on 101 targets,were identified by UPLC-MS/MS.They mediated 538 biological processes including immune response,positive regulation of gene expression,receptor binding,and cytokine activity.Meanuhile,116 signaling pathways,such as HIF-1,Toll-like receptor,JAK-STAT,T cell receptor,PI3K-Akt,and FoxO etc.were involved.The core targets were MAPK14,PTGS2,MMP9,PPARG,CCND1,etc..The results of molecular docking showed that formononetin and calycosin had strong docking binding activity with MAPK14.And molecular dynamics simulations further demonstrated that the binding between MAPK14 and formononetin or calycosin had good structural stability and binding affinity.Conclusion The results of serum pharmacochemistry,network pharmacology and molecular dynamics were verified to reveal the material basis and mechanism of Hedysari Radix in regulating immunity.The aim of this study is to provide scientific basis for its immunomodulatory mechanism.

Immunoscenescence plays a key role in the initiation and development of tumors. Furthermore, immunoscenescence also impacts drug delivery and cancer therapeutic efficacy. To reduce the impact of immunosenescence on anti-tumor therapy, this experimental plan aimed to use neutrophils with tumor tropism properties to deliver sialic acid (SA)-modified liposomes into the tumor, kill tumor cells via SA-mediated photochemotherapy, enhance infiltration of neutrophils into the tumor, induce immunogenic death of tumor cells with chemotherapy, enhance infiltration of CD8⁺ T cells into the tumor-draining lymph nodes and tumors of immunosenescent mice, and achieve SA-mediated photochemotherapy. We found that CD8⁺ T cell and neutrophil levels in 16-month-old mice were significantly lower than those in 2- and 8-month-old mice; 16-month-old mice exhibited immunosenescence. The anti-tumor efficacy of SA-mediated non-photochemotherapy declined in 16-month-old mice, and tumors recurred after scabbing. SA-mediated photochemotherapy enhanced tumor infiltration by CD8⁺ T cells and neutrophils, induced crusting and regression of tumors in 8-month-old mice, inhibited metastasis and recurrence of tumors and eliminated the immunosenescence-induced decline in antitumor therapeutic efficacy in 16-month-old mice via the light-heat-chemical-immunity conversion.

Objective:To investigate the changes of hippocampal gray matter volume and expression of candidate immune related genes in a rat model of schizophrenia established by repeated administration of dizocilpine(MK-801).Methods:Thirty SPF grade Sprague-Dawley male rats at postnatal day 28 were randomly divided into MK-801 medium-dose (0.25 mg/kg) group, MK-801 high-dose(0.50 mg/kg) group and normal saline (5 mL/kg) group according to random number table method, with 10 in each group.Rats were given continuous intraperitoneal administration according to grouping once a day for 14 days.Open field test, novel object recognition test and Y-maze test were used at postnatal day 60 to detect spontaneous activity, exploration ability, anxiety level, object recognition memory ability and spatial working memory of rats, respectively.At postnatal day 67, structural magnetic resonance imaging was used to detect the changes of hippocampal gray matter volume in rat.And at postnatal day 70, qRT-PCR was used to detect the expression of candidate immune-related genes in rat hippocampus.SPSS 25.0 was used for statistical analysis, one-way ANOVA was used for comparison among multiple groups, and Tukey test was used for further pairwise comparisons.Results:(1)The behavioral results showed that there were significant differences in the total movement distance, central area activity time, novel object recognition index, and spontaneous correct alternation rate among the three groups ( F=11.15, 10.11, 13.62, 11.99, all P<0.05). The total movement distances in MK-801 medium-dose group and MK-801 high-dose group ((21.44±2.17) m, (22.87±1.96)m) were higher than that in the normal saline group ((18.70±1.88) m) (both P<0.05). The activity time of the central area in the MK-801 medium-dose group and MK-801 high-dose group((3.24±1.58) s, (2.50±1.32) s) were lower than that of the normal saline group ((6.05±2.48)s) (both P<0.01). Novel object recognition indexes in the MK-801 medium-dose group and MK-801 high-dose group((56.10±3.99)%, (54.00±6.41)%) were both lower than that in the normal saline group ((65.90±5.65)%)(both P<0.01), and the rates of spontaneous correct alternation ((54.60±7.03)%, (51.60±8.84)%) in the two groups were lower than that of the normal saline group ((68.40±8.57)%) (both P<0.01). (2) The results of structural magnetic resonance imaging showed that there were significant differences in the volume of hippocampal gray matter among the three groups ( F=9.24, P<0.001). The volumes of hippocampal gray matter in MK-801 medium-dose group and MK-801 high-dose group were lower than that in normal saline group(both P<0.001). (3)By constructing protein-protein interaction network, four candidate immune related genes were screened out: neuropeptide Y (NPY), somatostatin (SST), cholecystokinin (CCK) and tachykinin 1 (TAC1). The results showed that the mRNA expression levels of NPY, SST and CCK in the hippocampus of the three groups were significantly different ( F=11.41, 10.43, 5.85, all P<0.05), but there was no statistical difference in the TAC1 mRNA expression level ( F=0.08, P>0.05). The mRNA levels of NPY, SST and CCK in the hippocampus of rats in the MK-801 high-dose group were lower than those in the normal saline group (all P<0.05). Conclusion:Both medium dose and high dose MK-801 administration can reduce the volume of hippocampal gray matter in schizophrenia model rats, but they have different effects on the expression of hippocampal immune related genes, of which high dose administration has a greater effect.

Background/Aims: Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. Methods: We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. Results: We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001). Conclusions IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

Objective: To summarize the clinical manifestations of IgG4-related diseases in the head and neck, explore treatment methods. Methods : The clinical data of 21 patients diagnosed with IgG4-related diseases were retrospectively analyzed. The clinical data and the results of glucocorticoid and immunosuppressive therapy were studied retrospectively. Results: All patients had swollen sclerotic masses, and CT showed irregular high-density masses with uniform enhancement in the enlarged glands. Some patients had mucosal thickening and mass-like changes in theoral cavity, nose, sinuses, throat and other tissues, and most of the patients had cervical lymphadenopathy and elevated serum IgG4 levels (≥ 1.35 g/L). Histopathological examination of affected exosine glands and affected mucosa and lymph nodes in all patients showed infiltration of lymphocytes, plasma cells and IgG4+ plasma cells. In 21 patients, the mass in the affected glands and mucosa (including head, neck and other tissues) disappeared, and the clinical symptoms were relieved after the application of glucocorticoids. However, with a reduction in glucocorticoids, the mass recurred or even worsened. Conclusion For patients with a single mass in the submandibular gland, parotid gland and other salivary glands, as well as lymph node enlargement, CT is the first choice to identify the nature of gland neoplasms. Combined with pathological examination, related auxiliary examination and peripheral blood examination are also needed to obtain a definitive diagnosis. Glucocorticoid therapy is used to achieve a good prognosis, and long-term follow-up and timely adjustment of medication regimens are required.

Guided by the emphasis on learning process, the educational reform has designed a "trinity" comprehensive evaluation system (quantitative clinical practice, in-class medical record analysis, and staged comprehensive written test) as the formative evaluation of the course. Through this assessment system, students' self-learning potential is stimulated, clinical skills practice is strengthened, and "taking exams to promote learning and taking exams to promote teaching" is realized. In the practice of teaching reform, it has been found that compared with the conventional teaching class, the students in the teaching reform class have higher participation and are more satisfied with the process assessment of the "trinity" comprehensive evaluation system.

Objective: To examine the outcome of surgical treatment in patients with stages Ⅱ-Ⅲ bisphosphonate-related osteonecrosis of the jaw. Methods: Twenty-nine patients with bisphosphonate-related osteonecrosis of the jaw were examined. The patients were followed up for more than 6 months, and the treatment outcome was reviewed. Results: After curettage of local lesions, 19 out of the 21 patients were cured, and 2 were relieved of symptoms. Six patients underwent subtotal resection of the maxilla, and the symptoms disappeared completely after the surgery. Two patients underwent partial resection of the mandible and recovered. Conclusion Surgical debridement is an effective measure for the treatment of patients with bisphosphonate-related osteonecrosis of the jaw in stages Ⅱ-Ⅲ. In most cases, curettage of local lesions via the intraoral approach can completely remove sequestrum and inflammatory granulomatous tissue. Subtotal maxillary resection or partial mandible resection is performed when the bone death reaches the level of the maxillary sinus floor or continues to the mandible. By timely surgical intervention, the bone lesion is removed to maintain the sterile, active bone microenvironment locally.

Objective: Predefining the most effective treatment for patients with depressive disorders remains a problem. We will examine the differential brain regions of gray matter (GM) in major depressive disorder (MDD) patients and the relationship between changes in their volume and the efficacy of early antidepressant treatment using magnetic resonance imaging (MRI). Methods: 159 never-medicated patients with first-episode MDD and 53 normal control subjects (NCs) were enrolled. The brains were scanned by MRI and measured with the 17-item Hamilton Depression Rating Scale (HAMD-17) at baseline and after 2 weeks of treatment with selective serotonin reuptake inhibitor (SSRI)s, and the non-responder group and responder group were obtained. The patients were analyzed by voxel-based morphological (VBM) and SPSS software. Receiver operator characteristics (ROC) analysis was performed for the difference between the responder group and the non-responder group in the differential brain regions, and Pearson correlations were computed between volume size and HAMD score reduction rate. Results: Smaller GM volume of the right superior temporal gyrus (STG), and the orbital parts of the right medial frontal gyrus and right inferior frontal gyrus were observed in MDD versus the NCs. The non-responder group demonstrated a significant volume reduction at the right STG compared with the responders, but no corresponding change in orbital part of right medial frontal gyrus and right inferior frontal gyrus. ROC analysis showed that Accuracy=71.2%. There was a positive correlation between the STG gray matter volume and the HAMD-17 score reduction rate (r=0.347, p=0.002). Conclusion The study results confirmed the local changes in brain structure in MDD and may initially predict the early treatment response produced by SSRIs as antidepressants.

Objective? To observe the correlation factors of venous injury caused by peripheral intravenous indwelling catheter, so as to guide the rational use of clinical intravenous indwelling catheter, so as to avoid venous injury and promote vascular recovery. Methods? This study was carried out in five Class Ⅲ Grade A hospitals. In each hospital, we randomly selected one of the departments: Digestive Internal Medicine, Nephrology, Hepatobiliary Surgery, Extraglandular Surgery and Respiratory Medicine as the research departments. The inpatients admitted from March to June 2018 were selected and included in the study as a whole with the consent of the patients. In this study, 81 qualified patients were successfully injected with the peripheral intravenous indwelling catheter infusion and observed. According to the prescription of the doctors and hospital department policies, peripheral intravenous indwelling catheter was used for infusion. Specialists were arranged to record the patients' infused solution, evaluate the puncture site of the indwelling catheter before puncture and the results of venous blood vessel evaluation before puncture. Observe and record the reasons for the removal of indwelling catheter, the patency during the removal, the indwelling time, the marking of indwelling vein, evaluate and record the condition of the puncture site of indwelling catheter and the grade of phlebitis. The elasticity and filling degree of venous vessels were evaluated and recorded on the 14th day after catheter removal. Results?(1)The severity of local phlebitis was positively correlated with the severity of vascular injury when removing intravenous indwelling catheter; the incidence of moderate and severe vascular injury was 9.09% when local symptoms were grade Ⅰ phlebitis; the incidence of moderate and severe vascular injury was 95.83% when local symptoms were grade Ⅱ and Ⅲ phlebitis when removing intravenous indwelling catheter; and there was statistical difference in the incidence of moderate and severe vascular injury between the two groups (P＜0.01). (2)No moderate or severe vascular injury occurred after asymptomatic removal of intravenous indwelling catheter, and the vascular recovery rate was 100.00%. The incidence of moderate or severe vascular injury was 42.37% and the vascular recovery rate was 57.63% in patients with symptomatic removal of intravenous indwelling catheter. There was a statistically significant difference in the incidence of venous injury and recovery between the two groups (P＜ 0.01). (3)There was no significant difference between the indwelling time of intravenous indwelling catheter and the incidence of phlebitis and the rate of vascular injury and recovery during the time period of this clinical study (P＞0.05). Conclusions? Phlebitis after peripheral intravenous indwelling catheter infusion is the main cause of vascular injury and hinders venous recovery. Preventive measures should be taken in clinical puncture and use of venous indwelling needles; the removal of indwelling catheters should not be based only on indwelling time; the symptoms of puncture sites and patients' reactions should be evaluated in accordance with the regulations to avoid phlebitis above grade Ⅱ; in order to avoid vascular injury caused by infusion of peripheral intravenous indwelling catheters, asymptomatic removal of intravenous indwelling catheter is recommended.