Detection of pathogenic variants in four patients with globozoospermia / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for 4 patients with globozoospermia.@*METHODS@#Semen and blood samples were collected from the patients for the determination of sperm concentration, viability, survival rate, morphology and acrosome antigen CD46. Meanwhile, DNA was extracted for whole exome sequencing (WES), and candidate variants were validated by Sanger sequencing.@*RESULTS@#All of the four patients were found to harbor variants of the DPY19L2 gene. Patients 1 ~ 3 had homozygous deletions of the DPY19L2 gene. Sanger sequencing confirmed that the DPY19L2 gene in patient 3 was disrupted at a recombination breakpoint area BP2, resulting in nonallelic homologous recombination and complete deletion of the DPY19L2 gene. Patients 2 and 3 respectively harbored novel homozygous deletions of exons 2 ~ 22 and exons 14 ~ 15. Patient 4 harbored heterozygous deletion of the DPY19L2 gene, in addition with a rare homozygous deletion of the 3' UTR region.@*CONCLUSION@#DPY19L2 gene variants probably underlay the globozoospermia in the four patients, which has fit an autosomal recessive pattern of inheritance and the characteristics of genomic diseases.

Gut microbiota: a new insight into neurological diseases / 中华医学杂志(英文版)

In the last decade, it has become increasingly recognized that a balanced gut microbiota plays an important role in maintaining the health of the host. Numerous clinical and preclinical studies have shown that changes in gut microbiota composition are associated with a variety of neurological diseases, e.g., Parkinson's disease, Alzheimer's disease, and myasthenia gravis. However, the underlying molecular mechanisms are complex and remain unclear. Behavioral phenotypes can be transmitted from humans to animals through gut microbiota transplantation, indicating that the gut microbiota may be an important regulator of neurological diseases. However, further research is required to determine whether animal-based findings can be extended to humans and to elucidate the relevant potential mechanisms by which the gut microbiota regulates neurological diseases. Such investigations may aid in the development of new microbiota-based strategies for diagnosis and treatment and improve the clinical management of neurological disorders. In this review, we describe the dysbiosis of gut microbiota and the corresponding mechanisms in common neurological diseases, and discuss the potential roles that the intestinal microbiome may play in the diagnosis and treatment of neurological disorders.

Research progress of maintenance therapy for cervical cancer / 国际肿瘤学杂志

Cervical cancer is a common malignant tumor that threatens women's life and health. Among them, the prognosis of recurrent or advanced cervical cancer is poor, and such patients often receive surgical treatment, radiotherapy, chemotherapy, etc., which makes it more difficult to choose a treatment plan. Even after the most effective treatment methods, the treatment failure rate of advanced cervical cancer is still high. Thanks to the research progress of tumor cell signaling pathway-related targets and immunotherapy, especially immune checkpoint inhibitors, new breakthroughs have been made in cervical cancer maintenance therapy. Targeted maintenance therapy, immune maintenance therapy, and multi-drug combination maintenance therapy are currently popular areas of cervical cancer maintenance therapy.

Discussion on problems and countermeasures of military medical radiation license management / 中国辐射卫生

@#Practice in military medical radiation license management in the new era of military reform have surfaced problems in military radiation protection, involving radiation protection management regulation, occupational health monitoring for radiation workers, inspection of radiation equipment and site protection, implementation of the “Three Synchronizations System” for construction, renovation, and extension projects of radiation facilities, as well as quality control for radiation protection and diagnosis and treatment. Efforts should be focused on radiation protection training, self-management of medical radiation institutions, supervision and regulation from medical radiation license management institutions, and joint coordination of relevant departments. Under new regulations and standards, creatively conducting medical radiation license management and running the army in accordance with the law in the new era of military reform are of great significance for standardizing military radiation protection and ensuring the healthy development of military medical radiation services.

Routine blood test results of Tibetan children and adolescents in plateau areas / 中国学校卫生

Objective@#To investigate routine blood test results and secular changes among Tibetan children and adolescents aged from 3 to 19 in the plateau, and to provide the basis for reference range of routine blood test for this population.@*Methods@#A total of 1 568 Tibetan children and adolescents aged from 3 to 19 living in Shigatse, Tibet were selected by cluster random sampling method. Routine blood test results and its secular trends were compared by age and gender.@*Results@#Significantly differences were found in red blood cell(RBC), hemoglobin(HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin(MCH), white blood cell(WBC), neutrophil(NEU), neutrophil percentage (NEU%), lymphocyte(LYM), lymphocyte percentage(LYM%)，monocyte percentage(MON%)，eosinophil percentage(EOS%),basophil percentage(BAS%) and platelet(PLT) among the four age groups of 3-5, 6-12, 13-15, and 16-19 years ( F/H =60.22, 179.41, 249.45, 115.03, 74.90, 14.33 , 33.46, 78.90, 49.20, 97.29, 24.45,24.28,42.65,20.10, P <0.05). Among red blood cell indexes, RBC, HGB, HCT,MCH increased with age in boys( F =148.77, 493.04, 623.14, 249.92, P <0.05), but there was no similar trend in girls( F =1.37, 0.15, 2.94, 0.11, P >0.05). HCT showed significant sex differences among the four age groups of 3-5 years, 6-12 years, 13-15 years, and 16-19 years [(41.33±2.31)% vs (41.98±2.40)%; (43.28±2.60)% vs ( 43.75 ±2.36)%; (46.20±3.11)% vs (44.83±2.67)%; (51.10±4.15)% vs (43.61±4.70)%, t =-2.10, -2.88, 3.50, 10.82, P <0.05]. WBC, NEU, NEU%, LYM, LYM%, monocyte(MON), and MON% increased significantly with age in both boys and girls ( P <0.05). From the age of 12 to 13, RBC, HGB and HCT in Tibetan male and female adolescents showed an opposite trend and widened gradually.@*Conclusion@#Red blood cell index shows significantly different trends among Tibetan adolescents and children of different ages and genders. Regional nationality, age, gender, and other factors should be considered when developing the reference value range of blood routine index.

Routine blood test results of Tibetan children and adolescents in plateau areas / 中国学校卫生

Objective@#To investigate routine blood test results and secular changes among Tibetan children and adolescents aged from 3 to 19 in the plateau, and to provide the basis for reference range of routine blood test for this population.@*Methods@#A total of 1 568 Tibetan children and adolescents aged from 3 to 19 living in Shigatse, Tibet were selected by cluster random sampling method. Routine blood test results and its secular trends were compared by age and gender.@*Results@#Significantly differences were found in red blood cell(RBC), hemoglobin(HGB), hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin(MCH), white blood cell(WBC), neutrophil(NEU), neutrophil percentage (NEU%), lymphocyte(LYM), lymphocyte percentage(LYM%)，monocyte percentage(MON%)，eosinophil percentage(EOS%),basophil percentage(BAS%) and platelet(PLT) among the four age groups of 3-5, 6-12, 13-15, and 16-19 years ( F/H =60.22, 179.41, 249.45, 115.03, 74.90, 14.33 , 33.46, 78.90, 49.20, 97.29, 24.45,24.28,42.65,20.10, P <0.05). Among red blood cell indexes, RBC, HGB, HCT,MCH increased with age in boys( F =148.77, 493.04, 623.14, 249.92, P <0.05), but there was no similar trend in girls( F =1.37, 0.15, 2.94, 0.11, P >0.05). HCT showed significant sex differences among the four age groups of 3-5 years, 6-12 years, 13-15 years, and 16-19 years [(41.33±2.31)% vs (41.98±2.40)%; (43.28±2.60)% vs ( 43.75 ±2.36)%; (46.20±3.11)% vs (44.83±2.67)%; (51.10±4.15)% vs (43.61±4.70)%, t =-2.10, -2.88, 3.50, 10.82, P <0.05]. WBC, NEU, NEU%, LYM, LYM%, monocyte(MON), and MON% increased significantly with age in both boys and girls ( P <0.05). From the age of 12 to 13, RBC, HGB and HCT in Tibetan male and female adolescents showed an opposite trend and widened gradually.@*Conclusion@#Red blood cell index shows significantly different trends among Tibetan adolescents and children of different ages and genders. Regional nationality, age, gender, and other factors should be considered when developing the reference value range of blood routine index.

The mediating effect of resilience between perceived stress and insomnia in medical staff / 中华行为医学与脑科学杂志

Objective:To explore the mediating effect of resilience between perceived stress and insomnia in medical staff.Methods:A questionnaire survey was conducted among 1 163 medical staff. All subjects were assessed with the insomnia severity index (ISI), simplified Chinese version of Connor-Davidson resilience scale (CD-RISC-10) and perceived stress scale (PSS-10). SPSS 20.0 software was used for common method biases test, descriptive statistics, difference analysis, correlation analysis, hierarchical regression analysis, and SPSS PROCESS V3.4 was used for Bootstrap mediating effect.Results:①The perceived stress (16.28±6.35) was positively correlated with insomnia (6.14±5.80)( r=0.404, P<0.01), and psychological resilience was negatively correlated with insomnia and perceived stress in medical staff ( r=-0.279, P<0.01, r=-0.399, P<0.01). ②Psychological resilience played a partial mediating role between perceived stress and insomnia in medical staff, with the mediating effect as 0.051, accounting of 13.82% of the total effect. Conclusion:Psychological resilience can reduce the negative effects of perceived stress on sleep and is a protective factor for insomnia in medical staff. Clinically, reducing perceived stress and improving psychological resilience can reduce insomnia in medical staff.

Regulation of Gut Microbiota Disrupts the Glucocorticoid Receptor Pathway and Inflammation-related Pathways in the Mouse Hippocampus

An increasing number of studies have recently indicated the important effects of gut microbes on various functions of the central nervous system.However, the underlying mechanisms by which gut microbiota regulate brain functions and behavioral phenotypes remain largely unknown. We therefore used isobaric tags for relative and absolute quantitation (iTRAQ)-based quantitative proteomic analysis to obtain proteomic profiles of the hippocampus in germ-free (GF), colonized GF, and specific pathogen-free (SPF) mice. We then integrated the resulting proteomic data with previously reported mRNA microarray data, to further explore the effects of gut microbes on host brain functions. We identified that 61 proteins were upregulated and 242 proteins were downregulated in GF mice compared with SPF mice. Of these, 124 proteins were significantly restored following gut microbiota colonization. Bioinformatic analysis of these significant proteins indicated that the glucocorticoid receptor signaling pathway and inflammation-related pathways were the most enriched disrupted pathways. This study provides new insights into the pathological mechanisms of gut microbiota-regulated diseases.

Simultaneous quantitative analysis of nine saponins in Gynostemma pentaphyllum before and after heat processing based on UPLC-Q-Trap-MS / 中国中药杂志

Heat-processed Gynostemma pentaphyllum has strong biological activity, and saponins are the main components. To investigate the changes of saponins in G. pentaphyllum before and after heat processing, the present study determined and analyzed the content of nine saponins in G. pentaphyllum from Zhangzhou of Fujian and Jinxiu of Guangxi by ultra-high performance liquid chromatography with quadrupole ion-trap mass spectrometry(UPLC-Q-Trap-MS). The separation of the analytes was performed on an ACQUITY UPLC BEH C_(18) column(2.1 mm×50 mm, 1.7 μm) at 30 ℃, with acetonitrile and 0.1% formic acid in water as the mobile phase by gradient elution, and the flow rate was 0.3 mL·min~(-1). Quantitative analysis was performed using electrospray ionization source(ESI) in the multiple reaction-monitoring(MRM) mode. The results showed that the content of saponins with biological activities increased after heat processing. Specifically, gypenoside L, gypenoside LI, damulin A, damulin B, ginsenoside Rg_3(S), and ginsenoside Rg_3(R) in G. pentaphyllum produced in Zhangzhou of Fujian increased by 7.369, 8.289, 12.155, 7.587, 0.929, and 1.068 μg·g~(-1), respectively, while the content of ginsenoside Rd, gypenoside LVI, and gypenoside XLVI, which were abundant in the raw materials, decreased by 0.779, 19.37, and 9.19 μg·g~(-1), respectively. The content of gypenoside L, gypenoside LI, damulin A, damulin B, ginsenoside Rg_3(S), and ginsenoside Rg_3(R) in G. pentaphyllum produced in Jinxiu of Guangxi increased by 0.100, 0.161, 0.317, 0.228, 3.280, and 3.395 μg·g~(-1), respectively, while the content of ginsenoside Rd, gypenoside LVI, and gypenoside XLVI in the raw materials was reduced by 1.661, 0.014, and 0.010 μg·g~(-1), respectively. The results suggest that heat processing is an effective way to transform rare gypenosides. Furthermore, it is found that there are great differences in the content of gypenosides in different regions.

Primary tumor location in lung cancer: the evaluation and administration / 中华医学杂志(英文版)

Lung cancer continues to be the leading cause of cancer-related death in the world, which is classically subgrouped into two major histological types: Non-small cell lung cancer (NSCLC) (85% of patients) and small-cell lung cancer (SCLC) (15%). Tumor location has been reported to be associated with the prognosis of various solid tumors. Several types of cancer often occur in a specific region and are more prone to spread to predilection locations, including colorectal cancer, prostate cancer, gastric cancer, ovarian cancer, cervical cancer, bladder cancer, lung tumor, and so on. Besides, tumor location is also considered as a risk factor for lung neoplasm with chronic obstructive pulmonary disease/emphysema. Additionally, the primary lung cancer location is associated with specific lymph node metastasis. And the recent analysis has shown that the primary location may affect metastasis pattern in metastatic NSCLC based on a large population. Numerous studies have enrolled the "location" factor in the risk model. Anatomy location and lobe-specific location are both important in prognosis. Therefore, it is important for us to clarify the characteristics about tumor location according to various definitions. However, the inconsistent definitions about tumor location among different articles are controversial. It is also a significant guidance in multimode therapy in the present time. In this review, we mainly aim to provide a new insight about tumor location, including anatomy, clinicopathology, and prognosis in patients with lung neoplasm.

Effect of Modified Cangfu Daotantang on Metabolism and Pregnancy in Patients with Polycystic Ovary Syndrome / 中国实验方剂学杂志

Objective:To observe the effect of modified Cangfu Daotantang on metabolism and pregnancy in patients with spleen deficiency and phlegm-dampness type polycystic ovary syndrome （PCOS）. Method:One hundred and twelve patients were randomly divided into control group and observation group according to the random number table. Both groups took non-pharmacological interventions， oral metformin hydrochloride， 500mg/time， 3 times/day； oral ethinyl estradiol and cyproterone tablets， 1 tablet/time， 1 time/day， starting from the third to fifth day of menstruation and lasting for twenty-one days， for a total of 3 menstrual cycles. Patients in control group additionally took Erchen pills orally， 10 g/time， 2 times/day， while patients in observation group additionally took modified Cangfu Daotantang orally， 1 dose/day. The course of treatment was six menstrual cycles in both groups （or termination after conception）. The waist-to-hip ratio （WHR）， body mass index （BMI）， insulin resistance index （HOMA-IR）， pancreatic <italic>β</italic>-cell function （HOMA-<italic>β</italic>）， triglycerides （TG）， low-density lipoprotein （LDL） and non-high-density lipoprotein （nHDL） elevation after treatment were compared. The number of ovulation cycles monitored by B-ultrasound （6 menstrual cycles）， ovulation rate， human chorionic gonadotropin （HCG） day endometrial thickness， follicle diameter， cervical mucus score>8 points and endometrial morphology type A rate were measured and recorded. The recovery of menstruation， pregnancy and early miscarriage were recorded. Luteinizing hormone （LH）， estradiol （E₂）， follicle stimulating hormone （FSH）， dehydroepiandrosterone sulfate （DHEAS）， testosterone （T）， anti-Müllerian hormone （AMH） levels， and insulin before and after treatment -Like growth factor-1 （IGF-1）， leptin （LP）， adiponectin （APN）， growth differentiation factor-9 （GDF-9） and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） levels were detected. Result:WHR， BMI and HOMA-IR levels of the observation group were lower than those of the control group （<italic>P</italic><0.05， <italic>P</italic><0.01）. HOMA-<italic>β</italic> level was higher than that in the control group （<italic>P</italic><0.01）. The increase rates of LDL， TG， and nHDL in the observation group were 19.61%（10/51），25.49%（13/51），23.53%（12/51）， respectively， lower than 41.18%（21/51），47.06%（24/51），45.10%（23/51）respectively in the control group （<italic>χ</italic>²=5.607， <italic>χ</italic>²=5.131， <italic>χ</italic>²=5.263， <italic>P</italic><0.05）. The menstrual recovery rate in the observation group was 90.20% （46/51）， higher than 72.55% （37/51） in the control group （<italic>χ</italic>²=5.239，<italic>P</italic><0.05）. The observation group had more ovulation cycles than the control group （<italic>P</italic><0.01）. The pregnancy rate in the observation group was 50.98% （26/51）， higher than 31.37% （16/51） in the control group （<italic>χ</italic>²=4.047，<italic>P</italic><0.05）. On HCG day after treatment， the endometrial thickness and follicle diameter in the observation group were better than those in the control group （<italic>P</italic><0.01）. The proportion of patients with cervical mucus score> 8 points was 78.43% （40/51） in the observation group， higher than 56.86% （29/51） in the control group （<italic>χ</italic>²=5.420，<italic>P</italic><0.05）. The intimal morphology type A rate in the observation group was 52.94% （27/51）， higher than 31.37% （16/51） in the control group （<italic>χ</italic>²=4.864，<italic>P</italic><0.05）. The levels of AMH， E₂， DHEAS， LH， T ， IGF-1， LP and TNF-<italic>α</italic> in the observation group were lower than those in the control group （<italic>P</italic><0.01）， while the APN and GDF-9 levels were superior to those in the control group （<italic>P</italic><0.01）. Conclusion:On the basis of conventional western medicine intervention， modified Cangfu Daotantang can regulate abnormal metabolism and reproductive endocrine in patients with PCOS， improve conception， and regulate the expression of IGF-1， GDF-9， adipocytokines and inflammatory factors， improve ovulation and improve pregnancy rate.

Mechanism of Quercetin in Protecting Articular Cartilage from Osteoarthritis Based on p38 MAPK Pathway / 中国实验方剂学杂志

Objective:To investigate the protective effect of quercetin （Qu） on articular cartilage of knee osteoarthritis and its mechanism by inhibiting p38 mitogen activated protein kinase （MAPK） signaling pathway. Method:Through the network pharmacology technology，we scientifically predicted and analyzed the target factors and signal pathways of Qu in the protection of articular cartilage in patients with osteoarthritis. We selected a prediction pathway closely related to osteoarthritis and validated it by cell experiment <italic>in vitro</italic>. The best intervention concentration of the drug was selected by cell counting kit-8 （CCK-8） method. The osteoarthritis and its closely related inflammatory factors interleukin（IL）-1<italic>β</italic> and tumor necrosis factor（TNF）-<italic>α</italic> were detected by enzyme linked immunosorbent assay（ELISA）. The expression of related mRNA and protein in p38 signal pathway after Qu intervention were detected by quantitative real time polymerase chain reaction（Real-time PCR） and Western blot. Result:It was predicted that MAPK signal pathway was closely related to osteoarthritis by network pharmacology，and p38 MAPK pathway，which was most closely related to osteoarthritis，was selected for study. The results showed that 100 μmol·L^-1 Qu had the most obvious effect in decreasing the expression of related inflammatory factors，inhibited the expression of p38，phosphorylated（p）-p38，matrix metalloproteinase-13（MMP-13），A disintegrin-like and metalloproteinase with thrombospondin type-1 motifs-4（ADAMTS-4） in the pathway，and promoted the expression of CollagenⅡ. Conclusion:Qu could decrease the expression of cartilage inflammatory factors in the prevention and treatment of osteoarthritis，and the effect can be well developed by intervening and inhibiting p38 MAPK pathway related factor expression level. All the results show that Qu can decrease osteoarthritis inflammatory factors and protect articular cartilage in patients with osteoarthritis.

Diffusion tensor imaging and resting-state functional magnetic resonance imaging in patients with delirium in intensive care unit / 中华危重病急救医学

Objective:To analyze the brain function of patients with delirium in intensive care unit (ICU) using resting-state functional magnetic resonance imaging (fMRI), further analyze the structural changes in the brain using diffusion tensor imaging (DTI), and explore the correlations of brain function with structural changes in patients with delirium in ICU from a new perspective of functional imaging, provide visual evidence for the diagnosis of delirium.Methods:Patients with delirium admitted to ICU of the Affiliated Hospital of Zunyi Medical University from January 1st to December 31st in 2017 were enrolled as subjects. During the same period, the healthy volunteers who matched the gender, age and education level of the patients with delirium were enrolled as control group. The intensive care delirium screening checklist (ICDSC) scores within 24 hours after ICU admission were recorded. All the subjects were scanned by fMRI and DTI. The abnormal changes in resting-state brain function of the patients with delirium were evaluated by cerebral regional homogeneity (ReHo) data analysis. The DTI data were processed by the FSL software, and the fractional anisotropy (FA) and mean diffusivity (MD) of the brain were extracted, respectively, to evaluate the damage to brain structure. The values of ReHo, FA and MD were compared between the two groups. The ReHo value of brain region with reduced ReHo value of patients with delirium as compared with the healthy volunteers was extracted for Pearson correlation analysis with ICDSC scores.Results:A total of 22 patients with delirium were included. Seven patients who did not cooperate in the examination, used sedatives or had false images in scanning, were excluded. Finally, 15 patients were enrolled in the delirium group, and 15 healthy volunteers in the healthy control group. ① No statistically significant difference was found in gender, age or education time between the two groups. ICDSC score of the delirium group was significantly higher than that of the healthy control group (6.07±1.28 vs. 1.07±0.88, P < 0.01). ② fMRI scanning and analysis results: compared with the healthy control group, the ReHo values of the cerebellum, right hippocampus, striatum, midbrain and pons in the delirium group were significantly increased (all P < 0.05, AlphaSim correction), while the ReHo values of bilateral superior frontal gyrus, bilateral median frontal gyrus, left inferior frontal gyrus, temporal lobe and parietal lobe were significantly lowered (all P < 0.05, AlphaSim correction). Correlation analysis showed that the ReHo value of the left superior frontal gyrus was negatively correlated with ICDSC score in the patients with delirium ( r = -0.794, P < 0.05), indicating that the changes in the functional area of the medial frontal gyrus was most closely related to delirium. ③ DTI scanning and analysis results: compared with the healthy control group, the FA values of the left cerebellum, bilateral frontal lobes, left temporal lobe, corpus callosum and left hippocampus in the delirium group were decreased significantly (all P < 0.05, AlphaSim correction), while the MD values of the medial frontal gyrus, right superior temporal gyrus, anterior cingulate gyrus, bilateral insular lobes and left caudate nucleus were enhanced significantly (all P < 0.05, AlphaSim correction), suggesting that the structural and functional damage was found in multiple brain regions in patients with delirium. Conclusions:Multiple brain regions of patients with delirium present abnormal resting-state brain function. The abnormal resting-state brain function of the left superior frontal gyrus is closely related to the occurrence of delirium. Structural damage is found in multiple brain regions of patients with delirium. The structural changes in the frontal lobe, temporal lobe, corpus callosum, hippocampus and cerebellum and their abnormal functions can be used as preliminary imaging indexes for the diagnosis of delirium.

Postoperative adjuvant targeted therapy for non-small cell lung cancer / 国际肿瘤学杂志

As one of the main methods of postoperative adjuvant therapy for non-small cell lung cancer (NSCLC) patients, the clinical effect of platinum-containing dual-drug chemotherapy has reached a ceiling effect and it is difficult to further improve the survival of patients with NSCLC. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors have become the standard first-line treatment for advanced NSCLC with EGFR mutation, but its value as postoperative adjuvant therapy is far to be investigated. Some studies have been carried out in this field in recent years.

Progress of diagnosis and treatment of intrahepatic cholangiocarcinoma / 国际外科学杂志

The incidence of intrahepatic cholangiocarcinoma (ICC) is increasing year by year,and the cause of its onset is still not clear.Enhanced CT or enhanced magnetic resonance imaging is a commonly used diagnostic method,and postoperative pathology inspection is the most important criterion for diagnosis.The overall therapeutic effect of ICC is not satisfactory.Surgical resection is the only curative treatment.However,the low resection rate and high recurrence rate are difficult treatments for the disease.This article reviews the etiology,diagnosis and treatment of ICC.

Progress of diagnosis and treatment of intrahepatic cholangiocarcinoma / 国际外科学杂志

The incidence of intrahepatic cholangiocarcinoma (ICC) is increasing year by year, and the cause of its onset is still not clear. Enhanced CT or enhanced magnetic resonance imaging is a commonly used diagnostic method, and postoperative pathology inspection is the most important criterion for diagnosis. The overall therapeutic effect of ICC is not satisfactory. Surgical resection is the only curative treatment. However, the low resection rate and high recurrence rate are difficult treatments for the disease. This article reviews the etiology, diagnosis and treatment of ICC.

Protective Effect of Cangxi Tongbi Capsule on Articular Cartilage of KOA Rats Based onp38 MAPK Signaling Pathway / 中国实验方剂学杂志

Objective:To observe the therapeutic effect and mechanism of Cangxi Tongbi capsule on knee osteoarthritis (KOA) model rats. Method:Sixty 4-week-old SPF healthy male SD rats were randomly divided into blank group, model group, dimethyl sulfoxide (DMSO) group, Cangxi Tongbi capsule group, SB203580 group and Cangxi Tongbi capsule combined with SB203580 group. In addition to the normal group, the modified Hulth method was used to establish the koa model. After the model was established successfully, the Cangxi Tongbi capsule group was given 0.25 g·kg-1 Cangxi Tongbi capsule solution by gavage every day, the SB203580 group was given 0.015 g·kg-1 SB203580 solution by gavage, the Cangxi Tongbi capsule combined with SB203580 group was given a mixed solution containing 0.015 g·kg-1 SB203580 and 0.25 g·kg-1 Cangxi Tongbi capsule by gavage, the DMSO group was given 1% DMSO solution by gavage, the model group and blank group were given normal saline by gavage The stomach was killed and the material was taken after 4 weeks of drug intervention. The expression levels of interleukin-1β （IL-1β） and tumor necrosis factor-α（TNF-α）in the supernatant of peripheral blood were detected by ELISA. p38, p-p38, matrix metalloproteinase-13(MMP-13), Collagen Ⅱ mRNA and protein in p38 MAPK signal pathway were detected by Real-time fluorescence quantification PCR （Real-time PCR） and Western blot, and the localization expression of p-p38 was detected by immunohistochemistry. Result:Compared with normal group，the expression levels of p38，p-p38，MMP-13 in articular cartilage of the model group were up-regulated (P<0.01), the expression levels of CollagenⅡ was down-regulated (P<0.01). The contents of IL-1β and TNF-α in serum were significantly increased (P<0.01). Compared with model group, the expression levels of p38，p-p38，MMP-13 in articular cartilage of the Cangxi Tongbi capsule group, SB203580 group and Cangxi Tongbi capsule combined with SB203580 group were down-regulated (P<0.01), the expression levels of CollagenⅡ was up-regulated (P<0.01). The contents of IL-1β and TNF-α in serum were significantly decreased (P<0.01). Conclusion:Cangxi Tongbi capsule can effectively protect the cartilage of KOA rats, and its mechanism may be related to the targeted blocking of p38 MAPK signal pathway.

Effect of p38 MAPK Signaling Pathway in Diagnosis and Treatment of Knee Ksteoarthritis by Traditional Chinese Medicine / 中国实验方剂学杂志

Knee osteoarthritis (KOA) is a kind of joint disease characterized by progressive degeneration of articular cartilage, synovitis and pain. Its pathogenesis is not yet completely clear. Generally, it is believed that age, sex, obesity, trauma, inflammation, genetic susceptibility and other mechanical and biological factors together lead to the degradation and synthetic coupling imbalance of cartilage cells, extracellular matrix and subchondral bone. In recent years, signaling pathway has become a hot spot in the research of KOA chondrocyte proliferation and apoptosis, and the research of signal pathway in the pathogenesis and targeted therapy of KOA also began. It usually involves the expressions of cytokines, relevant genes and proteins in KOA chondrocyte. These researches mainly focus on the proliferation and apoptosis of chondrocytes, the synthesis and degradation of extracellular matrix, and the sclerosis of subchondral bone. More studies focus on p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway. Literatures show that p38 MAPK signaling pathway can regulate the proliferation and apoptosis of chondrocytes, maintain the balance of extracellular matrix metabolism, regulate the production of matrix metalloproteinases and pro-inflammatory factors, participate in the degradation of collagen and proteoglycan, and play an important regulatory role in the pathological process of KOA. Traditional Chinese medicine(TCM) therapy under the guidance of holistic concept and dialectical treatment theory has a strong pertinence and remarkable curative effect, and can control the development of the disease fundamentally. Starting with the relationship between p38 MAPK and the pathogenesis of KOA, this paper summarizes the research progress of p38 MAPK signaling pathway in the diagnosis and treatment of KOA by TCM, and provides new targets for the clinical diagnosis and treatment of KOA.

Effects of Different Polar Parts of 5 Kinds of Alpinia on Function of Sympathetic-adrenal System in Gastric Ulcer Model Rats with Cold Syndrome / 中国药房

OBJECTIVE： To investigate the effects of different polar parts of 5 kinds of Alpinia on the function of sympathetic-adrenal system in gastric ulcer model rats with cold syndrome， such as the root of Alpinia officinarum， the rhizome and fruit of Alpinia galangal， the seed of Alpinia katsumadai， and the fruit of Alpinia oxyphylla. METHODS： SD rats were given Anemarrhena asphodeloides decoction at 4 ℃ and Glacial acetic acid solution intragastrically to induce gastric ulcer model with cold syndrome； the model rats were randomly divided into model group， Fuzi lizhong pills group （positive control， 9.0 g/kg）， cimetidine group （positive control， 0.003 3 g/kg）， low-dose and high-dose groups of petroleum ether， ethyl acetate， n-butanol and water extraction parts from 5 medicinal materials （hereinafter referred to as “gaoshidi” “gaoshigao” “dashidi” “dashigao” “hongshidi” “hongshigao” “caoshidi” “caoshigao” “yishidi” “yishigao” “gaoyidi” “gaoyigao” “dayidi” “dayigao” “hongyidi” “hongyigao” “caoyidi” “caoyigao” “yiyidi” “yiyigao” “gaozhengdi” “gaozhenggao” “dazhengdi” “dazhenggao” “hongzhengdi” “hongzhenggao” “caozhengdi” “caozhenggao” “yizhengdi” “yizhenggao” “gaoshuidi” “gaoshuigao” “dashuidi” “dashuigao” “hongshuidi” “hongshuigao” “caoshuidi” “caoshuigao” “yishuidi” “yishuigao”， 0.064/0.256， 0.032/ 0.128， 0.008/0.032， 0.075/0.3， 0.1/0.4， 0.064/0.256， 0.108/0.432， 0.16/0.64， 0.064/0.25， 0.125/0.5， 0.056/0.224， 0.108/0.432， 0.08/0.32， 0.2/0.8， 0.3/1.2， 0.14/0.56， 0.032/0.128， 0.028/0.112， 0.05/0.2， 0.087/0.348 g/kg， by mass of extraction parts）， with 10 rats in each group； and the blank group （normal temperature water） was set up. Next day after modeling， blank group and model group were given constant volume of normal temperature water intragastrically； administration group was given relevant solution 2 mL/100 g intragastrically， q12 h， 4 times in total. After last medication， urine contents of 17-OHCS， CAs substances （A， NE， DA） and serum contents of ACTH and D-β-H were determined by ELISA. RESULTS： Compared with blank group， the contents of 17-OHCS， A， NE and DA in urine， the contents of ACTH and D-β-H in serum were decreased significantly in model group （P＜0.01）. Compared with model group， the contents of 17-OHCS （Fuzi lizhong pills group， cimetidine group， gaoshidi， gaoshigao， dashigao， hongshigao， caoshigao and yishigao groups， ethyl acetate part groups of 5 medicinal materials， dazhenggao， hongzhenggao， caozhenggao and yizhenggao groups， gaoshuigao， dashuigao and hongshuigao groups）， A （Fuzi lizhong pills group， cimetidine group， gaoshigao， dashigao， hongshidi， hongshigao， caoshidi， caoshigao and yishigao groups， ethyl acetate part groups of 5 medicinal materials， gaozhenggao， dazhenggao， hongzhengdi， hongzhenggao， caozhenggao and yizhenggao groups， hongshuigao group）， NE （Fuzi lizhong pills group， cimetidine group， petroleum ether part， ethyl acetate part and n-butanol part groups of 5 medicinal materials， gaoshuigao， dashuigao and hongshuigao groups）， DA [Fuzi lizhong pills group， cimetidine group， petroleum ether part （except for gaoshidi group） and ethyl acetate part groups of 5 medicinal materials， gaozhenggao， dazhenggao， hongzhenggao， caozhenggao and yizhenggao groups， hongshuigao group] in urine， serum contents of ACTH [Fuzi lizhong pills group， petroleum ether part （except for gaoshidi， dashidi and caoshidi groups） and ethyl acetate part （except for dayidi and hongyidi groups） groups of 5 medicinal materials， hongzhenggao group， dashuigao group]， and D-β-H [Fuzi lizhong pills group， gaoshigao， dashigao， hongshidi， hongshigao and yishigao groups， ethyl acetate part groups of 5 medicinal materials （except for dayidi， hongyidi and yiyidi groups）， dazhenggao and hongzhenggao groups， hongshuigao group] were increased significantly （P＜0.05 or P＜0.01）. The contents of 17-OHCS and D-β-H in dashigao group， the contents of ACTH and D-β-H in caoshigao group and the contents of D-β-H in gaoshigao and yishigao groups were significantly lower than hongshigao group. The contents of DA in gaoyigao， caoyigao and yiyigao groups as well as the contents of D-β-H in gaoyigao， hongyigao， caoyigao and yiyigao groups were significantly lower than dayigao group； the contents of DA in gaoyigao and caoyigao groups were significantly lower than hongyigao group， the contents of ACTH in gaoyigao， dayigao， caoyigao and yiyigao groups were significantly higher than hongyigao group. The contents of 17-OHCS， DA and ACTH in gaozhenggao， dazhenggao， caozhenggao and yizhenggao groups， the contents of A in dazhenggao， caozhenggao and yizhenggao groups as well as the contents of D-β-H in gaozhenggao， caozhenggao and yizhenggao groups were significantly lower than hongzhenggao group. The contents of 17-OHCS and D-β-H in caoshuigao and yishuigao groups were significantly lower than dashuigao group. The contents of 17-OHCS， DA and D-β-H in caoshuigao and yishuigao groups as well as the contents of DA and D-β-H in gaoshuigao groups were significantly lower than hongshuigao group （P＜0.05 or P＜0.01）. CONCLUSIONS： Different polar parts of 5 kinds of Alpinia can improve gastric ulcer model rats with cold syndrome to different extents； among them， the fruit of A. galangal is the best， followed by the root of A. officinarum. Above medicinal materials can regulate the function of sympathetic-adrenal system by increasing the contents of 17-OHCS， CAs and D-β-H.

Clinical randomized controlled trial of laparoscopic totally extraperitoneal herniorrhaphy and totally extraperitoneal herniorrhaphy via hypogastric midline incision in treatment of bilateral inguinal hernias / 国际外科学杂志

Objective To explore the clinical value of laparoscopic totally extraperitoneal herniorrhaphy (LTEP) and open to tally extraperitoneal (OTEP) for bilateral inguinal hernias.Methods From January 2015 to December 2017,61 male patients with bilateral inguinal hernias,who were in accordance with the inclusion criteria,were prospectively randomized into laparoscopic totally extraperitoneal herniorrhaphy group (LTEP group,n =31)or totally extraperitoneal herniorrhaphy via hypogastric midline incision group(OTEP group,n =30).Operative outcomes,postoperative complications,recurrence,the levels of C-reactive protein (CRP) were analyzed.The data were analyzed by statistical software.Results The operative baselines of patients in two groups were equivalent.In patients who received laparoscopic totally extraperitoneal herniorrhaphy,decreased levels of CRP on the 1th day after operation,postoperative ambulation and hospital stay [(88.7 ± 18.5) mg/L vs (102.0 ±25.1) mg/L,P=0.022];[(5.6±2.2) h vs (20.0±5.5) h,P＜0.001;(3.0±0.6) dvs (4.5±1.0) d,P ＜ 0.001],were found compared with the OTEP group significantly,LTEP group had more hospitalization expense than OTEP group [(14 779.3 ± 1450.1) yuan vs (13 650.0 ± 1 787.3) yuan,P ＜ 0.001].There were no mesh infection,chronic pain,scrotal edema and recurrence of inguinal hernia in two groups.No difference was found between the two groups in the other operative outcomes and postoperative complications.Conclusion Both laparoscopic totally extraperitoneal herniorrhaphy and totally extraperitoneal herniorrhaphy via hypogastric midline incision are effective and safe in the treatment of bilateral inguinal hernias,each has both advantages and disadvantages,and complement each other.