Clinical study of internal jugular vein dilatation index in predicting septic shock volume responsiveness / 中华急诊医学杂志

Objective:To explore the value of severe ultrasound measurement of internal jugular vein dilation index (ΔIJV) combined with passive leg raising (PLR) in predicting the volume responsiveness of septic shock.Methods:Patients diagnosed with septic shock under complete mechanical ventilation in the ICU of Jinshan Hospital Affiliated to Fudan University from January 2020 to March 2021 were prospectively selected as the research objects. After 500 mL crystals were injected within 30 min, the patients having the "gold standard" left stroke volume (SV) increased by 15% were allocated to the volume response positive group, and patient having an SV increased by less than 15% to the volume response negative group. First, the maximum anterior posterior diameter (IJV max) and the minimum anterior posterior diameter (IJV min) in the respiratory cycle of internal jugular vein were measured by ultrasound, then SV before and after PLR was measured, and finally SV, IJV max and IJV min were measured again after rapid infusion of 500 mL crystals, and ΔIJV=(IJV max-IJV min)/(IJV mean)×100%. The Wilcoxon rank-sum test was used to compare the hemodynamic indexes before and after capacity expansion and PLR. Spearman rank method was used to analyze the change rate of SV (ΔSV) after PLR and the correlation between ΔIJV and ΔSV of the "gold standard". The sensitivity, specificity and relevant cut-off values were obtained by drawing the subject function curve to evaluate the value of ΔIJV and PLR in predicting the volume responsiveness of patients with sepsis. Results:A total of 56 patients were enrolled in the study, and they were divided into two groups: 32 patients in the volume response positive group and 24 patients in the volume response negative group. There was a positive correlation between ΔIJV and ΔSV after capacity expansion ( r=0.778, P<0.01). Taking ΔIJV>17.3% as the threshold, the area under the curve (AUC) was 0.846 (95% CI: 0.716~0.977), the sensitivity was 84.4% and the specificity was 83.3%. PLR was also positively correlated with ΔSV ( r=0.698, P<0.01). Taking ΔSV>15.5% after PLR as the threshold, the AUC was 0.895 (95% CI: 0.796~0.993), the sensitivity was 96.9%, and the specificity was 79.2%. When ΔIJV combined with PLR predicted volume reactivity, the AUC was 0.944 (95% CI: 0.862~1.000), the sensitivity was 99.8% and the specificity was 87.5%. Conclusions:The measurement of internal jugular vein respiratory dilation index by bedside ultrasound is a reliable index to predict volume responsiveness in patients with sepsis. When combined with PLR, the sensitivity and specificity of prediction can be improved.

Bilateral basal ganglia hemorrhage due to tentorial dural arteriovenous fistula: a case report and systematic literature review / 中华神经科杂志

Objective:To investigate the clinical characteristics of cerebral hemorrhage caused by tentorial dural arteriovenous fistula (TDAVF).Methods:An unusual TDAVF case admitted to the Department of Neurology, Qilu Hospital, Shandong University in March 2020, complicated with hypertension with successive bilateral basal ganglia hemorrhage in short term was reported. The characteristics of cerebral hemorrhage caused by TDAVF reported in the literature were summarized and analyzed.Results:Digital subtraction angiography (DSA) revealed that there was arteriovenous fistula in the tentorial foramen area of this patient (male, 33 years old), and the TDAVF was fed by the right meningohypophyseal trunk, bilateral middle meningeal artery and posterior cerebral artery. A shunted pouch was present in the tentorial foramen area, and retrograde reflux drainage was seen in the deep venous system, from the meningeal vein to superior sagittal sinus or sigmoid sinus. Transarterial embolization was performed and subsequently DSA showed obliteration of the fistula. This patient experienced no clinical decline or rehemorrhage during the 12 months follow-up period. Forty-one cases of TDAVF with hemorrhage of cerebral parenchyma which were reported before March 30, 2021 with detailed clinical and imaging data were summarized. The average age of onset of this group of patients was 57.2 years, and the ratio of male to female was about 3∶1. The hemorrhage was located in superior of the tentorium in 17 cases (41%), while in inferior of the tentorium in 24 cases (59%). Supratentorial intracerebral hemorrhage mainly occurred in occipital lobe and thalamus. DSA showed that the arteriovenous fistula was classified as Borden type Ⅲ or Cognard type Ⅳ in 36 cases (88%). Twenty-nine patients (71%) underwent a single surgical procedure, while 12 cases (29%) underwent combined surgical or other treatments. Overall, 37 patients (90%) achieved angiographically documented obliteration of the fistula and 39 patients (95%) experienced good or excellent outcomes.Conclusions:TDAVF often presents as cerebral parenchymal hemorrhage which is common in supratentorial region, but rare in basal ganglia region. The cause of cerebral hemorrhage in patients with hypertension may not be attributed to hypertension. Early diagnosis and intervention are of great significance to improve the prognosis of patients.

Mechanism of Xianlian Jiedu Prescription in Maintaining Cancer Relative Vascular Endothelial Cell Homeostasis and Inhibiting Tumor Neovascularization / 中国实验方剂学杂志

ObjectiveTo observe the effect of Xianlian Jiedu prescription （XLJDP） on the proliferation， apoptosis， and migration of cancer-relative endothelial （CRE） cells， and to decipher the mechanism of XLJDP in regulating angiopoietin2 （Ang2） to maintain CRE cell homeostasis and inhibit tumor neovascularization. MethodHuman umbilical vein endothelial cell line （HUVEC-c） was induced into CRE cells in the human colorectal cancer HCT-116 cell-conditioned medium. The CRE cells were assigned into the blank group， conditioned medium group， and XLJDP groups （1， 2， 3 g·L-1） and treated for 48 h. The proliferation of CRE cells was detected by methyl thiazolyl tetrazolium （MTT） colorimetry. The morphological changes of CRE cells were observed via an inverted microscope. The apoptosis rate was detected by flow cytometry. Wound healing test and Transwell migration assay were employed to detect the 2D/3D migration ability of CRE cells. The protein levels of vimentin， N-cadherin， matrix metalloproteinase-9 （MMP-9）， and Ang2 in CRE cells were measured by Western blot. ResultThe MTT results showed that the cell viability was higher in the conditioned medium group than in the blank group （P<0.05）. Compared with the conditioned medium group， XLJDP decreased the cell proliferation rate （P<0.01） and changed the cell morphology. The total apoptosis rates of all the XLJDP groups were higher than that of the conditioned medium group （P<0.01）. The 2D and 3D migration abilities of the conditioned medium group were higher than those of the blank group （P<0.05， P<0.01）. Compared with the conditioned medium group， XLJDP at all the concentrations weakened the 2D migration ability （P<0.01） and medium- and high-concentration XLJDP weakened the 3D migration ability （P<0.01）. The protein levels of N-cadherin， Vimentin， MMP-9， and Ang2 were up-regulated in the conditioned medium group compared with those in the blank group （P<0.05， P<0.01）. Compared with the conditioned medium group， XLJDP at all the concentrations down-regulated the protein level of Ang2 （P<0.05， P<0.01）， and medium- and high-concentration XLJDP down-regulated those of N-cadherin， vimentin， and MMP-9 protein （P<0.01）. ConclusionXLJDP may inhibit the proliferation， migration， differentiation， and apoptosis of CRE cells by down-regulating the expression of Ang2， inhibiting tumor neovascularization， and maintaining the cell homeostasis.

Effect of Xianlian Jiedu Prescription on Proliferation and Glycolysis of Human Colorectal Cancer HCT-116 Cells and Mechanism / 中国实验方剂学杂志

ObjectiveTo explore the effect of Xianlian Jiedu prescription （XLJDP） on the proliferation and glycolysis of human colorectal cancer HCT-116 cells and the underlying mechanism. MethodHCT-116 cells were cultured with XLJDP and then the survival rate was examined by methyl thiazolyl tetrazolium （MTT） assay. The effect on the HCT116 cell proliferation was detected by colony formation assay and 5-ethynyl-2′-deoxyuridine （EDU） incorporation assay. The amount of glucose consumed by HCT-116 cells was measured by glucose test kit， and the amount of produced lactic acid was determined by lactic acid test kit 48 h after the treatment with XLJDP. The expression of glycolysis-related proteins mammalian target of rapamycin （mTOR）， phosphorylated mTOR （p-mTOR）， glucose transporter 1 （GLUT1）， and lactate dehydrogenase （LDHA） was detected by Western blot. ResultThe half-maximal inhibitory concentration （IC50） of XLJDP against HCT-116 cells was 6.82 g·L-1. Compared with the blank group， XLJDP （1.625， 3.25， 6.50 g·L-1） inhibited the proliferation of HCT-116 cells （P<0.05， P<0.01）. Moreover， compared with the blank group， XLJDP （1.625， 3.25， 6.50 g·L-1） suppressed glucose uptake and lactic acid production in a dose-dependent manner （P<0.05， P<0.01）. The expression of p-mTOR/mTOR， LDHA， and GLUT1 was down-regulated by XLJDP （P<0.05， P<0.01）. ConclusionXLJDP can significantly inhibit the proliferation and the Warburg effect of glycolysis in colorectal cancer cells by regulating the mTOR signaling pathway and the down-regulating the expression of LDHA， GLUT1， and other key proteins and enzymes in glycolysis.

Analysis of the effect of double button plate combined with strengthened anchor in the treatment of acromioclavicular dislocation / 中国骨伤

OBJECTIVE@#To evaluate the efficacy and prognosis of double button plate combined with strengthened anchor technique and clavicular hook plate internal fixation for complete acromioclavicular joint dislocation.@*METHODS@#From July 2017 to September 2020, a total of 42 patients with acromioclavicular joint dislocation treated by surgery were choosen as study objects and divided into observation group (21 cases) and control group (21 cases). In the observation group, there were 14 males and 7 females, aged 21 to 63 years old, with an average of (45.05±8.70) years old. In the control group, there were 16 males and 5 females, aged 25 to 68 years old, with an average of(45.00±9.44) years old. The patients in the observation group were treated with double button plate combined with strengthened anchor technique, whereas those in the control group received clavicular hook plate internal fixation. The two groups were compared in terms of operating time, intraoperative blood loss, postoperative hospital stay, shoulder pain(visual analogue scale, VAS) score, shoulder function Constant-Murley score and postoperative complications.@*RESULTS@#There was no significant difference between the two groups in intraoperative blood loss or postoperative hospital stay(P>0.05). The operating time of double button plate combined with strengthened anchor technique group (65.24±5.36) min was significantly longer than that of the clavicular hook plate group (48.81±4.72) min, and the difference was statistically significant (P<0.05). There was no significant difference in shoulder function or pain degree between the two groups before operation (P>0.05). After 1 month, 3 months and 6 months, the Constant-Murley score of the observation group was 73.29±2.15, 85.43±1.47, 93.86±1.24 separately, which were significantly higher than those of the control group;and the VAS score was 2.76±0.62, 1.71±0.64, 0.57±0.51 separately, which were significantly lower than those of the control group (P<0.05). One instance of shoulder discomfort was found in the observation group, while 5 cases of shoulder pain, 2 cases of restricted shoulder mobility, and 1 case of subacromial bone absorption were found in the control group. In both group, there was no loss of reduction.@*CONCLUSION@#In the treatment of complete acromioclavicular joint dislocation double button plate combined with strengthened anchor technique achieves favorable clinical result. Internal fixation does not need to be removed. The recovery of shoulder joint function and pain relief are superior than clavicular hook plate internal fixation, which is more worthy of clinical promotion.

Progress in mechanism of tumor-derived exosomes on myeloid-derived suppressor cells / 中华微生物学和免疫学杂志

Myeloid-derived suppressor cells (MDSCs) play an important immunosuppressive role in the tumor microenvironment. Tumor cells can regulate the immunosuppressive function of MDSCs in the tumor microenvironment through exosomes, thereby affecting the development of tumors. Tumor-derived exosomes (TEXs) promote the development of MDSCs and improve their immunosuppressive function in the tumor microenvironment mainly by participating in the processes such as intercellular information exchange and information transmission. Moreover, the miRNAs in TEXs will also be transferred to recipient cells to inhibit the immunosuppressive function of MDSCs by inducing the negative regulation of target genes. This review summarized the progress in the mechanism of TEXs on MDSCs.

Application and progress of PET/CT imaging in hepatocellular carcinoma / 中华肝胆外科杂志

Primary liver cancer is a common digestive system malignant tumor. Positron emission tomography and computed tomography (PET/CT) is a new molecular imaging technique which can reflect the metabolic status of tumors and provide more biological information about tumors. Radiomics is used to extract and analyze quantitative features that can describe tumor features in medical images with a high throughput. This article reviews PET/CT radiomics and its application in the diagnosis and prognosis assessment of hepatocellular carcinoma.

Guideline interpretation: the 2021 European Group on Graves′ Orbitopathy Clinical Practice Guidelines for the Medical Management of Graves′ Orbitopathy / 中华内分泌代谢杂志

The 2021 European Group on Graves′ Orbitopathy (EUGOGO) Clinical Practice Guidelines for the Medical Management of Graves′ Orbitopathy was released in July, 2021. Based on the 2016 version, the new guidelines updated the first-line management algorithm for patients with Graves′ orbitopathy in moderate-to-severe and active period, provided multiple second-line treatment pathways and made detailed recommendations from aspects of clinical assessment, general measures, and management of specific conditions, etc. At the same time, efficacy evaluation and management during COVID-19 period were explained in detail. The new guidelines also mentioned some novel treatment strategies of GO which still need further efficacy and safety verification.

Research advances on chimeric antigen receptor cellular therapy for hepatocellular carcinoma / 中华肝胆外科杂志

Hepatocellular carcinoma is one of the most common cancers and causes of cancer-related death in the world, the insidious onset, rapid progression and poor prognosis make the treatment more difficult. At present, the current therapeutic options, include surgical resection, ablation, postoperative recurrenceare still with disadvantages. The efficacy of targeted drug therapy is also unsatisfactory. Immunotherapy is a promising research direction. Immunosuppressants at the molecular level have shown initial success, while adoptive immunocell therapy at the cellular level has also shown promising results, the typical example is chimeric antigen receptor cell therapy. The purpose of this review is to summarize the recent research progress on chimeric antigen receptor cellular therapy in liver cancer.

Molecular mechanism of topoisomerase I inhibitor in protecting against experimental acute pancreatitis in mice / 中华胰腺病杂志

Objective:To investigate the protective mechanism of topoisomerase I inhibitor on pancreatic acinar cells and lung during acute pancreatitis (AP) in mice.Methods:Eighteen Balb/C male mice were randomly divided into three groups using random number method: control group, AP group and CPT+ AP group. AP model was established by intraperitoneal injection of caerulein and lipopolysaccharide. CPT+ AP group received intraperitoneal injection of camptothecin (CPT, 50 mg/kg) before AP induction. Mice in control group were intraperitoneal injected with an equal volume of normal saline. The pathological examinations of pancreas and lung tissue were analyzed. The serum levels of amylase and lipase were detected by enzyme linked immunosorbent assay (ELISA) and the mRNA expression of IL-1 and IL-6 were analyzed by reverse transcription-polymerase chain reaction (RT-PCR); the infiltration of CD 45+ cells in pancreas and lung tissue as well as the expression of phosphorylated mixed lineage kinase domain-like protein(MLKL) in pancreas were detected by immunohistochemistry; the apoptosis index of pancreatic cells was analyzed by TUNEL assay. Results:The pathological scores of pancreas and lung tissue, serum levels of amylase and lipase in CPT+ AP group were [(2.30±0.31), (2.29±0.34), (1742.33±183.51)U/L and (46.90±2.17)U/L], which were significantly lower than those in AP group [(5.06±0.88), (3.40±0.09), (2385.33±383.10)U/L and (69.13±9.76)U/L]; the mRNA expression of IL-1 and IL-6 in pancreatic tissue were 95.79±48.11, 255.50±213.32, which were also remarkably lower than those in AP group (212.35±80.61, 1006.80±509.06); the infiltration of CD 45+ inflammatory cells in pancreas and lung were (14.25±5.32, 29.20±4.44)/high power field, which were notably lower than those in AP group (59.83±13.67, 58.25±5.91)/high power field; the apoptosis index of pancreatic cells was significantly higher than that in AP group [(3.64±1.16)% vs (1.92±0.29)%]; the histochemistry score of phosphorylated MLKL protein in pancreatic tissue was significantly lower than that in AP group (1.75±0.20 vs 4.53±1.28), and the differences were statistically significant (all P value <0.05). Conclusions:Topoisomerase I inhibitor could induce the apoptosis of pancreatic acinar cells and inhibit the death mode of necrotic pancreatic acinar cells during AP remodeling, thus reducing pancreatic local injury and AP-associated lung injury.

Correlation between perfusion index and the severity of disease in early neonates / 中国小儿急救医学

Objective:To analyze the role of perfusion index(PI)in assessing the severity of neonatal illnesses.Methods:A total of 502 newborns admitted to the Department of Neonatology within 24 hours of birth at Xinxiang Central Hospital from October 2018 to July 2019 were recruited.Neonatal critical illness score(NCIS)was graded within 24 hours of admission, and newborns were categorized into non-critical(NCIS>90 scores), critical(NCIS 70-90 scores)and extremely critical(NCIS<70 scores). PI was monitored in all newborns within 24 hours of birth in a resting state.A total of 502 PIs were recorded, including 341 cases of non-critical, 110 cases of critical and 51 cases of extremely critical.Results:The medium PI [ M( P25, P75)] of newborns in non-critical, critical and extremely critical groups were 1.80(1.40, 2.60), 0.96(0.74, 1.43)and 0.65(0.41, 1.10), respectively.PI values in extremely critical group was significantly lower than those in critical group and non-critical group( P<0.05). The medium PI [ M( P25, P75)] of full-term newborns, moderate/late preterm newborns and extremely/very preterm newborns were 1.70(1.20, 2.70), 1.60(1.10, 2.30) and 1.35(0.80, 2.30), respectively.PI in full-term newborns was significantly higher than those in moderate/late preterm newborns and extremely/very preterm newborns( P<0.05). PI was moderately positively correlated with NCIS in newborns( r=0.791, P<0.01). The area under the receiver operating characteristic curve of NCIS predicted by PI value was 0.846, and the prediction sensitivity and specificity were 85.0% and 70.8% when PI was 0.56. Conclusion:PI is correlated with NCIS in newborns, which is able to reflect the severity of neonatal illnesses.A low PI indicates severe conditions of neonatal illnesses.

Application of interactive communication mode combined with problem-based learning in clinical teaching of undergraduate nursing students / 中国实用护理杂志

Objective:To explore the application of interactive communication mode combined with problem-based learning in clinical teaching of undergraduate nursing students so as to provide basis for nursing teaching reform.Methods:A total of 62 undergraduate nursing students in Beijing Jishuitan Hospital were selected. Among them, 32 cases from September to November 2018 received traditional teaching (the control group), and 30 cases from September to November 2019 were given interactive communication mode combined with problem-based learning (the observation group). The assessment results, comprehensive ability, clinical communication ability, scientific research ability, and feedback results of teaching quality were compared between the two groups.Results:After intervention, the total score of assessment in the observation group was (90.62 ± 4.75) points, higher than that in the control group (83.84 ± 5.01) points, there was significant difference ( t=5.46, P<0.05). After intervention, the scores of observation ability, operation ability and teamwork ability in the observation group were (3.51 ± 0.59), (3.75 ± 0.50), (4.30 ± 0.77) points, higher than those in the control group (3.18 ± 0.44), (3.22 ± 0.46), (3.53 ± 0.81) points, there were significant differences ( t=2.51,4.35, 3.83, all P<0.05). After intervention, the scores of clinical communication and keen listening, determining patients′ problems, participating together, sending effective information, establishing harmonious doctor-patient relationship, and verifying perception ability in the observation group were (83.61 ± 10.18), (81.66 ± 8.92), (84.01 ± 9.17), (83.25 ± 9.73), (80.90 ± 9.99), (84.15 ± 8.08) points, higher than those in the control group (73.91 ± 9.73), (74.95 ± 8.05), (76.02 ± 8.22), (73.16 ± 8.02), (74.61 ± 8.54), (76.08 ± 8.25) points, there were significant differences ( t values were 2.67-4.47, all P<0.05). After intervention, the scores of literature reading ability, data processing ability and paper writing ability in the observation group were (14.29 ± 1.54), (13.02 ± 1.29), (14.91 ± 1.50) points, higher than those in the control group (13.08 ± 1.43), (11.44 ± 1.24), (12.36 ± 1.28) points, there were significant differences ( t=3.21, 4.92, 7.22, all P<0.05). The feedback scores of students about improving nursing humanistic quality, professional self-identity, learning interest, communication ability, clinical thinking ability and innovation ability in the observation group were (4.26 ± 0.75), (4.43 ± 0.81), (4.25 ± 0.77), (4.18 ± 0.66), (4.44 ± 0.90), (4.38 ± 0.94) points, higher than those in the control group (3.51 ± 0.64), (3.79 ± 0.70), (3.48 ± 0.84), (3.40 ± 0.76), (3.83 ± 0.89), (3.60 ± 0.89) points, there were significant differences ( t values were 2.68-4.30, all P<0.05). Conclusions:The interactive communication mode combined with problem-based learning can effectively improve assessment results of undergraduate nursing students, and promote the improvement of their comprehensive quality, which is conducive to the improvement of clinical communication ability and scientific research ability in nursing students.

Research progress of primary immunodeficiency disease with hyper IgE syndrome / 中华实用儿科临床杂志

The hyper IgE syndrome (HIES) is a rare primary immunodeficiency disorder characterized by atopic dermatitis, recurrent skin and lung infections along with elevated IgE levels.The JOB syndrome due to heterozygous loss-of-function mutations in the signal transduction and transcription activator-3(STAT3) gene is the prototype of HIES.However, several other immunodeficiency disorders with the phenotype of HIES have been identified over the past decade.This study aims to review these disorders and their molecular mechanisms, aiming to improve the understanding of this rare disease.

Clinical analysis of congenital coronary artery fistula in 71 children / 中华实用儿科临床杂志

Objective:To explore the clinical characteristics, therapeutic efficacy and prognosis of congenital coronary artery fistula (CAF) in children.Methods:Clinical data of 71 pediatric patients diagnosed with congenital CAF at Department of Cardiology and Department of Cardiac Surgery, Shanghai Children′s Medical Center, Shanghai Jiao Tong University School of Medicine from January 2013 to June 2019 were retrospectively analyzed.The median age was 2.2 years (0.1-14.0 years), and the median body weight was 18.3 kg (3.2-55.8 kg), including 37 males (52.1%) and 34 females (47.9%). They were divided into the transcatheter closure group (30 cases) and surgical repair group (41 cases). The therapeutic effect and follow-up data of the 2 groups were compared by the Fisher′ s exact test. Results:Among the 71 congenital CAF children, 70 had heart murmurs, 2 had chest tightness after activity, and 5 were prone to recurrent respiratory tract infection.Transcatheter closure and surgical repair were successfully performed in 22/30 (73.3%) and 41/41 (100.0%) cases with a statistically significant difference ( P=0.001). However, in the surgical repair group, 1 (2.4%) case died after operation and 2(4.9%) needed further transcatheter closure due to large residual shunt during the follow-up period.At the last follow-up, there were 2 cases with minimal or small residual shunt in both groups ( P=0.567). There were 2/71(2.8%) cases suffering from postoperative thrombosis. Conclusions:Cardiac murmur is the main sign of congenital CAF in children, and some of them may have frequent respiratory tract infection due to increased lung blood caused by a large amount of shunt.A few children have chest tightness and chest pain due to myocardial ischemia caused by coronary steal.Both percutaneous closure and surgical repair are safe and effective with few complications.

Moxibustion alleviates decreased ovarian reserve in rats by restoring the PI3K/AKT signaling pathway / 中西医结合学报

OBJECTIVE@#Moxibustion, a common therapy in traditional Chinese medicine, has potential benefits for treating decreased ovarian reserve (DOR). The present study investigates the protective effect of moxibustion in a rat model of DOR and explores the possible mechanisms.@*METHODS@#Sixty-four female Sprague-Dawley rats were randomly divided into four groups: control, DOR, moxibustion (MOX), and hormone replacement therapy (HRT). The DOR rat model was established by intragastric administration of 50 mg/kg Tripterygium glycoside suspension (TGS), once daily for 14 days. MOX and HRT treatments were given from the day TGS administration was initiated. The ovarian reserve function was evaluated by monitoring the estrus cycle, morphological changes in ovaries, levels of serum estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), and anti-Mullerian hormone (AMH), pregnancy rate and embryo numbers. Terminal-deoxynucleotidyl transferase-mediated nick-end-labeling staining was used to identify ovarian granulosa cell apoptosis, while the protein and mRNA expressions of Bax, B-cell lymphoma-2 (Bcl-2), phosphatidylinositol 3-kinase (PI3K) and protein kinase B (AKT) in ovarian tissues were examined by immunohistochemistry, Western blot and quantitative reverse transcription-polymerase chain reaction.@*RESULTS@#Compared with the DOR group, MOX improved the disordered estrous cycle, promoted follicular growth, reduced the number of atresia follicles, increased the concentrations of serum E2 and AMH, and decreased serum FSH and LH concentrations. More importantly, the pregnancy rate and embryo numbers in DOR rats were both upregulated in the MOX treatment group, compared to the untreated DOR model. Further, we found that the MOX group had reduced apoptosis of ovarian granulosa cells, increased Bcl-2 expression and reduced expression of Bax. Furthermore, the PI3K/AKT signaling pathway was triggered by the moxibustion treatment.@*CONCLUSION@#Moxibustion improved ovarian function and suppressed apoptosis of ovarian granulosa cells in a rat model of DOR induced by TGS, and the mechanism may involve the PI3K/AKT signaling pathway.

A comprehensive profile of TCF1+ progenitor and TCF1- terminally exhausted PD-1+CD8+ T cells in head and neck squamous cell carcinoma: implications for prognosis and immunotherapy / 国际口腔科学杂志·英文版

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8+PD1+TCF1+ progenitor exhausted T cells (TCF1+Texprog) and CD8+PD1+TCF1- terminally exhausted T cells (TCF1-Texterm). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1-Texterm represented a greater proportion of CD8+PD1+Tex than TCF1+Texprog in most patients. TCF1+Texprog produced abundant TNFα, while TCF1-Texterm expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1-Texterm exhibited a polyfunctional TNFα+GZMB+IFNγ+ phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1-Texterm were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1-Texterm was the major CD8+PD1+Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1-Texterm was associated with greater Treg abundance.

A Deep Mesencephalic Nucleus Circuit Regulates Licking Behavior / 神经科学通报·英文版

Licking behavior is important for water intake. The deep mesencephalic nucleus (DpMe) has been implicated in instinctive behaviors. However, whether the DpMe is involved in licking behavior and the precise neural circuit behind this behavior remains unknown. Here, we found that the activity of the DpMe decreased during water intake. Inhibition of vesicular glutamate transporter 2-positive (VGLUT2+) neurons in the DpMe resulted in increased water intake. Somatostatin-expressing (SST+), but not protein kinase C-δ-expressing (PKC-δ+), GABAergic neurons in the central amygdala (CeA) preferentially innervated DpMe VGLUT2+ neurons. The SST+ neurons in the CeA projecting to the DpMe were activated at the onset of licking behavior. Activation of these CeA SST+ GABAergic neurons, but not PKC-δ+ GABAergic neurons, projecting to the DpMe was sufficient to induce licking behavior and promote water intake. These findings redefine the roles of the DpMe and reveal a novel CeASST-DpMeVGLUT2 circuit that regulates licking behavior and promotes water intake.

Influence of enteral feeding initiation time on intestinal flora and metabolites in very low birth weight infants: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To study the influence of enteral feeding initiation time on intestinal flora and metabolites in very low birth weight (VLBW) infants.@*METHODS@#A total of 29 VLBW infants who were admitted to the Department of Neonatology, Children's Hospital of Chongqing Medical University, from June to December, 2020, were enrolled as subjects. According to the enteral feeding initiation time after birth, the infants were divided into two groups: <24 hours (n=15) and 24-72 hours (n=14). Fecal samples were collected at weeks 2 and 4 of hospitalization, and 16S rDNA high-throughput sequencing and gas chromatography-mass spectrometry were used to analyze the microflora and short-chain fatty acids (SCFAs) respectively in fecal samples.@*RESULTS@#The analysis of microflora showed that there was no significant difference between the two groups in Chao index (reflecting the abundance of microflora) and Shannon index (reflecting the diversity of microflora) at weeks 2 and 4 after birth (P>0.05). The analysis of flora composition showed that there was no significant difference in the main microflora at the phylum and genus levels between the two groups at weeks 2 and 4 after birth (P>0.05). The comparison of SCFAs between the two groups showed that the <24 hours group had a significantly higher level of propionic acid than the 24-72 hours group at week 4 (P<0.05), while there was no significant difference in the total amount of SCFAs and the content of the other SCFAs between the two groups (P>0.05).@*CONCLUSIONS@#Early enteral feeding has no influence on the diversity and abundance of intestinal flora in VLBW infants, but enteral feeding within 24 hours can increase the level of propionic acid, a metabolite of intestinal flora.

Proteomics of serum exosomes in children in the acute stage of Kawasaki disease: a prospective study / 中国当代儿科杂志

OBJECTIVES@#To study the biological processes and functions of serum exosomes in children in the acute stage of Kawasaki disease (KD), so as to provide new biomarkers for the early diagnosis of KD.@*METHODS@#In this prospective study, 13 children with KD who were treated in Children's Hospital of Soochow University from June 2019 to August 2020 were enrolled as the KD group, and 13 children who were hospitalized due to bacterial infection during the same period were enrolled as the control group. Whole blood was collected on the next morning after admission, serum samples were obtained by centrifugation, and exosomes were extracted through ultracentrifugation. Serum exosomes were analyzed by label-free quantitative proteomics, and differentially expressed proteins (DEPs) were screened out for functional enrichment analysis. A protein-protein interaction (PPI) network was plotted, and unique proteins were validated by targeted proteomics.@*RESULTS@#A total of 131 DEPs were screened out for the two groups, among which 27 proteins were detected in both groups. There were 48 unique DEPs in the KD group, among which 23 were upregulated and 25 were downregulated, and these proteins acted on "complement and coagulation cascades" and "the MAPK signaling pathway". Validation by targeted proteomics showed that FGG, SERPING1, C1R, C1QA, IGHG4, and C1QC proteins were quantifiable in the KD group. A total of 29 proteins were only expressed in the control group, among which 12 were upregulated and 17 were downregulated. Four proteins were quantifiable based on targeted proteomics, i.e., VWF, ECM1, F13A1, and TTR. A PPI network was plotted for each group. In the KD group, FGG and C1QC had close interaction with other proteins, while in the control group, VWF had close interaction with other proteins.@*CONCLUSIONS@#The serum exosomes FGG and C1QC in children in the acute stage of KD are expected to become the biomarkers for the early diagnosis of KD. For children with unexplained fever, detection of FGG, C1QC1, and VWF may help with etiological screening.

Effects of renal tubular epithelial cell necroptosis on kidney injury in patients with chronic kidney disease / 中华肾脏病杂志

Objective:To investigate the number of necroptotic renal tubular epithelial cells in renal tissues of patients with chronic kidney disease (CKD) and the correlation with clinicopathologic parameters, and explore its role in the progression of the excessive loss of renal tubular cells and chronic kidney injury.Methods:Renal tissue samples from 60 patients (18-65 years old) with CKD proven by kidney biopsy in the First Affiliated Hospital of Hainan Medical University from June 2017 to June 2019 were collected. According to internationally accepted K/DOQI guidelines, the patients were divided into 1-4 stages of CKD, with 15 cases in each stage. The number of necroptotic renal tubular epithelial cells in patients with different stages of CKD was detected using receptor-interacting protein 3 (RIP3) and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) fluorescent staining, and the expression of RIP3 and MLKL, marker protein of necroptosis, was detected by immunohistochemistry. Pearson correlation analysis was used to analyze the correlation between the percentage of necroptotic renal tubular epithelial cells and clinicopathologic parameters. In addition, the expression of angiotensinogen Ⅱ receptor (AT2R) in renal tissue and its correlation with the percentage of necroptotic renal tubular epithelial cells were analyzed.Results:With the development of CKD, the structural destruction of renal tubules in patients with CKD was gradually aggravated, and the renal tubules in the corresponding areas were atrophied, accompanied by worsening interstitial fibrosis. The adjacent renal tubules were focally dilated and numerous protein tubules were seen in the tubules. Importantly, renal tubular injury score in second and third stage of CKD was significantly higher than that in control group (both P<0.01). TUNEL+RIP3 immunofluorescence staining results showed that the percentage of TUNEL/RIP3 double positive renal tubular epithelial cells (necroptotic renal tubular epithelial cells) in renal tubules of the second and third stage of CKD was higher (all P<0.01). Immunohistochemical results showed that RIP3, MLKL and AT2R proteins were mainly expressed in cytoplasm of renal tubular epithelial cells, and the expression of RIP3, MLKL and AT2R in renal tubular epithelial cells was higher in the second and third stage of CKD patients (all P<0.05). Pearson correlation analysis showed that the percentage of necroptotic renal tubular epithelial cells was positively correlated with blood urea nitrogen ( r=0.514, P=0.003), serum creatinine ( r=0.507, P=0.019), serum cystatin C ( r=0.571, P=0.026), serum uric acid ( r=0.592, P=0.008), renal tubules injury score ( r=0.901, P<0.001), renal interstitial fibrosis index ( r=0.700, P=0.001) and the expression of AT2R protein in renal tissue ( r=0.715, P=0.001). Conclusions:As CKD progresses, necroptosis of renal tubular epithelial cells in CKD patients occurs. The necroptotic cell death may be an important factor leading to renal tubular epithelial cell excessive death and the progression of chronic kidney injury. Furthermore, necroptosis of renal tubular epithelial cells may be related to the high expression of AT2R in kidney tissue.