[Value of surgery combined chemotherapy and radiation therapy in locally advanced neuroendocrine carcinoma of the cervix: a single-center retrospective cohort study].

Objective: To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) . Methods: This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference (χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences (P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions: Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.

[Value of postoperative radiotherapy and analysis of prognostic factors in early-stage neuroendocrine carcinoma of cervix].

Objective: To evaluate the effect of postoperative radiotherapy and high-risk pathological factors on the prognosis of early-stage neuroendocrine carcinoma of cervix (NECC). Methods: A single-center retrospective cohort study of early-stage NECC in Peking Union Medical College Hospital from January 2011 to April 2022 were enrolled. The patients were treated with radical hysterectomy±adjuvant treatment. They were divided into postoperative non-radiation group and postoperative radiation group. The possible postoperative recurrence risk factors identified by univariate analysis were assessed using multivariate logistic regression. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Sixty-two cases were included in the study, including 33 cases in postoperative non-radiation group and 29 cases in postoperative radiation group. (2) The median follow-up time was 37 months (ranged 12-116 months), with 23 cases (37%) experienced recurrences. There were 7 cases (11%) pelvic recurrences and 20 cases (32%) distant recurrences, in which including 4 cases (6%) both pelvic and distant recurrences. Compared with postoperative non-radiation group, the postoperative radiation group had a lower pelvic recurrence rate (18% vs 3%; P=0.074) but without statistic difference, a slightly elevated distant recurrence rate (24% vs 41%; P=0.150) and overall recurrence rate (33% vs 41%; P=0.513) without statistically significances. Univariate analysis showed that lymph-vascular space invasion and the depth of cervical stromal invasion≥1/2 were risk factors for postoperative recurrence (all P<0.05). Multivariate analysis showed lymph-vascular space invasion was an independent predictor for postoperative recurrence (OR=23.03, 95%CI: 3.55-149.39, P=0.001). (3) During the follow-up period, 18 cases (29%, 18/62) died with tumor, with 10 cases (30%, 10/33) in postoperative non-radiation group and 8 cases (28%, 8/29) in postoperative radiation group, without significant difference (P=0.814). The postoperative 3-year and 5-year survival rate was 79.2%, 60.8%. The depth of cervical stromal invasion≥1/2 was more common in postoperative radiation group (27% vs 64%; P=0.011), and postoperative radiation in such patients showed an extended trend in PFS (32.3 vs 53.9 months) and OS (39.4 vs 73.4 months) but without statistic differences (P=0.704, P=0.371). Compared with postoperative non-radiation group, the postoperative radiation did not improve PFS (54.5 vs 37.3 months; P=0.860) and OS (56.2 vs 62.4 months; P=0.550) in patients with lymph-vascular space invasion. Conclusions: Postoperative radiation in early-stage NECC patients has a trend to reduce pelvic recurrence but not appear to decrease distant recurrence and overall recurrence, and has not improved mortality. For patients with the depth of cervical stromal invasion≥1/2, postoperative radiation has a trend of prolonging OS and PFS but without statistic difference. Lymph-vascular space invasion is an independent predictor for postoperative recurrence, but postoperative radiation in such patients does not seem to have any survival benefits.

[The effects of robotic-assisted versus laparoscopic-assisted radical right hemicolectomy on short-term outcome and long-term prognosis based on propensity score matching].

Objective: To compare the short-term and long-term outcomes between robotic-assisted and laparoscopic-assisted radical right hemicolectomy in patients with adenocarcinoma of the right colon. Methods: Retrospective review of a prospectively collected database identified 288 right colon cancer patients who underwent either robotic-assisted (n=57) or laparoscopic-assisted right hemicolectomy (n=231) between October 2014 and October 2020 at Department of Gastrointestinal Surgery, the Affiliated Hospital of Qingdao University. There were 161 males and 127 females, aging (60.3±12.8) years (range: 17 to 86 years). After propensity score matching as 1∶4 between robotic-assisted and laparoscopic-assisted right hemicolectomy, there were 56 cases in robotic group and 176 cases in laparoscipic group. Perioperative outcomes and overall survival were compared between the two groups using t test, Wilcoxon rank sum test, χ2 test, Fisher exact test, Kaplan-Meier method and Log-rank test, respectively. Results: The total operative time was similar between the robotic and laparoscopic group ((206.9±60.7) minutes vs. (219.9±56.3) minutes, t=-1.477, P=0.141). Intraoperative bleeding was less in the robotic group (50 (20) ml vs. 50 (50) ml, Z=-4.591, P<0.01), while the number of lymph nodes retrieved was significantly higher (36.0±10.0 vs. 29.0±10.1, t=4.491, P<0.01). Patients in robotic group experienced significantly shorter hospital stay, shorter time to first flatus, and defecation (t: -2.888, -2.946, -2.328, all P<0.05). Moreover, the overall peri-operative complication rate was similar between robotic and laparoscopic group (17.9% vs. 22.7%, χ²=0.596,P=0.465). The 3-year overall survival were 92.9% and 87.9% respectively and the 3-year disease-free survival rates were 83.1% and 82.6% with no statistical significance between the robotic and laparoscopic group (P>0.05). Conclusions: Compared to laparoscopic-assisted right hemicolectomy, robot-assisted right hemicolectomy could improve some short-term clinical outcomes. The two procedures are both achieving comparable survival.

[A prospective cohort study about the screening tests of mismatch repair protein and clinical criteria for Lynch syndrome associated endometrial carcinoma].

Objectives: Currently, the commonly used screening methods for Lynch syndrome in patients with endometrial cancer (EC) are clinical diagnostic criteria and immunohistochemical testing. Our study compared the accuracy of the two methods in this prospective cohort study. Methods: Mismatch repair (MMR) protein was detected by immunohistochemical in the pathological tissues of newly diagnosed EC patients in Peking Union Medical College Hospital, during December 2015 and June 2018. Lynch syndrome related mutation gene was detected in patients with MMR protein deficiency. At the same time, all the patients were evaluated by the clinical diagnostic criteria (Amsterdam Criteria Ⅱ and the revised Bethesda criteria). Results: A total of 121 newly diagnosed EC patients were enrolled in this study, and 41 cases (33.9%) were MMR protein deficient. All of them received Lynch syndrome related mutation gene detection, and 7 cases were finally diagnosed with Lynch syndrome. Only 6 cases of Lynch syndrome, however, were diagnosed by the clinical diagnostic criteria, with 1 case misdiagnosed and 2 cases missed diagnosed. Conclusion: The incidence of Lynch syndrome in endometrial cancer patients is 5.8%. And the clinical diagnostic criteria for Lynch syndrome in patients with EC will result in miss diagnosis and misdiagnosis.

Element-selective resonant state in M-doped SnTe (M = Ga, In, and Tl).

The band engineering of M-doped SnTe (M = Ga, In, and Tl) is investigated by using first-principles calculations. Being consistent with experimental measurements, our calculations found that Ga doping hardly changes the valence band, while In doping introduces an obvious resonant state near the Fermi level. The resonant state is demonstrated to be from the anti-bonding of In-s and Te-p orbitals. Unexpectedly, no resonant state was observed in Tl-doped SnTe, indicating the nonmonotonic behavior of the Ga-In-Tl series. We show that the absence of the resonant state in Tl-doped SnTe is due to the downward shift of the Tl-s orbital, which may be attributed to the effect of lanthanide contraction. The increase of the Seebeck coefficient in In-doped SnTe is numerically confirmed by Boltzmann transport calculations. Moreover, we find that the mutually matched resonant state location and valence band separation is the key precondition for the combination of the resonant state and band convergence in SnTe. A further enhanced Seebeck coefficient (∼230 µV K(-1)) and ZT value (1.8 at 920 K) are predicted in codoped SnTe by In-Hg, owing to the synergy of two kinds of band engineering.

[Mutation screening for the causative gene in a four-generation Chinese pedigree with progressive cardiac conduction defect].

OBJECTIVE: To define the potential causative gene mutation in a Chinese pedigree with progressive cardiac conduction defect (PCCD). METHODS: Sanger sequencing was performed to define potential causative gene mutation in a four-generation family with 68 members including seven PCCD patients (5 male) from 2010 to 2015.No causative gene was detected by screening known candidate genes related to PCCD including SCN5A, NKX2.5 and LMNA.High-throughput sequencing technology on exon-enriched DNA was then used to search the causative genes in 2 patients and one normal family member. RESULTS: Eight new non-synonymous single nucleotide variants including AQP7 gene (exon5: c.T343C: p.Y115H), CACNA1B gene (NM_001243812: exon19: c.A2986G: p.T996A), CATSPERB gene (exon27: c.C3254G: p.P1085R), CLCA2 gene (exon11: c.G1725T: p.W575C), CLCA3P gene (ncRNA_intronic), MYLK-AS1 gene (ncRNA_intronic), TTN gene (ncRNA_UTR3), LMNA gene (LMNA: NM_170708: exon5: c.C922T: p.Q308X) were identified by comparing and filtering the results with known public databases.Then, more detailed biological analysis on these 8 genes was conducted.Traditional Sanger sequencing validated the exome sequencing results, and found that the mutation c. 1725Gï¹¥T in gene CLCA2 segregated with the phenotype of this PCCD pedigree.The mutation c. 1725Gï¹¥T in gene CLCA2 was thus be considered as the causative PCCD gene in this pedigree from the perspective of genetics and genomics. CONCLUSION: The heterozygote mutation c. 1725Gï¹¥T in gene CLCA2 might be causative gene in this PCCD pedigree.This finding adds new gene mutation variant responsible for PCCD.

Band engineering and improved thermoelectric performance in M-doped SnTe (M = Mg, Mn, Cd, and Hg).

The electronic structures of M-doped SnTe (M = Mg, Mn, Cd, and Hg) are investigated by using first-principles calculations including spin-orbit coupling. It is found that Sn vacancy plays an important role in the band engineering of SnTe, showing a different property from its related compound PbTe. The enlarged band gap and reduced energy separation between two valence bands are in good agreement with experimental measurements. Both of the two band modifications lead to the increase of Seebeck coefficients, which is explicitly confirmed by the followed Boltzmann transport calculations. The calculated Seebeck coefficients for Mn-doped SnTe agree well with the experimental data in a broad range of carrier concentration. Owing to the improved Seebeck coefficients, Mn- and Cd-doped SnTe exhibit promising thermoelectric properties with ZT = 1.32 and 1.65 at around 800 K, respectively.

Thermoelectric properties of armchair and zigzag silicene nanoribbons.

Using the nonequilibrium Green's function method and nonequilibrium molecular dynamics simulations, we discuss the possibility of using silicene nanoribbons (SiNRs) as high performance thermoelectric materials. It is found that SiNRs are structurally stable if the edge atoms are passivated by hydrogen, and those with armchair edges usually exhibit much better thermoelectric performance than their zigzag counterparts. The room temperature ZT value of armchair SiNRs shows a width-dependent oscillating decay, while it decreases slowly with increasing ribbon width for the zigzag SiNRs. In addition, there is a strong temperature dependence of the thermoelectric performance of these SiNRs. Our theoretical calculations indicate that by optimizing the doping level and applied temperature, the ZT value of SiNRs could be enhanced to as high as 4.9 which suggests their very appealing thermoelectric applications.

The properties of BiSb nanoribbons from first-principles calculations.

The structural, electronic and magnetic properties of BiSb nanoribbons (BSNRs) with different widths and edge configurations are investigated via the first-principles pseudopotential method. It is found that the pristine BSNRs with armchair edges (ABSNRs) are semiconductors and the band gaps exhibit a width dependent odd-even oscillation. In contrast, the pristine BSNRs with zigzag edges (ZBSNRs) are found to be metallic. When all the edge atoms are passivated by hydrogen, both the ABSNRs and ZBSNRs become semiconducting and the corresponding band gaps decrease monotonically with the increasing width. If, however, the edge atoms are partially passivated, the ABSNRs can be either semiconducting or metallic. Moreover, local magnetism appears when all the edge Sb atoms are passivated and there are one or more unsaturated Bi atoms. Using the nonequilibrium Green's function (NEGF) approach, we find that all the investigated odd-numbered ABSNRs have almost the same peak value of the power factor around the Fermi level. This is not the case for the even-numbered ABSNRs, where the peaks are twice that of when they are n-type doped. Our calculations indicate that BSNRs can have a very high room temperature figure of merit (ZT value), which makes them very promising candidates for thermoelectric applications.

USP4 targets TAK1 to downregulate TNFα-induced NF-κB activation.

Lys63-linked polyubiquitination of transforming growth factor-ß-activated kinase 1 (TAK1) has an important role in tumor necrosis factor-α (TNFα)-induced NF-κB activation. Using a functional genomic approach, we have identified ubiquitin-specific peptidase 4 (USP4) as a deubiquitinase for TAK1. USP4 deubiquitinates TAK1 in vitro and in vivo. TNFα induces association of USP4 with TAK1 to deubiquitinate TAK1 and downregulate TAK1-mediated NF-κB activation. Overexpression of USP4 wild type, but not deuibiquitinase-deficient C311A mutant, inhibits both TNFα- and TAK1/TAB1 co-overexpression-induced TAK1 polyubiquitination and NF-κB activation. Notably, knockdown of USP4 in HeLa cells enhances TNFα-induced TAK1 polyubiquitination, IκB kinase phosphorylation, IκBα phosphorylation and ubiquitination, as well as NF-κB-dependent gene expression. Moreover, USP4 negatively regulates IL-1ß-, LPS- and TGFß-induced NF-κB activation. Together, our results demonstrate that USP4 serves as a critical control to downregulate TNFα-induced NF-κB activation through deubiquitinating TAK1.

Apoptosis induced by emodin is associated with alterations of intracellular acidification and reactive oxygen species in EC-109 cells.

Emodin (1,3,8-trihydroxy-6-methylanthraquinone), a natural anthraquinone derivative found in several herbal medicines, is highly active in suppressing the proliferation of various tumor cells such as breast, hepatocellular, and lung cancer cells under in vitro conditions. The mechanism of emodin-induced apoptosis in esophagus carcinoma cells, EC-109, is not completely understood. In this study, EC-109 cells treated with emodin underwent rapid apoptosis as judged by morphological changes and flow cytometry analysis. The addition of emodin to EC-109 cells led to the inhibition of growth in a time- and dose-dependent manner. Fluorescence measurements of cells indicated that the intracellular pH (pHi) decreased significantly by 0.47-0.78 units. The results obtained from flow cytometry suggested that bursts of reactive oxygen species took place after the application of emodin. The present study indicates that emodin may be a strong anticancer drug against esophagus cancer cells by causing various early events leading to growth inhibition, including the production of reactive oxygen species and decrease of pHi, which may result in cellular apoptosis.

Energetics of Stone-Wales defects in 4 A carbon nanotubes.

Density functional calculations have been performed to study the formation of Stone-Wales defects in 4 A single-wall carbon nanotubes, which were firstly synthesized inside the AFI zeolite template. The minimum energy paths from perfect tubes to defect-containing ones are calculated by the nudged elastic band method. It is found that the C--C bonds "along" the tube axis are more likely to be rotated than those bonds "around" the circumference. There is a marked chirality dependence of the formation barriers, which are found to be lower than that of graphite. Our results may raise a question on the origin of superconductivity observed in these 4 A tubes.

Risk factors for acute hepatitis B and its progression to chronic hepatitis in Shanghai, China.

BACKGROUND AND AIMS: The major risk factors for acute hepatitis B (AHB) in China and the viral factors determining the progression from acute to chronic hepatitis B remain largely unknown. METHODS: Epidemiological studies within a population-based surveillance for AHB in adults were performed in Shanghai, China, including 294 patients, 588 matched controls and 572 family members of the patients. RESULTS: Invasive medical procedures, household contact with hepatitis B virus (HBV) carriers, body care and beauty treatments, and lack of HBV vaccination were independently associated with AHB. Among those risks, pedicure in bath centres emerged. Sixty-eight of 128 patients with AHB were genotyped including 33 with HBV B2 and 35 with HBV C2. Twenty-five (8.50%) of the 294 patients, including 20 with HBV C2 and 5 with HBV B2 (p = 0.013), progressed to chronic infection. Multivariate analysis showed that HBV C2 was independently associated with chronicification of AHB. Patients with HBV B2 were younger and there was a higher proportion of women than those with HBV C2. The prevalence of HBV B2 was higher in the patients than in neighbourhood chronic carriers. The chronic carriers with HBV B2 showed higher viral loads, higher hepatitis B e antigen (HBeAg) seropositivity, and with higher proportion in men than those with HBV C2, implying that sexual contact plays a role in the transmission of HBV B2. Phylogenetic analysis showed that HBV C2 was frequently involved in transmissions within households. CONCLUSIONS: Despite lower viral load and HBeAg status in the chronic carriers, HBV C2 was more prone to causing chronic infection than was HBV B2.

Relationship between smoking and dyslipidemia in western Chinese elderly males.

The relationship between smoking and dyslipidemia was studied in 2,160 elderly Chinese males. Levels of triglycerides (TGs) in current smokers were shown to be significantly higher and levels of high-density lipoprotein cholesterol (HDL-C) lower than for those who had never smoked or had stopped smoking. Interestingly, the level of apoprotein B (apoB) was more frequently abnormal in very heavy smokers compared with light smokers, while low-density lipoprotein cholesterol (LDL-C) levels were more frequently normal in very heavy smokers. When comparing other factors that influence blood lipids, such as alcohol intake, body mass index (BMI), and age, smoking had the greatest influence and was shown to be an independent risk factor for dyslipidemia.

Evaluation of heavy metal inhibition of activated sludge by TTC and INT-electron transport system activity tests.

TTC and INT-electron transport system activity tests were compared for assessing heavy metal inhibition of activated sludge. The median inhibitory concentrations (IC50s) of Cu2+, Zn2+, Cd2+, Hg2+, Ni2+, Pb2+ and Ag+ measured via TTC test were lower than those measured via INT test, which indicates that the INT-electron transport system activity test was less sensitive to heavy metal toxicity than the TTC test. Tested heavy metals brought about similar decrease in TTC-electron transport system activity and COD removal rate, but less decrease in INT-electron transport system activity than COD removal rate, which suggests that the TTC-electron transport system activity is a better parameter for reflecting heavy metal inhibition of activated sludge than INT-electron transport system activity. The ranking of tested heavy metals in order of decreasing toxicity based on TTC test was Hg2+, Cd2+, Cu2+, Ag+, Zn2+, Ni2+ and Pb2+, and the ranking based on INT test was Hg2+, Ag+, Cu2+, Cd2+, Zn2+, Ni2+ and Pb2+.

[Bcl-2 and bax expression in rat cerebral ischemic preconditioning].

OBJECTIVE: To study the expression of apoptosis regulated genes bcl-2 and bax nocoprotein expression and its significance in rat cerebral ischemic preconditioning. METHODS: With immunohistochemical assay, bcl-2 and bax expression were studied in rat brains which were divided into four groups: the sham-operation control group, the cerebral ischemic group and the cerebral ischemic preconditioning group. RESULTS: Bcl-2 oncoprotein was induced in cerebral ischemic preconditioning control group. Bax oncoprotein expression had no obviously difference in four groups. CONCLUSIONS: The expression of bcl-2 and bax oncoprotein after sublethal ischemic preconditioning might be associated with the preconditioning protection against neuronal damage following subsequent lethal ischemia.

Molecular modeling on solvent effect and interaction mechanism of fentanyl analogs to mu-opioid receptor.

AIM: To do theoretical study about solvation effect and interaction mechanism of fentanyl analogs (FA) to mu opioid receptor (microOR). METHODS: Flexible docking (FlexiDock) was performed by using the possible active conformations of FA and optimized 3D structure of mu opioid receptor. Binding energies were calculated. Comparative molecular force field analysis (CoMFA) and quantitative structure activity relationship (QSAR) studies were carried out based on results of flexible docking. Solvation effects were considered by studying interaction of FA with water molecules. Partial least square (PLS) analysis was used to calculate regression equation for analgesic activities using binding energies as descriptive factor. RESULTS: 1) Binding conformations of these analogs derived by flexible docking were reasonable. 2) It was most possible for the FA to exist in water solution in the form of binding conformations. 3) Energetic calculation and QSAR analysis showed a good correlation between the calculated binding energies of FA and their analgesic activities. 4) Based on the 3D-model, the possible interaction mechanism of FA with mu opioid receptor can be illustrated reasonably. CONCLUSION: The nature of the correlation between the binding affinities and analgesic activities of FA was explained by our modeling result.