Chronically high stress hormone levels dysregulate sperm long noncoding RNAs and their embryonic microinjection alters development and affective behaviours.

Previous studies on paternal epigenetic inheritance have shown that sperm RNAs play a role in this type of inheritance. The microinjection of sperm small noncoding RNAs into fertilised mouse oocytes induces reprogramming of the early embryo, which is thought to be responsible for the differences observed in adult phenotype. While sperm long noncoding RNAs (lncRNAs) have also been investigated in a previous study, their microinjection into fertilised oocytes did not yield conclusive results regarding their role in modulating brain development and adult behavioural phenotypes. Therefore, in the current study we sought to investigate this further. We used our previously established paternal corticosterone (stress hormone) model to assess sperm lncRNA expression using CaptureSeq, a sequencing technique that is more sensitive than the ones used in other studies in the field. Paternal corticosterone exposure led to dysregulation of sperm long noncoding RNA expression, which encompassed lncRNAs, circular RNAs and transposable element transcripts. Although they have limited functional annotation, bioinformatic approaches indicated the potential of these lncRNAs in regulating brain development and function. We then separated and isolated the sperm lncRNAs and performed microinjections into fertilised oocytes, to generate embryos with modulated lncRNA populations. We observed that the resulting adult offspring had lower body weight and altered anxiety and affective behavioural responses, demonstrating roles for lncRNAs in modulating development and brain function. This study provides novel insights into the roles of lncRNAs in epigenetic inheritance, including impacts on brain development and behaviours of relevance to affective disorders.

Radiomics model and deep learning model based on T1WI image for acute lymphoblastic leukemia identification.

AIM: This study aimed to develop highly precise radiomics and deep learning models to accurately detect acute lymphoblastic leukemia (ALL) using a T1WI image. MATERIALS AND METHODS: A total of 604 brain magnetic resonance data of ALL group and normal children (NC) group. Two radiologists independently retrieved radiomics features after manually delineating the area of interest along the clivus at the median sagittal position of T1WI. According to the 9:1 ratio, all samples were randomly divided into the training cohort and the testing cohort. support vector machine was then used to classify the radiomics model using the features that had a correlation coefficient of greater than 0.99 in the training cohort. The Efficientnet-B3 network model received the training set images to create a deep learning model. The sensitivity, specificity, and area under the ROC curve were calculated in order to evaluate the diagnostic efficacy of the different models after the validation of two aforementioned models in the testing cohort. RESULTS: The deep learning model had a higher AUC value of 0.981 than the radiomics model's value of 0.962 in the testing cohort. Delong's test showed no statistical difference between the two models (P>0.05). The accuracy/sensitivity/specificity/negative predictive value/positive predictive value achieved 0.9180/0.9565/0.8947/0.9714/0.8462 for the radiomics model and 0.9344/0.8696/0.9737/0.9250/0.9524 for deep learning model. CONCLUSIONS: The deep learning and radiomics models showed high AUC values in the training and test cohorts. They also exhibited good diagnostic efficacy for predicting ALL.

The environmental and socioeconomic effects of tuberculosis patients in the southwest of China: a population-based study.

OBJECTIVE: The objective of this study was to assess the incidence of tuberculosis (TB) and find the risk factors of TB patients with a high burden of TB in socioeconomic level, the high level of TB incidence and the great changes of economic and social factors, explore the possible factors, construct scientific and robust prediction model, and analyse whether the task of stopping TB can be accomplished by the expected global deadline. STUDY DESIGN: This was an ecological study. METHODS: Descriptive analysis, spatial and space-time scan, correlation analysis, and regression analysis were carried out, based on cases of TB in Sichuan Province and ecological data from 2006 to 2017, to explore the characters of TB and ecological factors, using the transfer function-noise model to forecast the trend of TB until 2035. RESULTS: Factors affecting the incidence of TB, increasing per capita green area, reporting status of TB among Tibetans and Yi minorities, comprehensive treatment management, total cost of TB per capita for urban residents, proportion of males with high school education, 20 to 20 h of 24-h accumulated precipitation, reducing HIV at the same time as AIDS deaths, the increase in the proportion of males in junior high school education, and the increase in the number of registered TB cases can reduce the incidence of TB. CONCLUSIONS: There was concentration mainly on enhanced control of the environment and society measures, helpful in guiding government planning to control TB. Reinforcement is required to reduce the TB of population aged 15-24 and aged 25-64 in socioeconomic level by 2035.

Patients Engaged in Losing Weight Preoperatively Experience Improved Outcomes After Hiatal Hernia Repair.

BACKGROUND: Adherence to preoperative weight loss recommendations may serve as a surrogate for the level of engagement in hiatal hernia (HH) patients. This study aims to evaluate the relationship between achieving preoperative weight loss goals and outcomes after HH repair. METHODS: A retrospective review of 235 patients undergoing laparoscopic HH repair at a single institution was performed. Patients were grouped based on the percentage of weight loss goal achieved. Low achievement was defined as the bottom quartile of goal achievement (≤75%); high achievement was defined as the top quartile (≥140%). Baseline characteristics, clinical outcomes, and patient reported outcomes (PROMs) were compared between groups. RESULTS: 131/235 (55.7%) achieved their weight loss goal. No differences in baseline characteristics or clinical outcomes were observed between the low and high achievement groups. While both groups experienced improvements in PROMs postoperatively, patients in the high achievement group demonstrated significantly lower symptom burden at one-month postoperatively. Further, high-achievement patients were more likely to experience complete resolution of common HH symptoms at one-month postoperatively, including no difficulty swallowing food, no breathing difficulties or choking episodes, no choking when eating food, no choking when drinking liquid, and no regurgitation of food or liquid. CONCLUSIONS: In patients undergoing laparoscopic HH repair, patients achieving their preoperative weight loss goals experienced less overall symptom burden and lower prevalence of common symptoms one-month postoperatively than those with low levels of goal achievement. These results demonstrate that patients can take an active role in improving their own surgical outcomes and health status.

[Cancer incidence and mortality in China, 2022].

Objective: The National Central Cancer Registry estimates the number of new cancer cases and deaths in China in 2022, using incidence and mortality data collected by the National Cancer Center. Methods: According to the data of 700 cancer registries in 2018 and the data of 106 cancer registries from 2010 to 2018, the age-period-cohort model was used to estimate the incidence rate and mortality rate of all cancers and 23 types of cancer in 2022, stratified by gender and urban and rural areas. We estimated the number of new cancer cases and deaths in China in 2022 based on the estimated rate and population data in 2022. Results: The estimated results showed that in 2022, there were approximately 4 824 700 new cancer cases in China (2 533 900 in males and 2 290 800 in females), with an age-standardized incidence rate of Chinese population (ASIR) of 208.58 per 100 000 (212.67 per 100 000 for males and 208.08 per 100 000 for females). Approximately 2 903 900 new cancer cases occurred in urban areas, with an ASIR of 212.95 per 100 000. It was estimated about 1 920 800 new cancer cases in rural areas, and the ASIR was 199.65 per 100 000. The top five cancers (lung cancer 1 060 600, colorectal cancer 517 100, thyroid cancer 466 100, liver cancer 367 700 and female breast cancer 357 200) accounted for 57.4% of all new cases. The estimated number of deaths from cancer in China in 2022 was 2 574 200 (1 629 300 in males and 944 900 in females), with an age-standardized mortality rate of Chinese population (ASMR) of 97.08 per 100 000 (127.70 per 100 000 in males and 68.67 per 100 000 in females). The number of deaths from cancer in urban and rural areas was about 1 400 600 and 1 173 400, with the ASMR of 92.37 and 103.97 per 100 000 in urban and rural areas, respectively. The top five leading cause of cancers death (lung cancer 733 300, liver cancer 316 500, gastric cancer 260 400, colorectal cancer 240 000 and esophageal cancer 187 500) accounted for 67.5% of all cancer deaths. Lung cancer ranked first in the incidence and mortality in men and women. The incidence rate in urban areas was higher than that in rural areas, while the mortality rate was lower than that in rural areas. Conclusions: The burden of cancer in China is still relatively heavy, with significant differences in cancer patterns in gender, urban-rural, and regional. The burden of cancer presents a coexistence of developed and developing countries, and the situation of cancer prevention and control is still serious in China.

[Pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy in the treatment of chronic pancreatitis: initial experience in 11 cases].

Objective: To investigate the surgical strategy for chronic pancreatitis complicated with suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. Methods: This is a retrospective cohort study. Clinical data from 11 patients with chronic pancreatitis who underwent pancreaticoduodenectomy combined with longitudinal pancreaticojejunostomy(PD-L) were retrospectively collected(PD-L group) from the Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi'an Jiaotong University between December 2021 and September 2023. All patients were male with an age of (49.0±11.2) years(range:32 to 70 years). Their primary preoperative diagnoses included pancreatic lesions, chronic pancreatitis, pancreatolithiasis, and dilatation of the pancreatic duct. Data from 248 patients who underwent pancreaticoduodenectomy(PD) during the same period were retrospectively collected(PD group). There were 157 males and 91 females in the PD group, with an age of (61.5±10.8) years(range:27 to 82 years). Among them, 87 cases were diagnosed as pancreatic cancer or chronic pancreatitis. The propensity score matching method was used to reduce confounding bias between the two groups. The caliper value of 0.1 was used and the 1∶4 nearest neighbor matching method was used for the matching. Comparisons between the two groups were made using the independent sample t test, Mann-Whitney U test or χ2 test,respectively. Results: After complete excision of the specimen during pancreaticoduodenectomy, the key surgical step of PD-L was longitudinal pancreaticojejunostomy in the remaining pancreas. Intraoperative blood loss in the PD-L group was lower than that in the PD group [M(IQR)](300(200)ml vs. 500(500)ml, respectively; P<0.05). Similarly, hospitalization days(21.0(7.0)days vs. 25.0(8.5)days) and postoperative hospitalization days(13.0(8.0)days vs. 17.0(5.0) days) were also lower in the PD-L group compared to the PD group (P<0.05). There were no significant differences in the operation time and postoperative complication rate between the two groups(P>0.05). In the PD-L group, the postoperative follow-up time was 5(5)months(range: 3 to 21 months). One case was lost for follow-up. Abdominal pain was relieved in 10 patients. Additionally, abdominal distension and steatosis were alleviated in 8 cases. Furthermore, 5 cases of diabetes mellitus showed improved control of HbA1c and fasting blood glucose levels after surgery. Conclusions: PD-L treatment can be used to treat chronic pancreatitis complicated by suspected malignant lesions in the pancreatic head and pancreatolithiasis in the distal pancreas. PD-L also has advantages in removing stones from the pancreatic duct and evaporation of pancreatic fluid. However, due to the single-center design and the small sample size of this study, further practice and long-term follow-up are still necessary.

[Emphasizing the timing and procedure selection for vitrectomy in pathological myopic traction maculopathy].

Myopic maculopathy is the primary cause of irreversible visual impairment in patients with pathologic myopia, and myopic traction maculopathy often requires vitrectomy for treatment. Myopic traction maculopathy encompasses epiretinal membrane, foveoschisis, macular hole, and macular hole-related retinal detachment. It is recommended to perform vitrectomy combined with inner limiting membrane peeling for Type II epiretinal membrane, foveal-sparing inner limiting membrane peeling for foveoschisis, inverted inner limiting membrane flap technique for macular hole, and vitrectomy combined with macular buckle for refractory macular hole-related retinal detachment. Myopic traction maculopathy is a chronically progressive condition, and surgeons need to accurately determine the timing of surgery and choose appropriate procedures to maximize the benefits for patients.

[Preliminary study on automatic quantification and grading of leopard spots fundus based on deep learning technology].

Objective: To achieve automatic segmentation, quantification, and grading of different regions of leopard spots fundus (FT) using deep learning technology. The analysis includes exploring the correlation between novel quantitative indicators, leopard spot fundus grades, and various systemic and ocular parameters. Methods: This was a cross-sectional study. The data were sourced from the Beijing Eye Study, a population-based longitudinal study. In 2001, a group of individuals aged 40 and above were surveyed in five urban communities in Haidian District and three rural communities in Daxing District of Beijing. A follow-up was conducted in 2011. This study included individuals aged 50 and above who participated in the second 5-year follow-up in 2011, considering only the data from the right eye. Color fundus images centered on the macula of the right eye were input into the leopard spot segmentation model and macular detection network. Using the macular center as the origin, with inner circle diameters of 1 mm, 3 mm, and outer circle diameter of 6 mm, fine segmentation of the fundus was achieved. This allowed the calculation of the leopard spot density (FTD) and leopard spot grade for each region. Further analyses of the differences in ocular and systemic parameters among different regions' FTD and leopard spot grades were conducted. The participants were categorized into three refractive types based on equivalent spherical power (SE): myopia (SE<-0.25 D), emmetropia (-0.25 D≤SE≤0.25 D), and hyperopia (SE>0.25 D). Based on axial length, the participants were divided into groups with axial length<24 mm, 24-26 mm, and>26 mm for the analysis of different types of FTD. Statistical analyses were performed using one-way analysis of variance, Kruskal-Wallis test, Bonferroni test, and Spearman correlation analysis. Results: The study included 3 369 participants (3 369 eyes) with an average age of (63.9±10.6) years; among them, 1 886 were female (56.0%) and 1, 483 were male (64.0%). The overall FTD for all eyes was 0.060 (0.016, 0.163); inner circle FTD was 0.000 (0.000, 0.025); middle circle FTD was 0.030 (0.000, 0.130); outer circle FTD was 0.055 (0.009, 0.171). The results of the univariate analysis indicated that FTD in various regions was correlated with axial length (overall: r=0.38, P<0.001; inner circle: r=0.31, P<0.001; middle circle: r=0.36, P<0.001; outer circle: r=0.39, P<0.001), subfoveal choroidal thickness (SFCT) (overall: r=-0.69, P<0.001; inner circle: r=-0.57, P<0.001; middle circle: r=-0.68, P<0.001; outer circle: r=-0.72, P<0.001), age (overall: r=0.34, P<0.001; inner circle: r=0.30, P<0.001; middle circle: r=0.31, P<0.001; outer circle: r=0.35, P<0.001), gender (overall: r=-0.11, P<0.001; inner circle: r=-0.04, P<0.001; middle circle: r=-0.07, P<0.001; outer circle: r=-0.11, P<0.001), SE (overall: r=-0.20; P<0.001; inner circle: r=-0.19, P<0.001; middle circle: r=-0.20, P<0.001; outer circle: r=-0.20, P<0.001), uncorrected visual acuity (overall: r=-0.18, P<0.001; inner circle: r=-0.26, P<0.001; middle circle: r=-0.24, P<0.001; outer circle: r=-0.22, P<0.001), and body mass index (BMI) (overall: r=-0.11, P<0.001; inner circle: r=-0.13, P<0.001; middle circle: r=-0.14, P<0.001; outer circle: r=-0.13, P<0.001). Further multivariate analysis results indicated that different region FTD was correlated with axial length (overall: ß=0.020, P<0.001; inner circle: ß=-0.022, P<0.001; middle circle: ß=0.027, P<0.001; outer circle: ß=0.022, P<0.001), SFCT (overall: ß=-0.001, P<0.001; inner circle: ß=-0.001, P<0.001; middle circle: ß=-0.001, P<0.001; outer circle: ß=-0.001, P<0.001), and age (overall: ß=0.002, P<0.001; inner circle: ß=0.001, P<0.001; middle circle: ß=0.002, P<0.001; outer circle: ß=0.002, P<0.001). The distribution of overall (H=56.76, P<0.001), inner circle (H=72.22, P<0.001), middle circle (H=75.83, P<0.001), and outer circle (H=70.34, P<0.001) FTD differed significantly among different refractive types. The distribution of overall (H=373.15, P<0.001), inner circle (H=367.67, P<0.001), middle circle (H=389.14, P<0.001), and outer circle (H=386.89, P<0.001) FTD differed significantly among different axial length groups. Furthermore, comparing various levels of FTD with systemic and ocular parameters, significant differences were found in axial length (F=142.85, P<0.001) and SFCT (F=530.46, P<0.001). Conclusions: The use of deep learning technology enables automatic segmentation and quantification of different regions of theFT, as well as preliminary grading. Different region FTD is significantly correlated with axial length, SFCT, and age. Individuals with older age, myopia, and longer axial length tend to have higher FTD and more advanced FT grades.

[Analysis of clinical characteristics of 129 acute and chronic occupational brucellosis in HulunBuir City].

Objective: To analyze the epidemiological characteristics and clinical data of acute and chronic occupational brucellosis patients in order to provide a scientific basis for the prevention and treatment of occupational brucellosis. Methods: In October 2022, a study was conducted on 129 patients diagnosed with occupational brucellosis by HulunBuir Center for Disease Control and Prevention from January 2016 to December 2021. The epidemiological characteristics, clinical features, and laboratory test results of patients in the acute and chronic phases were compared and analyzed using chi-square test and student's t test. Results: The acute phase patients included 38 men and 4 women with an average age of (36.6±8.4) years old; the chronic phase patients included 73 men and 14 women with an average age of (38.4±7.9) years old. There were no significant differences in gender and age between the two groups (P>0.05). The patients had a clear history of occupational exposure, and the proportion of veterinarians in acute stage (21 cases, 50.0%) was significantly higher than that in chronic stage (25 cases, 28.7%), the difference was statistically significant (P<0.05). The symptoms of fever and loss of appetite in acute phase of occupational brucellosis were significantly higher than those in chronic phase, and the symptoms of fatigue and joint muscle pain were significantly lower than those in chronic phase, with statistical significances (P<0.05). The increase of alanine aminotransferase, aspartate aminotransferase, C-reactive protein, erythrocyte sedimentation rate and positive rate of blood culture in acute stage were significantly higher than those in chronic stage, with statistical significances (P<0.05) . Conclusion: Occupational brucellosis patients are predominantly middle-aged men, the acute phase is characterized by fever, loss of appetite, and increased inflammatory indicators and liver enzymes, while the chronic phase is characterized by symptoms such as fatigue and joint muscle pain. Brucellosis related occupational exposure population should seek medical treatment as soon as possible when the above symptoms occur, timely detection and treatment of occupational diseases.

Cyclic Homo- and Heterohalogen Di-λ3-diarylhalonium Structures.

In the context of the ever-growing interest in the cyclic diaryliodonium salts, this work presents synthetic design principles for a new family of structures with two hypervalent halogens in the ring. The smallest bis-phenylene derivative, [(C6H4)2I2]2+, was prepared through oxidative dimerization of a precursor bearing the ortho-disposed iodine and trifluoroborate groups. We also report, for the first time, the formation of cycles containing two different halogen atoms. These present two phenylenes linked by hetero-(I/Br) or -(I/Cl) halogen pairs. This approach was also extended to the cyclic bis-naphthylene derivative [(C10H6)2I2]2+. The structures of these bis-halogen(III) rings were further assessed through X-ray analysis. The simplest cyclic phenylene bis-iodine(III) derivative features the interplanar angle of ∼120°, while a smaller angle of ∼103° was found for the analogous naphthylene-based salt. All dications form dimeric pairs through a combination of π-π and C-H/π interactions. As the largest member of the family, a bis-I(III)-macrocycle was also assembled using the quasi-planar xanthene backbone. Its geometry enables the two iodine(III) centers to be bridged intramolecularly by two bidentate triflate anions. In a preliminary manner, the interaction of the phenylene- and naphthalene-based bis-iodine(III) dications with a new family of rigid bidentate bis-pyridine ligands was studied in solution and the solid state, with an X-ray structure showing the chelating donor bonding to just one of the two iodine centers.

Exome-wide screening identifies novel rare risk variants for bone mineral density.

Bone mineral density (BMD) is an independent risk factor of osteoporosis-related fractures. We performed gene-based burden tests to assess the association between rare variants and BMD, and identified several BMD candidate genes. PURPOSE: BMD is highly heritable and a major predictor of osteoporotic fractures, but its genetic basis remains unclear. We aimed to identify rare risk variants contributing to BMD. METHODS: Utilizing the newly released UK Biobank 200,643 exome dataset, we conducted a gene-based exome-wide association study in males and females, respectively. First, 100,639 males and 117,338 females with BMD values were included in the polygenic risk scores (PRS) analysis. Among individuals with lower 30% PRS, cases were individuals with top 10% BMD, and individuals with bottom 10% BMD were the controls. Considering the effects of vitamin D (VD), individuals with the highest 30% VD concentration were selected for VD-BMD analysis. After quality control, 741 males and 697 females were included in the BMD analysis, and 717 males and 708 females were included in the VD-BMD analysis. The variants were annotated by ANNOVAR software, then BMD and VD-BMD qualified variants were imported into the SKAT R-package to perform gene-based burden tests, respectively. RESULTS: The gene-based burden test of the exonic variants identified genome-wide candidate associations in ANKRD18A (P = 1.60 × 10-5, PBonferroni adjust = 2.11 × 10-3), C22orf31 (P = 3.49 × 10-4, PBonferroni adjust = 3.17 × 10-2), and SPATC1L (P = 1.09 × 10-5, PBonferroni adjust = 8.80 × 10-3). For VD-BMD analysis, three genes were associated with BMD, such as NIPAL1 (P = 1.06 × 10-3, PBonferroni adjust = 3.91 × 10-2). CONCLUSIONS: Our study suggested that rare variants contribute to BMD, providing new sights for broadening the genetic structure of BMD.

RNase H1C collaborates with ssDNA binding proteins WHY1/3 and recombinase RecA1 to fulfill the DNA damage repair in Arabidopsis chloroplasts.

Proper repair of damaged DNA is crucial for genetic integrity and organismal survival. As semi-autonomous organelles, plastids have their own genomes whose integrity must be preserved. Several factors have been shown to participate in plastid DNA damage repair; however, the underlying mechanism remains unclear. Here, we elucidate a mechanism of homologous recombination (HR) repair in chloroplasts that involves R-loops. We find that the recombinase RecA1 forms filaments in chloroplasts during HR repair, but aggregates as puncta when RNA:DNA hybrids accumulate. ssDNA-binding proteins WHY1/3 and chloroplast RNase H1 AtRNH1C are recruited to the same genomic sites to promote HR repair. Depletion of AtRNH1C or WHY1/3 significantly suppresses the binding of RNA polymerase to the damaged DNA, thus reducing HR repair and modulating microhomology-mediated double-strand break repair. Furthermore, we show that DNA polymerase IB works with AtRNH1C genetically to complete the DNA damage repair process. This study reveals the positive role of R-loops in facilitating the activities of WHY1/3 and RecA1, which in turn secures HR repair and organellar development.

[Application of novel non-endoscopic device in the screening and early diagnosis of esophageal cancer].

Esophageal cancer (EC) is a dreadful disease with a poor prognosis and poses heavy health burden worldwide. Developing effective methods to identify high-risk individuals is urgently needed for preliminary screening before endoscopy. The novel non-endoscopic device has the potential advantages of low cost, simple operation, and minimal invasiveness. Approximately 90% of participants can swallow the device successfully with high safety profiles, and sufficient esophageal exfoliated cells can be collected for cytological examination and biomarker detection. Cytological examination based on the device combined with trefoil factor 3 (TFF3) protein or DNA methylation examinations could effectively screen Barrett's esophagus-associated dysplasia and early esophageal adenocarcinoma, but large prospective studies are needed to further validate the diagnostic value of this device to improve the quality of evidence. Although the device-based cytological examination in combination with biomarker detection holds promise in the early screening of esophageal squamous dysplasia and early esophageal squamous cell carcinoma, related research is still in its infancy, and there is still a lack of sufficient evidence for population screening in China. Active research into the application of this novel non-endoscopic device in EC screening and early diagnosis is of great significance for optimizing EC screening strategies and improving the early diagnosis of EC.

[Efficacy and safety evaluation of immunotherapy combined with targeted therapy as second-line treatment in patients with metastatic non-clear cell renal cell carcinoma].

Objective: This study aimed to evaluate the efficacy and safety of programmed death-1 (PD-1) inhibitor combined tyrosine kinase inhibitor (TKI) therapy versus TKI monotherapy as the second-line regimen for patients with metastatic non-clear cell renal carcinoma (nccRCC) who failed first-line TKI therapy. Methods: The clinicopathological data of 67 patients with metastatic nccRCC who failed first-line TKI therapy between October 2011 and September 2020 were retrospectively analyzed, including 22 patients who received TKI monotherapy and 45 patients who received TKI plus PD-1 inhibitor as the second-line therapy. The efficacy was assessed according to Response Evaluation Criteria in Solid Tumors version 1.0/1.1 (RECIST 1.0/1.1), the Kaplan-Meier method was used to plot the survival curves, and the Log rank test was used to analyze the differences in the survival between the two groups. Treatment-related adverse events (AEs) after treatment were observed in both groups. Results: The overall objective response rate (ORR) and disease control rate (DCR) were 37.3% (25/67) and 56.7% (38/67), respectively. The overall second-line progression-free survival (PFS) was 7.7 months and Overall Survival (OS) was 25.2 months. The ORR and DCR of patients in the combination therapy group were 48.9% (22/45) and 71.1% (32/45), respectively, which were significantly improved compared with the TKI monotherapy group [13.6% (3/22) and 27.3% (6/22), respectively] (P=0.007 and P=0.001, respectively). The median PFS of 9.2 months for second-line treatment was longer in patients in the combination therapy group than in the TKI monotherapy group (5.2 months, P=0.001), but the median OS was not statistically different between the two groups (28.2 months vs 20.8 months, P=0.068). Common treatment-related AEs included hypertension, diarrhea, fatigue, stomatitis, hand-foot syndrome, and hypothyroidism. The incidence of hypothyroidism was higher in the combination therapy group [40.0% (18/45)] than in the TKI monotherapy group [22.7% (5/22), P=0.044]; the incidence of other treatment-related AEs between the two groups were not statistically significant (all P>0.05). Conclusion: Immune-targeted combination therapy was more effective than TKI monotherapy alone and was well tolerated in the treatment of metastatic nccRCC patients who failed first-line TKIs.

[Cancer statistics in China, 2016].

Objective: Data for 2016 from cancer registries were used to estimate cancer incidence and mortality in China in 2016. Methods: According to the quality control process of the National Central Cancer Registry, the data from 683 cancer registries submitted by each province were evaluated, and the data of 487 cancer registries were qualified and included in the final analysis. Age-specific incidence and mortality rates were calculated by area (urban/rural), sex, age and cancer site, combined with national population data to estimate cancer incidence and mortality in China in 2016. Chinese population census in 2000 and Segi's population were used for age-standardized incidence and mortality rates. Results: Total population covered by 487 cancer registries was 381 565 422 (192 628 370 in urban and 188 937 052 in rural areas). The percentages of morphologically verified (MV%) and death certificate-only cases (DCO%) accounted for 68.31% and 1.40%, respectively, and the mortality to incidence ratio was 0.61. It was estimated about 4 064 000 new cases occurred in China in 2016, with the crude incidence rate being 293.91/100 000 (the rates of males and females were 315.52/100 000 and 271.23/100 000), age-standardized incidence rates by Chinese standard population (ASIRC) and by world standard population (ASIRW) were 190.76/100 000 and 186.46/100 000, with the cumulative incidence rate (0-74 years old) being 21.42%. The crude incidence and ASIRC were 314.74/100 000 and 196.38/100 000 in urban areas, whereas in rural areas, they were 265.90/100 000 and 182.21/100 000, respectively. It was estimated about 2 413 500 cancer deaths occurred in China in 2016, the crude mortality rate was 174.55/100 000 (216.16/100 000 in males and 130.88/100 000 in females), the age-standardized mortality rates by Chinese standard population (ASMRC) and by world standard population (ASMRW) were 106.00/100 000 and 105.19/100 000, and the cumulative mortality rate (0-74 years old) was 11.85%. The crude mortality and ASMRC were 180.31/100 000 and 104.44/100 000 in urban areas, whereas in rural areas, they were 166.81/100 000 and 108.01/100 000, respectively. The most common cancer cases include lung, colorectal, stomach, liver and female breast cancers. The top five cancers accounted for about 57.27% of all cancer cases. The most common cancer deaths included lung, liver, stomach, colorectal and esophageal cancers. The top five cancers accounted for about 69.25% of all cancer deaths. Conclusions: The burden of cancer shows a continuous increasing trend in China. Regional and gender differences in cancer burden are obvious. The cancer patterns still show the coexistence of cancer patterns in developed countries and developing countries. The situation of cancer prevention and control is still serious in China.

[A case of disseminated nocardiosis in a non-immunosuppressed host].

Nocardia is an opportunistic pathogen that most commonly affects immunosuppressed hosts, while disseminated infections in healthy hosts are rare. In this paper, we described a case of disseminated Nocardia infection in a non-immunosuppressed host whose initial imaging was strikingly similar to systemic metastasis from a tumor. Since no tumor cells were found in any of the numerous biopsies taken, we considered infection by specific pathogens before metagenomic next-generation sequencing of a lumbar spine tissue biopsy finally confirmed the diagnosis of Nocardia infection. To help doctors better understand this condition and avoid misdiagnosis a, this article provided a summary of the clinical characteristics, diagnostic techniques, and therapeutic options for disseminated nocardiosis.

[Effect of pancreatic extracorporeal shock wave lithotripsy on chronic pancreatitis stones].

Objective: To analyze the therapeutic effect and safety of pancreatic extracorporeal shock wave lithotripsy(P-ESWL) for patients with chronic pancreatitis complicated by stones of the pancreatic duct and to investigate the influencing factors. Methods: A retrospective analysis was performed on clinical data from 81 patients with chronic pancreatitis complicated by pancreatic duct calculus treated with P-ESWL in the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi 'an Jiaotong University from July 2019 to May 2022. There were 55 males(67.9%) and 26 females(32.1%). The age was (47±15)years (range: 17 to 77 years). The maximum diameter(M(IQR)) of the stone was 11.64(7.60) mm, and the CT value of the stone was 869 (571) HU. There were 32 patients (39.5%) with a single pancreatic duct stone and 49 patients(60.5%) with multiple pancreatic duct stones. The effectiveness, remission rate of abdominal pain, and complications of P-ESWL were evaluated. Student's t test, Mann Whitney U test, χ2 test, or Fisher's exact test was used to compare the characteristics between the effective and ineffective groups of lithotripsy. The factors influencing the effect of lithotripsy were analyzed by univariate and multivariate logistic regression analysis. Results: Eighty-one patients with chronic pancreatitis were treated with P-ESWL 144 times, with an average of 1.78 (95%CI:1.60 to 1.96) times per person. Among them, 38 patients(46.9%) were treated with endoscopy. There were 64 cases(79.0%) with effective removal of pancreatic duct calculi and 17 cases(21.0%) with ineffective removal. Of the 61 patients with chronic pancreatitis accompanied by abdominal pain, 52 cases(85.2%) had pain relief after lithotripsy. After lithotripsy treatment, 45 patients(55.6%) developed skin ecchymosis, 23 patients(28.4%) had sinus bradycardia, 3 patients(3.7%) had acute pancreatitis, 1 patient(1.2%) had a stone lesion, and 1 patient(1.2%) had a hepatic hematoma. Univariate and multivariate logistic regression analysis showed that the factors affecting the efficacy of lithotripsy included the age of patient(OR=0.92, 95%CI: 0.86 to 0.97), the maximum diameter of the stone(OR=1.12,95%CI:1.02 to 1.24) and the CT value of the stone(OR=1.44, 95%CI: 1.17 to 1.86). Conclusions: P-ESWL is effective in the treatment of patients with chronic pancreatitis complicated by calculi of the main pancreatic duct.Factors affecting the efficacy of lithotripsy include patient's age, maximum stone diameter, and CT value of calculi.

[Attention should be paid to the lifelong monitoring of diabetic retinopathy in people with diabetes].

Diabetic retinopathy (DR) is one of the severe complications of diabetes, and also the most common reason of vision loss in Chinese adults over 30 years old. Regular fundus examination and continuous glucose monitoring can prevent 98% of blindness caused by DR. However, due to the irrational allocation of medical resources and the weak awareness of DR patients, only about 50% to 60% of diabetes patients have an annual DR screening. Therefore, it is necessary to build a follow-up system for early screening, prevention, treatment and lifelong monitoring of DR patients. In this review, we discuss the importance of lifelong monitoring, the hierarchical medical system and the follow-up of pediatric DR patients. Novel and multi-level screening methods are cost-saving to patients and cost-effective to healthcare systems, and also can help improve the detection and early treatment of DR.

[Analysis of the correlation between peripapillary retinal nerve fiber layer cross-sectional area and myopia in individuals aged 50 years and above].

Objective: To measure the peripapillary retinal nerve fiber layer (RNFL) cross-sectional area in individuals aged 50 years and above with different refractive errors, and analyze its correlation with axial length and refractive error. Methods: This was a cross-sectional study conducted as part of the "Beijing Eye Study". The study was population-based and longitudinally designed. In 2001, a cohort of individuals aged 40 years and above from five urban communities in Haidian District and three rural communities in Daxing District, Beijing, were surveyed. Follow-up examinations were conducted in 2011. In this study, the follow-up data from 2011 were collected and analyzed. One eye of each participant was randomly selected, and the participants were categorized into four groups based on their spherical equivalent: emmetropia group (-0.50 D≤spherical equivalent≤0.50 D), low myopia group (-3.00 D≤spherical equivalent<-0.50 D), moderate myopia group (-6.00 D≤spherical equivalent<-3.00 D), and high myopia group (spherical equivalent<-6.00 D). Spectral-domain optical coherence tomography (OCT) was used to perform circular scans with a diameter of 12° centered on the optic disc. ImageJ software and Heidelberg Eye Explorer software were used to calculate the RNFL cross-sectional area. One-way analysis of variance was used to compare the differences in RNFL thickness and RNFL cross-sectional area among different groups. Linear regression analysis was performed to analyze the correlation between RNFL thickness and axial length and spherical equivalent, as well as the correlation between RNFL cross-sectional area and axial length and spherical equivalent. Results: A total of 184 participants (184 eyes) were included in the study, including 88 males and 96 females. The median age was 59 (54, 66) years, with 87 right eyes and 97 left eyes. There were 50 participants (50 eyes) in the emmetropia group, low myopia group, and moderate myopia group, and 34 participants (34 eyes) in the high myopia group. There were no significant differences in age, gender, and eye laterality among the groups (all P>0.05). The RNFL cross-sectional areas in the emmetropia, low myopia, moderate myopia, and high myopia groups were (1.115±0.106), (1.122±0.136), (1.105±0.105), and (1.096±0.106) mm2, respectively, with no significant differences observed (F=0.43, P=0.730). The RNFL thickness in the emmetropia, low myopia, moderate myopia, and high myopia groups were (102.5±9.5), (102.5±12.1), (94.2±8.3), and (90.2±8.9) µm, respectively, with a significant difference observed (F=16.42, P<0.001). Univariate linear regression analysis was performed with spherical equivalent as the independent variable and peripapillary RNFL thickness as the dependent variable, yielding the regression equation: peripapillary RNFL thickness=102.651+1.634 × spherical equivalent (R2=0.21, P<0.001). Similarly, when axial length was used as the independent variable and peripapillary RNFL thickness as the dependent variable, the regression equation was: peripapillary RNFL thickness=174.161-3.147 × axial length (R2=0.18, P<0.001). There was no significant correlation between RNFL cross-sectional area and spherical equivalent (P=0.065) or axial length (P=0.846). Conclusions: There were no significant differences in peripapillary RNFL cross-sectional area among individuals aged 50 years and above with different axial lengths or refractive errors.

[A retrospective analysis of 147 cases of orbital exenteration].

Objective: To investigate the main indications and prognosis of patients undergoing orbital exenteration (OE). Methods: It was a retrospective case series study. The medical records were collected of patients who underwent OE surgery at Beijing Tongren Hospital from January 2007 to December 2021, and their general information, tumor characteristics, lymph node metastasis, diagnosis and treatment, specific surgical techniques, pathological diagnosis and prognosis were analyzed. Kaplan-Meier survival curves were used to evaluate overall survival and recurrence-free survival. Results: A total of 147 patients were included, with a median age of 58 (48, 68) years. Among them, 82 patients (55.8%) were male and 65 (44.2%) were female, and all underwent unilateral OE. Five patients (3.4%) had benign lesions. Among the 142 patients with malignant tumors, conjunctival malignancies (37.3%) were the most common, followed by eyelid (29.6%), orbital (19.0%), and ocular (14.1%) malignancies. Among the 53 patients with conjunctival tumors, 38 (71.7%) had conjunctival melanoma and 14 (26.4%) had squamous cell carcinoma. Among the 42 patients with eyelid malignancies, 19 (45.2%) had sebaceous gland carcinoma and 16 (38.1%) had basal cell carcinoma. Among the 20 patients with ocular malignancies, 10 (50.0%) had choroidal melanoma and 9 (45.0%) had retinoblastoma. The most common pathological types among the 142 patients with malignant tumors were melanoma (51 cases, 35.9%), squamous cell carcinoma (20 cases, 14.1%), sebaceous gland carcinoma (19 cases, 13.4%), and basal cell carcinoma (16 cases, 11.3%). Of the 135 patients included in the survival analysis, all 5 patients with benign lesions were alive at the last follow-up. The median follow-up time for the 130 patients with malignant tumors was 6.9 (2.5, 6.9) years, ranging from 0.2 to 14.0 years. The overall survival rates at 1, 3, and 5 years after surgery were 90.9% (95%CI: 85.8%-96.0%), 68.4% (95%CI: 59.6%-77.2%), and 60.1% (95%CI: 50.5%-69.7%), respectively. The recurrence-free survival rates of patients with and without lymph node metastasis before surgery were 57.6% and 56.7%, respectively (OR=1.062, 95% CI: 0.525-2.148, P=0.864), and the overall survival rates were 61.5% and 57.7%, respectively (OR=1.019, 95% CI: 0.512-2.033, P=0.957), with no significant differences both. The recurrence-free survival rates of patients with melanoma (47 cases) and non-melanoma (83 cases) were 40.4% and 67.5%, respectively (OR=2.576, 95% CI: 1.390-4.775, P<0.001), and the overall survival rates were 42.6% and 67.5%, respectively (OR=2.845, 95% CI: 1.549-5.225, P<0.001), with significant differences both. Conclusions: The primary indications for OE are malignant tumors of the conjunctiva and eyelids, with melanoma being the most common malignant tumor of the conjunctiva. Melanoma patients who undergo OE have a lower survival rate compared to other types of malignant tumors. Nevertheless, even in the presence of tumor lymph node metastasis, patients can achieve a relatively good prognosis through OE.