The pathogenesis of hyperlipidemic acute pancreatitis caused by pancreatic duct hypertension / 临床肝胆病杂志

Compared with acute pancreatitis caused by other factors， hyperlipidemic acute pancreatitis often has a higher rate of severe conditions， greater difficulties in predicting prognosis， and a more complex and unclear pathogenesis. At present， the pathogenesis of hyperlipidemic acute pancreatitis may be associated with the elevation of serum free fatty acids， but the lipid-lowering treatment regimens do not reduce the incidence rate of this disease. Recent studies have further confirmed that pancreatic duct hypertension is an important pathogenesis of acute pancreatitis. The latest research advances have shown that hyperlipidemia can lead to pancreatic duct obstruction by causing pancreatic duct hyperplasia， forming protein embolism at the biliary-pancreatic junction， and damaging the secretory function of the pancreatic duct， while pancreatic duct obstruction can in turn cause pancreatic duct obstruction. This article reviews the latest research advances in hyperlipidemia in causing pancreatic duct obstruction and emphasizes that pancreatic duct hypertension is one of the important pathogeneses of hyperlipidemic acute pancreatitis， which will provide new ideas for exploring the pathogenesis of hyperlipidemic acute pancreatitis.

Review of evaluation and influencing factors of oral drug absorption fraction / 药学学报

Fraction absorbed (Fa) is an important parameter to describe the absorption level of oral drugs, and an important basis for the development and optimization of the formulation process. Because it is easily confused with the concept of absolute bioavailability, it has not received enough attention from the industry. There are many complex factors affecting Fa. There are three time-related factors that directly affect the extent of Fa: the release time, the absorption time, and the residence time. The relationship between these three time-related factors determines the extent of Fa. Generally, we are more concerned about the apparent factors that affect the extent of Fa, including independent variables and covariates; The independent variables include administered dose, route, dosage form, etc. The covariates are divided into internal and external factors, and external factors include food factors, drug interactions, etc. Internal causes include age, sex, disease, etc. This paper analyzes and systematically combs how independent variables and covariates directly or indirectly affect the three time-related factors by affecting the body's physiology and internal environment, thus changing the complex process of Fa. Understanding this theoretical framework can better optimize the independent variables to reduce the impact of covariates on Fa. In addition, this paper also introduces the latest progress of prediction and evaluation of Fa, including the progress of complex dissolution device and the status of software prediction.

A network pharmacology-based approach to explore mechanism of kaempferol-7 -O -neohesperidoside against prostate cancer / 中国药理学通报

Aim To explore the effect of kaempferol-7- 0-neohesperidoside (K70N) against prostate cancer (PCa) and the underlying mechanism. Methods The effect of K70N on the proliferation of PCa cell lines PC3, DU145, C4-2 and LNCaP was detected using CCK8 assay. The effect of K70N on migration ability of DU145 cells was determined by wound healing assay. The targets of K70N and PCa were screened from SuperPred and other databases. The common targets both related to K70N and PCa were obtained from the Venny online platform, a protein-protein interaction network (PPI) was constructed by the String and Cyto- scape. Meanwhile, the GO and KEGG functional enrichment were analyzed by David database. Then, a "drug-target-disease-pathway" network model was constructed. Cell cycle of PCa cells treated with K70N was analyzed by flow cytometry. The expressions of cycle-associated proteins including Skp2, p27 and p21 protein were detected by Western blot. Molecular docking between Skp2 and K70N was conducted by Sybyl X2. 0. Results K70N significantly inhibited the proliferation and migration of PCa cells. A total number of 34 drug-disease intersection targets were screened. The String results showed that Skp2 and p27, among the common targets, were the key targets of K70N for PCa treatment. Furthermore, GO and KEGG functional en-richment indicated that the mechanism was mainly related to the cell cycle. Flow cytometry showed that K70N treatment induced cell cycle arrest at the S phase. Compared with the control group, the protein expression level of Skp2 was significantly down-regulated, while the protein expression levels of p27 and p21 were up-regulated. The network molecular docking indicated that the ligand K70N had a good binding ability with the receptor Skp2. Conclusions K70N could inhibit the proliferation and migration of PCa cells, block the cell cycle in the S phase, which may be related to the regulation of cell cycle through the Skp2- p27/p21 signaling pathway.

Epidemiological characteristics of norovirus acute gastroenteritis outbreaks and influencing factors in China, 2007-2021 / 中华流行病学杂志

Objective: To analyze the epidemiological characteristics of norovirus-caused acute gastroenteritis outbreaks in China, identify the factors influencing the scale of outbreaks, and provide scientific evidences for early control of norovirus infection outbreaks. Methods: The descriptive epidemiological analysis approach was applied to analyze the incidence of national norovirus infection outbreaks by using the data from the Public Health Emergency Event Surveillance System in China from January 1, 2007 to December 31, 2021. The unconditional logistic regression model was applied to analyze the risk factors that affected the outbreaks' scale. Results: A total of 1 725 norovirus infection outbreaks were recorded in China from 2007 to 2021, with an upward trend in the number of the reported outbreaks. The southern provinces had their annual outbreak peaks from October to March; the northern provinces had two outbreak peaks from October to December and from March to June annually. The outbreaks occurred mainly in southeastern coastal provinces with a trend of gradual spread to central, northeastern and western provinces. The outbreaks mainly occurred in schools and childcare setting (1 539 cases, 89.22%), followed by enterprises and institutions (67 cases, 3.88%) and community households (55 cases, 3.19%). Human to human transmission was the main infection route (73.16%), and norovirus GⅡ genotype was the predominate pathogen causing the outbreaks (899 cases, 81.58%). The time interval between the onset of the primary case and the outbreak reporting M (Q1, Q3) was 3 (2, 6) days and the case number of the outbreak M (Q1, Q3) was 38 (28, 62). The timeliness of outbreak reporting was improved in recent years and the scale of the outbreaks showed a decreasing trend over the years, the differences in reporting timeliness and outbreak scale among different settings were significant (P<0.001). The factors that affected outbreaks' scale included the outbreak setting, transmission route, outbreak reporting timeliness and type of living areas (P<0.05). Conclusions: From 2007 to 2021, the number of the norovirus-caused acute gastroenteritis outbreaks increased in China and the more areas were affected. However, the outbreak scale showed a decreasing trend and the outbreak reporting timeliness was improved. It is important to further improve the surveillance sensitivity and reporting timeliness for the effective control of the outbreak scale.

Developmental effects of TCIPP and TnBP on zebrafish (Danio rerio) embryos / 中华预防医学杂志

Objective: To investigate the toxicity of tris (2-chloropropyl) phosphate (TCIPP) and tributyl phosphate (TnBP) on the growth and development of zebrafish embryos, as well as to explore the underlying mechanisms at the transcriptional level. Methods: With zebrafish as a model, two hpf zebrafish embryos were exposed to TCIPP and TnBP (0.1, 1, 10, 100, 500, and 1 000 μmol/L) using the semi-static method, and their rates of lethality and hatchability were determined. The transcriptome changes of 120 hpf juvenile zebrafish exposed to environmentally relevant concentrations of 0.1 and 1 μmol/L were measured. Results: The 50% lethal concentrations (LC50) of TCIPP and TnBP for zebrafish embryos were 155.30 and 27.62 μmol/L (96 hpf), 156.5 and 26.05 μmol/L (120 hpf), respectively. The 72 hpf hatching rates of TCIPP (100 μmol/L) and TnBP (10 μmol/L) were (23.33±7.72)% and (91.67±2.97)%, which were significantly decreased compared with the control group (P<0.05). Transcriptome analysis showed that TnBP had more differential genes (DEGs) than TCIPP, with a dose-response relationship. These DEGs were enriched in 32 pathways in total, including those involved in oxidative stress, energy metabolism, lipid metabolism, and nuclear receptor-related pathways, using the IPA pathway analysis. Among them, three enriched pathways overlapped between TCIPP and TnBP, including TR/RXR activation and CAR/RXR activation. Additionally, DEGs were also mapped onto pathways of LXR/RXR activation and oxidative stress for TnBP exposure only. Conclusion: Both TCIPP and TnBP have growth and developmental toxicities in zebrafish embryos, with distinct biomolecular mechanisms, and TnBP has a stronger effect than TCIPP.

Latent period and incubation period with associated factors of COVID-19 caused by Omicron variant / 中华预防医学杂志

Objective: To estimate the latent period and incubation period of Omicron variant infections and analyze associated factors. Methods: From January 1 to June 30, 2022, 467 infections and 335 symptomatic infections in five local Omicron variant outbreaks in China were selected as the study subjects. The latent period and incubation period were estimated by using log-normal distribution and gamma distribution models, and the associated factors were analyzed by using the accelerated failure time model (AFT). Results: The median (Q1, Q3) age of 467 Omicron infections including 253 males (54.18%) was 26 (20, 39) years old. There were 132 asymptomatic infections (28.27%) and 335 (71.73%) symptomatic infections. The mean latent period of 467 Omicron infections was 2.65 (95%CI: 2.53-2.78) days, and 98% of infections were positive for nucleic acid test within 6.37 (95%CI: 5.86-6.82) days after infection. The mean incubation period of 335 symptomatic infections was 3.40 (95%CI: 3.25-3.57) days, and 97% of them developed clinical symptoms within 6.80 (95%CI: 6.34-7.22) days after infection. The results of the AFT model analysis showed that compared with the group aged 18-49 years old, the latent period [exp(β)=1.36 (95%CI: 1.16-1.60), P<0.001] and incubation period [exp(β)=1.24 (95%CI: 1.07-1.45), P=0.006] of infections aged 0-17 years old were prolonged. The latent period [exp(β)=1.38 (95%CI: 1.17-1.63), P<0.001] and the incubation period [exp(β)=1.26 (95%CI: 1.06-1.48), P=0.007] of infections aged 50 years old and above were also prolonged. Conclusion: The latent period and incubation period of most Omicron infections are within 7 days, and age may be a influencing factor of the latent period and incubation period.

Qishen Yiqi Dripping Pills for Cardiovascular Diseases: Effects and Mechanisms / 中国结合医学杂志

Qishen Yiqi Dripping Pills (QSYQ) is a compound of Chinese medicine, which has been used to treat coronary heart disease and cardiac dysfunction. Its natural components include astragaloside IV, flavonoids, danshensu, protocatechualdehyde, salvianolic acid B, salvianolic acid A, ginsenosides Rg1, ginsenosides Rb1, and essential oils, etc. It exerts effects of nourishing qi and promoting blood circulation to relieve pain. In this review, the bioactive components of QSYQ and its effects for treating cardiovascular diseases and possible mechanism were summarized, providing references for further study and clinical application of QSYQ.

Clinical Significance of Minimal Residual Disease in Pediatric Patients with TCF3/PBX1+ B-cell Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To explore the consistency of flow cytometry (FCM) method and polymerase chain reaction (PCR) technique in the detection of minimal residual disease (MRD) at different treatment stages in pediatric patients with TCF3/PBX1+ B-cell acute lymphoblastic leukemia (B-ALL) and the correlations between the detection results and prognosis.@*METHODS@#The clinical data of 64 newly diagnosed pediatric patients with TCF3/PBX1+ B-ALL admitted to the Department of Pediatrics of Peking University People's Hospital from January 2005 to December 2017 were retrospectively analyzed. FCM and PCR methods were used to monitor the MRD level in bone marrow samples from 64 children during the same period of treatment on d33 and d90 respectively, and the detection results were analyzed.@*RESULTS@#There were 37 males and 27 females in the 64 patients, with a median age of 8 years(range 0.8 to 16 years). The complete remission (CR) rate after the first cycle of induction chemotherapy was 98.4% (62/63), with overall CR rate of 100%. 12 patients experienced recurrence, with a median recurrence time of 16.9 (5.3-46.3) months. The median follow-up time of the 64 patients was 77.2 (1.0-184.8) months , and the 5-year overall survival (OS) rate and event-free survival (EFS) rate were 82.8%±4.7% and 75.0%±5.4%, respectively. On d90, the concordance rate of the MRD results from the two methods was 98.4%, and the related kappa value was 0.792 (P < 0.001), which were significantly higher than those on d33. After induction chemotherapy (d33), the 5-year EFS rate of MRD-FCM- group (79.3%±5.3%) was significantly better than that of MRD-FCM+ group (40.0%±21.9%) (P =0.028), there were no significant differences in the 5-year OS rate and EFS rate between MRD-PCR+ group and MRD-PCR- group, and the 5-year EFS rate of MRD-FCM-/PCR- group (85.4%±5.5%) was significantly better than that of MRD-FCM+/PCR+ group (40.0 %±21.9%) (P =0.026).@*CONCLUSION@#In children with TCF3/PBX1+ B-ALL, the MRD results detected by FCM and PCR methods show good consistency, especially in consolidation therapy period (d90). The MRD level at the end of induction therapy (d33) is an important factor affecting the long-term prognosis, especially the MRD results detected by FCM method, which is significantly associated with prognosis.

A case of neonatal-onset type I hyperlipoproteinemia with bloody ascites / 中国当代儿科杂志

This report presents a case of a male infant, aged 32 days, who was admitted to the hospital due to 2 days of bloody stools and 1 day of fever. Upon admission, venous blood samples were collected, which appeared pink. Blood biochemistry tests revealed elevated levels of triglycerides and total cholesterol. The familial whole genome sequencing revealed a compound heterozygous variation in the LPL gene, with one variation inherited from the father and the other from the mother. The patient was diagnosed with lipoprotein lipase deficiency-related hyperlipoproteinemia. Acute symptoms including bloody stools, fever, and bloody ascites led to the consideration of acute pancreatitis, and the treatment involved fasting, plasma exchange, and whole blood exchange. Following the definitive diagnosis based on the genetic results, the patient was given a low-fat diet and received treatment with fat-soluble vitamins and trace elements, as well as adjustments to the feeding plan. After a 4-week hospitalization, the patient's condition improved and he was discharged. Follow-up showed a decrease in triglycerides and total cholesterol levels. At the age of 1 year, the patient's growth and psychomotor development were normal. This article emphasizes the multidisciplinary diagnosis and treatment of familial hyperlipoproteinemia presenting with symptoms suggestive of acute pancreatitis, including bloody ascites, in the neonatal period.

Genotype-phenotype correlations, surgical selections, and postoperative complications of 5α-reductase 2 deficiency in 69 children with hypospadias / 亚洲男科学杂志(英文版)

5α-reductase 2 deficiency prevents testosterone from being converted to dihydrotestosterone, which causes abnormal urogenital sinus development. The aim of this study was to analyze the relationship between genotype-phenotype, surgical selections, and postoperative complications of 5α-reductase 2-deficient patients with hypospadias. We retrospectively evaluated the medical records of patients who were diagnosed with 5α-reductase 2 deficiency after genetic testing in the Department of Endocrinology and underwent initial hypospadias surgery in the Department of Urology in Beijing Children's Hospital, Capital Medical University (Beijing, China), from April 2007 to December 2021. A total of 69 patients were included in this study; the mean age at surgery was 34.1 months, and the average follow-up time was 54.1 months. Sixty children were treated with preoperative hormone stimulation (PHS) to promote penile growth. The average penis length and glans width were increased by 1.46 cm and 0.62 cm, respectively. The most frequent mutations were p.R227Q (39.1%, 54/138), p.Q6* (15.2%, 21/138), p.G203S (12.3%, 17/138), and p.R246Q (11.6%, 16/138). In 64 patients who were followed up, 43 had a one-stage operation and 21 had a staged operation, and there were significant differences in external masculinization score (EMS) ( P = 0.008) and the average number of operation required to cure ( P < 0.001) between one-stage and staged operations. PHS had a positive effect ( P < 0.001) on penile development. The p.R227Q mutation was associated with higher EMS and less severe hypospadias. One-stage surgery can be selected if conditions permit. The growth and development of children are acceptable in the long term, but penis growth remains unsatisfactory. Long-term complications of hypospadias should be considered during puberty.

Metabolic Disease Management Guideline for National Metabolic Management Center(2nd edition) / 中华内分泌代谢杂志

The latest epidemiological data suggests that the situation of adult diabetes in China is severe, and metabolic diseases have become significant chronic illnesses that have a serious impact on public health and social development. After more than six years of practice, the National Metabolic Management Center(MMC) has developed distinctive approaches to manage metabolic patients and has achieved a series of positive outcomes, continuously advancing the standardized diagnosis and treatment model. In order to further improve the efficiency, based on the first edition, the second edition guideline was composed by incorporating experience of the past six years in conjunction with the latest international and domestic guidelines.

Bone turnover markers, hip bone geometry parameters and metabolic syndrome in community overweight postmenopausal women / 中华内分泌代谢杂志

Objective:To explore the changes of bone turnover markers and geometric parameters of hip bone in overweight postmenopausal women with metabolic syndrome(MS), as well as the influence of MS components. To analyze the association of these factors with the risk of fracture.Methods:A total of 505 overweight postmenopausal female patients who underwent health check-up in Lianhu Community Service Center, Danyang City, Jiangsu Province from January to December 2017 were selected. According to the MS diagnostic criteria of the International Diabetes Federation(2009), the patients were divided into MS group( n=331)and non-MS group( n=174). Blood samples were collected to determine the level of procollagen type 1 N-terminal propeptide(P1NP)and carboxy-terminal cross-linked telopeptide of type 1 collagen(CTX). Bone mineral density and hip bone geometry parameters were tested with dual-energy X-ray absorptiometry and hip structural analysis software. Results:The incidence of osteoporotic fracture and hip fracture in MS group was significantly higher than that in non-MS group(21.1% vs 13.8%, 4.8% vs 1. 1%, P<0.05). However, the bone mineral density of lumbar vertebra 1-4, femoral neck, and total hip in MS group was significantly higher than that in non-MS group, which remained after adjusting for age( P<0.05), but the difference disappeared after further adjustment for body mass index( P>0.05). The P1NP, CTX, femur strength index(FSI), section modulus(SM), and cross-sectional area(CSA)of MS group were significantly lower than those of non-MS group, the buckling ration(BR)was significantly higher than that in non-MS group, and the differences were still statistically significant after adjusting for age and body mass index( P<0.05). There was no significant difference in bone mineral density of lumbar vertebra 1-4, femoral neck, total hip, P1NP, and CTX between fracture group and non-fracture group in patients with MS. But FSI, SM, cross-sectional moment of inertia(CSMI), and CSA were significantly lower, BR was significantly higher( P<0.05) and femur strength decreased in patients with fracture. Regression analysis showed that high BR was an independent risk factor for fracture risk, while high FSI, SM, CSMI, and CSA were protective factors. Multivariate linear regression analysis showed that wasit circumference, diastolic blood pressure, and fasting plasma glucose were the main MS components affecting bone mineral density, bone turnover indexes, and hip bone geometry parameters. Conclusions:Overweight postmenopausal MS patients had decreased bone turnover rate, femoral strength, and relatively poor bone quality. Hip bone geometry parameters can be used as one of the methods to assess fracture risk in MS patients. Waist circumference, diastolic blood pressure, and fasting blood glucose are the important MS components affecting bone mass and bone quality.

The predictive value of the epithelial cell proliferation pathway genes for the prognosis of elderly non-small cell lung cancer patients receiving immunotherapy / 中华老年医学杂志

Objective:To investigate the predictive value of the epithelial cell proliferation(ECP)pathway genes for the prognosis of elderly non-small cell lung cancer patients treated with immunotherapy.Methods:A total of 106 elderly patients aged 70 years and over receiving immunotherapy in the POPLAR and OAK clinical trials were retrospectively analyzed in October 2022.According to the mutation status, patients were divided into an ECP pathway-related gene mutation group(ECP mutation group, n=25)and an ECP pathway-related gene non-mutation group(ECP non-mutation group, n=81). The primary endpoints were overall survival(OS)and progression-free survival(PFS). Differences in survival and efficacy between the two groups were compared, and subgroup analysis was performed on clinical factors and genes involved in the pathway.Pyclone was used to calculate the distribution of major clones and subclones in each patient, and differences in survival were compared.Results:Survival outcomes were worse in the ECP(+ )group than in the ECP(-)group(mOS: 10.9 months vs.17.1 months, HR=1.84, 95% CI: 1.09-3.08, P<0.05; mPFS: 2.8 months vs.4.2 months, HR=1.58, 95% CI: 1.00-2.51, P<0.05). Of all mutations in ECP pathway-related genes, mutations in the RB1 gene had a significant prognostic effect on all patients, with the negative prognostic effect especially prominent in ECP(+ )patients.Compared with ECP(-)patients, ECP(+ )patients had a shorter mOS(6.9 months vs.12.6 months, HR=3.14, 95% CI: 1.10-8.97, P=0.024). Ten patients had clonal mutations and 15 patients had sub-clonal mutations in ECP pathway-related genes and the former had a shorter mPFS than the latter(1.3 months vs.5.3 months, HR=3.23, 95% CI: 1.25-8.37, P=0.011). Conclusions:Gene mutations in the epithelial cell proliferation pathway are a negative prognostic factor in elderly non-small cell lung cancer patients receiving immunotherapy, and mutations located in the clonal cluster have a stronger impact on the prognosis.

A retrospective analysis of Osimertinib in treatment of elderly patients with advanced lung adenocarcinoma with epidermal growth factor receptor mutation / 中华老年医学杂志

Objective:To evaluate the efficacy and safety of Osimertinib in the second-line and above treatment of elderly patients with advanced lung adenocarcinoma with epidermal grouth factor receptor(EGFR)mutation.Methods:A retrospective analysis of 51 elderly patients with advanced lung adenocarcinoma aged 65 years and over was performed.EGFR gene mutations were detected at baseline.The patients were treated with Osimertinib as second or later-line treatment after disease progression on prior epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKI)therapy.Results:The median age of the patients was 72 years old, and the median progression-free survival(PFS)with Osimertinib was 13 months(95% CI: 10.8-15.2 months). Patients with exon 19 deletion(19del)treated with Osimertinib had longer PFS than patients with EGFR 21 exon L858R mutation(12 vs.24 month, P=0.028). In patients with EGFR resistance mutation T790M(T790M-positive), the PFS of patients with 19del combined with T790M(19del / T790M-positive)was better than that of patients with L858R combined with T790M(L858R / T790M-positive)(10 vs.28 months, P=0.029). After Osimertinib treatment, 43.8% of patients had brain or meningeal progression.The most commonly used agents for treatment after resistance to Osimertinib are antiangiogenic drugs.The common adverse reactions of Osimertinib were diarrhea(31.4 %), followed by dry skin with itching(29.4%)and rash(25.5 %). Most adverse reactions were grade 1 to 2, and one patient discontinued the drug intermittently due to grade 3 hematological adverse reactions. Conclusions:Osimertinib is effective and well tolerated in elderly patients with advanced EGFR-mutant lung adenocarcinoma.

Progress on Prevention and Treatment of Cerebral Small Vascular Disease Using Integrative Medicine / 中国结合医学杂志

Cerebral small vessel disease (CSVD) is a senile brain lesion caused by the abnormal structure and function of arterioles, venules and capillaries in the aging brain. The etiology of CSVD is complex, and disease is often asymptomatic in its early stages. However, as CSVD develops, brain disorders may occur, such as stroke, cognitive dysfunction, dyskinesia and mood disorders, and heart, kidney, eye and systemic disorders. As the population continues to age, the burden of CSVD is increasing. Moreover, there is an urgent need for better screening methods and diagnostic markers for CSVD, in addition to preventive and asymptomatic- and mild-stage treatments. Integrative medicine (IM), which combines the holistic concepts and syndrome differentiations of Chinese medicine with modern medical perspectives, has unique advantages for the prevention and treatment of CSVD. In this review, we summarize the biological markers, ultrasound and imaging features, disease-related genes and risk factors relevant to CSVD diagnosis and screening. Furthermore, we discuss IM-based CSVD prevention and treatment strategies to stimulate further research in this field.

Relationship between cadmium exposure and pulmonary function level and chronic obstructive pulmonary disease / 中华劳动卫生职业病杂志

Objective: To analyze the levels and distribution characteristics of blood cadmium and urinary cadmium in American adults, to analyze the relationship between blood cadmium and urinary cadmium and pulmonary function dose response, and to explore the effect of this index on the risk of chronic obstructive pulmonary disease. Methods: In March 2022, 3785 patients from 2007 to 2012 in NHANES database were selected as the subjects. Collect demography data such as gender and age, and test data such as lung function, blood cadmium concentration and Urine cadimium concentration. The relationship between blood and urine cadmium levels and lung function and pulmonary function and chronic obstructive pulmonary diease (COPD) was analyzed by Mann-Whitney U test or Kruskal-Wallis H test, multivariate linear regression and restricted cubic spline method. Results: The geometric mean of blood cadmium and urine cadmium in American adults was 0.37 g/L and 0.28 g/L, FEV(1) and FEV(1)/FVC among different cadmium exposure groups was statistically significant, and there was a negative linear dose-response relationship between serum Cd and urine Cd concentrations and FEV(1)/FVC levels (P(overall)<0.001, P(non-linear)=0.152; P(overall)<0.001, P(non-linear)=0.926). Compared with the lowest quartile concentration (Q1), the highest quartile blood cadmium concentration (Q4) (OR=1.934, P(trend)=0.000) and urinary cadmium concentration (OR=1.683, P(trend)=0.000) may increased the risk of chronic obstructive pulmonary disease. Conclusion: There is a negative correlation between blood cadmium, urinary cadmium levels and lung function in American adults, and cadmium may increase the risk of chronic obstructive pulmonary disease.

The predictive value of warning scores for intensive care unit admission in coronavirus disease 2019 patients / 中华内科杂志

To evaluate the predictive value of early warning scores for intensive care unit (ICU) admission in patients with coronavirus disease 2019 (COVID-19). For COVID-19 patients who were admitted to Shijiazhuang People's Hospital from January 2021 to February 2021, national early warning score (NEWS), national early warning score 2 (NEWS2), rapid emergency medicine score (REMS), quick sepsis-related organ failure (qSOFA), altered consciousness, blood urea nitrogen, respiratory rate, blood pressure, and age-65 (CURB-65) were used to evaluate the inpatient condition and the predictive value for ICU admission. A total of 368 patients were included, and 32 patients (8.7%) were transferred to the ICU. The median age was 49.0 (34.0,61.0) years. The scores of NEWS, NEWS2, REMS, and CURB-65 were 1 (0, 2), 1 (0, 2), 4 (2, 6) and 0 (0, 1), respectively. The receiver operating characteristic (ROC) cure (AUC) was used to evaluate the predictive value in detecting patients who are at risk of being transferred to the ICU. Area under the ROC AUC of NEWS was 0.756, sensitivity 65.6%, and specificity 71.3%. ROC AUC of NEWS2 was 0.732, sensitivity 62.5%, and specificity 61.3%. ROC AUC of REMS was 0.787, sensitivity 84.4%, and specificity 64.6%. ROC AUC of CURB-65 was 0.814, sensitivity 81.3%, and specificity 76.8%. The predictive value of NEWS and NEWS2 combined with age were significantly improved. The ROC AUC of NEWS combined with age was 0.885, sensitivity 85.1%, and specificity 75.0%. The ROC AUC of NEWS2 combined with age was 0.883, sensitivity 84.2%, and specificity 75.0%. NEWS and NEWS2 combined with age can be used as a predictive tool for whether COVID-19 patients will be admitted to the ICU.

Clinical and genetic characteristics of children with dopa-responsive dystonia caused by tyrosine hydroxylase gene variations / 中华儿科杂志

Objective: To explore the clinical and genetic characteristics of children with dopa-responsive dystonia (DRD) caused by tyrosine hydroxylase (TH) gene variations. Methods: Clinical data of 9 children with DRD caused by TH gene variations diagnosed in the Department of Children Rehabilitation, the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2022 were retrospectively collected and analyzed, including the general conditions, clinical manifestations, laboratory tests, gene variations and follow-up data. Results: Of the 9 children with DRD caused by TH gene variations, 3 were males and 6 were females. The age at diagnosis was 12.0 (8.0, 15.0) months. The initial symptoms of the 8 severe patients were motor delay or degression. Clinical symptoms of the severe patients included motor delay (8 cases), truncal hypotonia (8 cases), limb muscle hypotonia (7 cases), hypokinesia (6 cases), decreased facial expression (4 cases), tremor (3 cases), limb dystonia (3 cases), diurnal fluctuation (2 cases), ptosis (2 cases), limb muscle hypertonia (1 case) and drooling (1 case). The initial symptom of the very severe patient was motor delay. Clinical symptoms of the very severe patient included motor delay, truncal hypotonia, oculogyric crises, status dystonicus, hypokinesia, decreased facial expression, and decreased sleep. Eleven TH gene variants were found, including 5 missense variants, 3 splice site variants, 2 nonsense variants, and 1 insertion variant, as well as 2 novel variants (c.941C>A (p.T314K), c.316_317insCGT (p.F106delinsSF)). Nine patients were followed up for 40 (29, 43) months, and no one was lost to follow-up. Seven of the 8 severe patients were treated by levodopa and benserazide hydrochloride tablets and 1 severe patient was treated by levodopa tablets. All the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets. Although the weight of the patients increased and the drug dosage was not increased, the curative effect remained stable and there was no obvious adverse reaction. One severe patient developed dyskinesia in the early stage of treatment with levodopa and benserazide hydrochloride tablets and it disappeared after oral administration of benzhexol hydrochloride tablets. Until the last follow-up, motor development of 7 severe patients returned to normal and 1 severe patient still had motor delay due to receiving levodopa and benserazide hydrochloride tablets for only 2 months. The very severe patient was extremely sensitive to levodopa and benserazide hydrochloride tablets and no improvement was observed in this patient. Conclusions: Most of the DRD caused by TH gene variations are severe form. The clinical manifestations are varied and easily misdiagnosed. Patients of the severe patients responded well to levodopa and benserazide hydrochloride tablets or levodopa tablets, and it takes a long time before full effects of treatment become established. Long-term effect is stable without increasing the drug dosage, and no obvious side effect is observed.

Clinicopathological features and prognosis of SMARCA4-deficient non-small cell lung carcinoma: an analysis of 127 cases / 中华病理学杂志

Objective: To investigate and elucidate the clinicopathological and prognostic characteristics of SMARCA4-deficient non-small cell lung cancer. Methods: The clinicopathological and prognostic data were collected in 127 patients with SMARCA4-deficient non-small cell lung cancer diagnosed in Shanghai Pulmonary Hospital, Shanghai, China from January 2020 to March 2022. The variation and expression of biomarkers related to treatment were retrospectively reviewed. Results: One hundred and twenty-seven patients were eligible for enrollment. Among them 120 patients (94.5%) were male and 7 cases (5.5%) were female, while the average age was 63 years (range 42-80 years). There were 41 cases (32.3%) of stage Ⅰ cancer, 23 cases (18.1%) of stage Ⅱ, 31 cases (24.4%) of stage Ⅲ and 32 cases (25.2%) of stage Ⅳ. SMARCA4 expression detected by immunohistochemistry was completely absent in 117 cases (92.1%) and partially absent in 10 cases (7.9%). PD-L1 immunohistochemical analyses were performed on 107 cases. PD-L1 was negative, weakly positive and strongly positive in 49.5% (53/107), 26.2% (28/107) and 24.3% (26/107) of the cases, respectively. Twenty-one cases showed gene alterations (21/104, 20.2%). The KRAS gene alternation (n=10) was most common. Mutant-type SMARCA4-deficient non-small cell lung cancer was more commonly detected in females, and was associated with positive lymph nodes and advanced clinical stage (P<0.01). Univariate survival analysis showed that advanced clinical stage was a poor prognosis factor, and vascular invasion was a poor predictor of progression-free survival in patients with surgical resection. Conclusions: SMARCA4-deficient non-small cell lung cancer is a rare tumor with poor prognosis, and often occurs in elderly male patients. However, SMARCA4-deficient non-small cell lung cancers with gene mutations are often seen in female patients. Vascular invasion is a prognostic factor for disease progression or recurrence in patients with resectable tumor. Early detection and access to treatment are important for improving patient survivals.

Circular RNA expression profiles and circRNA-miRNA-mRNA crosstalk in pre-eclamptic placenta / 中华妇产科杂志

Objective: To identify the expression profile of circular RNA (circRNA) in placenta of pre-eclampsia (PE) pregnant women by high-throughput sequencing, and to construct the circRNA-microRNA (miRNA)-messenger RNA (mRNA) interaction network, so as to reveal the related pathways and regulatory mechanisms of PE. Methods: The clinical data and placentas of 42 women with PE (PE group) and 30 normal pregnant women (control group) who delivered in West China Second University Hospital from November 2019 to June 2021 were collected. (1) High-throughput sequencing was used to establish the differentially expressed circRNA profiles in placental tissues of 5 pairs of PE group and the control group. (2) Real-time quantitative PCR (qRT-PCR) was used to verify the expression levels of 6 differentially expressed circRNAs in placental tissues of PE group and control group. (3) Bioinformatics analysis was used to predict the target miRNA and analyze the co-expressed mRNA to construct a competitive endogenous RNA (ceRNA) network. The differentially expressed circRNAs were analyzed by Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) pathways. (4) Logistic regression analysis, Pearson correlation and Kendall's tau-b correlation analysis were used to test the correlation between the three differentially expressed circRNAs and the risk of PE and clinical characteristics. (5) circRNA_05393 was selected for subsequent functional study. Small interfering RNA (siRNA) and overexpression plasmid were used to knock down or increase the expression level of circRNA_05393 in trophoblast cell line HTR-8/SVneo cells, respectively. Transwell assay was used to detect the migration and invasion ability of the trophoblasts in vitro. Cell counting kit-8 assay was used to detect the proliferation ability of the trophoblasts. Results: (1) Seventy-two differentially expressed circRNAs were identified by high-throughput sequencing, of which 35 were up-regulated and 37 were down-regulated. (2) qRT-PCR showed that compared with the control group, circRNA_00673 (1.306±0.168 vs 2.059±0.242; t=2.356, P=0.021) and circRNA_07796 (1.275±0.232 vs 1.954±0.230; t=2.018, P=0.047) were significantly increased, while circRNA_05393 (1.846±0.377 vs 0.790±0.094; t=3.138, P=0.002) was significantly decreased. (3) The circRNA-miRNA-mRNA interaction network contained 3 circRNAs, 8 miRNAs and 53 mRNAs. GO functional annotation analysis showed that the biological process was mainly enriched in iron ion homeostasis, membrane depolarization during action potential and neuronal action potential. In terms of cellular components, they were mainly enriched in cytoskeleton and membrane components. In terms of molecular function, they were mainly enriched in the activity of voltage-gated sodium channel and basic amino acid transmembrane transporter. KEGG pathway enrichment analysis showed that mRNAs in the interaction network were mainly enriched in complement and coagulation cascade, glycine, serine and threonine metabolism, p53 signaling pathway and peroxisome proliferators-activated receptors (PPAR) signaling pathway. (4) Logistic regression analysis showed that down-regulation of circRNA_05393 expression was a risk factor for PE (OR=0.044, 95%CI: 0.003-0.596; P=0.019). Correlation analysis showed that circRNA_05393 was significantly correlated with systolic blood pressure and diastolic blood pressure in PE pregnant women (both P<0.05). (5) Knock down or overexpression of circRNA_05393 significantly reduced or increased the migration and invasion abilities of HTR-8/SVneo cells (all P<0.05), but had no significant effect on the ability of tube formation and proliferation (all P>0.05). Conclusions: The construction of circRNA expression profile in placenta and the exploration of circRNA-miRNA-mRNA interaction network provide the possibility to reveal the regulatory mechanism of specific circRNA involved in PE. Inhibition of circRNA_05393 may induce the progression of PE by reducing the migration and invasion of trophoblasts.