This paper summarized the game mechanism, application status and application effect of serious games in self-management education for children and adolescents with type 1 diabetes mellitus (T1DM), and put forward the existing shortcomings and suggestions, which can provide references for Chinese medical personnel to carry out health education and develop relevant serious games in the future.

As known, the benefits of photothermal therapy (PTT) are greatly limited by the heat tolerance of cancer cells resulting from overexpressed heat shock proteins (HSPs). Then HSPs further trigger the formation of stress granules (SGs) that regulate protein expression and cell viability under various stress conditions. Inhibition of SG formation can sensitize tumor cells to PTT. Herein, we developed PEGylated pH (low) insertion peptide (PEG-pHLIP)-modified hollow copper sulfide nanoparticles (HCuS NPs) encapsulating the SG inhibitor ISRIB, with the phase-change material lauric acid (LA) as a gate-keeper, to construct a pH-driven and NIR photo-responsive controlled smart drug delivery system (IL@H-PP). The nanomedicine could specifically target slightly acidic tumor sites. Upon irradiation, IL@H-PP realized PTT, and the light-controlled release of ISRIB could effectively inhibit the formation of PTT-induced SG to sensitize tumor cells to PTT, thereby increasing the antitumor effect and inducing potent immunogenic cell death (ICD). Moreover, IL@H-PP could promote the production of reactive oxygen species (ROS) by tumor-associated macrophages (TAMs), repolarizing them towards the M1 phenotype and remodeling the immunosuppressive microenvironment. In vitro/vivo results revealed the potential of PTT combined with SG inhibitors, which provides a new paradigm for antitumor and anti-metastases.

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.

Intelligent responsive drug delivery system opens up new avenues for realizing safer and more effective combination immunotherapy. Herein, a kind of tumor cascade-targeted responsive liposome (NLG919@Lip-pep1) is developed by conjugating polypeptide inhibitor of PD-1 signal pathway (AUNP-12), which is also a targeted peptide that conjugated with liposome carrier through matrix metalloproteinase-2 (MMP-2) cleavable peptide (GPLGVRGD). This targeted liposome is prepared through a mature preparation process, and indoleamine-2,3-dioxygenase (IDO) inhibitor NLG919 was encapsulated into it. Moreover, mediated by the enhanced permeability and retention effect (EPR effect) and AUNP-12, NLG919@Lip-pep1 first targets the cells that highly express PD-L1 in tumor tissues. At the same time, the over-expressed MMP-2 in the tumor site triggers the dissociation of AUNP-12, thus realizing the precise block of PD-1 signal pathway, and restoring the activity of T cells. The exposure of secondary targeting module II VRGDC-NLG919@Lip mediated tumor cells targeting, and further relieved the immunosuppressive microenvironment. Overall, this study offers a potentially appealing paradigm of a high efficiency, low toxicity, and simple intelligent responsive drug delivery system for targeted drug delivery in breast cancer, which can effectively rescue and activate the body's anti-tumor immune response and furthermore achieve effective treatment of metastatic breast cancer.

OBJECTIVETo observe the effects of acupuncture at opposite acupoints on expression of hepatocyte growth factor (HGF) in rats with skeletal muscle contusion, and to explore the mechanism of acupuncture at opposite acupoints on skeletal muscle contusion.

METHODSFifty-four Sprague Dawley (SD) rats were randomly divided into a blank group (6 rats), a model group (24 rats) and an opposing needling group (24 rats). The model group and opposing needling group were further divided into 1-day subgroup, 3-day subgroup, 5-day subgroup and 7-day subgroup, 6 rats in each one. No intervention was given in the blank group, while the model of skeletal muscle contusion was established in the model group and opposing needling group by self-made contusion device. 24 hours after contusion, electroacupuncture (EA) was applied at "Zusanli" (ST 36) and the corresponding points ofpoints at health side for 15 min, once a day. The subgroups of opposing needling group were treated for 1 day, 3 days, 5 days and 7 days, respectively. No treatment was given in the model group. Samples were collected in the subgroups 1 day, 3 days, 5 days and 7 days after treatment. The morphological change of injured gastrocnemius muscle was observed by using microscope after HE staining. The positive cell rate of proliferating cell nuclear antigen (PCNA) was detected by immunohistochemistry. The expression levels of HGF protein and PCNA protein were observed by Western blot.

RESULTS① The results of HE staining showed that, 1 day after contusion, the inflammatory cells of gastrocnemius muscle in the opposing needling group were less than those in the model group; 3 days and 5 days after contusion, myoblasts and myotubes in the opposing needling group were more than those in the model group; 7 days after contusion, the neonatal muscle cells in the opposing needling group were more than those in the model group. ② The results of immunohistochemistry showed that, 1 day, 3 days and 5 days after contusion, the positive cell rate of PCNA in the opposing needling group was significantly higher than that in the model group (all<0.001); 7 days after contusion, the positive cell rate of PCNA in the opposing needling group was significantly less than that in the model group (<0.001). ③ The results of Western blot showed that, 1 day, 3 days and 5 days after contusion, the expression of HGF protein and PCNA protein in the opposing needling group was significantly higher than that in the model group (all<0.05); 7 days after contusion, the expression of HGF protein and PCNA protein in the opposing needling group was significantly lower than that in the model group (all<0.05).

CONCLUSIONAcupuncture at opposite acupoints could regulate the expression of HGF and promote the activation, proliferation, migration and differentiation of muscle satellite cells in rats with skeletal muscle contusion, which could speed up the process of skeletal muscle injury repair.

Objective To observe the effects of massage on inflammation,oxidative stress and autophagy during the repair of acute contusion of skeletal muscles so as to explore its biological mechanisms.Methods Forty-two adult Sprague-Dawley rats were randomly divided into a control group (n =6),a model group (n =18),and a treatment group (n =18).Acute contusion of the gastrocnemius muscles of the rats in the model and treatment groups was inflicted using a home-made impactor.Beginning forty-eight hours later,15 minutes of massage was administered daily for two weeks.After one,7 and 14 days of the massage treatment,the injured gastrocnemius was resected from 6 rats of both the model and treatment groups.Morphological changes were observed using haematoxylin and eosin (HE) staining.The serum content of tumor necrosis factor alpha (TNF-α),interleukin1β (IL-1 β),C reactive protein (CRP) and prostaglandin E2 (PGE2) were detected using enzyme-linked immunosorbent assay (ELISA).The serum content of superoxide (SOD) and malondialdehyde (MDA) were detected using spectrophotometry.The expression of microtubule-associated protein 1 light chain 3 (LC3),Bcl-2 homeodomain protein Beclin1 and ubiquitin binding protein P62 were detected using Western blotting.Results The HE staining showed more significant collapse and swelling of cells in the model group than in the control group at each time point.New muscle cells were observed at days 7 and 14 in the model group.At each time point,significantly better recovery was observed in the treatment group compared to the model group,with more new muscle cells and better cell morphology.According to the ELISA results,a significant increase in serum pro-inflammatory factors occurred in the model group compared to the control group and compared to the treatment group after one day and 7 days of treatment.The average serum content of SOD and MDA in the model group was significantly higher than in the control group,while the average serum content of SOD in the treatment group was significantly higher than in the model group and that of MDA was significantly lower.Western blotting showed a significant decrease in LC3 (Ⅱ/Ⅰ) and Beclin1,as well as a significant increase in P62 in the model group at each time point compared with the treatment group and the controls.Conclusion Inflammation and oxidative stress increase significantly in a skeletal muscle after injury,but autophagy decreases significantly.Massage can effectively reduce the inflammatory response and oxidative stress and promote autophagy,which leads to quicker repair of skeletal muscles.

Objective To explore the effects and mechanism of electroacupuncture (EA) on denervation-induced atrophy in rats. Methods A total of 18 male Sprague-Dawley rats were divided into sham group (n=6), model group (n=6) and EA group (n=6). The latter two groups were clamped right sciatic nerve to establish atrophy model of skeletal muscle. On the second day after modeling, EA group accepted electroacupuncture on right Zusanli (ST36) and Huantiao (GB30) for two weeks. Their gastrocnemius muscles were obtained after intervention, and the wet weight ratio of the gastrocnemius muscles was calculated. The cross-sectional area (CSA) and diameter of muscle fibers were measured after HE staining. The protein expression of mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), 70-KD ribosomal protein S6 kinase (p70S6K) and phosphorylated p70S6k (p-p70S6k) was tested with Western blotting. The gene expression of mTOR and p70S6K was detected with real-time quantitative polymerase chain reaction. Results Compared with the sham group, the wet weight ratio of the gastrocnemius muscle, CSA and diameter of the muscle fibers decreased in the model group and EA group (P<0.001), which were more in EA group than in the model group (P<0.01); the protein expression of mTOR, p-mTOR, p70S6K and p-p70S6K increased in the model group (P<0.01), and increased more in EA group (P<0.05); the gene expression of mTOR and p70S6K increased in the model group (P<0.05) , and increased more in EA group (P<0.05).Conclusion Electroacupuncture delays the atrophy of denervated skeletal muscles, which may relate to activation of mTOR/p70S6K signal pathway to impact synthesis of skeletal muscle proteins.

Irrespective of physiological or pathological skeletal muscle atrophy, the endocrine and motor functions of skeletal muscle are impaired. The mechanism of acupuncture to prevent and treat skeletal muscle atrophy is not only related to classical protein synthesis and decomposition, but also involves apoptosis, autophagy, muscle satellite cell proliferation and differentiation, muscle fiber type conversion, neuromuscular junction conduction, and cell energy metabolism conversion.

Objective To observe the effect of the electroacupuncture ( EA) on the expression of cyclin-de-pendent kinase 5 ( Cdk5 ) in rats with muscle contusion and to explore its mechanism. Methods Thirty-two Sprague-Dawley rats were randomly divided into a normal group of 4, a model group of 4, a natural recovery group ( NR) of 12 and an EA group of 12. All except those in the normal group had acute skeletal muscle contusion induced through a heavy blow. The EA group was treated with 15 minutes of EA daily beginning 48 h after the injury while the other rats received no EA. The model group was sacrificed 24 h after modeling, and rats from the NR and EA groups were sacrificed on the 7th, 14th and 21st day after the modeling to collect tissues. Hematoxylin eosin ( HE) staining, Western blotting and quantitative real-time fluorescence PCR were used to observe any histological changes, as well as Cdk5 protein and mRNA expression. Results The HE staining showed that the other 3 groups displayed larger a-mounts of muscle fiber fracture, dissolution and inflammatory cell invasion than was observed in the normal group. Compared with the NR group, quicker recovery was seen in the EA group as evidenced by faster muscle satellite cell proliferation and more new muscle fiber generation. The average Cdk5 protein expression in both the NR and EA groups was higher than in the normal group, and that of the EA group was significantly lower than that of the NR group. Conclusions Muscle contusion can increase Cdk5 expression in skeletal muscles, at least in rats. EA can promote the restoration of skeletal muscle function, probably by inhibiting CDK5 protein and mRNA expression.

Traditional Chinese Medicine as a rare heritage from our progenitor is becoming more and more important in the world. A lot of foreign students have come to China for learning TCM , and the number of foreign students has increased with time. A lot of issues occur during the teaching process for the foreign students. The problems including the source of students' quality, language, teaching material and clinic practice during the teaching process for the foreign students were ana-lyzed in the article, and the resolutions according to the problems were put forward to attract more and more foreign students to learn TCM and promote TCM in the world.