[Epidemiological characteristics of pulmonary tuberculosis in Guangdong province from 2016 to 2020].

Objective: To analyze the epidemiological characteristics of pulmonary tuberculosis (TB) in Guangdong province from 2016 to 2020 and provide evidence for the prevention and control of pulmonary TB. Methods: Descriptive epidemiological methods were used to analyze the incidence data of pulmonary TB reported in Guangdong from 2016 to 2020. Dynamic geometric series averaging and circular distribution methods were used to reveal the epidemic pattern. Results: A total of 356 748 pulmonary TB cases were reported in Guangdong from 2016 to 2020. The reported incidence of pulmonary TB decreased from 71.82/100 000 to 50.40/100 000 (trend χ2=6 905.57,P<0.001) , with an annual decline rate of 8.47%. Results from the circular distribution methods showed that the incidence peak would occur on May 4th-5th (Z=1 176.96,P<0.05), and the incidence was relatively higher in May compared with other months. The area distribution of the pulmonary TB epidemic was uneven, and the reported average annual incidence was in the order of the eastern area (72.15/100 000), the northern area (68.14/100 000), the western area (65.31/100 000) and the Pearl River Delta area (60.05/100 000). Results of dynamic geometric series averaging analysis showed a declining trend in the reported incidence of pulmonary TB in all areas, except Dongguan, with the average growth rate less than 0.00. The decline rate in the eastern area (-10.90%) and northern area (-10.63%) was higher than the provincial average (-8.47%). The male to female ratio of the cases was 2.63∶1 (258 562∶98 186). The reported average annual pulmonary TB incidence in men (88.37/100 000) was higher than that in women (36.86/100 000), the difference was significant (χ2=75.19, P<0.001). The reported incidence of pulmonary TB generally increased with age (trendχ2=123 849.44, P<0.001), and reached peak in age group ≥65 years (164.54/100 000). Dynamic geometric series averaging analysis showed an increasing trend of the reported pulmonary TB incidence in age groups 5-14 years and 15-24 years, with the average growth rate of 0.05% and 3.60%. Conclusions: The reported annual incidence of pulmonary TB showed a declining trend year by year in Guangdong from 2016 to 2020. However, an increasing incidence was reported in children and adolescents. Active case finding should be strengthened in the elderly and other key populations. With comprehensive TB prevention and control measures, it is still necessary to pay attention to the prevention and control of pulmonary TB in men, low-income groups and less developed areas in Guangdong and strengthen the comprehensive prevention and control in winter and spring.

Repurposing Ivermectin to augment chemotherapy's efficacy in osteosarcoma.

BACKGROUND: Osteosarcoma is the most frequent malignant bone malignancy and the current treatments are ineffective. Ivermectin, an anti-protozoal drug, has been shown to have anti-cancer activity. This work investigated the potential of repurposing ivermectin to augment chemotherapy's efficacy in osteosarcoma. METHODS: Proliferation, migration and apoptosis assays were performed in ivermectin-treated osteosarcoma cells. Combination studies were performed. Osteosarcoma xenograft mouse model was established to investigate the in vivo efficacy of ivermectin. Intracellular reactive oxygen species (ROS) and mitochondrial superoxide, membrane potential, ATP, 8-OHdG level, protein carbonylation and lipid peroxidation were determined after ivermectin treatment. RESULTS: Ivermectin was effective and acted synergistically with doxorubicin in osteosarcoma cells regardless of cellular origin and genetic profiling. This was achieved through suppressing inhibiting growth and migration, and inducing caspase-dependent apoptosis. Ivermectin also significantly inhibited osteosarcoma growth in vivo and its combination with doxorubicin resulted in much greater efficacy than doxorubicin alone. Importantly, the effective dose of ivermectin was clinically feasible and did not cause significant toxicity in mice. Mechanistical analysis showed that ivermectin induced oxidative stress and damage, and mitochondrial dysfunction. CONCLUSIONS: Our findings indicate that ivermectin has utility in treating patients with osteosarcoma, especially those resistant to chemotherapy.

[Update on the medical management of parathyroid carcinoma].

Parathyroid carcinoma is a rare endocrine malignancy with an increasing rate of incidence. Most parathyroid carcinoma patients will develop local recurrence or metastases leading to poor prognosis. Medical management is the mainstay of treatment for patients with unresectable parathyroid carcinoma. However, the therapeutic outcome of medical management remains unsatisfactory restricted by limited options and efficacy. With the deepening of research, several novel drugs have been reported to be applied in the treatment of parathyroid carcinoma. Calcimimetics and receptor activator for nuclear factor-κB ligand inhibitors aiming to control hypercalcemia have been applied in the endocrine therapy of parathyroid carcinoma. Besides, preliminary studies have shown the therapeutic effects of targeted therapy and immunotherapy on parathyroid carcinoma. These new drugs have shed light on this clinical dilemma; however, their clinical efficacy remains to be determined. In this article, the recent progress in the medical management of parathyroid carcinoma is updated.

[Evaluation of severity and prognosis of acute pancreatitis by CT severity index and modified CT severity index].

Objectives: To explore the role of computed tomography (CT) severity index (CTSI) and modified CT severity index (MCTSI) in assessing the severity of acute pancreatitis (AP) under the revised Atlanta classification (RAC) and predicting the clinical prognosis. Methods: Based on the prospectively entered AP database, the clinical data of consecutive adult AP inpatients admitted to the Department of Gastroenterology of the First Affiliated Hospital of Nanchang University from January 2012 to December 2020 were retrospectively screened. The imaging data were independently evaluated by two radiologists and entered to the database to calculate the CTSI and MCTSI scores. Their relationship with the difference of RAC severity grade and clinical prognosis was analyzed. Compared with Acute Physiology and Chronic Health Assessment Ⅱ (APACHE Ⅱ) score, the receiver operating characteristic curve was used to evaluate the predictive value of CTSI and MCTSI scores for persistent organ failure and infectious pancreatic necrosis (IPN). Results: A total of 2 612 patients with AP, aged (50±15) years, were included in the study, including 1 547 males (59.2%) and 1 065 females (40.8%). According to RAC standard, AP was divided into 699 cases (26.8%) of mild pancreatitis (MAP), 1 098 cases (42.0%) of moderately severe pancreatitis (MSAP), and 815 cases (31.2%) of severe pancreatitis (SAP). MCTSI judged AP severity similarly to RAC, with 668 cases of MAP (25.6%), 1 207 cases of MSAP (46.2%) and 737 cases of SAP (28.2%), while CTSI judged SAP patients less(400 cases, 15.3%). The severity of AP determined by CTSI and MCTSI scores was significantly correlated with clinical prognosis (r=0.06-0.43, all P<0.05). Compared with APACHE Ⅱ score, CTSI had the highest area under the curve (AUC) for predicting IPN (AUC=0.85, 95%CI: 0.83-0.87), followed by MCTSI (AUC=0.82, 95%CI: 0.80-0.85). APACHE Ⅱ was more accurate in predicting persistent organ failure than CTSI and MCTSI scores,with AUC of 0.73 (95%CI: 0.71-0.75), 0.72 (95%CI: 0.70-0.74) and 0.72 (95%CI: 0.70-0.74), respectively. Conclusions: AP severity judged by MCTSI is consistent with RAC, and SAP patients judged by CTSI are less than RAC. CTSI and MCTSI are significantly correlated with clinical prognosis. CTSI and MCTSI have higher accuracy in predicting IPN, but lower accuracy in predicting persistent organ failure than APACHE Ⅱ.

[Relationship between nutritional factors and clinical outcome in children with tuberculous meningitis].

Objective: To investigate the relationship between nutritional risk status and clinical outcome in children with tuberculous meningitis (TBM). Methods: The clinical data (basic information, clinical symptoms and laboratory test results) of 112 patients with TBM, who were admitted to Department of Pediatric Infectious Diseases of West China Second Hospital of Sichuan University,from January 2013 to December 2020 were retrospectively analyzed. The patients were divided into the nutritional risk group and the non-nutritional risk group according to the assessment of the nutritional risk by the STRONGkids Scale. The variables of basic information, clinical symptoms and laboratory test measurements etc. were compared between the two groups by using Student t test, Rank sum test or Chi-square test. Multivariate Logistic regression analysis were used to analyze nutritional risk factors. Results: Among 112 patient with TBM, 55 were males and 57 females. There were 62 cases in the nutritional risk group and 50 cases in the non-nutritional risk group. The proportion of cases with nutritional risk was 55.4% (62/112). Patients in the nutritional risk who lived in rural areas, had symptoms of brain nerve damage, convulsions, emaciation and anorexia, with a diagnosis time of ≥21 days, and the level of cerebrospinal fluid (CSF) protein were all higher than those in the non-nutritional risk group ((50 cases (80.6%) vs. 32 cases (64.0%), 20 cases (32.3%) vs.8 cases (16.0%), 33 cases (53.2%) vs. 15 cases (30.0%), 30 cases (48.4%) vs. 2 cases (4.0%), 59 cases (95.2%) vs. 1 case (2.0%),41 cases (66.1%) vs.18 cases (36.0%), 1 406 (1 079, 2 068) vs. 929 (683, 1 208) mg/L, χ2=3.91, 3.90, 6.10, 26.72, 98.58, 10.08, Z=4.35, all P<0.05). The levels of serum albumin,hemoglobin,lymphocyte count, white blood cell count, and CSF glucose were significantly lower in patients with nutritional risk ((36±5) vs. (41±4) g/L, (110±17) vs. (122±14) g/L, 1.4 (1.0, 2.0)vs. 2.3 (1.6, 3.8)×109/L, 7.8 (6.3, 10.0)×109 vs. 10.0 (8.3, 12.8)×109/L, 1.0 (0.8, 1.6) vs. 2.1 (1.3, 2.5) mmol/L, t=-6.15, -4.22, Z=-4.86, -3.92, -4.16, all P<0.05).Increased levels of serum albumin (OR=0.812, 95%CI:0.705-0.935, P=0.004) and lymphocyte count (OR=0.609, 95%CI:0.383-0.970, P=0.037) may reduce the nutritional risk of children with TBM; while convulsions (OR=3.853, 95%CI:1.116-13.308, P=0.033) and increased level of CSF protein (OR=1.001,95%CI:1.000-1.002, P=0.015) may increase the nutritional risk of children with TBM. Similarly, the rate of complications and drug-induced liver injury was higher in the nutritional risk group (47 cases (75.8%) vs. 15 cases(30.0%), 31 cases (50.0%) vs.8 cases (16.0%), χ2=23.50, 14.10, all P<0.05). Moreover, the length of hospital stay was also longer in the nutritional risk group ((27±13) vs. (18±7) d, t=4.38, P<0.05). Conclusions: Children with TBM have a high incidence of nutritional risk. Convulsive, the level of serum albumin, the level of lymphocyte count and CSF protein may affect the nutritional risk of children with TBM. The nutritional risk group has a high incidence of complications and heavy economic burden.It is necessary to carry out nutritional screening and nutritional support for children with TBM as early as possible.

A prospective study on vulvovaginal candidiasis: multicentre molecular epidemiology of pathogenic yeasts in China.

BACKGROUND: Vulvovaginal candidiasis (VVC) is frequent in women of reproductive age, but very limited data are available on the epidemiology in cases of VVC in China. OBJECTIVES: The current study has been conducted to reveal the prevalence, species distribution of yeast causing VVC and molecular genetics of Candida albicans in China. METHODS: Vaginal swabs were collected from 543 VVC outpatients recruited in 12 hospitals in China between September 2017 and March 2018. They were preliminarily incubated on Sabouraud dextrose agar and then positive subjects of which were then transmitted to our institute for further identification. CHROMagar™ was used to isolate Candida species, and all isolates were finally identified by DNA sequencing. Multilocus sequence typing (MLST) was used to analyse phylogenetic relationships of the various C. albicans isolates. RESULTS: Eleven different yeast species were identified in 543 isolates, among which C. albicans (84.7%) was the most frequent, followed by C. glabrata (8.7%). We obtained 117 unique diploid sequence types from 451 clinical C. albicans isolates and 92 isolates (20.4%) belonged to a New Clade. All the strains appearing in the New Clade were from northern China and they were isolated from non-recurrent VVC. CONCLUSIONS: Our findings suggest that C. albicans are still the main cause of VVC in China and the majority of C. albicans isolates belongs to Clade 1 with DST 79 and DST 45 being two most common. Moreover, the New Clade revealed in our study seems to be specific to northern China.

Malnutrition Prolongs the Hospitalization of Patients with COVID-19 Infection: A Clinical Epidemiological Analysis.

OBJECTIVES: During the 2019 coronavirus disease (COVID-19) outbreak, malnutrition may contribute to COVID-19 adverse outcomes. We conducted a clinical epidemiological analysis to investigate the association of malnutrition with hospitalized duration in patients with COVID-19. DESIGN: Retrospective survey study. SETTING: Taikang Tongji (Wuhan) hospital in Wuhan, China. PARTICIPANTS: 139 patients with COVID-19. METHODS: In total, 139 patients with COVID-19 from patients in the Infection Department of Taikang Tongji (Wuhan) hospital from February 2020 to April 2020 were analyzed retrospectively. We used the "Global leadership Initiative on Malnutrition(GLIM)" assessment standard published in 2019 to assess nutritional status. Prolonged hospitalization was lasting more than the median value of the hospitalized days (17 days) in this population. RESULTS: According to the assessment results of GLIM nutrition assessment, the patients were divided into malnutrition group and normal nutrition group. Compared with the patients in the normal nutrition group, the hospitalization time was longer(15.67±6.26 days versus 27.48±5.04 days, P = 0.001). Kaplan-Meier analysis showed patients with malnutrition were more likely to be hospitalized longer compared with those normal nutrition (mean with 95% confidence interval [CI]: 28.91[27.52-30.30] versus 22.78[21.76-23.79], P = 0.001). COX regression analysis showed that malnutrition (hazard ratio [HR] = 3.773, P for trend = 0.001) was proportional associated with being discharged from hospital delayed. CONCLUSION AND IMPLICATIONS: Present findings suggested that malnutrition contributed to predicting a probability of prolonged hospitalization in patients with COVID-19 infection, to whom extra attentions and precautions should be paid during clinical treatments. Based on the existing results, it is recommended that inpatients with nutritional risk or malnutrition start nutritional support treatment as soon as possible.

Scoring system to predict the success rate of external cephalic versions and determine the timing of the procedure.

OBJECTIVE: We aimed to examine the prenatal clinical characteristics of women with single pregnancies undergoing external cephalic version (ECV) without anesthesia, develop a novel scoring system for predicting the ECV success rate, and demonstrate that this scoring system can be used to individualize the timing of ECV attempts. PATIENTS AND METHODS: We enrolled 270 women who underwent ECV without anesthesia at 37-40 weeks of gestation in the Fujian Maternity and Child Health Hospital from 2016 to 2019 and divided them into two ECV outcome groups (success vs. failure). We identified five clinical features (the fetal buttocks' station, the sum of the fundal height and station, the fetal head location, and whether the fetal head or buttocks could be grasped) as independent factors affecting the ECV success rate, and we scored them using a regression coefficient. RESULTS: Women with scores of 0-3 points had ECV success rates, vaginal delivery rates, and delivery gestational ages at 16.67%, 16.67%, and 38.88 weeks, respectively; those with scores of 4-6 points had ECV success rates, vaginal delivery rates, and delivery gestational ages at 65.75%, 58.90%, and 39.62 weeks, respectively; and those with scores of 7-9 points had ECV success rates, vaginal delivery rates, and delivery gestational ages at 93.71%,74.83%, and 40.00 weeks, respectively. CONCLUSIONS: The ECV success and vaginal delivery rates increased with the score, and the delivery gestational age showed an initial increase. To optimize the ECV procedure and reduce the hospital burden, this scoring system should be used routinely to predict the ECV success rate and determine the timing of ECV attempts.

Effects of inoculated mycorrhizal fungi and non-mycorrhizal beneficial micro-organisms on plant traits, nutrient uptake and root-associated fungal community composition of the Cymbidium hybridum in greenhouse.

AIMS: The aim of this study was to assess the effects of beneficial micro-organisms on the growth, nutrient accumulation and root-associated fungal species composition of pot orchids grown in the greenhouse. METHODS AND RESULTS: A greenhouse pot experiment was conducted to investigate the beneficial effects of a mycorrhizal fungus, Epulorhiza repens isolate ML01, an endophytic fungus, Umbelopsis nana isolate ZH3A-3 and a mixed commercial inoculum Rem, alone or in combination. Nested PCR assays showed that both isolates ML01 and ZH3A-3 can successfully establish in inoculated soil. All the inoculants significantly increased the plant total dry weight of Cymbidium hybridum 'Golden Boy', whereas only co-inoculation with the endophytic fungus ZH3A-3 and the Rem enhanced the fresh weight and height of host plants. The mycorrhizal fungus positively affected P, K, Ca, Mg content in shoots and Zn content in roots, while the endophytic fungus improved N, P, Ca accumulation in shoots and roots. Co-inoculation with the Rem and ML01 improved root to shoot translocation of Fe and Zn. In addition, inoculation with ZH3A-3, ML01+Rem and ZH3A-3+Rem decreased the relative frequency of Fusarium sp. on orchid roots. Trichoderma sp. were isolated from the roots treated with ML01, ML01+Rem and ZH3A-3+Rem. CONCLUSIONS: Both mycorrhizal and endophytic fungi had the potential to create favourable microflora in the orchid roots and stimulate the growth of transplanted plantlets under greenhouse condition. SIGNIFICANCE AND IMPACT OF THE STUDY: The newly isolated endophytic strain ZH3A-3 showed significant application value in orchid production.

[Survival time and related factors of antiretroviral therapy among HIV/AIDS patients in Liangshan Prefecture, during 2005-2015].

Objective: To analyze the survival time and to explore the releated factors of antiretroviral therapy among HIV/AIDS patients in LiangShan Prefecture, Sichuan Province for reduction of AIDS death rate. Methods: The retrospective research method was used to collect relevant information from the Management Database of Antiviral Treatment from the National AIDS Comprehensive Prevention Information System. The Kaplan-Meier method was used to describe the survival distribution and to analyze the survival time by single factor and the model of Cox proportional riskanalysis was performed to analyze the survival time of HARRT by multi-factors analysis. Results: Total 14 219 adults and young persons aged ≥15 HIV/AIDS patients received antiviral treatment from 2005 to 2015. The average age of all cases was (36.10±9.41) years old and 10 021 were males (70.5%). The main route of infection was intravenous drug use (61.0%, 8 678 cases). At the end of the observation, 10001 cases (70.3%) were still treated, and 1 425 cases (10.0%) died; Cox Regression analysis showed that female (0.67 (0.55-0.81)), route of sexual infection (0.67 (0.56-0.79)), baseline CD4+T lymphocyte count 200-350 (0.41 (0.35-0.47)) and ≥350 (0.28 (0.24-0.34)), was a protective factor in death. At the beginning of treatment, the patient is clinically staging stage Ⅱ (0.70 (0.58-0.84)) and abnormal BMI (1.75 (1.50-2.03)), is a risk factor for death (P<0.05). Conclusion: Early antiviral treatment is of great significance in improving the anti-viral treatment effect of AIDS. Compliance education should be further strengthened so as to enhance their knowledge. And it is feasible to enhance the effect of treatment through nutritional support for prolonging patients survival time and improving the quality of life.

[Prevalence and risk factors of Blastocystis infections among primary school students in Jiangjin District, Chongqing City].

OBJECTIVE: To investigate the prevalence and risk factors of Blastocystis infections among primary school students in Jiangjin District, Chongqing City. METHODS: A cross-sectional questionnaire survey was conducted among students sampled from a primary school in Jiangjin District, Chongqing City on April, 2018, and their stool samples were collected for microscopic examinations, in vitro culture and PCR assays to analyze the prevalence of Blastocystis infections and subtype of the parasite. In addition, the risk factors of Blastocystis infections among primary school students were identified using univariate analysis and multivariate logistic regression analysis. RESULTS: A total of 466 primary students were surveyed, and the subjects had a mean age of (9.81±1.66) years and included 236 males (50.64%) and 230 females (49.36%). The prevalence of Blastocystis infections was 15.24% (71/466) among the study students, and there was no significance difference in the prevalence between male and fe- male students (16.52% vs. 13.91%; χ2 = 0.616, P = 0.433). In addition, there was a significant difference in the prevalence of Blastocystis infections among grade 1 (6.35%, 4/63), grade 2 (5.17%, 3/58), grade 3 (21.74%, 15/69), grade 4 (25.30%, 21/83), grade 5 (10.19%, 11/108) and grade 6 students (20.00%, 17/85) (χ2 = 15.410, P = 0.009). There were four Blastocystis subtypes characterized (ST1, ST3, ST6 and ST7), in which ST6 was the most common subtype (45.07%, 32/71), followed by ST3 (25.35%, 18/71). Multivariate logistic regression analysis revealed that minority ethnicity [odds ratio (OR) = 4.259, 95% confidential inter- val (CI) : (1.161, 15.621)] and low maternal education level (primary school and below) [OR = 9.038, 95% CI: (1.125, 72.642)] were identified as risk factors of Blastocystis infection among primary school students in Jiangjin District, Chongqing City. CONCLUSIONS: There is a high prevalence of Blastocystis infections detected among primary school students in Jiangjin District, Chongqing City, and ST6 and ST3 are predominant subtypes. Minority ethnicity and low maternal education level (primary school and below) are risk factors for Blastocystis infections in primary school students.

[A multicenter, randomized, open and positive parallel controlled clinical study of clotrimazole vaginal expansion suppository and vaginal tablet in the treatment of mild and moderate vulvovaginal candidiasis].

Objective: Using clotrimazole vaginal tablet as a positive control, to evaluate the results of clotrimazole vaginal expansion suppository in the treatment of mild and moderate vulvovaginal candidiasis in terms of efficacy, patient satisfaction, side effects, and recurrence rate. Methods: This study was jointly conducted by 5 hospitals from August 2017 to October 2018, patients with mild and moderate vulvovaginal candidiasis confirmed by fungal culture and symptoms scores were selected. They were randomized to experimental group and control group as 1∶1 ratio. In the experimental group (n=105), the subjects applied clotrimazole vaginal expansion suppository (150 mg) daily at night for 7 days. In the control group (n=106), the subjects used a single dose of clotrimazole vaginal tablet (500 mg). Follow-ups were performed at (8±3) and (30±5) days after the discontinuation of the drugs, respectively. The difference in clinical symptoms and signs scores was used to evaluate the improvement of clinical symptoms, and the patient's satisfaction and side effects were recorded. Results: At the first follow-up, the experimental group and control group were followed up by fungal culture on the cure rate [66.7% (70/105) versus 63.2% (67/106), P>0.05] and total effective rate [98.1% (103/105) versus 99.1% (105/106), P>0.05], the differences were not statistically significant. At the second follow-up, the recurrence rates of the experimental group and the control group were 5.7% (4/70) and 14.9% (10/67), respectively, with no significant difference (P>0.05). In the evaluation of patient satisfaction, the leakage of the drug in the experimental group was significantly better than that in the control group (P<0.01). The side effects mainly included vaginal stimulation, itching and burning sensation, and there was no statistical difference between the two groups (χ2=1.070, P=0.586). Conclusions: In the treatment of mild and moderate vulvovaginal candidiasis, clotrimazole vaginal expansion suppository is no less effective than clotrimazole vaginal tablet, and there is no significant difference in the recurrence rate between the two. In terms of patient satisfaction, clotrimazole vaginal expansion suppository is superior to clotrimazole vaginal tablet.

Low expression of lncRNA MGC27345 is associated with poor prognosis in gastric cancer patients.

OBJECTIVE: A series of evidence showed that long non-coding RNAs (lncRNAs) play an essential regulatory role in the occurrence and development of human cancer, and is a potential biological target in the fight against cancer. PATIENTS AND METHODS: In this research, we investigated the role of lncRNA MGC27345 in gastric cancer (GC), the expression of MGC27345 in GC was detected by quantitative Real-Time PCR in GC tissue from 235 patients. The correlations between MGC27345 expression and clinicopathological variables and survival were evaluated by the Chi-square test. Kaplan-Meier method (log-rank test), univariate and multivariate Cox regression assays were carried out for the identification of the survival and independent risk factors for GC. RESULTS: MGC27345 expression levels were significantly decreased in GC tissues than in adjacent normal specimens. Lower expression of MGC27345 was found in advanced tumor stages. GC patients with low-expression of MGC27345 had a poorer overall survival compare to those with high-expression of MGC27345. Furthermore, MGC27345 was an independent protective prognosis factor in GC development. CONCLUSIONS: Our data indicated that MGC27345 may have a diagnostic and prognostic value for patients with advanced gastric cancer and assist to improve clinical outcomes for GC patients.

Immunocyte density in parathyroid carcinoma is correlated with disease relapse.

PURPOSE: Parathyroid carcinoma (PC) is an endocrine malignancy with a poor prognosis. The tumour immune microenvironment is a critical factor influencing the outcomes of multiple cancer types. However, knowledge of the immune microenvironment in PC remains limited. METHODS: The intratumoural density of immunocytes and the Ki-67 index were evaluated immunohistochemically in 51 PC patient samples and were compared with clinicopathological features and parafibromin staining results. The Kaplan-Meier method and Cox proportional hazards analysis were used to estimate the effects of these variables on clinical outcomes. RESULTS: Intratumoural immunocyte density was not correlated with age, gender, urolithiasis, or palpation of a neck mass. The Ki-67 index was correlated with the intratumoural density of CD3+ cells (P = 0.022) and CD8+ cells (P = 0.021) and serum calcium levels (P = 0.022). In the intratumoural area of primary foci, Kaplan-Meier method showed that the risk factors associated with recurrence/metastasis were a low density of CD3+ (P = 0.017), CD8+ (P = 0.019) and CD45+ cells (P = 0.047), a high density of CD163+ cells (P = 0.003) and a high Ki-67 index (P = 0.004). Cox regression multivariate analysis revealed that CD163+ cell density (hazard ratio (HR) 16.19, 95% confidence interval (CI) 1.99-131.66; P = 0.009) and CD8+ cell density (HR 0.13, 95% CI 0.02-0.76, P = 0.024) were independent factors associated with PC relapse. CONCLUSION: The immune microenvironment is an important factor influencing the relapse of PC. The intratumoural density of CD3+, CD8+, CD45+, and CD163+ immunocytes was correlated with disease-free survival (DFS) in patients with PC. Immunotherapy based on T lymphocytes or tumour-associated macrophages may be a promising treatment strategy.

Cost-effectiveness of bivalent versus monovalent vaccines against hand, foot and mouth disease.

OBJECTIVES: Enterovirus 71 (EV71) and coxsackievirus A16 (CA16) were responsible for 43.3% (235 123/543 243) and 24.8% (134 607/543 243) of all laboratory-confirmed hand, foot and mouth disease (HFMD) cases during 2010-2015 in China. Three monovalent EV71 vaccines have been licensed in China while bivalent EV71/CA16 vaccines are under development. A comparative cost-effectiveness analysis of bivalent EV71/CA16 versus monovalent EV71 vaccination would be useful for informing the additional value of bivalent HFMD vaccines in China. METHODS: We used a static model parameterized with the national HFMD surveillance data during 2010-2013, virological HFMD surveillance records from all 31 provinces in mainland China during 2010-2013 and caregiver survey data of costs and health quality of life during 2012-2013. We estimated the threshold vaccine cost (TVC), defined as the maximum additional cost that could be paid for a cost-effective bivalent EV71/CA16 vaccine over a monovalent EV71 vaccine, as the outcome. The base case analysis was performed from a societal perspective. Several sensitivity analyses were conducted by varying assumptions governing HFMD risk, costs, discounting and vaccine efficacy. RESULTS: In the base case, choosing the bivalent EV71/CA16 over monovalent EV71 vaccination would be cost-effective only if the additional cost of the bivalent EV71/CA16 compared with the monovalent EV71 vaccine is less than €4.7 (95% CI 4.2-5.2). Compared with the TVC in the base case, TVC increased by up to €8.9 if all the test-negative cases were CA16-HFMD; decreased by €1.1 with an annual discount rate of 6% and exclusion of the productivity loss; and increased by €0.14 and €0.3 with every 1% increase in bivalent vaccine efficacy against CA16-HFMD and differential vaccine efficacy against EV71-HFMD, respectively. CONCLUSIONS: Bivalent EV71/CA16 vaccines can be cost-effective compared with monovalent EV71 vaccines, if suitably priced. Our study provides further evidence for determining the optimal use of HFMD vaccines in routine paediatric vaccination programme in China.