OBJECTIVE To systematically evaluate the methodological quality of the postoperative chemotherapy guidelines/ consensuses for ovarian epithelial tumor. METHODS A search was conducted across databases including PubMed， Embase， Web of Science， CBM， VIP， Chinese Medical Journal Data， Wanfang Data， and CNKI， as well as the official websites of GIN， NICE， Medlive， AHRQ， CSCO， ASCO， and NCCN. The search period was from the establishment of the databases/websites to March 10， 2025. The quality of the included guidelines/consensus was evaluated by using the AGREE-Ⅱ tool. RESULTS A total of 16 guidelines/consensuses were included. The domain scores of AGREE-Ⅱ evaluation were as follows： scope and purpose of 85.07%， participants of 47.92%， rigor of development of 57.49%， clarity of presentation of 88.02%， applicability of 8.20%， and independence of 53.39%. Among them， 14 were recommended at grade B and 2 were recommended at grade C. The subgroup analysis by different countries/regions and different types of studies showed that the scores for participants， rigor of development， and independence of the guidelines/consensuses in China were significantly lower than foreign countries （P＜0.05）； the scores for participants and rigor of development of the guidelines were significantly higher than consensuses （P＜0.05）. The guideline/ consensus recommendation results indicated that grade B guidelines/consensus recommend platinum-based combination chemotherapy as the preferred adjuvant chemotherapy regimen for stage Ⅰ high-grade serous carcinoma patients；platinum-based combination chemotherapy±bevacizumab was recommended as the preferred adjuvant chemotherapy regimen for stage Ⅱ-Ⅳ high- grade serous carcinoma patients and for platinum-sensitive recurrent high-grade serous carcinoma patients； non-platinum single- agent chemotherapy±bevacizumab was recommended as the preferred chemotherapy regimen for platinum-resistant recurrent high- grade serous carcinoma patients. CONCLUSIONS The overall quality of postoperative chemotherapy guidelines/consensuses for ovarian epithelial tumor is not high. The methodological quality of guidelines/consensuses in China is still lagging behind that of foreign countries. The recommendations differ from those in foreign countries. It is recommended to improve the aspects of participants， rigor of development， and independence， to recommend treatment plans based on the different stages of ovarian cancer， and develop guidelines/consensuses that align with China’s national conditions.

BACKGROUND: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

OBJECTIVES: To investigate the regulatory role of astrocytes in the dorsomedial hypothalamus (DMH) during sevoflurane anesthesia emergence. METHODS: Forty-two male C57BL/6 mice were randomized into 6 groups (n=7) for assessing astrocyte activation in the dorsomedial hypothalamus (DMH) under sevoflurane anesthesia. Two groups of mice received microinjection of agfaABC1D promoter-driven AAV2 vector into the DMH for GCaMP6 overexpression, and the changes in astrocyte activity during sevoflurane or air inhalation were recorded using calcium imaging. For assessing optogenetic activation of astrocytes, another two groups of mice received microinjection of an optogenetic virus or a control vector into the DMH with optic fiber implantation, and sevoflurane anesthesia emergence was compared using behavioral experiments. In the remaining two groups, electroencephalogram (EEG) recording during sevoflurane anesthesia emergence was conducted after injection of the hChR2-expressing and control vectors. Anesthesia induction and recovery were assessed by observing the righting reflex. EEG data were recorded under 2.0% sevoflurane to calculate the burst suppression ratio (BSR) and under 1.5% sevoflurane for power spectrum analysis. Immunofluorescence staining was performed to visualize the colocalization of GFAP-positive astrocytes with viral protein signals. RESULTS: Astrocyte activity in the DMH decreased progressively as sevoflurane concentration increased. During 2.0% sevoflurane anesthesia, the mice injected with the ChR2-expressing virus exhibited a significantly shortened wake-up time (P<0.05), and optogenetic activation of the DMH astrocytes led to a marked reduction in BSR (P<0.001). Under 1.5% sevoflurane anesthesia, optogenetic activation resulted in a significant increase in EEG gamma power and a significant decrease in delta power in ChR2 group (P<0.01). CONCLUSIONS Optogenetic activation of DMH astrocytes facilitates sevoflurane anesthesia emergence but does not significantly influence anesthesia induction. These findings offer new insights into the mechanisms underlying anesthesia emergence and may provide a potential target for accelerating postoperative recovery and managing anesthesia-related complications.
Animals ; Astrocytes/physiology* ; Sevoflurane ; Mice, Inbred C57BL ; Mice ; Male ; Electroencephalography ; Anesthetics, Inhalation/pharmacology* ; Hypothalamus/cytology* ; Anesthesia Recovery Period ; Methyl Ethers/pharmacology*

Objective:To verify the therapeutic effect of Astragalus on mice with acute respiratory distress syndrome with sepsis and to explore its mechanism.Methods:Seventy SPF-grade C57 mice were divided into astragalus group ( n=30), control group ( n=30) and sham surgery group ( n=10) according to random number table method, and CLP surgery was performed on Astragalus group and control group to induce sepsis acute respiratory distress syndrome, and CLP sham surgery was performed in the sham surgery group. After surgery, the astragalus group was treated with astragalus decoction for gastric gavage, the sham surgery group and the control group were gavaged with normal saline, and the mice were sacrificed 12 hours and 24 hours after the operation, and the lung histopathology was observed, the ratio of dry to wet weight of lung tissue, the protein concentration of alveolar lavage fluid was determined, the alveolar lavage fluid and serum were analyzed proteomics, and the differential proteins were enriched and analyzed. Results:Astragalus reduced the total protein concentration of BALF in ARDS mice, reduced the dry-to-wet ratio of ARDS mice, and HE staining of lung tissues showed that Astragalus decoction improved acute alveolar injury in ARDS mice. Proteomic analysis of serum samples and BALF samples showed that there were certain differential proteins between astragalus group and control group, and enrichment analysis showed that it was mainly enriched in the pathway of inflammatory factors, confirming that astragalus decoction may play a role by inhibiting the activation and release of inflammatory factors.Conclusions:Astragalus decoction can effectively reduce the inflammatory exudation of lung tissue in acute respiratory distress syndrome of sepsis, and its mechanism of action may be to inhibit the expression of inflammatory factors.

Objective To investigate the role of glutamatergic neurons in the dorsomedial periaqueductal grey(dmPAG)in regulating excessive defensive behaviors in mice with post-traumatic stress disorder(PTSD).Methods Eight-week-old male C57BL/6 mice were subjected to stereotactic injections of different recombinant adeno-associated viral vectors(rAAV2/9-CaMKⅡ-mCherry,rAAV2/9-CaMKⅡ-hM3Dq-mCherry and rAAV2/9-CaMKⅡ-hM4Di-mCherry)into the bilateral dmPAG for chemogenetic activation or inhibition of the glutamatergic neurons,followed 2 weeks later by PTSD modeling by single prolonged stress.The looming test,response to whisker stimulation test and contextual fear conditioning(CFC)test were used to observe changes in defensive behaviors of the PTSD mice.The activity of glutamatergic neurons in the dmPAG were observed using immunofluorescence staining.Results Compared with the control mice,the mouse models of PTSD showed a shortened latency of flights with increased time spent in the nest,response scores of defensive behaviors and freezing time(all P<0.01).Immunofluorescence staining revealed significantly increased c-fos-positive glutamatergic neurons in the dmPAG of PTSD mice with defensive behaviors.Activation of the glutamatergic neurons in the dmPAG(in PTSD hM3Dq group)did not cause significant changes in the latency of flights or time in nest but obviously increased response scores of defensive behaviors and freezing time of the mice,whereas inhibiting the glutamatergic neurons in the dmPAG(in PTSD hM4Di group)caused the reverse changes and obviously alleviated defensive behaviors in the PTSD mice(P<0.05 or 0.01).Conclusion Inhibiting the activity of glutamatergic neurons in the dmPAG can alleviate defensive behaviors in mice with PTSD.

Objective To investigate the role of glutamatergic neurons in the dorsomedial periaqueductal grey(dmPAG)in regulating excessive defensive behaviors in mice with post-traumatic stress disorder(PTSD).Methods Eight-week-old male C57BL/6 mice were subjected to stereotactic injections of different recombinant adeno-associated viral vectors(rAAV2/9-CaMKⅡ-mCherry,rAAV2/9-CaMKⅡ-hM3Dq-mCherry and rAAV2/9-CaMKⅡ-hM4Di-mCherry)into the bilateral dmPAG for chemogenetic activation or inhibition of the glutamatergic neurons,followed 2 weeks later by PTSD modeling by single prolonged stress.The looming test,response to whisker stimulation test and contextual fear conditioning(CFC)test were used to observe changes in defensive behaviors of the PTSD mice.The activity of glutamatergic neurons in the dmPAG were observed using immunofluorescence staining.Results Compared with the control mice,the mouse models of PTSD showed a shortened latency of flights with increased time spent in the nest,response scores of defensive behaviors and freezing time(all P<0.01).Immunofluorescence staining revealed significantly increased c-fos-positive glutamatergic neurons in the dmPAG of PTSD mice with defensive behaviors.Activation of the glutamatergic neurons in the dmPAG(in PTSD hM3Dq group)did not cause significant changes in the latency of flights or time in nest but obviously increased response scores of defensive behaviors and freezing time of the mice,whereas inhibiting the glutamatergic neurons in the dmPAG(in PTSD hM4Di group)caused the reverse changes and obviously alleviated defensive behaviors in the PTSD mice(P<0.05 or 0.01).Conclusion Inhibiting the activity of glutamatergic neurons in the dmPAG can alleviate defensive behaviors in mice with PTSD.

Using chemoproteomic techniques, we first identified EIF2AK2, eEF1A1, PRDX3 and VPS4B as direct targets of berberine (BBR) for its synergistically anti-inflammatory effects. Of them, BBR has the strongest affinity with EIF2AK2 via two ionic bonds, and regulates several key inflammatory pathways through EIF2AK2, indicating the dominant role of EIF2AK2. Also, BBR could subtly inhibit the dimerization of EIF2AK2, rather than its enzyme activity, to selectively modulate its downstream pathways including JNK, NF-κB, AKT and NLRP3, with an advantage of good safety profile. In EIF2AK2 gene knockdown mice, the inhibitory IL-1β, IL-6, IL-18 and TNF-α secretion of BBR was obviously attenuated, confirming an EIF2AK2-dependent anti-inflammatory efficacy. The results highlight the BBR's network mechanism on anti-inflammatory effects in which EIF2AK2 is a key target, and inhibition of EIF2AK2 dimerization has a potential to be a therapeutic strategy against inflammation-related disorders.

A series of new monobactam sulfonates is continuously synthesized and evaluated for their antimicrobial efficacies against Gram-negative bacteria. Compound 33a (IMBZ18G) is highly effective in vitro and in vivo against clinically intractable multi-drug-resistant (MDR) Gram-negative strains, with a highly druglike nature. The checkerboard assay reveals its significant synergistic effect with β-lactamase inhibitor avibactam, and the MIC values against MDR enterobacteria were reduced up to 4-512 folds. X-ray co-crystal and chemoproteomic assays indicate that the anti-MDR bacteria effect of 33a results from the dual inhibition of the common PBP3 and some class A and C β-lactamases. Accordingly, preclinical studies of 33a alone and 33a‒avibactam combination as potential innovative candidates are actively going on, in the treatment of β-lactamase-producing MDR Gram-negative bacterial infections.

Objective:To investigate the diagnostic value of postsystolic shortening (PSS) and early systolic lengthening (ESL) on myocardial microvascular dysfunction in patients with ST-segment elevation myocardial infarction (STEMI) after percutaneous coronary intervention (PCI).Methods:A total of 83 patients with STEMI who received emergency PCI in Renmin Hospital of Wuhan University from June to October 2021 were retrospectively collected. All patiets underwent two-dimensional echocardiography and myocardial contrast echocardiography (MCE) within 7 days after PCI. The patients were divided into global normal perfusion group and poor perfusion group according to global myocardial perfusion score index (MPSI). Left ventricular myocardium was divided into left anterior descending branch (LAD), left circumflex branch (LCx) and right coronary artery (RCA) regions, which were divided into regional normal perfusion group and poor perfusion group based on whether there were segments with microvascular dysfunction. Left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were measured by modified biplane Simpson method. Tomtec software was used to obtain conventional echocardiographic parameters, global longitudinal strain (GLS), as well as PSS and ESL parameters including postsystolic index (PSI), duration of postsystolic shortening (PSSduration), early systolic index (ESI) and duration of early systolic lengthening (ESLduration). Differences of parameters of global normal and poor perfusion groups, as well as regional normal and poor perfusion groups were compared. ROC curve was used to analyze the diagnostic value of PSS and ESL parameters and GLS in myocardial regions with microvascular dysfunction.Results:Significant differences were observed in LVEF, LVESV, GLS, PSI, ESI and PSSduration between global poor perfusion group and global normal perfusion group (all P<0.05). Compared with regional normal perfusion group, PSI, ESI and ESLduration of LAD and LCx regions, as well as PSI of RCA region in regional poor perfusion group were increased (all P<0.05). For GLS in different myocardial regions, LAD-GLS was the only parameter that decreased in regional poor perfusion group compared to regional normal perfusion group ( P<0.05). ROC curve analysis showed LAD-PSI, LAD-GLS, LCx-PSI, LCx-ESLduration and RCA-PSI were valuable parameters for diagnosis of myocardial microvascular dysfunction in different regions, among which LAD-PSI had the highest area under curve (AUC=0.809). Conclusions:PSS and ESL parameters are helpful for early diagnosis of myocardial microvascular dysfunction in STEMI patients after PCI, and can provide regional myocardial perfusion information according to the blood supply of different coronary arteries.

Objective:To explore the monitoring value of left ventricular functional parameters obtained by bedside ultrasound combined with clinically relevant indicators in patients with veno-arterial extracorporeal membrane oxygenation (VA-ECMO).Methods:A retrospective study was conducted. A total of 24 patients receiving VA-ECMO adjuvant support in Renmin Hospital of Wuhan University from June 2018 to January 2020 were selected. The bedside ultrasound was performed on the first day of ECMO support, the day before weaning, the clinical indicators before weaning were obtained. The differences in clinical indicators and the left ventricular functional parameters between the two groups of whether weaning successfully were compared; univariate Logistic regression analysis was used to screen out the related factors affecting weaning.Results:Sixteen patients were successful weaned and 8 patients failed. Compared with the weaning failure group, patients in the weaning success group required less continuous renal replacement therapy (CRRT, cases: 4 vs. 6, P < 0.05), mean arterial pressure (MAP) before weaning was higher [mmHg (1 mmHg = 0.133 kPa): 84.64±9.55 vs. 62.30±8.79, P < 0.05], and the pulse oxygen saturation (SpO 2) was also higher (0.966±0.670 vs. 0.866±0.061, P < 0.05), while vasoactive-inotropic score (VIS), serum creatinine (SCr) and serum lactic acid (Lac) were lower [VIS score: 7.27±1.42 vs. 16.93±8.52, SCr (μmol/L): 123.60±83.64 vs. 213.10±117.39, Lac (mmol/L): 1.94±0.91 vs. 5.62±5.48, all P < 0.05]. Univariate Logistic regression analysis showed that the MAP, VIS, SCr, Lac, SpO 2 before weaning were the related factors affecting weaning [odds ratio ( OR) were 0.306, -0.740, -0.011, -0.632, -4.069; 95% confidence interval (95% CI) were 1.065-1.732, 0.235-0.899, 0.979-0.999, 0.285-0.992 and 0.001-0.208; P values were 0.014, 0.022, 0.038, 0.047, 0.002]. In the weaning success group, left ventricular ejection fraction (LVEF), velocity of mitralannulus in systolic (LatSa), maximum flow velocity of aortic valve (AV-Vmax), velocity-time integral (VTI), left ventricular global longitudinal strain (LVGLS), left ventricular global longitudinal strain rate (LVGLSr) were all increased on the day before ECMO weaning compared with the first day of ECMO support [LVEF: 0.40±0.05 vs. 0.28±0.07, LatSa (cm/s): 6.81±0.91 vs. 4.62±1.02, AV-Vmax (cm/s): 104.81±33.98 vs. 64.44±16.85, VTI (cm): 14.56±3.11 vs. 7.96±1.98, LVGLS: (-8.95±2.59)% vs. (-5.26±1.28)%, LVGLSr (1/s): -0.48±0.11 vs. -0.29±0.09], whereas the ECMO flow was significantly reduced (L/min: 1.46±0.47 vs. 2.64±0.31), the differences were statistically significant (all P < 0.05). There was no significant difference in left ventricular functional parameters between the first day of ECMO support and the day before ECMO weaning in the weaning failure group. Compared with the weaning failure group, the weaning success group had higher LVEF, LatSa, AV-Vmax, VTI, LVGLS, LVGLSr on the day before ECMO weaning [LVEF: 0.40±0.05 vs. 0.26±0.07, LatSa (cm/s): 6.81±0.91 vs. 4.31±1.03, AV-Vmax (cm/s): 104.81±33.98 vs. 67.67±18.46, VTI (cm): 14.56±3.11 vs. 7.75±2.77, LVGLS: (-8.95±2.59)% vs. (-4.81±1.81)%, LVGLSr (1/s): -0.48±0.11 vs. -0.30±0.10, all P < 0.05] and lower ECMO flow (L/min: 1.46±0.47 vs. 2.20±0.62, P < 0.05). Conclusion:Bedside echocardiographic left ventricular function parameters (LVEF, LatSa, AV-Vmax, VTI, LVGLS, LVGLSr) combined with clinical indicators (MAP, VIS, SCr, Lac, SpO 2) were helpful to evaluate the therapeutic effect of patients receiving VA-ECMO support and can provide important guiding value in the selection of VA-ECMO weaning timing and the judgment of prognosis.