Enhancing therapeutic efficacy in luminal androgen receptor triple-negative breast cancer: exploring chidamide and enzalutamide as a promising combination strategy.

Extensive exploration of the molecular subtypes of triple-negative breast cancer (TNBC) is critical for advancing precision medicine. Notably, the luminal androgen receptor (LAR) subtype has attracted attention for targeted treatment combining androgen receptor antagonists and CDK4/6 inhibitors. Unfortunately, this strategy has proven to be of limited efficacy, highlighting the need for further optimization. Using our center's comprehensive multiomics dataset (n = 465), we identified novel therapeutic targets and evaluated their efficacy through multiple models, including in vitro LAR cell lines, in vivo cell-derived allograft models and ex vivo patient-derived organoids. Moreover, we conducted flow cytometry and RNA-seq analysis to unveil potential mechanisms underlying the regulation of tumor progression by these therapeutic strategies. LAR breast cancer cells exhibited sensitivity to chidamide and enzalutamide individually, with a drug combination assay revealing their synergistic effect. Crucially, this synergistic effect was verified through in vivo allograft models and patient-derived organoids. Furthermore, transcriptomic analysis demonstrated that the combination therapeutic strategy could inhibit tumor progression by regulating metabolism and autophagy. This study confirmed that the combination of histone deacetylase (HDAC) inhibitors and androgen receptor (AR) antagonists possessed greater therapeutic efficacy than monotherapy in LAR TNBC. This finding significantly bolsters the theoretical basis for the clinical translation of this combination therapy and provides an innovative strategy for the targeted treatment of LAR TNBC.

Safety of embryo cryopreservation: insights from mid-term placental transcriptional changes.

BACKGROUND: In recent years, with benefits from the continuous improvement of clinical technology and the advantage of fertility preservation, the application of embryo cryopreservation has been growing rapidly worldwide. However, amidst this growth, concerns about its safety persist. Numerous studies have highlighted the elevated risk of perinatal complications linked to frozen embryo transfer (FET), such as large for gestational age (LGA) and hypertensive disorders during pregnancy. Thus, it is imperative to explore the potential risk of embryo cryopreservation and its related mechanisms. METHODS: Given the strict ethical constraints on clinical samples, we employed mouse models in this study. Three experimental groups were established: the naturally conceived (NC) group, the fresh embryo transfer (Fresh-ET) group, and the FET group. Blastocyst formation rates and implantation rates were calculated post-embryo cryopreservation. The impact of FET on fetal growth was evaluated upon fetal and placental weight. Placental RNA-seq was conducted, encompassing comprehensive analyses of various comparisons (Fresh-ET vs. NC, FET vs. NC, and FET vs. Fresh-ET). RESULTS: Reduced rates of blastocyst formation and implantation were observed post-embryo cryopreservation. Fresh-ET resulted in a significant decrease in fetal weight compared to NC group, whereas FET reversed this decline. RNA-seq analysis indicated that the majority of the expression changes in FET were inherited from Fresh-ET, and alterations solely attributed to embryo cryopreservation were moderate. Unexpectedly, certain genes that showed alterations in Fresh-ET tended to be restored in FET. Further analysis suggested that this regression may underlie the improvement of fetal growth restriction in FET. The expression of imprinted genes was disrupted in both FET and Fresh-ET groups. CONCLUSION: Based on our experimental data on mouse models, the impact of embryo cryopreservation is less pronounced than other in vitro manipulations in Fresh-ET. However, the impairment of the embryonic developmental potential and the gene alterations in placenta still suggested it to be a risky operation.

Double Cascading Charge Transfer at Integrated Perovskite/Organic Bulk Heterojunctions for Extended Near-Infrared Photoresponse and Enhanced Photocurrent.

Nowadays, nearly 48.7% near-infrared (NIR) irradiation (>800 nm) of the full solar spectrum has actually not been fully utilized since the state-of-the-art perovskite film usually can only absorb the most UV-vis sunlight radiation. Herein, high efficiency integrated Cs0.15 FA0.85 PbI3 perovskite/organic bulk (PC61 BM:D18:Y6) heterojunction solar cells with enhanced low energy photon harvest until 931 nm and a high maintained open circuit voltage of 1.04 V is successfully obtained. In particular, the favorable double cascading charge transfer paths pave an interesting possibility to spatially separate electrons upon visible light excitation and holes upon NIR photon absorption simultaneously at interfaces, significantly suppressing non-radiative bimolecular recombination and reaching the photocurrent density as high as 27.48 mA cm-2 and power conversion efficiency of 20.31%. Besides, the strong hydrophobicity of the ternary organic film has effectively prevented ambient humidity penetration and improves the stability of the perovskite in the continuous aging test (humidity > 60%) compared with the control device. This work has opened a significantly new window to improve the NIR light harvest for next generation highly efficient solar cells with full spectrum response.

The effect of a novel anticonvulsant chemical Q808 on gut microbiota and hippocampus neurotransmitters in pentylenetetrazole-induced seizures in rats.

BACKGROUND: The gut microbiota can modulate brain function and behavior and is increasingly recognized as an important factor in mediating the risk of epilepsy and the effects of seizure interventions. Drug therapy is one of the factors that influence the composition of the intestinal microbiota. Q808 is an innovative chemical with strong anticonvulsant activity and low neurotoxicity. However, studies evaluating the effect of Q808 on gut microbial communities are lacking. In this study, we aimed to evaluate the anticonvulsant activity of Q808 on a pentylenetetrazol (PTZ)-induced seizure model and analyze and compare the intestinal microbiota composition of non-PTZ vehicle control group, the PTZ-induced seizure model rats with and without Q808, through 16S rDNA sequencing. Neurotransmitter levels in the hippocampus were quantitatively estimated using HPLC-MS. RESULTS: The results suggest that Q808 effectively alleviates seizures in chronic PTZ-kindled model rats. Additionally, based on the analyzed abundance of the gut microbiota, dysbacteriosis of model rats was found to be corrected after Q808 treatment at the phylum level. The unique bacterial taxa (e.g., Lactobacillus) that are associated with acetylcholine production, were significantly increased. Several short-chain fatty acids (SCFAs)-producing bacteria, including Roseburia, Alloprevptella, Prevotellaceae_NK3B31_group, Prevotellaceae_UCG-001, and Prevotella_9, were enriched. In the hippocampus, the contents of acetylcholine increased, whereas the levels of 3-methoxytyramine, glutamine, and 5-hydroxyindole acetic acid (5-HIAA) decreased after Q808 treatment. CONCLUSIONS: This study demonstrates that Q808 can be used to remodel the dysbiosis of the gut microbiome and influence neurotransmitter levels in the hippocampus of PTZ-induced seizure model rats. We hope that these novel findings prompt further research on the interaction between gut microbiota and seizures and the mechanism of Q808.

Iterative Non-Negative Matrix Factorization Filter for Blind Deconvolution in Photon/Ion Counting.

A digital filter based on non-negative matrix factorization (NMF) enables blind deconvolution of temporal information from large data sets, simultaneously recovering both photon arrival times and the instrument impulse response function (IRF). In general, the measured digital signals produced by modern analytical instrumentation are convolved by the corresponding IRFs, which can complicate quantitative analyses. Common examples include photon counting (PC), chromatography, super resolution imaging, fluorescence imaging, and mass spectrometry. Scintillation counting, in particular, provides a signal-to-noise advantage in measurements of low intensity signals, but has a limited dynamic range due to pulse overlap. This limitation can complicate the interpretation of data by masking temporal and amplitude information on the underlying detected signal. Typical methods for deconvolution of the photon events require advanced knowledge of the IRF, which is not generally trivial to obtain. In this work, a sliding window approach was developed to perform NMF one pixel at a time on short segments of large (e.g., 25 million point) data sets. Using random initial guesses for the IRF, the NMF filter simultaneously recovered both the deconvolved photon arrival times and the IRF. Applying the NMF filter to the analysis of triboluminescence (TL) data traces of active pharmaceutical ingredients enabled discrimination between different hypothesized physical origins of the signal.

A Reduced Graphene Oxide/Disodium Terephthalate Hybrid as a High-Performance Anode for Sodium-Ion Batteries.

As a promising candidate for large-scale energy storage systems, sodium-ion batteries (SIBs) are experiencing a rapid development. Organic conjugated carboxylic acid anodes not only have tailorable electrochemical properties but also are easily accessible. However, the low stability and electrical conductivity hamper their practical applications. In this study, disodium terephthalate (Na2 TP), the most favorable organic conjugated carboxylic acid anode material for SIBs, was proposed to integrate with graphene oxide (GO) by an anti-solvent precipitation process, which ensures the uniform and tight coating of GO on the Na2 TP surface. GO is electrochemically reduced during the first several cycles of the electrochemical measurement, which buffers the volume change and improves the electrical conductivity of Na2 TP, resulting in a better cyclic and rate performance. The incorporation of only 5 wt % GO onto Na2 TP leads to a reversible capability of 235 mA h g-1 after 100 cycles at a current rate of 0.1 C, which is the best among the state of the art organic anodes for SIBs. The one-step synthesis together with the low costs of the raw materials show a promise for the scalable preparation of anode materials for practical SIBs.

Differential diagnosis between hepatic metastases and benign focal lesions using DWI with parallel acquisition technique: a meta-analysis.

We aim to investigate the diagnostic capability of diffusion-weighted imaging using parallel acquisition technique for the differentiation between hepatic metastases and benign focal lesions with a meta-analysis. The meta-analysis included a total of 858 hepatic metastases and 440 benign liver lesions from nine studies. The pooled sensitivity and specificity of diffusion-weighted imaging (DWI) were 0.87 (95% CI, 0.84-0.89) and 0.90 (95% CI, 0.87-0.93), respectively. The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were 8.50 (95% CI, 4.97-14.52) and 0.17 (95% CI, 0.11-0.26), respectively. The P value for χ (2) heterogeneity for all pooled estimates was <0.05. From the fitted summary receiver operating characteristics (SROC), the area under the curve (AUC) and Q* index were 0.95 and 0.88, respectively. Publication bias is not present (t = -0.76, P = 0.471). The meta-regression analysis indicated that evaluated covariates included patient number, patient population, mean age, maximum of b factor, number of cysts, number of hemangiomas, and field were not sources of heterogeneity (all P value >0.05). Diffusion-weighted imaging was useful for differentiation between hepatic metastases and benign focal lesions. The diffusion characteristics of the benign hepatocellular lesions, including cases of focal nodular hyperplasia (FNH) and adenoma, have rarely been reported and need further studies. The diagnostic capability of DWI with parallel acquisition technique for differentiation between metastases and benign hepatic focal lesions might be overestimated.

Crystallization scale purification of α7 nicotinic acetylcholine receptor from mammalian cells using a BacMam expression system.

AIM: To report our methods for expression and purification of α7 nicotinic acetylcholine receptor (α7-nAChR), a ligand-gated pentameric ion channel and an important drug target. METHODS: α7-nAChRs of 10 different species were cloned into an inducible BacMam vector with an N-terminal tag of a tandem maltose-binding protein (MBP) and a TEV cleavage site. This α7-nAChR fusion receptor was expressed in mammalian HEK293F cells and detected by Western blot. The expression was scaled up to liters. The receptor was purified using amylose resin and size-exclusion chromatography. The quality of the purified receptor was assessed using SDS-PAGE gels, thermal stability analysis, and negative stain electron microscopy (EM). The expression construct was optimized through terminal truncations and site-directed mutagenesis. RESULTS: Expression screening revealed that α7-nAChR from Taeniopygia guttata had the highest expression levels. The fusion receptor was expressed mostly on the cell surface, and it could be efficiently purified using one-step amylose affinity chromatography. One to two milligrams of the optimized α7-nAChR expression construct were purified from one liter of cell culture. The purified α7-nAChR samples displayed high thermal stability with a Tm of 60 °C, which was further enhanced by antagonist binding but decreased in the presence of agonist. EM analysis revealed ring-like structures with a central hydrophilic hole, which was consistent with the pentameric assembly of the α7-nAChR channel. CONCLUSION: We have established methods for crystallization scale expression and purification of α7-nAChR, which lays a foundation for high-resolution structural studies using X-ray crystallography or single particle cryo-EM analysis.

Incidence and mortality of liver cancer in China in 2011.

BACKGROUND: Liver cancer is a common cancer with poor prognosis in China. In this study, the national population-based cancer registration data were used to evaluate and analyze liver cancer incidence and mortality in China in 2011 and provide a reference for liver cancer prevention and control. METHODS: We collected and evaluated the incidence and mortality data of liver cancer in 2011 from 177 cancer registries with qualified data. These data were used in the final analysis including calculating crude, standardized, and truncated incidences and mortalities, and estimated new liver cancer cases and deaths using age-specific rates and the corresponding populations. The national census in 2000 and Segi's population were used for age-standardized rates. RESULTS: The estimates of new liver cancer cases and deaths were 355,595 and 322,416, respectively, in China in 2011. The crude incidence, age-standardized rate of incidence by Chinese standard population (ASRIC), and age-standardized rate of incidence by world standard population (ASRIW) of liver cancer were 26.39/100,000, 19.48/100,000, and 19.10/100,000, respectively; the crude mortality, age-standardized rate of mortality by Chinese standard population (ASRMC), and age-standardized rate of mortality by world standard population (ASRMW) of liver cancer were 23.93/100,000,17.48/100,000, and 17.17/100,000, respectively. The incidence and mortality were higher in rural areas than in urban areas and higher in males than in females. The age-specific incidence and mortality of liver cancer increased greatly with age, particularly after 30 years and peaked at 80-84 or 85+ years. CONCLUSIONS: Liver cancer is a common cancer in China, particularly for males and residents in rural areas. Targeted prevention, early detection, and treatment programs should be carried out.

A method to evaluate the effect of contact with excipients on the surface crystallization of amorphous drugs.

Amorphous drugs are used to improve the solubility, dissolution, and bioavailability of drugs. However, these metastable forms of drugs can transform into more stable, less soluble, crystalline counterparts. This study reports a method for evaluating the effect of commonly used excipients on the surface crystallization of amorphous drugs and its application to two model amorphous compounds, nifedipine and indomethacin. In this method, amorphous samples of the drugs were covered by excipients and stored in controlled environments. An inverted light microscope was used to measure in real time the rates of surface crystal nucleation and growth. For nifedipine, vacuum-dried microcrystalline cellulose and lactose monohydrate increased the nucleation rate of the ß polymorph from two to five times when samples were stored in a desiccator, while D-mannitol and magnesium stearate increased the nucleation rate 50 times. At 50% relative humidity, the nucleation rates were further increased, suggesting that moisture played an important role in the crystallization caused by the excipients. The effect of excipients on the crystal growth rate was not significant, suggesting that contact with excipients influences the physical stability of amorphous nifedipine mainly through the effect on crystal nucleation. This effect seems to be drug specific because for two polymorphs of indomethacin, no significant change in the nucleation rate was observed under the excipients.

The incidences and mortalities of major cancers in China, 2010.

To estimate the cancer incidences and mortalities in China in 2010, the National Central Cancer Registry (NCCR) of China evaluated data for the year of 2010 from 145 qualified cancer registries covering 158,403,248 people (92,433,739 in urban areas and 65,969,509 in rural areas). The estimates of new cancer cases and cancer deaths were 3,093,039 and 1,956,622 in 2010, respectively. The percentage of morphologically verified cases were 67.11%; 2.99% of incident cases were identified through death certification only, with the mortality to incidence ratio of 0.61. The crude incidence was 235.23/100,000 (268.65/100,000 in males and 200.21/100,000 in females). The age-standardized rates by Chinese standard population (ASR China) and by world standard population (ASR world) were 184.58/100,000 and 181.49/100,000, respectively, with a cumulative incidence (0-74 years old) of 21.11%. The crude cancer mortality was 148.81/100,000 (186.37/100,000 in males and 109.42/100,000 in females). The ASR China and ASR world were 113.92/100,000 and 112.86/100,000, respectively, with a cumulative mortality of 12.78%. Lung, breast, gastric, liver, esophageal, colorectal, and cervical cancers were the most common cancers. Lung, liver, gastric, esophageal, colorectal, breast, and pancreatic cancers were the leading causes of cancer deaths. The coverage of cancer registration has rapidly increased in China in recent years and may reflect more accurate cancer burdens among populations living in different areas. Given the increasing cancer burden in the past decades, China should strengthen its cancer prevention and control.

Nasopharyngeal carcinoma incidence and mortality in China in 2010.

Nasopharyngeal carcinoma (NPC) is common in South China. Although regional epidemiological data on NPC in China is available, national epidemiological data have been unavailable up to now. The goal of this study was to analyze the NPC incidence and mortality data in some domestic cancer registries, estimate these rates in China in 2010, and provide scientific information that can be harnessed for NPC control and prevention. To accomplish this goal, NPC incidence and mortality data for 2010 were collected from 145 Chinese cancer registries from which data were included in the 2013 National Cancer Registry Annual Report. Such indices as its incident and death numbers, crude rates, age-standardized rates and truncated rates were calculated and analyzed. The incidence and mortality in China and constituent areas were estimated according to the national population in 2010. An estimated 41,503 new cases and 20,058 deaths were attributed to NPC in China in 2010, accounting for 1.34% of all new cancer cases and 1.03% of all cancer-related deaths that year in China. Crude incidence and mortality were 3.16/100,000 and 1.53/100,000, respectively. World age-standardized incidence and mortality were 2.44/100,000 and 1.18/100,000, respectively. Incidence and mortality were higher among males than among females and slightly higher in urban areas than in rural areas. Among seven Chinese administrative regions, NPC incidence and mortality were obviously higher in South China than in other regions and lowest in North China. The male and female age-specific incidence and mortality both rose quickly from age 25-29 years, but peaked at different ages and varied by location. These results demonstrated that NPC incidence and mortality in China especially in South China were at high levels in the world, and suggested that control and prevention efforts should be enhanced.

Incidence and mortality of liver cancer in China, 2010.

Liver cancer is a common malignant tumor in China and a major health concern. We aimed to estimate the liver cancer incidence and mortality in China in 2010 using liver cancer data from some Chinese cancer registries and provide reference for liver cancer prevention and treatment. We collected and evaluated the incidence and mortality data of liver cancer in 2010 from 145 cancer registries, which were included in the 2013 Chinese Cancer Registry Annual Report, calculated crude, standardized, and truncated incidences and mortalities, and estimated new liver cancer cases and deaths from liver cancer throughout China and in different regions in 2010 from Chinese practical population. The estimates of new liver cancer cases and deaths were 358,840 and 312,432, respectively, in China in 2010. The crude incidence, age-standardized rate by Chinese standard population (ASR China), and age-standardized rate by world standard population (ASR world) were 27.29/100,000, 21.35/100,000, and 20.87/100,000, respectively; the crude, ASR China, and ASR world mortalities were 23.76/100,000, 18.43/100,000, and 18.04/100,000, respectively. The incidence and mortality were the highest in western regions, higher in rural areas than in urban areas, and higher in males than in females. The age-specific incidence and mortality of liver cancer showed a rapid increase from age 30 and peaked at age 80-84 or 85+. Our results indicated that the 2010 incidence and mortality of liver cancer in China, especially in undeveloped rural areas and western regions, were among high levels worldwide. The strategy for liver cancer prevention and treatment should be strengthened.

[Trend analysis of cervical cancer incidence and mortality rates in Chinese women during 1989-2008].

OBJECTIVE: To evaluate the trend of cervical cancer incidence and mortality rates during 1989-2008 in Chinese women, so as to inform the development of relevant policies and strategies in China. METHODS: The incidence and mortality rates of cervical cancer during 1989-2008 in urban and rural areas were calculated based on the data from the National Cancer Registry Database. Age-standardized rates were calculated using the Chinese population of 1982 and World Segi's population of 1985. Joinpoint regression analysis was performed to obtain annual percentage changes (APC) so as to assess the trend of incidence and mortality rates over the period from 1989 to 2008. RESULTS: The crude incidence rate of cervical cancer in Chinese women increased from 3.06/10(5) in 1989-1990 to 11.87/10(5) in 2007-2008 (from 4.96/10(5) to 11.98/10(5) in urban registration areas and from 2.39/10(5) to 11.77/10(5) in rural registration areas).The crude mortality rate slightly increased from 2.19/10(5) in 1989-1990 to 3.20/10(5) in 2007-2008 (from 3.21/10(5) to 2.56/10(5) in urban registration areas and from 1.82/10(5) to 3.75/10(5) in rural registration areas). Generally, the upward trends of crude incidence rates were shown over the year 1989-2008, with an APC of 14.4% after 1997 in urban areas and 22.5% after 1999 in rural areas.After age standardization of world population, the APC of incidence rates in recent decade in urban areas remained stable, and the one in rural areas slightly decreased.Although the overall crude and world age-standardized mortality rates had no significant changes during 1989-2008, the crude mortality rates increased by 8.1% annually after 1999.The upward trends were also shown for crude and world age-standardized mortality rates in urban areas after 2001 with an APC of 7.3%.The crude mortality rates in rural areas increased by 3.9% annually during 1989-2008, but no significant change was found after age standardization. CONCLUSIONS: Over the last decade, the cervical cancer incidence and mortality rates ascended by year in China. It is particularly urgent to establish a comprehensive prevention and control system that combines cervical cancer screening and human papillomavirus vaccination, so as to reduce the burden of cervical cancer in Chinese women.

Cocrystals of nicotinamide and (R)-mandelic acid in many ratios with anomalous formation properties.

We report a remarkable system of cocrystals containing nicotinamide (NIC) and (R)-mandelic acid (RMA) in numerous stoichiometric ratios (4:1, 1:1 in two polymorphs, and 1:2) with anomalous formation properties. The formation of these cocrystals decreases energy but expands volume, in contrast to most physical processes, but similar to water freezing. The decrease of energy upon cocrystallization agrees with the exothermic mixing of NIC and RMA liquids (a base and an acid). Volume expansion is general for the formation of all NIC cocrystals for which data exist (n = 40): +3.9 Å(3)/molecule or +17 cm(3)/kg on average, corresponding to a 2% expansion. This volume expansion correlates with the shortening and strengthening of hydrogen bonds upon cocrystallization, analogous to water freezing. The NIC-RMA binary phase diagram was constructed that contains the congruent and incongruent melting of six crystalline phases. These results are relevant for understanding the nature of cocrystallization and why some molecules are prolific cocrystal formers.

Liver cancer incidence and mortality in China, 2009.

Liver cancer is a common cancer and a leading cause of cancer deaths in China. To aid the government in establishing a control plan for this disease, we provided real-time surveillance information by analyzing liver cancer incidence and mortality in China in 2009 reported by the National Central Cancer Registry. Liver cancer incidence and cases of death were retrieved from the national database using the ICD-10 topography code "C22". Crude incidence and mortality were calculated and stratified by sex, age, and location (urban/rural). China's population in 1982 and Segi (world) population structures were used for age-standardized rates. In cancer registration areas in 2009, the crude incidence of liver cancer was 28.71/100,000, making it the fourth most common cancer in China, third most common in males, and fifth most common in females. The crude mortality of liver cancer was 26.04/100,000, making it the second leading cause of cancer death in China and urban areas and the third leading cause in rural areas. Incidence and mortality were higher in males than in females and were higher in rural areas than in urban areas. The age-specific incidence and mortality were relatively low among age groups under 30 years but dramatically increased and peaked in the 80-84 years old group. These findings confirm that liver cancer is a common and fatal cancer in China. Primary and secondary prevention such as health education, hepatitis B virus vaccination, and early detection should be carried out both in males and females, in urban and rural areas.

Nasopharyngeal carcinoma incidence and mortality in China in 2009.

Nasopharyngeal carcinoma (NPC) is rare globally but common in China and exhibits a distinct ethnic and geographic distribution. In 2009, the National Central Cancer Registry in China provided real-time surveillance information on NPC. Individual NPC cases were retrieved from the national database based on the ICD-10 topography code C11. The crude incidence and mortality of NPC were calculated by sex and location (urban/rural). China's population in 1982 and Segi's world population structures were used to determine age-standardized rates. In regions covered by the cancer registries in 2009, the crude incidence of NPC was 3.61/100,000 (5.08/100,000 in males and 2.10/100,000 in females; 4.19/100,000 in urban areas and 2.42/100,000 in rural areas). Age-standardized incidences by Chinese population (ASIC) and Segi's world population (ASIW) were 2.05/100,000 and 2.54/100,000, respectively. The crude mortality of NPC was 1.99/100,000 (2.82/100,000 in males and 1.14/100,000 in females; 2.30/100,000 in urban areas and 1.37/100,000 in rural areas). The age-standardized mortalities by Chinese population (ASMC) and world population (ASMW) were 1.04/100,000 and 1.35/100,000, respectively. The incidence and mortality of NPC were higher in males than in females and higher in urban areas than in rural areas. Both age-specific incidence and mortality were relatively low in persons younger than 30 years old, but these rates dramatically increased. Incidence peaked in the 60-64 age group and mortality peaked in the over 85 age group. Primary and secondary prevention, such as lifestyle changes and early detection, should be carried out in males and females older than 30 years of age.

[Incidence and mortality of oral cavity and pharyngeal cancer in China, 2009].

OBJECTIVE: To analyze the incidence and mortality of oral cavity and pharyngeal cancer in cancer-registration areas of China in 2009. METHODS: We collected data about incidence of oral cavity and pharyngeal from 72 cancer registry sites of National Central Registry Database in 2009, covering 85 470 522 person (57 489 009 were from urban areas, 27 981 513 were from rural areas).Incidence and mortality rates, proportions, cumulative rate (0-74 years old), cut rate (35-64 years old), age-specific rate were then calculated and analyzed respectively. The age-standardized rate was calculated and adjusted by the Chinese standard population in 1982 as well as the Segi's world standard population. RESULTS: There were 2803 new diagnosed oral cavity and pharyngeal cancer cases, 1793 male and 1010 female, with the sex ratio at 1.78: 1. The crude incidence rate of oral cavity and pharyngeal cancer was 3.28/100 000(2803/85 470 522). The crude incidence rate of males was 4.15/100 000(1793/43 231 554) while it was 2.39/100 000(1010/42 238 968) among females. The age-standardized incidence rates by Chinese standard population (ASIRC) and the world standard population were 1.72/100 000 and 2.23/100 000 respectively, and the cumulative rate and cut rate was separately 0.26% and 4.02/100 000. The crude incidence and ASIRC of oral cavity and pharyngeal cancers were 3.87/100 000 (2225/57 489 009) and 1.97/100 000 in urban areas, whereas in rural areas, they were 2.07/100 000(578/27 981 513) and 1.17/100 000. There were 1172 death cases, including 825 males and 347 females. The crude mortality rate was 1.37/100 000 (1172/85 470 522), while it was 1.91/100 000(825/43 231 554) among males and 0.82/100 000(347/42 238 968) among females. The age-standardized incidence rates were 0.64/100 000 and 0.88/100 000 respectively, by Chinese standard population (ASMRC) and the world standard population. The cumulative mortality rate (0-74 age years old) and cut rate were separately 0.10% and 1.34/100 000. The mortality and ASMRC were 1.59/100 000(915/57 489 009) and 0.72/100 000 in urban areas, whereas in rural areas, they were 0.92/100 000(257/27 981 513) and 0.48/100 000 respectively. CONCLUSIONS: Both the incidence and mortality of oral cavity and pharyngeal cancer in China were still low in 2009.

Liver cancer epidemic in China: past, present and future.

Primary liver cancer is the second most common malignancy, and currently results in 360,000 incident cases, and 350,000 deaths a year in China. For the past four decades, three national surveys on cancer mortality during the periods of 1973-1975, 1990-1992, and 2004-2005 have made it possible to estimate China's past and present liver cancer epidemic. The mortality rates of liver cancer were 17.6 and 7.3 per 100,000 for males and females in 1973-1975, 29.0 and 11.2 per 100,000 in 1990-1992, and 37.55 and 14.45 per 100,000 in 2004-2005, respectively. Recent monitoring from some regional cancer registries, which cover 5.7% of the total population in China, has revealed the distribution, disparities and trends of liver cancer in rural and urban areas. HBV and aflatoxins have been identified as major causal factors, that act individually and synergistically of liver cancer in the etiology. Other agents such as HCV, genetic susceptibility or genetic polymorphisms may also play important roles in the development of liver cancer. Great effort aimed at primary and Secondary prevention of this cancer, such as universal hepatitis B vaccination in children, chemoprevention in selected population, and early detection in at-risk population, has been undertaken. These strategies might be further emphasized in the future for the effective prevention of liver cancer in China.

Bidirectional crosstalk between therapeutic cancer vaccines and the tumor microenvironment: Beyond tumor antigens.

Immunotherapy has rejuvenated cancer therapy, especially after anti-PD-(L)1 came onto the scene. Among the many therapeutic options, therapeutic cancer vaccines are one of the most essential players. Although great progress has been made in research on tumor antigen vaccines, few phase III trials have shown clinical benefits. One of the reasons lies in obstruction from the tumor microenvironment (TME). Meanwhile, the therapeutic cancer vaccine reshapes the TME in an ambivalent way, leading to immune stimulation or immune escape. In this review, we summarize recent progress on the interaction between therapeutic cancer vaccines and the TME. With respect to vaccine resistance, innate immunosuppressive TME components and acquired resistance caused by vaccination are both involved. Understanding the underlying mechanism of this crosstalk provides insight into the treatment of cancer by directly targeting the TME or synergizing with other therapeutics.