Serum nutritional predictive biomarkers and risk assessment for anastomotic leakage after laparoscopic surgery in rectal cancer patients

BACKGROUND Anastomotic leakage(AL)is one of the severest complications after laparoscopic surgery for middle/low rectal cancer,significantly impacting patient outcomes.Identifying reliable predictive factors for AL remains a clinical challenge.Serum nutritional biomarkers have been implicated in surgical outcomes but are un-derexplored as predictive tools for AL in this setting.Our study hypothesizes that preoperative serum levels of prealbumin(PA),albumin(ALB),and transferrin(TRF),along with surgical factors,can accurately predict AL risk.AIM To determine the predictive value of preoperative serum nutritional biomarkers for rectal cancer AL following laparoscopic surgery.METHODS In the retrospective cohort study carried out at a tertiary cancer center,we examined 560 individuals who underwent laparoscopic procedures for rectal cancer from 2018 to 2022.Preoperative serum levels of PA,ALB,and TRF were measured.We employed multivariate logistic regression to determine the independent risk factors for AL,and a predictive model was constructed and evaluated using receiver operating characteristic curve analysis.RESULTS AL occurred in 11.96%of cases,affecting 67 out of 560 patients.Multivariate analysis identified PA,ALB,and TRF as the independent risk factor,each with an odds ratio of 2.621[95%confidence interval(CI):1.582-3.812,P=0.012],3.982(95%CI:1.927-4.887,P=0.024),and 2.109(95%CI:1.162-2.981,P=0.031),respectively.Tumor location(<7 cm from anal verge)and intraoperative bleeding≥300 mL also increased AL risk.The predictive model demonstrated an excellent accuracy,achieving an area under the receiver operating characteristic curve of 0.942,a sensitivity of 0.844,and a specificity of 0.922,demonstrating an excellent ability to discriminate.CONCLUSION Preoperative serum nutritional biomarkers,combined with surgical factors,reliably predict anastomotic leakage risk after rectal cancer surgery,highlighting their importance in preoperative assessment.

17beta-estradiol stimulates proliferation of spermatogonia in experimental cryptorchid mice

Aim： To investigate whether estrogen stimulates the proliferation of spermatogonia or induces spermatogenesis in cryptorchid mice. Methods： Mice were surgically rendered cryptorchid, then treated with different doses of 17β- estradiol （E2） s.c. once a day. Mice were killed at sexual maturity （45 days of age）, and histological analysis and inununofluorescence were performed. Serum follicle stimulating hormone （FSH）, estradiol, testosterone and luteinizing hormone （LH） were measured. Results： Low doses of E2 had no notable effect on spermatogonia, but at higher doses, E2 stimulated the proliferation of spermatogonia. Conclusion： E2 has a dose-related mitogenic effect on spermatogonia.

Early Warning Factors of Death in COVID-19 Patients

The infectious coronavirus disease 2019(COVID-19)has spread all over the world and been persistently evolving so far.The number of deaths in the whole world has been rising rapidly.However,the early warning factors for mortality have not been well ascertained.In this retrospective,single-centre cohort study,we included some adult inpatients(≥18 years old)with laboratory-confirmed COVID-19 from Renmin Hospital of Wuhan University who had been discharged or had died by Apr.8,2020.Demographic,clinical and laboratory data at admission were extracted from electronic medical records and compared between survivors and non-survivors.We used univariable analysis,Cox proportional hazard model analysis and receiver operating characteristic(ROC)curve to explore the early warning factors associated with in-hospital death.A total of 159 patients were included in this study,of whom 86 were discharged and 73 died in hospital.Hypertension(52.1%vs.29.1%,P=0.003)and coronary heart disease(28.8%vs.12.8%,P=0.012)were more frequent among non-survived patients than among survived patients.The proportions of patients with dyspnoea(67.1%vs.25.6%,P<0.001),chest distress(58.9%vs.26.7%,P<0.001)and fatigue(64.4%vs.25.6%,P<0.001)were significantly higher in the non-survived group than in the survived group.Regression analysis with the Cox proportional hazards mode revealed that increasing odds of in-hospital death were associated with higher IL-6(odds ratio 10.87,95%CI 1.41–83.59;P=0.022),lactate(3.59,1.71–7.54;P=0.001),older age(1.86,1.03–3.38;P=0.041)and lower lymphopenia(5.44,2.71–10.93;P<0.001)at admission.The areas under the ROC curve(AUCs)of IL-6,lymphocyte,age and lactate were 0.933,0.928,0.786 and 0.753 respectively.The AUC of IL-6 was significantly higher than that of age(z=3.332,P=0.0009)and lactate(z=4.441,P<0.0001)for outcome prediction.There was no significant difference between the AUCs of IL-6 and lymphocyte for outcome prediction(z=0.372,P=0.7101).It was concluded that the potential risk factors of higher IL-6,lactate,older age and lower lymphopenia at admission could help clinicians to identify patients with poor prognosis at an early stage.

Computational model investigating the effect of magnetic field on neural–astrocyte microcircuit

Extremely low-frequency magnetic field is widely used as a noninvasive stimulation method in clinical practice and basic research. Electrical field induced from magnetic pulse can decrease or increase neuronal electrical activity. However, the cellular mechanism underlying the effects of magnetic field is not clear from experimental data. Recent studies have demonstrated that "non-neuronal" cells, especially astrocytes, may be the potential effector for transcranial magnetic stimulation(TMS). In the present study, we implemented a neural–astrocyte microcircuit computational model based on hippocampal architecture to investigate the biological effects of different magnetic field frequencies on cells. The purpose of the present study is to elucidate the main influencing factors of MS to allow a better understanding of its mechanisms.Our model reproduced the basic characteristics of the neuron and astrocyte response to different magnetic stimulation. The results predict that interneurons with lower firing thresholds were more active in magnetic fields by contrast to pyramidal neurons. And the synaptic coupling strength between the connected neurons may be one of the critical factor to affect the effect of magnetic field on cells. In addition, the simulations show that astrocytes can decrease or increase slow inward currents(SICs) to finely tune neuronal excitation, which suggests their key role in excitatory–inhibitory balance. The interaction between neurons and astrocytes may represent a novel target for effective therapeutic strategies involving magnetic stimulation.

Efficient GSH delivery using PAMAM-GSH into MPP-induced PC12 cellular model for Parkinson’s disease

Glutathione(GSH)depletion has been an important contributor to the dysfunction of dopamine neurons.Polyamidoamine-GSH(PAMAM-GSH)was synthesized and the delivery effect of GSH into PC12 cells was tested.MTT assessment for cytotoxicity and reactive oxygen species(ROS)as well as nitrite oxide(NO)and intracelluar superoxide dismutase(SOD)detection for antioxidative ability were performed.Furthermore,the antiapoptotic ability was analysed by assessing caspase-3,JNK1/2 and Erk1/2 expression.Our data indicated that PAMAM-GSH is an effective agent to replenish GSH into PC12 cells.PAMAM-GSH developed its antioxidative and protective ability for 1-methyl-4-phenylpyridinium(MPP)-induced PC12 cells by reducing the intracellular levels of ROS and SOD activity as well as decreasing the release of NO.Meanwhile,PAMAM-GSH could inhibit caspase-3 activation and might show its antiapoptotic ability to MPP-induced PC12 cells through JNK2/Erk1/2 pathway.In summary,these studies suggest that PAMAM-GSH conjugate has an intrinsic ability to penetrate PC12 cells and deliver GSH into these cells which may provide a new strategy for clinical applications in the treatment of Parkinson’s disease.