[Construction of a risk prediction model for diabetes after kidney transplantation based on genome-wide association study].

Objective: To explore the clinical risk factors and susceptibility genes of diabetes after kidney transplantation (PTDM) and construct a risk prediction model for PTDM. Methods: The data of kidney transplant recipients who underwent follow-up in the Affiliated Lihuili Hospital, Ningbo University and Sir Run Run Shaw Hospital, Zhejiang University School of Medicine from January 2001 to December 2022 were retrospectively analyzed. The recipients were divided into PTDM group and Non-PTDM group according to whether they were complicated with PTDM. The differences in clinical indicators between the two groups were compared, the risk factors affecting the incidence of PTDM were determined, and susceptibility genes of PTDM were screened by genome-wide association study (GWAS). PTDM risk prediction models based only on clinical indicators (Model 1) and clinical indicators combined with susceptibility genes (Model 2) were established respectively, and the predictive performance of the two prediction models was compared. Finally, the Nomogram of the optimal model was drawn, and the discrimination, calibration and clinical applicability of the model were evaluated. Results: A total of 113 kidney transplant recipients (70 males and 43 females) were included, with an average age of (46.2±10.8) years. There were 51 cases in PTDM group and 62 cases in Non-PTDM group. The related factors screened by GWAS and logistic regression analysis included family history of diabetes (OR=88.912, 95%CI: 5.827-1 356.601, P=0.001), preoperative triglyceride (TG) (OR=1.888, 95 %CI: 1.150-3.098, P=0.012), uric acid (UA) (OR=1.011, 95%CI: 1.000-1.022, P=0.045) and rs802707 (OR=10.046, 95%CI: 1.462-69.042, P=0.019). The area under the curve (AUC) of the receiver operating characteristics analysis (ROC) predicted by Model 1 for PTDM was 0.891 (95%CI: 0.811-0.972), with the sensitivity of 0.889 and the specificity of 0.742. The AUC of ROC curve predicted by Model 2 for PTDM was 0.930 (95%CI: 0.864-0.995), with the sensitivity of 0.885 and the specificity of 0.900. Conclusions: Family history of diabetes, preoperative TG and UA, and rs802707 are significantly associated with the occurrence of PTDM. In addition, the combination of susceptibility genes could improve the predictive ability of clinical indicators for the risk of PTDM.

[Clinical characteristics and prognostic factors of patients with anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis associated interstitial lung disease].

Objective: To analyze the clinical characteristics and prognostic factors of patients with anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis associated interstitial lung disease (DM-ILD). Methods: The patients with MDA5+DM-ILD who were admitted to Department of Respiratory Medicine, Nanjing Drum Tower Hospital from January 2017 to March 2021 were enrolled. The clinical data and survival information were analyzed retrospectively. Patients were divided into survival group or death group, and rapid progressive ILD (RP-ILD) group or non-rapid progressive ILD group, according to their survival status and clinical progression. Results: A total of 105 patients with anti-MDA5+DM-ILD (median age of onset 54 years) were enrolled, 58% being female (61 cases). The main sub-type of dermatomyositis was amyopathic dermatomyositis (n=74, 70%), followed by dermatomyositis (n=31, 30%). The main extrapulmonary manifestations were skin lesions (n=60, 57.1%), muscle manifestations(n=20, 19%) and arthralgia/arthritis (n=20, 19%). 15.4% of the patients had positive ANA (antibody titer≥1∶320), and 61.9% of the patients had anti-RO-52 kDa antibody. A total of 66 patients (62.8%) developed RP-ILD, and 58 patients (56.3%) died. Lower oxygenation index (OR=0.974, 95%CI:0.954-0.994, P=0.012) and no joint pain (OR=0.032, 95%CI: 0.002-0.663 P=0.026) were independent risk factors for RP-ILD. Cox regression analysis showed that RP-ILD (HR=3.194, 95%CI:1.025-9.954, P=0.045), older than 53 years (HR=3.450, 95%CI: 1.388-8.577, P=0.008), ferritin level more than 1 330.5 ng/ml (HR=3.032, 95%CI 1.208-7.610, P=0.018) and C-reactive protein (CRP) above 16.95 mg/L (HR=2.794, 95%CI:1.102-7.084, P=0.030) were independent predictors of mortality. Conclusions: The clinical manifestations of patients with anti-MDA5+DM-ILD presenting to the respiratory department were heterogeneous, with most being amyopathic dermatomyositis, and both the incidence of RP-ILD and the risk of death were high. Even in the absence of associated rash, joint, or muscle manifestations, anti-MDA5 antibody screening should be considered in patients with rapidly progressive ILD who were negative on baseline autoantibody screening but positive for anti-RO52kDa antibody.

Helical micro-swimmer: hierarchical tail design and propulsive motility.

Helical micro-swimmers have markedly extended the reach of human beings in numerous fields, ranging from in vitro tasks in lab-on-a-chip to in vivo applications for minimally invasive medicine. The previous studies on the propulsive motility optimization of the micro-swimmers mainly focused on the distinct actuation principles (e.g., chemically powered, magnetic- or ultrasound energy-driven) and paid little attention to the structural design of these swimming machines themselves. The improvements of the structures can assist the externally powered motors in providing propulsion in a tiny scale and satisfy the agile locomotion demands. This paper presents the design, mechanics modeling and available experiments of a novel type of hierarchical helical swimming robot that significantly enhances the motility of the helix-based swimmers. Validated by the resistive force theory, our numerical model can well analyze the mechanical properties with a variety of geometric parameters. The motion performance of the hierarchical and conventional helical structures in low Reynolds regimes is presented, highlighting the advantages of hierarchical swimmers over the existing typical swimmers. In addition, the stability and resilience of the hierarchical swimmers can be maintained at a decent level. Moreover, the variable forward velocity resulting from the combined hierarchical structures is investigated here, which can thereby serve as a reliable design strategy. The proposed hierarchical helical design enables enticing opportunities for various device systems of medical robots and bio-integrated electronics.

[Study on the influence of sleeve height and implant length on accuracy of static computer-assisted implant surgery].

Objective: To evaluate the influence of the sleeve lengths and implant lengths on accuracy of static computer-assisted implant surgery (sCAIS). Methods: Twenty-eight models of bilateral mandibular single tooth loss were included. Fifty-five implants were placed under the guidance of sCAIS (Straumann Bone Level 4.1 mm×10 mm). According to the height of metal sleeve of static guide plate, 55 implants were divided into 11 groups (free hand group, 1 mm group, 2 mm group, 3 mm group, 4 mm group, 5 mm group, 6 mm group, 7 mm group, 8 mm group, 9 mm group, 10 mm group), with 5 implants in each group. Eight research models were included. Group with 5 mm sleeve guides were used to place implants of different length, (Straumann Bone Level width 4.1 mm, height was 8 mm, 10 mm and 14 mm), 5 implants in each group. Eighteen patients with mandibular single tooth loss were included in the Department of Oral Implantology, Tianjin Stomatological Hospital from October 2018 to June 2019. There were 10 males and 8 females, 18-46(33.7±7.9) years old. A total of 18 implants were implanted and divided into 3 groups (free hand group, 3 mm group and 5 mm group) with 6 implants in each group. Digital software was used to compare the implant positions before and after implantation. Non-parametric Kruskal-Wallis test or one-way ANOVA were used to analyze the results. Results: There was no significant difference in implant vertical deviation between different sleeve height groups (1-10 mm) and free hand group, but the neck deviation in free hand group[(1.04±0.13) mm] was significantly higher than that in different sleeve height groups (1-10 mm) (P<0.05). The tip deviations of free hand group, 1 mm group and 2 mm group [(1.32±0.43), (0.83±0.10) and (0.78±0.11) mm, respectively] was significantly higher than that of 10 mm group [(0.31±0.14) mm](P<0.05). The angle deviation of free hand group and 1 mm group (3.99°±0.85° and 2.59°±0.69°), respectively] was significantly higher than that of 10 mm group (0.61°±0.03°) (P<0.05). The tip deviations of implants in the 14 mm group [(0.83±0.22) mm] was significantly higher than that in the 8 mm and 10 mm groups [(0.44±0.07) and (0.49±0.06) mm, respectively]. Clinical studies showed that there was no significant difference in neck deviation, tip deviation and angle deviation between 3 mm group and 5 mm group (P>0.05), but deviations were significantly lower than those in free hand group (P<0.05). Conclusions: The length of the sleeves has significant influence on the accuracy of the surgical guide. There was no significant difference in accuracy of the implant guide with 3 mm or 5 mm metal sleeves. The vitro study has some limitations and needs further systematic research.

The alteration of PTEN tumor suppressor expression and its association with the histopathological features of human primary hepatocellular carcinoma.

PURPOSE: Although deletions or inactivating mutations of the tumor suppressor gene PTEN (phosphatase and tensin homolog deleted on chromosome 10) are involved in the development of a variety of tumors including glioblastoma, melanoma, prostate cancer, breast cancer, endometrial cancers etc., the role of PTEN expression in human primary hepatocellular carcinoma (HCC) has not yet been clarified. The aim of this study is to investigate the involvement of PTEN mRNA and protein expression in HCC. METHODS: The level of PTEN mRNA expression in HCC specimens was analyzed by Northern blot. PTEN poly-clonal antibody was raised by immunizing New Zealand white rabbit with (His)(6)-tagged PTEN fusion protein and characterized by Western blot. The level of PTEN protein expression was determined by immunohistochemistry. The significance of PTEN in HCC was analyzed by comparing its expression level with the clinicopathological parameters of HCC patients. RESULTS: Four transcripts of PTEN mRNA at 5.5 kb, 4.4 kb, 2.4 kb, and 1.8 kb were detected in most para-carcinoma liver tissues, and the expression level of PTEN mRNA in carcinoma liver tissues was found to decrease significantly. The poly-clonal antibody raised against histidine-tagged fusion PTEN protein showed specific immuno-reactivity to PTEN protein. Using the specific poly-clonal antibody prepared and characterized by ourselves, we found that PTEN protein was significantly down-regulated in HCC tissues compared with paired para-carcinoma tissues. The protein expression of PTEN is negatively associated with the pathological grading and presence of cancer thrombus of HCC. CONCLUSIONS: Down-regulation of PTEN expression may play an important role in the development of HCC and the level of PTEN expression may be a potential adjuvant parameter in forecasting the progression and prognosis of HCC patients.

[Changes of plasma motilin concentration in pregnancy and early postpartum period].

Plasma motilin concentration were determined by radioimmunoaction from 180 women during pregnancy and early postpartum period as compared with 20 healthy non-pregnant women. The results showed that mean plasma motilin concentration (384.40 +/- 110.30 ng/L) was higher in the first trimester of pregnancy than that of healthy non-pregnant women (366.12 +/- 96.23 ng/L), however, this difference did not reach statistical significance (P > 0.05). The mean plasma motilin concentration (323.90 +/- 125.10 ng/L) was lower in the second trimester of pregnancy than in the first trimester of pregnancy (P < 0.05), while the mean plasma motilin concentration in the third trimester of pregnancy (121.04 +/- 27.00 ng/L) was significantly lower than in second (P < 0.01) and the mean plasma motilin concentration in 3-5 d after delivery (443.05 +/- 140.79 ng/L) reached an even higher value (P < 0.01). Our results suggests that pregnancy appears to have a profound inhibitory effect on plasma motilin and this may in part be responsible for the gastrointestinal hypomotility during pregnancy.

[Color pulsed Doppler ultrasound measurement of fetal umbilical and uterine arteries blood flow for early predict of intrauterine growth retardation].

The fetal umbilical and uterine arteries blood flow in 180 pregnant women (normal group and suspected IUGR group are separately 90 pregnancy) were measured by color pulsed Doppler ultrasound in this report. The predicting value for IUGR of Doppler ultrasound was comprised with that of the diagram of pregnancy and real-time ultrasound. There were 39 cases of IUGR, three cases of perinatal death and 138 normal infants in total 180 pregnancy. The sensitivity, specificity and positive predicting value of fetal umbilical flow for predicting IUGR were separately 78.57%, 93.75% and 91.67%. The results suggest that Doppler ultrasound blood flow measurement can predict IUGR much earlier than the diagram of pregnancy and real-time ultrasound. Combining to use Doppler ultrasound with real-time ultrasound measurement have highest sensitivity and accuracy.

[Relation between motilin concentration and progesterone level in normal pregnancy and early postpartum].

Plasma motilin and serum progesterone concentrations were measured in 180 women with gestational age between 5-40 weeks and 3-5 days after delivery. In addition, motilin and progesterone concentrations were also measured in blood collected from 20 healthy nonpregnant women at midcycle. There was no significant difference of plasma motilin levels between nonpregnant women (366.12 +/- 96.23 ng/L) and women in the 1st trimester of pregnancy (384.40 +/- 110.30 ng/L). The motilin concentration was significantly lower in the 2nd trimester (323.96 +/- 125.10 ng/L) compared with that in the 1st trimester, P < 0.05. then it reached to the lowest level in the 3rd trimester (121.04 +/- 27.88 ng/L) with P < 0.01. At 3-5 days after delivery, motilin concentration (443.05 +/- 147.70 ng/L) was significantly higher than that in the 3rd trimester. The mean level of serum progesterone was 11.00 +/- 2.70 nmol/L in midcycle, whereas 84.42 +/- 40.00, 175.73 +/- 85.69 and 1438.35 +/- 331.88 nmol/L in the 1st, 2nd and 3rd trimester of pregnancy respectively. However, progesterone level decreased rapidly after delivery and reached to a significantly lower level (13.54 +/- 9.88 nmol/L). The results demonstrated that progesterone levels were increased along with gestational age whereas motilin levels were decreased. A negative correlation was found between them (r = -0.42, P < -0.01). It suggested that progesterone appeared to have a profound inhibitory effect on motilin. The decreased motilin level might partially be responsible for gastrointestinal hypomotility during pregnancy.

[Plasma endothelin level in patients with pregnancy induced hypertension and its correlation with atrial natriuretic peptide].

Plasma levels of endothelin (ET) and atrial natriuretic peptide (ANP) were measured in 32 normal pregnant women and 26 patients with pregnancy induced hypertension (PIH). The correlation between ET and ANP were examined. This study indicated that the levels of ET and ANP in hypertensive pregnancy were higher than those of the normal pregnancy (P < 0.01). There was no correlation between ET and ANP in normal pregnancy (r = 0.18, P > 0.05), but significant inverse correlation in the patient with PIH (r = -0.57, P < 0.05). There findings suggested that ET may play an important role in the pathogenesis of PIH. An imbalance of increased amount of ET relative to deficient ANP may lead to PIH.

[Motilin and gastrin in human milk].

The concentrations of motilin and gastrin were determined in the blood and milk of 45 women 3-5 days postpartum, and in the blood of 20 healthy non-pregnant women as control. Plasma motilin concentration (443.05 +/- 140.79 ng/L) and serum gastrin level (301.32 +/- 100.98 ng/L) were significantly higher in postpartum women than those in the control (366.12 +/- 96.23 ng/L and 76.13 +/- 13.11 ng/L, respectively) (P < 0.01). The concentrations of both motilin and gastrin in the milk were approximately one half of those in the blood and they were not present in the boiled milk. The results indicated that both hormones in the human milk may be important for development and maturation of gastro-intestinal function in neonates, especially for immature babies.

Observation of organochlorine pesticides in the air of the Mt. Everest region.

High mountains have been suggested to play an important role in the global transport of persistent organic pollutants, yet observation of these pollutants in high mountains is very limited. In the summer of 2002, air samples were collected at Dingri at a height of 4400 m above sea level (m a.s.l.) and at Rongbuk Valley (4976 m a.s.l.) in the Mt. Everest region and analyzed using large volume injection gas chromatography tandem mass spectrometry. The mean concentrations of organochlorine pesticides (OCPs) in the samples were 19.2, 11.2, 7.7, 8.9, 10.4, 27.6, 5.1, 5.1, and 3.7 pg m(-3) for alpha-HCH, beta-HCH, gamma-HCH, HCB, heptachlor, alpha-endosulfan, p,p'-DDE, o,p'-DDT, and p,p'-DDT, respectively. Backward trajectories were used to assess the association between source regions, transport paths, and observed OCP concentrations. During the sampling period, the o,p'-DDT/p,p'-DDT concentration ratios were observed to be between 1.23 and 1.41, much higher than that of technical DDT, indicating the existence of a DDT source other than technical DDTs in the source regions.

Isolation and characterization of a bacterial strain of the genus Ochrobactrum with methyl parathion mineralizing activity.

AIMS: To isolate and characterize a methyl parathion (MP)-mineralizing bacterium, and to elucidate the degradative pathway of MP and localize the responsible degrading genes. METHODS AND RESULTS: A bacterial strain, designated B2, capable of mineralizing MP was isolated from the MP-polluted soil. Analysis of the 16S rRNA gene sequence and phenotypic analysis suggested that strain B2 had a close relationship with Ochrobactrum anthropi. B2 could totally degrade MP and four metabolites [p-nitrophenol (PNP), 4-nitrocatechol (4-NC), 1,2,4-benzenetriol (BT) and hydroquinone (HQ)] were identified by HPLC and gas chromatography-mass spectrometry analyses. Plasmid curing of strain B2 resulted in the loss of ability of B2 to degrade PNP, but not the ability to hydrolyse MP. CONCLUSIONS: Ochrobactrum sp. B2 can mineralize MP rapidly via PNP, 4-NC, BT and HQ pathway. B2 harbours a plasmid encoding the ability to degrade PNP, while MP-hydrolysing activity is encoded on the bacterial chromosome. SIGNIFICANCE AND IMPACT OF THE STUDY: This new bacterial strain (B2) capable of mineralizing MP will be useful in a pure-culture remediation process of organophosphate pesticides and their metabolites such as nitroaromatics.

Charging and interaction of individual impurities in a monolayer organic crystal.

We use a scanning tunneling microscope to study the charging of Ag-doping centers in a monolayer of C(60) molecules supported on a thin Al(2)O(3) film grown on the NiAl(110) surface. Differential conductance spectroscopy shows that charging affects the conduction through C(60) molecules located around the doping centers. This effect is used to observe the electrostatic interaction of a pair of centers. Charging of one doping center affects the energy levels of the other, an analogue of the field-effect action.

Vibrational spectroscopy of individual doping centers in a monolayer organic crystal.

A scanning tunneling microscope (STM) is used to study individual Ag doping centers in a monolayer of C60 molecules supported on a thin Al2O3 film grown on the NiAl(110) surface. Vibronic states of the doping centers are observed with differential conductance (dIdV) spectroscopy. The double-barrier nature of the junction results in bipolar transport: same states participate in charge transport at both bias voltage polarities. Identification of the dIdV features corresponding to bipolar conduction enables a new mode of vibrational spectroscopy with STM.

Mechanisms of reversible conformational transitions in a single molecule.

The reversible interconversion between two nonplanar conformations of single Zn(II) Etioporphyrin I molecules adsorbed on a NiAl(110) surface at 13 K was induced by a scanning tunneling microscope (STM). The threshold voltage for the conformational change at negative sample bias depends linearly on the tip-sample distance, suggesting an electrostatic force mechanism. The reverse conversion involves inelastic electron tunneling via a molecular electronic resonance at 1.25 eV. In contrast with the photon-induced conformational changes, an electrically induced mechanism is realized with the STM.

Vibrationally resolved fluorescence excited with submolecular precision.

Tunneling electrons from a scanning tunneling microscope (STM) were used to excite photon emission from individual porphyrin molecules adsorbed on an ultrathin alumina film grown on a NiAl(110) surface. Vibrational features were observed in the light-emission spectra that depended sensitively on the different molecular conformations and corresponding electronic states obtained by scanning tunneling spectroscopy. The high spatial resolution of the STM enabled the demonstration of variations in light-emission spectra from different parts of the molecule. These experiments realize the feasibility of fluorescence spectroscopy with the STM and enable the integration of optical spectroscopy with a nanoprobe for the investigation of single molecules.

Visualization and spectroscopy of a metal-molecule-metal bridge.

Artificial nanostructures, each composed of a copper(II) phthalocyanine (CuPc) molecule bonded to two gold atomic chains with a controlled gap, were assembled on a NiAl(110) surface by manipulation of individual gold atoms and CuPc molecules with a scanning tunneling microscope. The electronic densities of states of these hybrid structures were measured by spatially resolved electronic spectroscopy and systematically tuned by varying the number of gold atoms in the chains one by one. The present approach provides structural images and electronic characterization of the metal-molecule-metal junction, thereby elucidating the nature of the contacts between the molecule and metal in this junction.

Vibronic states in single molecule electron transport.

A scanning tunneling microscope was used to study the electron transport through individual copper phthalocyanine molecules adsorbed on an ultrathin Al(2)O(3) film grown on a NiAl(110) surface. The differential conductance spectra display series of equally spaced features, which are attributed to vibronic states of individual molecules. The coupling of the electron current to the vibronic modes was observed to depend on the structures of the adsorbed molecules. Vibronic features were not observed for molecules adsorbed on the bare NiAl(110) surface due to spectral broadening.

Atomic engineering of photon emission with a scanning tunneling microscope.

We present measurements of photon emission from individual several-atom silver chains on the NiAl(110) surface, excited by tunneling electrons in a scanning tunneling microscope (STM). The chains were assembled by manipulating single silver atoms on the NiAl(110) surface with the STM. The photon energy of this emission can be tuned by appending a single atom to the chain. These changes in photon emission result from changes in the electronic structure of the silver chain, each electronic state inside the chain being associated with a distinct channel of emission.