Although immunotherapy has made a breakthrough in the treatment of cancer,the emergence of drug resistance has limited be-nefits in most patients,and reversing immunotherapy resistance remains a hotly debated and unresolved issue.The tumor microenviron-ment(TME)comprises a large number of T lymphocytes.During the biological processes of proliferation,activation,and the effect of tumor-infiltrating lymphocytes(TILs),TILs face severe local metabolic stress,resulting in metabolic reprogramming to meet the markedly increased energy demand and biosynthesis requirements.This process of adaptive changes in the metabolic pattern is closely related to the pheno-type and function of TILs,affecting immunotherapy efficacy and mediating immunotherapy resistance.In recent years,with the study of TIL metabolism and the search for specific metabolic regulatory points,targeting the TIL metabolic pathway could restore the tumor-killing func-tion and reverse immunotherapy resistance.This review explores the relationship between the metabolic reprogramming of TILs and im-mune resistance,and provides a new strategy for reversing immune resistance.

Objective:To explore the protective effect of methyl eugenol (Me) on islet ischemia/reperfusion (I/R) injury and elucidate its underlying mechanism.Methods:The islets were isolated and purified from 6-8 week male BALB/c mice and divided into four groups of normal control (normal culture without any treatment), hypoxia/reoxygenation (H/R treatment), H/R+ dimethyl sulfoxide (DMSO dosing plus H/R treatment) and H/R+ Me (Me dosing plus H/R). Viability of islet cells in each group was detected by acridine orange (AO)/propidium iodide (PI) double stain.Function of islet cells (insulin secretion) was measured by enzyme-linked immunosorbent assay (ELISA). Murine islet β Min6 cells were selected for detecting the effect of Me on the proliferative activity of normal cultured and H/R treated islet cells under different concentration gradients by CCK8.Then Min6 cells were divided into four groups of normal, H/R, H/R+ DMSO and H/R+ Me.The definition of group was the same as that of primary murine islets.Flow cytometry and Hoechst 33342 nuclear stain were utilized for detecting cell apoptotic rate in each group.The protein expressions of p-JNK, p-p38, JNK, p38, Bcl-2 and Bax were detected by Western blot.And the data were processed by one-way ANOVA or t test.Results:The proportion of dead islet cells in H/R group was (29.47±2.65)% and it was significantly lower than that in normal group (7.63±1.53)%.And the inter-group differences were statistically significant ( P<0.001). The proportion of dead islet cells was (20.63±3.07)% in H/R+ Me group.It was higher than that in H/R group (29.47±2.65)% and in H/R+ DMSO group (30.13±1.50)% and inter-group difference was statistically significant ( P<0.05 & P<0.01). Under the stimulation of high glucose, the insulin secretion level of islet in H/R+ Me group was (1.76+ 0.08) mg/L, which was higher than that in H/R group and H/R+ DMSD group(1.24±0.14)mg/L and(1.27±0.05)mg/L, and the difference was statistically significant[(1.76±0.08) vs. (1.24±0.14) mg/L; (1.76±0.08) vs.(1.27±0.05) mg/L, P<0.01]. There was no significant effect on cell viability after Me dosing within a certain concentration range (0-40 μmol/L). After Me dosing (5 μmol/L), cell viability of H/R-treated Min6 cells was significantly higher than that without Me.And the difference was statistically significant[(1.19±0.03) vs.(1.00±0), P<0.01]. As compared with H/R and H/R+ DMSO groups, overall apoptotic rate declined in H/R+ Me group (Hoechst 33342 stain: 14.50%±1.05% vs. 23.30%±1.18%, 14.50%±1.05% vs. 22.77%±1.75%, P<0.001; Flow cytometry: 4.36%±0.54% vs. 21.44%±1.02%, 4.36%±0.54% vs. 21.68%±3.06%, P<0.01). The expressions of p-JNK and p-p38 were down-regulated (p-JNK: 0.77±0.06 vs. 1.03±0.05, 0.77±0.06 vs.0.93±0.04, P<0.001; p-p38: 0.80±0.05 vs. 1.01±0.08; 0.80±0.05 vs. 1.00±0.05, P<0.05) while Bcl-2/Bax ratio rose (1.62±0.13 vs. 0.72±0.10, 1.62±0.13 vs. 0.74±0.13, P<0.01). Conclusions:Me can improve the viability and function of islets and suppress the apoptosis of Min6 cells after H/R.The mechanism is correlated with JNK and p38 MAPK signaling pathways.

ObjectiveTo explore the forest type and soil environment suitable for Panax ginseng. MethodThe yield， quality， soil chemical properties， soil enzyme activity， and soil microbial metabolism of 9-year-old P. ginseng under different forests were investigated. ResultThe quality of P. ginseng was significantly different among forest types. To be specific， P. ginseng under the Quercus mongolica forest had the highest quality， with the total saponin content of 2.27% which was 51.89% higher than that in P. ginseng under Larix gmelinii forest. The yield of P. ginseng under Q. mongolica forest and L. gmelinii forest （30 g·m^-2） was the highest， 62.5% higher than that under Betula platyphylla forest. The soil content of organic matter， Cu， and Zn， and activity of sucrase and urease under Q. mongolica forest were lower than those under other forest types. The utilization rate of D-galacturonic acid by soil microorganisms under Q. mongolica forest was higher than that under other forest types， but the utilization rate of L-phenylalanine was lower than that under other forest types. The utilization rate of 2-hydroxybenzoic acid by soil microorganisms of B. platyphylla forest was significantly lower than that under other forest types. There was a negative correlation between soil Zn and ginsenoside Rb₁ and Rc， and between soil K and ginsenoside Rb₂ and Rb₃. Mn and Cu were positively correlated with most saponins. The results of redundancy analysis showed that the soil microorganisms using carbon sources of amino acids， esters， acids， and sugars were the main factors causing the differences in P. ginseng among different forest types. ConclusionThe yield and quality of P. ginseng under Q. mongolica forest were the best， followed by the forest with different tree species， and coming in last was the B. platyphylla forest. This study is expected to provide theoretical support for the improvement of P. ginseng yield and quality and the improvement of ecological planting technology.

Objective:To report the clinical features, imaging findings and gene mutation features of a Chinese family with cerebral autosomal dominant arteriopathy with subcritical infarcts and leukoencephalopathy (CADASIL).Methods:We summarized the clinical and imaging features of a CADASIL family confirmed by gene sequencing. NOTCH3 gene sequencing was conducted for the proband, and the structure of the protein encoded by the mutant gene was predicted. Results:The patients in this family mainly presented with recurrent lacunar infarction and hypertension, without headache and emotional disorders such as anxiety or depression. Head MRI of the proband showed multiple lacunar infarctions and extensive white matter degeneration. Susceptibility-weighted imaging showed multiple small intracranial hemorrhages. The analysis of NOTCH3 gene showed that the proband had c.697T>A mutation. The 3D structure prediction of the protein encoded by this mutation locus showed that this locus could lead to the conversion of cysteine to serine at the 233rd position. Conclusions:The patients of this CADASIL family have a c.697T>A mutation of NOTCH3 gene. This mutation may cause the change of amino acid in the structure of the wild type Notch3 protein, which may lead to increased formation of β-folding structures in the surrounding region, thus changing the structure and function of protein and causing disease.

Migraine is one of the most common primary headache with high disability rate and heavy disease burden. Cardiovascular diseases are common comorbidities in migraine patients; different cardiovascular diseases have different correlations with migraine. For some cardiovascular events with poor prognosis, timely discovery and preventive measures can effectively help to avoid the adverse events. The article illustrates the associations between different cardiovascular diseases and migraine to improve the clinician's attention to such patients.

Objective:To study the relationship between somatization symptoms and body mass index (BMI), sleep and cognitive function in patients with depression.Methods:A total of 119 patients with depression were selected from January to December in 2019.According to the score of patient health questionnaire-15(PHQ15), they were divided into mild somatization group ( n=75) and moderate severe somatization group ( n=44). Hamilton depression scale-24(HAMD-24), patient health questionnaire-15, Pittsburgh sleep quality index(PSQI) and Montreal cognitive assessment(MoCA) were used to evaluate all subjects.SPSS 23.0 software was used for data analysis.Independent sample t-test was used to compare BMI, sleep and cognitive function scores between the two groups.Pearson correlation analysis was used to study the correlation between somatization symptoms and sleep quality and cognitive function. Results:There were significant differences in BMI((21.70±3.09)kg/m 2, (23.31±3.51)kg/m 2), PSQI((12.56±4.37), (14.37±3.72)), sleep quality(1.87±0.86), (2.21±0.80)), sleep disorder ((1.24±0.59), (1.65±0.53))and daytime dysfunction((2.45±0.81), (2.77±0.48)) between the two groups ( t=-3.783--2.133, all P<0.05), but no difference was found in cognition ( P>0.05). Correlation analysis showed that after controlling HAMD, PHQ-15 was positively correlated with PSQI, sleep quality, sleep disorder, daytime dysfunction and language score in MoCA ( r=0.205-0.298, all P<0.05). Conclusion:The severity of somatization in patients with depression is related to BMI, sleep quality, sleep disorder, daytime dysfunction and language function, suggesting that they may play an important role in the pathogenesis of depression with somatization.

Cognitive impairment includes several clinical processes from mild cognitive impairment to dementia, and now it has been a serious public health problem, as there is no effective treatment, it has caused a heavy economic and psychological burden on the family and society, therefore, it seems important to find effective intervention means.Vitamin D is an essential nutrient element for the human body, more and more evidences show that it also participates in many extraskeletal biological reactions, such as nervous system regulatory processes, in addition to calcium and phosphorus metabolism.Several researches have revealed that Vitamin D deficiency is associated with impaired cognition, the mechanisms mediating this link are poorly understood, what's more, for further clinical application, we need to solve the problems like choosing the suitable populations and drug dosage, therefore, this article summarizes and analyzes the effects of serum Vitamin D levels on the cognitive function of different populations, the research progress of Vitamin D intervention research and its possible mechanism of action, hoping to provide references for the clinical application of Vitamin D in the treatment of cognitive impairment.The results show that Vitamin D deficiency is related to the decline of cognitive function in different populations, and Vitamin D can improve cognitive function through reducing Aβ toxicity, anti-inflammatory and anti-oxidative stress and other mechanisms, its supplementation is expected to be an important measure of treating cognitive impairment, in the future, large-scale longitudinal cohort studies are needed to determine the optimal dosage and duration of treatment.

Objective:To introduce a surgical technique of implant-based immediate breast reconstruction using the "latent orifice" procedure after skin-sparing mastectomy and to investigate the clinical value of this procedure.Methods:Clinical data of 72 patients who underwent immediate breast reconstruction using the "latent orifice" procedure (we placed the silicone prosthesis in a "latent orifice" consisting of fascia and underlying muscles) from Jan. 2016 to Dec. 2019 were collected. Characteristics of surgical technique and the effect of the reconstruction surgery were analyzed.Results:70 patients underwent nipple-areola complex sparing mastectomy (NSM) . Two patients’ nipples were resected due to intraoperative frozen pathology suggesting carcinoma existing in the nipples. The nipple epidermal necrosis occurred in 3 patients. No seroma, incision infection or capsular contracture occurred. According to the evaluation scale, the overall aesthetic score was 9.39 points. The average score of each subscale was: 9.57 points for breast volume, 9.43 for breast contour, 9.84 for placement of implant, 9.38 for scars, 9.27 for lower pole projection and 9.21 for inframammary fold definition. BREAST-Q questionnaires were filled by patients. Scores of psychosocial well-being ranged from 62 to 93 points, with the median score of 77 points. Satisfaction with breasts scores ranged from 58 to 100 points, with the median score of 71 points.Conclusion:The "latent orifice" procedure is a simple, safe, practicable, aesthetic and satisfying type of immediate implant-based breast reconstruction, which is worth practicing and promoting.

Migraine is the most common type of primary headache with disabling brain dysfunction. The prevalence of the migraine in Chinese population is 9.3%, and the ratio of female to male is 3∶1, which seriously affect people′s quality of life. Depression is one of the most common psychiatric disorders in migraine comorbidity. Compared with non-migraine patients, the risk of depression comorbidity in migraine patients is more than 2.5 times higher. The frequency and severity of migraine are closely related to depressive symptoms. Depressive symptoms have different effects on headache-related pain signal transduction, which is susceptible to neuroendocrine network disorders in the process of transmission from thalamus to cortex. Neuroendocrine network plays an important role in the depression of migraine comorbidity. Therefore, exploring the pathogenesis of neuroendocrine network in comorbidity provides a theoretical basis for screening more suitable depressive drugs for migraine comorbidity.

Objective? To systematically analyze the research status and development trend of postoperative sleep nursing from 2008 to 2017 in China. Methods? We systematically retrieved literatures on postoperative sleep nursing published in Chinese Biology Medicine disc (CBM), China National Knowledge Infrastructure (CNKI), WanFang Data and Vip Database from 1st January 2008 to 31st December 2017. The bibliometrics was used to statistical analysis. Results? A total of 485 literatures met criteria were included finally. From 2008 to 2017, the number of literatures had a growth trend every year. Literatures were published in 145 journals in China with 8.0% in the nursing core journals. A total of 10.1% of the researches had fund support, 61.6% of literatures had been quoted and 10.2% of them were quoted ≥10 times. Authors were from 28 provinces in China and the cooperative rate was 53.0% with 2.21 for the cooperative level. The research type focused on intervention study, and diseases were main in cancer, orthopedics and mixed surgery patients, and research contents mainly included symptoms of decline, influencing factors and intervention of postoperative sleep quality. Conclusions? In China, researches on postoperative sleep nursing have development tendency but with problems such as uneven regional development, insufficient research support, single assessment tool and imperfect study design. The overall quality needs to be improved.