Immune checkpoint inhibitors (ICIs) have demonstrated unparalleled clinical responses and revolutionized the paradigm of tumor treatment, while substantial patients remain unresponsive or develop resistance to ICIs as a single agent, which is traceable to cellular metabolic dysfunction. Although dysregulated metabolism has long been adjudged as a hallmark of tumor, it is now increasingly accepted that metabolic reprogramming is not exclusive to tumor cells but is also characteristic of immunocytes. Correspondingly, people used to pay more attention to the effect of tumor cell metabolism on immunocytes, but in practice immunocytes interact intimately with their own metabolic function in a way that has never been realized before during their activation and differentiation, which opens up a whole new frontier called immunometabolism. The metabolic intervention for tumor-infiltrating immunocytes could offer fresh opportunities to break the resistance and ameliorate existing ICI immunotherapy, whose crux might be to ascertain synergistic combinations of metabolic intervention with ICIs to reap synergic benefits and facilitate an adjusted anti-tumor immune response. Herein, we elaborate potential mechanisms underlying immunotherapy resistance from a novel dimension of metabolic reprogramming in diverse tumor-infiltrating immunocytes, and related metabolic intervention in the hope of offering a reference for targeting metabolic vulnerabilities to circumvent immunotherapeutic resistance.
Humans ; Neoplasms/pathology* ; Immunotherapy/methods* ; Immune Checkpoint Inhibitors/therapeutic use*

Objective:To improve the prognosis stratification, especially early mortality(EM), of elderly patients with newly diagnosed multiple myeloma(NDMM).Methods:In this retrospective study, univariate and multivariate Cox regression analysis were conducted to identify the independent prognostic factors associated with overall survival(OS)and the chi-square test and multivariate Logistic analysis were used to identify the prognostic factors associated with EM in 223 elderly patients(age≥65 years)with NDMM from three centers in the country.Results:Increased NT-pro-BNP(≥300 pg/ml), ECOG-PS≥2 and stage Ⅲ R-ISS were identified as three independent adverse prognostic factors of OS.The rates of EM3, EM6, EM12 and EM24 were 12.1%, 20.1%, 32.2% and 60%, respectively.The most common cause for EM6(particularly EM3)was disease-related complications resulting from ineligibility for treatment due to poor physical performance, severe organ dysfunction or treatment discontinuation due to treatment intolerance, while the most common cause for EM12(particularly EM24)was disease progression or relapse mainly as a result of inadequate treatment.R-ISS staging failed to predict EM, while decreased eGFR, ECOG-PS≥2, and increased NT-pro-BNP were able to estimate the risk of EM, with increased NT-pro-BNP as a common independent factor for EM12( P=0.03)and EM24( P=0.015). Conclusions:R-ISS staging, which primarily reflects MM biology, cannot predict EM.However, factors such as NT-pro-BNP, eGFR and ECOG-PS associated with frailty and impairment of organ functions can be used to estimate the risk of EM, among which NT-pro-BNP may be the most important independent factor for EM.Therefore, incorporation of these frailty-related biomarkers into R-ISS staging may be able to more precisely estimate the prognosis and particularly early death of elderly patients with NDMM.

Objective:To observe any effect of electroacupuncture (EA) on the expression of phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2) and phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) in the spinal dorsal horns of diabetics experiencing neuropathic pain.Methods:Eight rats were randomly selected from 30 healthy male Sprague-Dawley rats as the normal group (N), and the remaining twenty-two rats were treated with a single high-dose intraperitoneal injection of streptozotocin (STZ) to establish a neuropathic pain model. The rats modeled successfully were randomly divided into a model group (M, n=8) and an EA group ( n=8). In the EA group, electroacupuncture was applied at the bilateral Hou san li and Kunlun acupoints starting on the 15th day after the STZ injection. The daily sessions lasted 30 minutes for 1 week. Body weight (BW), fasting blood glucose (FBG) and paw withdrawal latency (PWL) were observed before the STZ injection and on the 7th, 14th, and 21st days afterward. The expression of p-ERK1/2 and p-CREB in the dorsal horns of the rats′ spinal cords was detected using western blotting. The count of p-CREB-positive cells in the dorsal horns and their co-localization with neurons was detected using immunofluorescence. Results:In comparison with the N group, the average BW of the M group on the 7th, 14th and 21st days after the STZ injection was significantly lower, while the average FBG was significantly higher. There was no significant difference between the M and N groups in the average PWL on the 7th day after the STZ injection, but it had decreased significantly in the M group on the 14th and 21st days. Compared with the M group, the average PWL of the EA group was significantly longer on the 21st day after the injection. The expression of p-ERK1/2 and p-CREB protein in the spines of the M group was significantly higher than in the N group. p-CREB positive cells were more numerous in the M group compared with the N group, while in the EA group they were fewer. P-CREB was co-located with neurons in the spinal dorsal horn.Conclusion:EA can alleviate neuropathic pain effectively, perhaps by inhibiting the expression of p-ERK1/2 and p-CREB in the dorsal horns of the spinal cord.

Nasopharyngeal carcinoma (NPC) is a common malignant tumor in China. Radiotherapy is the first-line treatment. After appropriate radiotherapy, about 5%-15% patients experience recurrence. In view of the poor efficacy and high incidence of severe late toxicities associated with re-irradiation, salvage surgery by the transnasal endoscopic approach is recommended for recurrent NPC (rNPC). Compared with re-irradiation, endoscopic surgery can better prolong survival, improve the quality of life, and reduce complications and medical expenses of patients with rNPC. However, the complexity of the nasopharyngeal skull base enhances the difficulty and risk of surgery. Expanding the boundary of surgical resection remains a clinical challenge for otolaryngologists. In this regard, to help more advanced patients with rNPC, the surgical innovative system of NPC needs to be established by multi-disciplinary cooperation, involving skull base anatomy-based investigation, appropriate administration of the internal carotid artery (ICA), repair of skull base defect, and establishment of various types of endoscopic endonasal nasopharyngectomy.

Objective:To investigate risk factors for early mortality (EM) in patients with newly diagnosed multiple myeloma (NDMM) and to build an EM-predictive model.Methods:In a cohort of 275 patients with NDMM, risk factors for EM at 6, 12, and 24 months after diagnosis (EM6, EM12, and EM24, respectively) were determined to establish a model to predict EM.Results:The rates of EM6, EM12, and EM24 were 5.5% , 12.7% , and 30.2% , respectively. The most common cause for EM was disease progression/relapse, accounting for 60.0% , 77.1% , and 84.3% of EM6, EM12, and EM24, respectively. EM6 was associated with corrected serum calcium >2.75 mmol/L and platelet count <100×10 9/L, whereas risk factors for EM12 included age >75 years, ISS Ⅲ, R-ISS Ⅲ, corrected serum calcium >2.75 mmol/L, serum creatinine >177 μmol/L, platelet count <100×10 9/L, and bone marrow plasma cell ratio ≥ 60% . In addition to the risk factors for EM12, EM24 was also associated with male sex and 1q21 gain. By multivariate analysis, age >75 years, platelet count <100×10 9/L, and 1q21 gain were independent risk factors for EM24 but there were no independent risk factors significantly associated with EM6 and EM12. Using a scoring system including these three risk factors, a Cox model for EM24 was generated to distinguish patients with low (score<3) and high (score ≥ 3) risk. The sensitivity and specificity of the model were 20.7% and 99.2% , respectively. Further, an internal validation performed in a cohort of 183 patients with NDMM revealed that the probability of EM24 in high-risk patients was 26 times higher than that in low-risk patients. Moreover, this model was also able to predict overall survival. The median overall survival of patients with scores of 0, 1, 2, 3, 4, and 5 were 59, 41, 22, 17.5, and 16 months, respectively. Conclusion:In the study cohort, the EM6, EM12, and EM24 rates were 5.5% , 12.7% , and 30.2% , respectively, and disease progression or relapse were main causes of EM. An EM24-predictive model built on three independent risk factors for EM24 (age>75 years, platelet count<100×10 9/L, and 1q21 gain) might predict EM risk and overall survival.

Objective: To understand the current status of follow up of people living with HIV/AIDS by health service at grass root in rural area of Jiangxi province and related factors, and provide references for the promotion of the follow up by grass root health service. Methods: People living HIV/AIDS aged ≥18 years and diagnosed before 31 December 2017 in 6 townships of Xinjian, Yushan counties and Guixi city were included in the study in Jiangxi province. They had been followed up for more than one time after the first epidemiologic survey. The information about their demographic characteristics and HIV infection status were collected by using self-designed questionnaire. Univariate and multivariate logistic regression analyses were conducted to identify the factors that influencing the acceptance of follow up by grass root health service. Results: Of the 373 surveyed HIV infected subjects aged (53.06±16.15) years, 261 were males (70.0%, 261/373). Among the surveyed subjects, the illiteracy and people who received only primary school education accounted for 54.7% (204/373). The rate of follow up of the HIV infected subjects by grass root health service was 55.8% (208/373), and those through heterosexual contact were 58.5% (190/325). The multivariate regression analysis showed that the acceptance of follow up by grass root health service was higher in those who were farmers (OR=7.36, 95%CI: 2.52-21.45), had family support (OR=16.01, 95%CI: 2.25-49.73), didn’t worry about discrimination (OR=12.97, 95%CI: 4.75-35.42), trusted health care provider (OR=5.07, 95%CI: 2.19-11.76) and showed AIDS symptoms (OR=10.58, 95%CI: 2.25- 49.73). Conclusions The performance of follow up of people living with HIV/AIDS by grass root health service was well, suggesting it is a feasible management model. Being famer or not, family member supporting or not, worry about discrimination or not, trusting health care provider or not and showing AIDS symptoms or not were the main factors influencing the acceptance of follow up by grass root health service.

Objective To investigate the correlation between pathologic features and contrast?enhanced ultrasound in patients with breast ductal papilloma. Methods From January 2014 to January 2016,80 patients with breast intraductal tumor treated in our hospital were selected,including 20 cases of breast ductal carcinoma (ductal carcinoma group) and 60 cases of benign tumor (benign group). Both groups received conventional ultrasound, ultrasonic angiography,and pathological feature analysis. Results Breast surrounding hyperecho,internal micro calcification,border edge burr and posterior echo attenuation were more frequently seen onconventional ultrasound in ductal carcinoma groupthan inbenign group(P<0.05). The average scores of contrast?enhanced ultrasound were significantly higher in ductal carcinoma group than in the control group(P<0.05). In the ductal carcinoma group, there were statistical significant differences betweenpatientswith different lymph node metastasis dukes staging ,and differentiation types (P < 0.05). Spearman rank correlation coefficient analysis showed that breast intraductal carcinoma lymph node metastasis and dukes staging,differentiation types were markedly correlated with pathological features and ultrasound imaging (r=0.341,0.368,and-0.289;P<0.05). Conclusions Conventional ultrasound and contrast?enhanced ultrasound have very good imaging featuresin the diagnosis of breast intraductal cancer ,and there is correlation between pathologic features and contrast?enhanced ultrasound in patients with breast ductal papilloma,which can provide values for early diagnosis of breast ductal carcinoma.

OBJECTIVE:To establish a method for simultaneous determination of tanshinol,caffeic acid,rosmarinic,salviano-lic acid B,salvianolic acid A,tanshinoneⅠ,cryptotanshinone,tanshinone ⅡA and ursolic acid in Compound xueshuantong cap-sules. METHODS:UPLC-MS/MS method was adopted. The determination was performed on ACQUITY UPLC? BEH C18 column with mobile phase consisted of acetonitrile-0.1%formic acid(gradient elution)at the flow rate of 0.2 mL/min. The column tempera-ture was 40 ℃,and the temperature of injector was 10 ℃. Analysis time was 7 min,and sample size was 5 μL. The electrospray ionization source(ESI)was used;ion source temperature was 150℃;capillary voltage was 3.5 kV;cone flow was 50 L/h;desol-vation temperature was 350 ℃;desolvation gas flow was 650 L/h;nebuliser pressure was 7 × 105 Pa;ion monitoring and multiple reaction monitoring (MRM) was performed. RESULTS:The linear ranges of tanshinol,caffeic acid,rosmarinic,salvianolic acid B,salvianolic acid A,tanshinoneⅠ,cryptotanshinone,tanshinone ⅡA and ursolic acid were 10.0-100.0 μg/mL (r=0.9998), 0.1-1.0 μg/mL(r=0.9998),4.0-40.0 μg/mL(r=0.9999),10.0-100.0 μg/mL(r=0.9999),15.0-150.0 μg/mL(r=0.9997), 8.0-80.0 μg/mL(r=0.9998),10.0-100.0 μg/mL(r=0.9997),50.0-500.0 μg/mL(r=0.9997)and 6.0-60.0 μg/mL(r=0.9998), respectively. The limits of quantitation were 40.0,9.6,38.0,88.0,130.0,39.0,4.4,3.2 and 10.0 ng/mL,separately. The limits of detection were 12.0,3.0,11.0,26.0,39.0,12.0,1.3,1.0 and 3.0 ng/mL,respectively. RSDs of precision,stability and repro-ducibility tests were all lower than 3%. The recoveries were 97.34%-103.20%(RSD=2.19%,n=6),97.22%-102.39%(RSD=2.03%,n=6),98.51%-101.70%(RSD=1.32%,n=6),97.86%-102.49%(RSD=2.09%,n=6),96.75%-103.12%(RSD=2.36%,n=6),98.43%-101.65%(RSD=1.25%,n=6), 97.59%-101.50%(RSD=1.50%,n=6), 96.45%-102.88%(RSD=2.58%,n=6),97.02%-103.11%(RSD=2.38%,n=6),separately. CONCLUSIONS:The method is simple and accurate,and can be used for simultaneous determination of 9 components in Compound xueshuantong capsules.

Objective To preliminarily test the value of gastroesophageal reflux disease questionnaire (GERD-Q) in auxiliary diagnosis of gastroesophageal reflux disease(GERD) in infants and young children.Methods From January 2011 to February 2014,148 infants and 87 young children with suspected GERD symptoms were enrolled in the outpatient and inpatient departments of Wuhan Women and Children's Medical Care Center.The diagnosis of GERD were made through 24 h esophageal pH monitoring and upper gastrointestinal hysterosalpingography.Those with any examinations being positive were brought into GERD group,and the others into the control group.All cases had been surveyed with GERD-Q.Using SPSS17.0 statistical software,the ratio was compared with chi-square test,and the difference of the scores between groups with t test.Results In infants (1 to 11 months),the individual symptom scores (ISS) of the 6 symptoms in the GERD group (n =111) were all higher than those in the control group (37 cases) (P ＜ 0.05),and the composite and symptom scores (CSS) [(131.43 ± 66.56) scores] in the GERD group was higher than that [(33.70 ± 40.03) scores] in the control group (t =8.42,P ＜ 0.05).In young children (1 to 3 years old),the ISS in the GERD group(55 cases) were all higher than those in the control group(32 cases),and the CSS[(98.58 ± 66.75) scores] in the GERD group was also higher than that [(28.50 ± 35.95) scores] in the control group(t =5.49,P ＜ 0.05).Conclusions There is a good correlation for age-specific GERD-Q to distinguish GERD symptoms in infants and young children,which is suitable for the assessment of GERD.

Objective To investigate hand hygiene status of health care workers (HCWs)in a hospital,and pro-vide guides for improving hand hygiene compliance.Methods Hand hygiene intervention was adopted in a hospital between 2012 and 2014,hand hygiene compliance among HCWs and healthcare-associated infection in patients be-tween August 1 and August 31 of each year were investigated and analyzed statistically.Results In 2102 -2014, hand hygiene compliance rate of HCWs was 59.55%,62.13%,and 65.16% respectively,which showed a increased trend (χ2 =10.018,P =0.002),HAI rate was 2.13%,1 .48% and 1 .06% respectively,which showed a decreased trend (χ2 =82.377,P <0.001 );hand hygiene compliance rate of doctors was lower than nurses (57.97% vs 65.97%);Of different hand hygiene moments,hand hygiene compliance rate was the lowest before touching a pa-tient(41 .32%),and highest after body fluid exposure (76.47%).Conclusion Comprehensive hand hygiene inter-vention in this hospital has achieved preliminary results,improvement of HCWs’hand compliance is helpful for pre-venting HAI.