[Clinicopathological features and prognosis of sporadic mismatch repair deficient colorectal cancer].

Objective: To investigate the clinicopathological characteristics and prognostic factors of sporadic mismatch repair deficient (dMMR) colorectal cancer. Methods: A total of 120 cases of sporadic dMMR colorectal cancer from July 2015 to April 2021 were retrospectively collected in Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College. Patients with Lynch syndrome; synchronous multiple colorectal cancers; preoperative anti-tumor treatments such as chemotherapy and radiotherapy; and those with incomplete follow-up information were excluded based on family history and next-generation sequencing (NGS) test results. Immunohistochemical stains were used to detect the expression of mismatch repair proteins, methylation-specific PCR for methylation testing, and fluorescent PCR for BRAF V600E gene mutation detection. The clinical and pathological data, and gene mutation status were analyzed. Follow-up was done to assess survival and prognosis including progression-free survival and overall survival rate. Results: Sporadic dMMR colorectal cancer occurred more frequently in the right side of the colon, in females, and in the elderly. Morphologically, it was mostly moderately-differentiated, and most patients had low-grade tumor budding. In terms of immunohistochemical expression, MLH1 and PMS2 loss were dominant, and there were age and location-specificities in protein expression. MLH1 methylation was commonly detected in elderly female patients and rare in young male patients; while MLH1 and PMS2 deficiency, and BRAF V600E mutation occurred more often on the right side (P<0.05). The 3-year and 5-year progression-free survival rates were 90.7% and 88.7% respectively, and the 3-year and 5-year overall survival rates were 92.8% and 90.7% respectively. Tumor budding status was an independent risk factor affecting patient recurrence (hazard ratio=3.375, 95% confidence interval: 1.060-10.741, P=0.039), patients with low-grade tumor budding had better prognosis, and those with medium or high-grade tumor budding had poor prognosis. Conclusion: For dMMR colorectal cancer patients, tumor budding status is an independent risk factor for recurrence.

[Application effects of 3D visualization reconstruction technique in pheochromocytoma/ paraganglioma surgery].

To investigate the value of 3D visualization reconstruction technology in pheochromocytoma/paraganglioma surgery.The clinical data of 87 patients with pheochromocytoma/paraganglioma admitted to the Department of Urology of Peking Union Medical College Hospital between January 2019 and December 2022 were retrospectively analyzed, and 3D visualization model reconstruction was performed preoperatively in 47 patients [Group A:males was 24 cases,the age M(Q1, Q3)42.00(30.00, 54.00)]. while the remaining 40 patients [Group B: males was 23 cases,the age M(Q1, Q3) 44.00(30.25, 53.75)] was not. The maximum tumor diameter, operation time, intraoperative bleeding, drain retention time and postoperative hospital stay were compared between the two groups. Surgery was successfully completed in both groups. 37 (78.7%) patients in group A underwent laparoscopic surgery, 7 (14.9%) patients underwent open surgery, and 3 (6.4%) patients underwent laparoscopic-to-open surgery. Thirty-one (77.5%) patients in group B underwent laparoscopic surgery, 5 (12.5%) patients underwent open surgery, and 4 (10.0%) patients underwent laparoscopic to open surgery. There was a difference in the maximum diameter of the tumor between the two groups [(6.09±3.02) cm vs (5.32±1.76) cm, P<0.05], the retention time of the drainage tube was significantly shorter in group A compared with group B [(3.20±1.38) d vs (4.02±1.98) d, P<0.05], and the length of the hospital stay after surgery was significantly shorter [(5.75±2.12) d vs (6.49±3.37) d, P<0.05]. Comparison of operation time and intraoperative bleeding between the two groups showed no statistically significant difference (P>0.05).Two cases of postoperative anemia and one case of pulmonary atelectasis in group B patients improved before discharge. Conclusion when the tumor diameter is>6 cm or has a close relationship with the surrounding organs and blood vessels, the use of 3D visual reconstruction technology can formulate and implement a more accurate and safe surgical plan, shorten the retention time of the drainage tube and postoperative hospitalization time, which is conducive to the patient's postoperative recovery and reduce postoperative complications.

[Epidemiological characteristics of typhoid fever and paratyphoid fever in China, 2004-2020].

Objective: To analyze the incidence trend and epidemiological characteristics of typhoid fever and paratyphoid fever in China from 2004 to 2020, understand the high-incidence population and hotspot areas, and provide evidences to develop more targeted prevention and control measures. Methods: The descriptive epidemiological method and spatial analysis method were applied to analyze the epidemiological characteristics of typhoid fever and paratyphoid fever in China during this period by using the surveillance data collected from the National Notifiable Infectious Disease Reporting System of Chinese Center for Disease Control and Prevention. Results: A total of 202 991 cases of typhoid fever were reported in China from 2004 to 2020. More cases occurred in men than in women (sex ratio: 1.18∶1). Most cases were reported in adults aged 20-59 years (53.60%). The incidence rate of typhoid fever decreased from 2.54/100 000 in 2004 to 0.38/100 000 in 2020. The highest incidence rate was reported in young children aged <3 years after 2011, ranging from 1.13/100 000 to 2.78/100 000, and during this period the proportion of cases in this age group increased from 3.48% to 15.59%. The proportion of the cases in the elderly aged ≥60 years increased from 6.46% in 2004 to 19.34% in 2020. The hotspot areas existed in Yunnan, Guizhou, Guangxi and Sichuan Provinces and expanded to Guangdong, Hunan, Jiangxi, and Fujian Provinces. A total of 86 226 paratyphoid fever cases were reported from 2004 to 2020, the male to female ratio of the cases was 1.21∶1. Most cases were reported in adults aged 20-59 years (59.80%). The incidence rate of paratyphoid fever decreased from 1.26/100 000 in 2004 to 0.12/100 000 in 2020. The highest incidence rate of paratyphoid fever was in young children aged <3 years after 2007, ranging from 0.57/100 000 to 1.19/100 000, and during this period the proportion of the cases in this age group increased from 1.48% to 30.92%. The proportion of the cases in the elderly aged ≥60 years increased from 4.52% in 2004 to 22.28% in 2020. The hotspot areas expanded to the east, including Guangdong, Hunan and Jiangxi Provinces, from Yunnan, Guizhou, Sichuan, and Guangxi Provinces. Conclusions: The results showed a low level of incidence of typhoid fever and paratyphoid fever in China with a trend of decreasing per year. The hotspots were mainly in the of Yunnan, Guizhou, Guangxi and Sichuan Provinces, with an expanding trend to eastern China. It is necessary to strengthen the typhoid fever and paratyphoid fever prevention and control in southwestern China, among young children aged <3 years and the elderly aged ≥60 years.

Toward discovering a novel family of peptides targeting neuroinflammatory states of brain microglia and astrocytes.

Microglia are immune-derived cells critical to the development and healthy function of the brain and spinal cord, yet are implicated in the active pathology of many neuropsychiatric disorders. A range of functional phenotypes associated with the healthy brain or disease states has been suggested from in vivo work and were modeled in vitro as surveying, reactive, and primed sub-types of primary rat microglia and mixed microglia/astrocytes. It was hypothesized that the biomolecular profile of these cells undergoes a phenotypical change as well, and these functional phenotypes were explored for potential novel peptide binders using a custom 7 amino acid-presenting M13 phage library (SX7) to identify unique peptides that bind differentially to these respective cell types. Surveying glia were untreated, reactive were induced with a lipopolysaccharide treatment, recovery was modeled with a potent anti-inflammatory treatment dexamethasone, and priming was determined by subsequently challenging the cells with interferon gamma. Microglial function was profiled by determining the secretion of cytokines and nitric oxide, and expression of inducible nitric oxide synthase. After incubation with the SX7 phage library, populations of SX7-positive microglia and/or astrocytes were collected using fluorescence-activated cell sorting, SX7 phage was amplified in Escherichia coli culture, and phage DNA was sequenced via next-generation sequencing. Binding validation was done with synthesized peptides via in-cell westerns. Fifty-eight unique peptides were discovered, and their potential functions were assessed using a basic local alignment search tool. Peptides potentially originated from proteins ranging in function from a variety of supportive glial roles, including synapse support and pruning, to inflammatory incitement including cytokine and interleukin activation, and potential regulation in neurodegenerative and neuropsychiatric disorders.

Proteomic study on CUMS-induced senile depression mice's frontal lobe cortex and the regulating effect of KTLD formula.

OBJECTIVE: The aim of this study was to investigate the protein expression of chronic unpredictable mild stress (CUMS)-induced senile depression in SAMP-8 mice's frontal lobe cortex and the regulating effect of the kidney tonifying and liver dispersing (KTLD) formula. MATERIALS AND METHODS: A total of 15 male SAMP-8 mice were randomly divided into control, CUMS, and KTLD groups. CUMS and KTLD mice were subjected to CUMS for 21 days. Control group mice were kept to normal feeding. At the same time as molding, the herbal gavage (KTLD formula, 19.5 g/kg/d) was given from the beginning of the stress stimulation, while the control group and the CUMS group mice were given the same volume of saline for 21 days. Open-field testing (OFT) was used to assess the mice's depression levels. Isobaric tags for relative and absolute quantification (iTRAQ) were used to identify differentially expressed proteins (DEPs) in mice's frontal lobe cortex. Bioinformatics analysis including Gene Ontology (GO); Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) networks were utilized to study the DEPs connections. RESULTS: Results revealed that mice with senile depression experienced more anxiety and depression than control mice, whereas KTLD mice had the opposite experience. Biological processes including transport, regulation of transcription, and DNA-templated were identified in both KTLD and CUMS. The KEGG enrichment study of the DEPs in KTLD revealed their involvement in the MAPK signaling pathway, glutamatergic synapse, dopaminergic synapse, axon guidance, and ribosome. KEGG pathway enrichment showed that the mechanism of senile depression and the pathway of KTLD are closely related to axonal conductance and ribosomes. According to the PPI analysis, disease-related proteins regulated by KTLD revealed that some proteins, such as GLOI1 and TRRAP, have potential interactions. This provides fresh insight into how KTLD works to cue senile depression. CONCLUSIONS: KTLD treats senile depression via multiple targets and pathways, which may include regulations of 467 DEPs. Proteomics showed significant changes in protein levels in geriatric depression and after KTLD intervention. Senile depression involves the cross-linking and modulation of signal pathways, presenting a pattern of multiple pathways and multiple targets. According to a protein pathway enrichment and protein interaction model of KTLD in senile depression, KTLD is capable of treating senile depression via multiple pathways and targets.

Digitalization of hydraulic rotary drilling process for continuously mechanical profiling of siliciclastic sedimentary rocks.

Hydraulic rotary drilling can offer the essential information and core samplesa for the researches on solid earth. Recording the factual field drilling data and analyzing the hydraulic rotary coring process are challenging yet promising to utilize the massive drilling information in geophysics and geology. This paper adopts the drilling process monitoring (DPM) technique and records the four parameters of displacement, thrust pressure, upward pressure, and rotation speed in real-time series for profiling the siliciclastic sedimentary rocks along 108 m deep drillhole. The digitalization results with 107 linear zones represent the spatial distribution of drilled geomaterials including superficial deposits (fill, loess, gravelly soil), mudstone, silty mudstone, gritstone, and fine sandstone. The constant drilling speeds varying from 0.018 to 1.905 m/min present the in-situ coring resistance of drilled geomaterials. Furthermore, the constant drilling speeds can identify the strength quality of soils to hard rocks. The thickness distributions of the six basic strength quality grades are presented for all the sedimentary rocks and each individual type of the seven soil and rocks. The in-situ strength profile determined in this paper can be used to assess and evaluate the in-situ mechanical behavior of geomaterial along the drillhole and can provide a new mechanical-based assessment for determining the spatial distribution of geological strata and structures in subsurface. They are important since the same stratum at different depths can have different mechanical behavior. The results provide a novel quantitative measurement for continuously in-situ mechanical profiling by digital drilling data. The findings of the paper can offer a new and effective method for refinement and upgrading of in-situ ground investigation, and can provide researchers and engineers with a novel tool and valuable reference to digitize and utilize factual data of current drilling projects.

[Transmission characteristics of student tuberculosis: a 12-year prospective population-based genomic epidemiological study].

Objective: To analyze the transmission characteristics of student tuberculosis (TB) from a population-wide perspective using the data from a prospective molecular epidemiology study of tuberculosis conducted in Wusheng county, Sichuan Province. Methods: From July 1, 2009 to December 31, 2020, isolates from culture-positive TB patients in Wusheng were collected for whole-genome sequencing. Genomic clusters were defined with a threshold distance of 12-single-nucleotide-polymorphisms. The risk for student patients clustering was analyzed by logistic regression. Epidemiological investigations were performed on clustered patients to clarify epidemiological links. Transmission direction was inferred using phybreak based on whole-genome sequencing and diagnosis time. Results: In total, there were 1 289 culture-positive patients in Wusheng during the study period, of which 7.6% (98/1 289) were students. Among student patients, 71.4% (70/98) were high school students, 45.9% (45/98) were grade three senior school students, and 16.3% (16/98) were junior school and senior school freshmen. The clustering rate for student patients was 59.2% (58/98), and their risk of clustering was 4.54 times higher (95%CI 2.44-8.45) than that of non-student patients. Of the transmission events that included student patients, 33.3% (11/33) were transmitted between student patients and 66.7% (22/33) were between student and non-student patients; and among the transmission events between student and non-student patients, only 22.7% (5/22) occurred at home, and the remaining 77.3% (17/22) occurred outside the home. The interval between diagnoses was 1.3 (0.4, 2.7) years for student patients and 5.3 (1.9, 6.8) years for student and non-student patients, with a statistically significant difference (Z=2.86, P=0.004). Conclusions: Student tuberculosis was mainly caused by recent transmission. Most of the transmission occurred between students and non-students, and primarily outside the home. Student tuberculosis screening strategies identified the patients earlier. The TB control and prevention strategies of school and community must be combined to achieve the desired results..

[Progress of researches on medical big data analytics technology].

The use of the big data analytics technology to collect, summarize and analyze medical big data is effective to precisely mine and explore the underlying information, which greatly facilitates medical science research and clinical practices. Currently, the medical big data analytics technology mainly includes artificial intelligence, databases and programming languages, which have been widely employed in medical imaging, disease risk prediction, disease control, healthcare management, follow-up, and drug and therapy development. This review summarizes the currently available medical big data analytics technologies and their applications, with aims to facilitate the related studies.

[A case of bromadiolone poisoning leading to digestive tract, abdominal hemorrhage and secondary paralytic ileus].

Bromadiolone, commonly known as super warfarin, is a long-acting coumarin dicoumarin rodenticide. The mechanism of bromadiolone is mainly to inhibit vitamin K1 epoxide reductase and affect the synthesis of coagulation factors Ⅱ, Ⅶ, Ⅸ and Ⅹ, which causes blood coagulation dysfunction and systemic multiple organ hemorrhage. Here, we report of a case of bromadiolone poisoning patient who had digestive tract, abdominal hemorrhage, as well as secondary paralytic ileus. After blood product transfusion and vitamin K1 supplementation, the patient was discharged after the physical condition was improved. It's suggestied that clinicians should pay attention to rare complications to prevent missed diagnosis when treating other bromadiolone poisoning.

[Host factors and characteristics of hospitalized patients with pneumocystis jirovecii pneumonia].

Objectives: To describe the underlying diseases, microbiologic examination and severity of hospitalized patients with Pneumocystis jirovecii pneumonia (PJP) in a tertiary Chinese hospital. Methods: We conducted a retrospective analysis of 485 identified PJP patients who were admitted to our hospital between January 2013 and December 2021. Results: Among the 485 enrolled PJP cases, there were 237 males and 248 females, aging (53.3±16.2) years (range from 14 y to 88 y). They were divided into 8 subgroups with variable underlying diseases. There were 209 cases with connective tissue diseases(CTD), 27 cases with non-hematologic malignancies, 38 cases with hematologic malignancies, 81 cases with kidney diseases, 33 cases with idiopathic interstitial pneumonia(IIP), 30 cases infected with human immunodeficiency virus (HIV), and 42 cases with miscellaneous underlying diseases. In the CTD group, there was more females than males, while male patients were predominant in both the malignant and the HIV groups. The Pneumocystis was identified in 44.95%(218/485) sputum samples and 92.01%(265/288) bronchoscopic samples. Pneumocystis asci were observed at direct microscopic examination with Grocott's methenamine silver stain in 4.95%(24/485)sputum samples and 9.72%(28/288)bronchoscopic samples. Pneumocystis DNA fragments were identified by PCR analysis in 43.09%(209/485)sputum samples and 90.63%(261/288)bronchoscopic samples. Among the 8 groups, cytomegaviremia and respiratory failure were most common in the HIV-infected PJP group, but the rates of mechanic ventilation, intensive care unit (ICU) admission and death were the lowest. There were less PJP patients in the IIP group (IIP-PJP) who received mechanic ventilation and admitted to ICU than the other groups except HIV-infected PJP group. However, the mortality rate was highest for the IIP-PJP group. Conclusions: CTD was the most common predisposed underlying disease for our enrolled PJP cases. Cytomegaviremia and respiratory failure were common in HIV-infected PJP patients, but the prognosis of HIV-PJP was slightly better than the others. The disease was more severe, rapidly progressive and fatal in the IIP-PJP group.

[Clinical analysis of autoimmune diseases associated with interstitial lung diseases initially presented with idiopathic pulmonary fibrosis].

Objectives: To describe the clinical characteristics of patients with autoimmune diseases associated interstitial lung diseases (AID-ILD) initially presented with idiopathic pulmonary fibrosis (IPF) in a tertiary Chinese hospital. Methods: We conducted a retrospective analysis of 14 patients diagnosed with AID-ILD during the IPF follow-up between January 2016 and December 2021. Among the 14 enrolled AID-ILD cases, there were 13 males and 1 female, (69.71±9.07) years old (range from 55 y to 87 y). Results: Detailed clinical consultation and further laboratory analysis were performed during the follow-up when the IPF patients showed exaggerated dyspnea (7 cases), fever of unknown causes (6 cases), microscopic hematuria (5 cases), arthralgia and swelling (4 cases), arthralgia (2 cases), morning stiffness (2 cases) and renal failure (2 cases). Finally, 6 patients showed positive MPO-ANCA, one patient showed positive PR3-ANCA and 7 patients showed positive anti-CCP. During the IPF periods, 7 patients had received antifibrotic agents and 5 patients had been prescribed with N-acetylcysteine, and 1 patient had received antifibrotic agents after N-acetylcysteine. Among them, no medication was prescribed for one IPF patient. After they were diagnosed with AID-ILD, glucocorticoids and/or immunosuppressants were added for 13 of them. Thirteen of cases improved or stable after these treatments, but one didn't show significant changes. Conclusions: AID-UIP, especially ANCA-UIP, AAV-UIP or RA-UIP should be considered when the IPF patients showed fever of unknown origin, microscopic hematuria and/or arthritis related symptoms. They might benefit from the add-on glucocorticoids and/or immunosuppressants.

[A case of acute carbon monoxide poisoning with secondary intestinal obstruction and thrombosis].

Acute carbon monoxide poisoning can cause multiple organ damage due to hypoxia. In severe cases, it can be life-threatening and has a high fatality rate. Intestinal obstruction and thrombosis are rare complications of carbon monoxide poisoning. A case of carbon monoxide poisoning was reported. In addition to the central nervous system lesion, intestinal obstruction and lower limb thrombosis were also found. In the treatment of carbon monoxide poisoning patients, the clinician was able to treat the common complications, attention should be paid to gastrointestinal tract, thrombotic disease and other rare complications, so as to avoid missed diagnosis.

[Research advances in transmission dynamic models on hand, foot, and mouth disease].

Hand, foot, and mouth disease (HFMD) is a common childhood infectious disease caused by various enteroviruses. China has the most significant number of reported cases and deaths of HFMD over the globe. Understanding the epidemic laws of HFMD can provide a scientific basis for designing prevention and control measures. The dynamic transmission models focus on the transmission mechanism of infectious diseases. They can simulate the actual situation to study the epidemic rules of diseases by adding, deleting, and subdividing compartments. More researchers have paid attention to dynamic models because of their high flexibility. To carry out the dynamic model of the HFMD research more effectively, a comprehensive understanding of related research progress in this field is deeply needed. In this paper, based on various researchers' different research purposes of dynamic models, the research progress was classified and summarized, providing meaningful guidance for model construction methods and future research directions and references for dynamic modeling of other models of infectious diseases. It was found that most studies used the SIR dynamic model or its extended model (such as the SEIR model), and few studies contained a complex factor compartment. Some important epidemiological parameters (such as R0) were obtained by studying the HFMD cases in a specific region, simulating different intervention scenarios to evaluate the effect of measures, or revealing the future trend by model prediction. However, there is no dynamic model simultaneously considering age structure, population moving, seasonality and periodicity, and vaccination.

[Meta analysis on acceptance rate of HIV pre-exposure prophylaxis among men who have sex with men in China].

Objective: To systematically evaluate the acceptance of pre-exposure prophylaxis (PrEP)among men who have sex with men (MSM) in China, so as to provide reference for the promotion of preventive drug use before human immunodeficiency virus exposure in China. Methods: By searching the databases of China national knowledge infrastructure, VIP database, Wanfan knowledge service platform, PubMed, Web of Science, Embase and The Cochrane Library with key words of "men who have sex with men" "pre-exposure prophylaxis" "PrEP" and "MSM". The literature on the willingness of Chinese MSM population to accept PrEP was systematically collected, and the data of the literature meeting the inclusion criteria were extracted for Meta analysis. Results: A total of 12 articles were selected in this study, including 6 articles in English and 6 in Chinese. The score of bias risk assessment of eligible articles was 14-18, which was more than 70% of the total score. The total number of samples was 11 269. The overall acceptance rate of PrEP was 0.77(95%CI:0.71-0.82). In subgroup analysis, the acceptance rates of different nationalities, marriage, household registration, age, education background, income, sexual orientation, sexual behavior and awareness of PrEP were statistically significant. Conclusion: In general, the acceptance rate of PrEP in MSM population is higher, but the awareness rate is low. There are differences in the acceptance rate among different groups.