[Surgical treatment and prognosis analysis of hilar cholangiocarcinoma].

Objective: To investigate the surgical treatment effect and prognostic factors of hilar cholangiocarcinoma. Methods: This is an ambispective cohort study. From August 2005 to December 2022,data of 510 patients who diagnosed with hilar cholangiocarcinoma and underwent surgical resection at the Hepatobiliary Center of the First Affiliated Hospital of Nanjing Medical University were retrospectively collected. In the cohort,there were 324 males and 186 females,with an age of (M (IQR)) 63(13)years (range:25 to 85 years). The liver function at admission was Child-Pugh A (343 cases,67.3%) and Child-Pugh B (167 cases,32.7%). Three hundred and seventy-two(72.9%) patients had jaundice symptoms and the median total bilirubin was 126.3(197.6) µmol/L(range: 5.4 to 722.8 µmol/L) at admission. Two hundred and fourty-seven cases (48.4%) were treated with percutaneous transhepatic cholangial drainage or endoscopic nasobiliary drainage before operation. The median bilirubin level in the drainage group decreased from 186.4 µmol/L to 85.5 µmol/L before operation. Multivariate Logistic regression was used to identify the influencing factors for R0 resection,and Cox regression was used to construct multivariate prediction models for overall survival(OS) and disease-free survival(DFS). Results: Among 510 patients who underwent surgical resection,Bismuth-Corlett type Ⅲ-Ⅳ patients accounted for 71.8%,among which 86.1% (315/366) underwent hemi-hepatectomy,while 81.9% (118/144) underwent extrahepatic biliary duct resection alone in Bismuch-Corlett type Ⅰ-Ⅱ patients. The median OS time was 22.8 months, and the OS rates at 1-,3-,5-and 10-year were 72.2%,35.6%,24.8% and 11.0%,respectively. The median DFS time was 15.2 months,and the DFS rates was 66.0%,32.4%,20.9% and 11.0%,respectively. The R0 resection rate was 64.5% (329/510), and the OS rates of patients with R0 resection at 1-,3-,5-and 10-year were 82.5%, 48.6%, 34.4%, 15.2%,respectively. The morbidity of Clavien-Dindo grade Ⅲ-Ⅴ complications was 26.1%(133/510) and the 30-day mortality was 4.3% (22/510). Multivariate Logistic regression indicated that Bismuth-Corlett type Ⅰ-Ⅲ (P=0.009), hemi-hepatectomy and extended resection (P=0.001),T1 and T2 patients without vascular invasion (T2 vs. T1:OR=1.43 (0.61-3.35),P=0.413;T3 vs. T1:OR=2.57 (1.03-6.41), P=0.010;T4 vs. T1, OR=3.77 (1.37-10.38), P<0.01) were more likely to obtain R0 resection. Preoperative bilirubin,Child-Pugh grade,tumor size,surgical margin,T stage,N stage,nerve infiltration and Edmondson grade were independent prognostic factors for OS and DFS of hilar cholangiocarcinoma patients without distant metastasis. Conclusions: Radical surgical resection is necessary to prolong the long-term survival of hilar cholangiocarcinoma patients. Hemi-hepatectomy and extended resection,regional lymph node dissection and combined vascular resection if necessary,can improve R0 resection rate.

[Studies on the DNA damage in the transformed bronchial epithelial cells induced by hexavalent chromium].

Objective: To investigate DNA damage in the transformed human bronchial epithelial cells (16HBE) induced by hexavalent chromium (Cr(6+)) and further elucidate the potential carcinogenesis mechanism of Cr(6+). Methods: 16HBE were treated with different concentration of Cr(6+ ()0, 0.625, 1.25, 2.5 µmol/L) for 15 weeks. The malignant degrees of transformed cells were identified by the assays for anchorage-independent growth and tumorigenicity. According to the single cell gel electrophoresis (SCGE) assay, the DNA damage rate was calculated. The expression level of 53BP1 was determined by Western blot. Results: Chromium-treated cells could form colonies in soft agar and tumors in nude mice. Compared with the control group, colony formation efficiency of 1.25µmol/L and 2.5 µmol/L Cr(6+)-treated cells in soft agar showed significant increases (p<0.05) . The 2.5 µmol/L Cr(6+)-treated cells also formed tumors subcutaneously in nude mice. Cr(6+) could cause different degree of DNA damage to 16HBE cells in a dose-dependent manner. In addition, Western blot analyses showed that 53BP1 was aberrantly down-regulated at 2.5 µmol/L dose and has no significant changes at 0.625 µmol/L and 1.25 µmol/L dose under the treatment of Cr(6+). Conclusion: The declined expression of 53BP1 may mediate Cr(6+)-induced DNA damage and further involved in the cell malignant transformation.

[Trichloroethylene-induced abnormal methylation on promoter region of SET in hepatic L-02 cells].

Objective: To explore the trichloroethylene-induced alteration of methylation on the promoter region of SET and related mechanisms in hepatic L-02 cells. Methods: L-02 cells were treated with different concentrations of TCE(0 mmol/L, 1 mmol/L, 2 mmol/L, 4 mmol/L, 8 mmol/L) for 24 h. The genomic DNA were then extracted and modified by bisulfite sodium. The DNA methylation was then analyzed using bisulfite sequencing PCR (BSP). Results: The overall methylation on promoter region of SET was decreased along with the increased concentrations of TCE in hepatic L-02 cells. Moreover, 73 CpG islands were found abnormally altered, among which 9 were predicted in transcriptional factor binding regions. Conclusion: The decreased levels of CpG islands in the transcriptional factor binding region may contribute to the elevation of SET in TCE-induced hepatotoxicity.

[An investigation of trichloroethylene-induced effects on histone methylation in L-02 hepatic cells].

Objective: To further explore TCE-induced hepatotoxicity and its mechanisms by identification of trichloroethylene (TCE) induced abnormal histone methylation in human liver cells. Methods: L-02 cells were treated with 0 and 8 mmol/L TCE for 24 h. Histones were extracted by acid. Liquid chromatography electrospray ionization tandem mass spectrometry (ESI-LC-MS/MS) were used to identify and quantify TCE related histone methylations. TCE induced abnormal methylation of H3K79 me2 and H3K79 me3 were validated by Western blot analysis. The further analysis of the function of histone abnormal methylation modifications were done by single cell gel electrophoresis (SCGE) and Western blot analysis of p53 and ɤH2AX. Results: After treatment with TCE for 24 h in L-02 cells, the 36 TCE related histone methylation sites in 28 peptide segments were identified by MS. After treatment with TCE in concentrations of 0 and 8.0 mmol/L in L-02 cells for 24 h, the relative expression level of histone H3K79 me3 were 1.00±0.06, 0.70±0.09 (t=15.01, P=0.015); the relative expression level of histone H3K79 me2 were 1.00±0.05, 0.74±0.07 (t=16.69, P=0.018); the Olive Tail Moment about DNA damage were 1.46±0.28, 3.12± 0.68 (t=15.22, P=0.018); the relative expression levels of p53 were 1.00±0.04, 1.24±0.04 (t=18.71, P= 0.012); and the relative expression levels of ɤH2AX were 1.00 ± 0.03, 1.56 ± 0.11 (t=8.32, P=0 045). Conclusion: TCE can induce changes in the relative expression level of H3K79 me2 and H3K79 me3 in L-02 cell, and induce DNA damage, suggesting that TCE may induce changes in the relative expression level of H3K79 me2 and H3K79 me3 by DNA damage.

Update meta-analysis of the CYP2E1 RsaI/PstI and DraI polymorphisms and risk of antituberculosis drug-induced hepatotoxicity: evidence from 26 studies.

WHAT IS KNOWN AND OBJECTIVE: Several studies have investigated the association of the CYP2E1 RsaI/PstI and/or DraI polymorphisms with susceptibility to antituberculosis drug-induced hepatotoxicity (ATDH), but the results have been inconsistent. Therefore, we performed a large meta-analysis to determine a more precise estimation of this relationship. METHODS: The PubMed, EMBASE, China National Knowledge Infrastructure and Chinese Biomedical Literature databases were systematically searched to identify relevant studies. Meta-analyses based on the entire population and subgroups were performed to examine the association between CYP2E1 polymorphisms and susceptibility to ATDH. The odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of the associations. RESULTS AND DISCUSSION: Twenty-six studies with a total of 7423 participants were analysed. The overall ORs of relevant studies demonstrated that the CYP2E1 RsaI/PstI C1/C1 genotype was associated with an elevated risk of ATDH (OR = 1·32, 95% CI 1·03-1·69, P = 0·027), but for the DraI polymorphism there was no increase in risk (OR = 1·05, 95% CI 0·80-1·37, P = 0·748). In subgroup analyses of the RsaI/PstI polymorphism, significant results were found in East Asians, patients who used isoniazid + rifampicin + pyrazinamide + ethambutol and patients with twice the upper limit of normal as the minimum standard for defining ATDH. WHAT IS NEW AND CONCLUSION: This meta-analysis suggests that there is an increased risk of ATDH in individuals carrying the C1/C1 genotype of the CYP2E1 RsaI/PstI polymorphism. However, no association was found for the DraI polymorphism.

[Epidemiological analysis on a family cluster of COVID-19].

Objective: To understand the possible transmission route of a family cluster of COVID-19 in Zhengzhou and the potential infectivity of COVID-19 in incubation period, and provide scientific evidence for the timely control of infectious source and curb the spread of the epidemic. Methods: Epidemiological investigation was conducted for a family cluster of COVID-19 (8 cases) with descriptive epidemiological method, and respiratory tract samples of the cases were collected for the nucleic acid detection of virus by RT-PCR. Results: Two primary cases, which occurred on 31 January and 1 February, 2020, respectively, had a common exposure history in Wuhan. The other six family members had onsets on 30 January, 31 January, 1 February (three cases) and 3 February, 2020. Conclusions: In this family cluster of COVID-19, six family members were infected through common family exposure to the 2 primary cases. Five secondary cases had onsets earlier than or on the same day as the primary cases, indicating that COVID-19 is contagious in incubation period, and the home isolation in the early phase of the epidemic might lead to the risk of family cluster of COVID-19.

Long non-coding RNA MEG3 represses cholangiocarcinoma by regulating miR-361-5p/TRAF3 axis.

OBJECTIVE: The aim of this study was to investigate the effect of long non-coding RNA MEG3 (MEG3) and microRNA-361-5p (miR-361-5p) on cholangiocarcinoma cells and to explore the molecular mechanisms. PATIENTS AND METHODS: The level of MEG3 and miR-361-5p was detected using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The relationship between miR-361-5p and MEG3/TNF receptor-associated factor 3 (TRAF3) was confirmed by the Dual-Luciferase Reporter Assay. 3-(4,5)-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay and flow cytometry analysis were used to determine cell viability and cell apoptosis. Moreover, the protein level of TRAF3, p65, and p-p65 was measured by Western blot assay. RESULTS: We found that MEG3 was downregulated in CCA tissues and cell lines, especially in TFK1 and QBC939 cells. MEG3 directly bind to miR-361-5p, which was highly expressed in CCA tissues and cell lines. Further analysis indicated that MEG3-plasmid could inhibit cell viability and induce cell apoptosis in CCA cells, but these effects were significantly reversed by miR-361-5p mimic. Moreover, we proved that TRAF3 was a direct target of miR-361-5p and it was downregulated in CCA tissues and cell lines. In addition, we found that miR-361-5p downregulation significantly inhibited CCA cell viability and induced cell apoptosis, and these effects were eliminated by the knockdown of TRAF3. Further functional analysis showed that the knockdown of TRAF3 upregulated the expression of p-p65 decreased by miR-361-5p inhibitor in CCA cells. CONCLUSIONS: Our results suggested that MEG3 repressed cholangiocarcinoma by downregulating miR-361-5p expression. Meanwhile, the suppression of miR-361-5p might improve CCA survival by targeting TRAF3 and inhibiting the NF-κB pathway, which might help to develop new strategies for CCA therapy.

Assembly of disperse red 1 molecules in the channels of AlPO4-5 single crystals for second-harmonic generation.

Disperse red 1 (DR1) molecules have been successfully incorporated into the one-dimensional channels of AlPO4-5 single crystals by means of vapor-phase diffusion. Polarizing microscope and SHG results indicate that the DR1 molecules are well aligned in a preferred direction along the crystal channels. The p-polarization (parallel to the c-axis of AlPO4-5 crystal) SH intensity (Ip-ex), and s-polarization (perpendicular to the c-axis of AlPO4-5 crystal) SH intensity (Is-ex) of DR1-loaded AlPO4-5 single crystals can be well fitted as a function of input polarization angle (alpha): Ip-ex = 0.69 cos4 alpha + 0.37 sin4 alpha - 0.17, Is-ex = 0.69 cos2 alpha sin2 alpha + 0.06, respectively. This polarization angle dependence can be well explained by three different SHG processes of Ip (0 degrees), Ip (90 degrees), and Is (45 degrees), originated from different combinations of two polarized photons.

[The prevalence of temporomandibular disorder symptoms in 898 university students and its relationship with psychological distress and sleep quality].

OBJECTIVE: To investigate the prevalence of temporomandibular disorders(TMD) symptoms, psychological distress and sleep quality in a population of Chinese university students, and discuss the relationship between psychological distress, sleep quality and TMD symptoms. METHODS: A total of 898 stomatological university students from 5 Chinese universities(342 males and 556 females with a mean age of 20.5 years) were included in the study. Self-reported TMD symptoms using diagnostic criteria for temporomandibular disorders symptom questionnaire were collected. Depression, anxiety and stress scales-21(DASS-21) and Pittsburgh sleep quality index(PSQI) were used to measure psychological distress and sleep quality. RESULTS: 61.9% (556/898) of the students had TMD symptoms. The most common symptoms were pain and clicking of joint, with a prevalence of 42.3% (380/898) and 34.2% (307/898), respectively. The prevalence of depression, anxiety, stress and sleep quality among the students who had TMD symptoms was 33.5%(186/556), 63.1%(351/556), 29.5%(164/556) and 30.2%(243/556), respectively, which was significantly higher than those who had no TMD symptoms(24.3% [83/342], 48.5% [166/342], 21.6%[74/342] and 21.9%[75/342])(P<0.05). Stepwise logistic regression analysis demonstrated that anxiety (OR 1.57, 95%CI 1.14-2.15) and female(OR 1.57, 95%CI 1.19-2.08) were possible risk indicators for TMD symptoms(P<0.05). CONCLUSIONS: Chinese university students reported a high prevalence of TMD symptoms, which may have a correlation with psychological distress symptoms such as anxiety.

The analgesic and respiratory depressant actions of metorphamide in mice and rabbits.

Metorphamide (MET) elicited a potent, dose-dependent analgesia and respiratory depression in mice and rabbits. MET induced-analgesia was naloxone reversible and potentiated by bestatin. Naloxonazine, a relatively selective mu 1 blocker, at certain dosage (50 micrograms per rabbit, icv), could abolish the analgesia but not the respiratory inhibition produced by MET. Our result indicates that mu 1 receptors mediate the MET induced-analgesia but not its respiratory effect. Since MET is a mu- and kappa-ligand with very low delta activity, the MET induced respiratory depression may be mediated by mu 2 or kappa binding sites.

[Evaluation of the causative bacteria of pneumonia in the elderly in recent years].

A study of 62 cases of elderly pneumonia (EP) in their sixties and eighties with etiologic bacteria confirmed by cultures of sputum, blood or pleural effusion was carried out Greater change of etiologic bacteria of EP in patients of eighties has been found when they were compared with those of sixties. In the group of eighties the incidence of Gram-negative bacilli increased (77%), including pseudomonas aeruginosa (48.39%), Klebsiella pneumoniae (17.35%) and Enteric coli (9.68%), while Staphylococcus aureus accounted only for 16.1%. There were 2 species of Streptococcus pneumoniae; both were mixed with other bacteria in cultures. In patients of eighties the etiologic agents isolated from pneumonia were more resistant to many common antibiotics. The above mentioned results suggest that the diagnosis of etiology of pneumonia in the elderly should be emphasized.

[Diagnosis of cyanosis and digital clubbing caused by liver cirrhosis].

Six cases of cyanosis and digital clubbing caused by liver cirrhosis were reported. The mean levels of PaO2 and PaCO2 were 6.4 +/- 0.8 kPa (48.3 +/- 6.2 mmHg) and 3.9 +/- 0.8 kPa (29.5 +/- 6.1 mmHg) respectively. The cause of cyanosis and digital clubbing in liver cirrhosis was discussed. Abnormal intrapulmonary shunting (IPS), which was proved in 4 cases by whole-body radionuclide scanning with 99mTc-MAA, is suggested as the major cause of cyanosis in liver cirrhosis. Clinically IPS is usually associated with debilitating conditions characterized by hyperventilation, abnormality of lung diffusion and orthodeoxia or platypnea. The authors suggest that whole-body radionuclide scanning with 99mTc-MAA may be performed for establishing IPS if liver cirrhosis is highly suspected to be the cause of severe hypoxemia.

Inhibition of sympathetic nervous system by acupuncture.

The central and peripheral sympathetic activities were measured both physiologically and biochemically in either human subjects or conscious rabbits. Acupuncture reduced NE levels in perfusates of certain brain areas as well as in blood circulation, accompanied with a rise of pain threshold, and changes of certain physiological indices (palm temperature, fingerplethysmogram and pain tolerance threshold) which are related with functions of sympathetic nervous system. These results suggest that the NE neurons of NE ascending dorsal fasciculus has some antagonizing effect on acupuncture analgesic effect, acupuncture inhibits sympathetic activities, and such inhibition plays a favorable role in acupuncture analgesia.

Construction and implementation of QRST-wave simulation model.

Computer simulation study of the electrical activity of the heart is one of the frontier subjects of electrocardiogram (ECG) theory study. A new algorithm for simulating excitation propagation within the heart is presented in this paper. On the basis of this, computer simulation of QRST-wave is completed on an IBM PC microcomputer. All performance of the model is compared favourably with that of the models implemented on main frames or on high-performance work stations abroad.

[Diagnosis and treatment of chronic eosinophilic pneumonia].

A case of chronic eosinophilic pneumonia (CEP), confirmed by transfibroptic bronchoscope lung biopsy, was reported. CEP is a chronic interstitial lung disease characterized by cough, dyspnea, malaise, fever, night sweats, weight loss, variable degree of blood eosinophilia and film revealing peripheral nonsegmental nonmigratory infiltrates. It usually responds dramatically to corticosteroids. The authors suggested that a tentative diagnosis is often made on clinical grounds only without biopsy confirmation and corticosteroid therapy is instituted. It is necessary to perform lung biopsy for establishing the diagnosis when the patient has normal eosinophilic count, nonpheripheral lung infiltrats or other atypical manifestations.

[Virtual heart studies and its applications].

This paper presents the development of virtual heart studies and its applications.