Animal experiments are essential tools in biomedical research, serving as a bridge between basic research and clinical trials. Systematic reviews and meta-analyses (SRs/MAs) of animal experiments are crucial methods for integrating evidence from animal experiment, which can facilitate the translation of findings into clinical research, reduce translational risks, and promote resource integration in basic research. With the continuous development of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology, its application in SRs/MAs of animal experiments has gained increasing attention. This article first outlines the principles and specific applications of the GRADE methodology in SRs/MAs of animal experiments, including qualitative descriptive systematic reviews, meta-analyses, and network meta-analyses. It then deeply analyzes the misuse of the GRADE methodology in practice, including incorrect evidence grading, improper classification of evidence, misapplication in qualitative systematic reviews, inconsistencies between the documentation of the upgrading and downgrading process and results, and inappropriate use for making recommendations. Furthermore, this article comprehensively discusses the factors influencing the grading of evidence certainty in SRs/MAs of animal experiments, including the impact of bias risk, indirectness, inconsistency, imprecision, and publication bias on evidence downgrading, as well as the role of large effect sizes and cross-species consistency in evidence upgrading. Finally, in response to the issues discussed, improvement strategies are proposed, including further research and optimization of the GRADE methodology for SRs/MAs of animal experiments, the development of reporting guidelines tailored to the characteristics of SRs/MAs in animal experiment research, and enhanced professional training for researchers in the GRADE methodology. This article aims to improve the quality of evidence in SRs/MAs of animal experiments, strengthen their reliability in clinical decision-making, and promote the more efficient translation of findings from animal experiment research into clinical practice.

Objective: To explore the changes of mechanosensitive channels Piezos (Piezo 1 and Piezo 2) in neurogenic bladder (NB) of young rats and their effects，so as to provide reference for clinical search of new therapeutic targets. Methods: A total of 30 female young SD rats were divided into 5 groups based on random number table method：sham operation group (sham)，2-week nerve transection group (NB-2W)，6-week nerve transection group (NB-6W)，2-week nerve transection + Piezos inhibitor group (NB-P-2W) and 6-week nerve transection + Piezos inhibitor group (NB-P-6W)，with 6 rats in each group.The NB models were constructed by transecting the L6 and S1 spinal nerves of young rats.The NB-2W and NB-6W groups were not intervened after modeling，while the NB-P-2W and NB-P-6W groups were intraperitoneally injected with Piezos inhibitor GsMTx4 (10 mg/kg) every 2 days after modeling.Bladder cystometry and ultrasound were performed after 2 and 6 weeks of transection.The expressions of Piezos and fibrosis-related indexes (Collagen Ⅰ and α-smooth muscle actin) were detected in bladder tissues. Results: The results of bladder cystometry showed that the basal bladder pressure in NB-2W group was significantly increased，while it was slightly decreased but was still higher in NB-6W group than in the sham group (P<0.05).Basal bladder pressure was lower in NB-P-2W group than in NB-2W group，but was higher than that in the sham group; basal bladder pressure was lower in NB-P-6W group than in NB-6W group，but higher than that in the sham group (P<0.05).Compared with the sham group，the NB-2W and NB-6W groups had firstly increased and then decreased maximum cystometric capacity (MCC) (P<0.05).Compared with NB-2W group，NB-P-2W group had lower bladder leakage point pressure (BLPP)，but higher MCC and bladder compliance (BC) (P<0.05).Compared with NB-6W group，NB-P-6W group had significantly lower BLPP but higher MCC and BC (P<0.05).HE and MASSON staining and ultrasound results showed that，with the extension of nerve transection time，bladder fibrosis gradually worsened，the bladder wall became rough and thickened，calculi were visible inside，and hydronephrosis gradually appeared; the degree of fibrosis in NB-P-2W and NB-P-6W groups was less than that in NB-2W and NB-6W groups，and no hydronephrosis was observed in the upper urinary tract.In addition，Western blotting and immunohistochemical results showed that NB-2W and NB-6W groups had significantly higher relative expression levels of Piezos，Collagen Ⅰ and α-SMA than the sham group (P<0.01)，while NB-P-2W and NB-P-6W groups had lower relative expression levels of Piezos,Collagen Ⅰ and α-SMA than NB-2W and NB-6W groups (P<0.01). Conclusion: The increased expressions of mechanosensitive channels Piezos in NB young rats may be involved in the progression of bladder fibrosis，but its mechanism needs further study.

Objective: This study compares the effects of lithium disilicate glass ceramic onlays and full crowns in restoring cracked teeth that have undergone root canal therapy, providing a reference for the restoration method of cracked teeth that have undergone root canal therapy. Methods: This study was approved by the hospital’s medical ethics committee, and all patients signed the informed consent form. Patients with cracked teeth who underwent root canal treatment in our hospital from January 2022 to January 2023 were enrolled in this study. According to the inclusion and exclusion criteria, 60 patients were screened and enrolled, with a total of 60 affected teeth. The patients were divided into the onlay group and full crown group at a ratio of 2:3 using the random number table method. Lithium disilicate glass ceramic onlays were used to restore the affected teeth in the onlay group (24 cases), and lithium disilicate glass ceramic full crowns were used to restore the affected teeth in the full crown group (36 cases). At 3, 6, and 12 months after the repair, the restoration effect was evaluated and compared with the modified USPH Standard (the aesthetic, functional, and biological aspects of restorations). According to the biological definition of survival, survival analysis was conducted on the affected teeth in both groups. Results: At 3, 6, and 12 months after the repair, 85% of cases in the onlay group achieved grade A, while 80% of cases in the full crown group achieved grade A. There was no statistically significant difference in the restoration effects between the onlay group and the full crown group (P > 0.05). The 12-month survival rate of cracked teeth in the onlay group reached 95.65%, and the 12-month survival rate of cracked teeth in the full crown group reached 94.12%. There was no statistically significant difference in the retention of the affected teeth (P > 0.05). There was no significant effect of age, gender, tooth position, dentition, direction of cracks, the number of marginal ridges associated with cracks, or the type of restoration on the survival status of cracked teeth. (P > 0.05). Conclusion For cracked teeth that have undergone root canal therapy, the short-term effect of lithium disilicate glass ceramic onlays is comparable to that of full crowns, and both have good short-term effects. Onlays are less invasive and are expected to become an alternative restoration method to full crowns.

The incidence and mortality rates of lung cancer remain high, making it the leading cause of cancer-related deaths. In women, the predominant histological subtype is lung adenocarcinoma, commonly associated with epidermal growth factor receptor (EGFR) mutations, and EGFR-tyrosine kinase inhibitors (EGFR-TKIs) can significantly improve patient prognosis. Metastasis of primary lung cancer to the endometrium is extremely rare and is often misdiagnosed as a primary reproductive system tumor, and its occurrence indicates poor prognosis. This article reports a case of an advanced lung adenocarcinoma patient with EGFR mutation, who developed abnormal vaginal bleeding after EGFR-TKIs treatment failure, and biopsy confirmed endometrial metastasis. A review of similar cases is also presented.
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Humans ; Female ; ErbB Receptors/metabolism* ; Endometrial Neoplasms/genetics* ; Lung Neoplasms/genetics* ; Protein Kinase Inhibitors/therapeutic use* ; Adenocarcinoma of Lung/drug therapy* ; Treatment Failure ; Middle Aged ; Adenocarcinoma/genetics*

OBJECTIVE To explore the effects of levosimendan on cardiac function， hemodynamics and prognosis of patients with septic shock complicated with myocardial depression， and evaluate the safety of levosimendan. METHODS Patients with septic shock complicated with myocardial depression who were admitted to the Department of Critical Care Medicine of Chongqing University Three Gorges Hospital from April 2021 to August 2023， underwent adequate fluid resuscitation， had a mean arterial pressure （MAP） ≥65 mmHg， and received pulse indicator continuous cardiac output （PiCCO） monitoring were enrolled. The patients were randomly divided into dobutamine group and levosimendan group according to a random number table， with 20 patients in each group. Both groups received intravenous infusion of Norepinephrine bitartrate injection at a dose of 0.1-2.0 μg/（kg·min）. On this basis， the dobutamine group additionally received intravenous infusion of Dobutamine hydrochloride injection at a dose of 5- 10 μg/（kg·min） for 3 to 7 days， while the levosimendan group additionally received intravenous infusion of Levosimendan injection at a dose of 0.1-0.2 μg/（kg·min） for 24 hours. Heart rate （HR） and hemodynamic parameters [systolic blood pressure， diastolic blood pressure， MAP， central venous pressure （CVP）]， PiCCO monitoring parameters [cardiac function index （CFI）， cardiac index （CI）， stroke volume index （SVI）， extravascular lung water index， global end-diastolic volume index， pulmonary vascular permeability index （PVPI）， global ejection fraction （GEF）， systemic vascular resistance index， left ventricular contractility index]， and prognosis indicators [death within 3 days after administration， mechanical ventilation time，intensive care unit （ICU） stay time， 28-day mortality rate] were compared between the two groups before treatment and at 24 and 72 hours after treatment. Adverse reactions were E-mail：recorded for both groups. RESULTS Compared with before treatment in the same group， CFI， CI and GEF at 24 hours after treatment， CI and GEF at 72 hours after treatment in the dobutamine group， as well as SVI at 24 hours after treatment and SVI and GEF at 72 hours after treatment in the levosimendan group were significantly increased； PVPI at 72 hours after treatment in the dobutamine group was significantly decreased （P＜0.05）. Compared with the dobutamine group during the same period， patients in the levosimendan group had significantly lower HR and significantly higher CVP at 24 hours after treatment （P＜0.05）. Within 3 days after administration， there were no deaths in either group； there were no statistically significant differences in mechanical ventilation time， ICU stay time， 28-day mortality rate， or the incidence of adverse reactions between the two groups （P＞0.05）. CONCLUSIONS For patients with septic shock complicated with myocardial depression who have undergone adequate fluid resuscitation and have a MAP of ≥65 mmHg， levosimendan is comparable to dobutamine in improving cardiac function and hemodynamic parameters， without affecting patients’ prognosis or increasing the risk of adverse reactions such as hypotension.

Integrating evidence from animal experiments is a critical component of biomedical research, providing essential prior information for in-depth investigations of disease mechanisms and new drug development. Animal models have played an irreplaceable role in simulating human diseases. However, the integration of evidence from animal experiments has faced numerous challenges, including insufficient emphasis, significant heterogeneity in study designs, high publication bias, and discrepancies with clinical research practices. This paper first identifies existing issues in the original research evidence from animal experiments, such as the selection and applicability of animal models, considerations in the design of experimental studies, and factors influencing the translation of animal experimental evidence. It then discusses various methods for integrating this evidence, including systematic review and meta-analysis, overview of systematic review/umbrella review, scoping review, and evidence mapping, while highlighting recent advancements in their application. Finally, the paper addresses the main challenges currently encountered in the integration of evidence from animal experiments and proposes targeted improvement strategies aimed at enhancing the efficiency of translating research outcomes into clinical practice and promoting the advancement of evidence-based medicine. By continuously optimizing original experimental research protocols and evidence integration practices, this work aims to establish a more efficient and scientific environment for the synthesis of evidence from animal experiments, ultimately contributing to clinical trials and human health.

[Objective]To elaborate the significance of modulating the spirit and the mechanism of five elements music concrete hypnosis technique,so as to provide new ideas for the diagnosis and treatment of clinical post-stroke depression.[Methods]From the perspective of"modulating the spirit",this paper expounds the significance of five elements music concrete hypnosis technique in"modulating the spirit"by studying ancient and modern literature,explores its mechanism of action,and introduces five elements music concrete hypnosis technique in detail,and finally analyzes it combining with the clinical trial results.[Results]"Those who have the spirit prosper,those who are absent-minded die",modulating the spirit plays an important role in the treatment of clinical diseases,especially in the treatment of psychosomatic diseases.Five elements music concrete hypnosis technique plays a role in regulating the spirit by vibrating viscera,deducing concrete thinking,condensing breath and gathering Qi.The clinical application has achieved satisfactory results.[Conclusion]Five elements music concrete hypnosis technique in the treatment of post-stroke depression fully embodies the thought of"regulating the spirit"of traditional Chinese medicine,and its curative effect is considerable,which is worthy of further exploration and promotion.

Objective : To investigate the protective effect of melatonin (MT) on formaldehyde (FA) inhalation-in- duced acute lung injury (ALI) in rats and its mechanism through the regulation of nuclear factor E2-related factor 2 (Nrf2) signaling pathway． Methods : Fifty female Wistar rats were randomly divided into Control group ，FA group，FA + MT 5 mg / kg group，FA + MT 10 mg / kg group and FA + MT 20 mg / kg group，with 10 rats in each group．Except for the Control group，all other groups inhaled 3 mg / m3 FA daily for 21 d consecutively to construct the tainted model，and then treated with different MT doses for 14 d．The tainting was continued during the MT treatment．Hematoxylin-eosin (HE) staining was used to observe the histopathological changes in lung tissue，lung water content and lung coefficient were weighed and measured，glutathione ( GSH) ，superoxide dismutase (SOD) and 8-hydroxydeoxyguanosine ( 8-OHdG) levels were measured by absorbance photometric method ，and enzyme linked immunosorbent assay(ELISA) was used to measure the levels of tumor necrosis factor-alpha (TNF-α) ，in- terleukin (IL) -6，and IL-1 β concentrations，Western blot to detect the protein expression levels of Nrf2，heme ox- ygenase-1 (HO-1) ，nuclear factor-κB ( NF-κB) ，and phosphorylated nuclear factor-κB ( p-NF-κB) in lung tis- sues，and quantitative polymerase chain reaction(qPCR) to detect the Nrf2，HO-1，and Kelch-like ECH-associated protein 1 (Keap1) mRNA expression levels. Results : Compared with the control group，lung injury was obvious in rats in the FA group ; lung tissue GSH and SOD levels were reduced ，and 8-OHdG levels were elevated ( P < 0. 05) ; alveolar lavage fluid TNF-α , IL-6，and IL-1 β levels were elevated (P＜0. 05) ; Nrf 2 and HO-1 protein expression levels were reduced in the lung tissue (P＜0. 05) ，and p-NF-κB protein expression levels were was ele- vated (P＜0. 05) ; the relative mRNA expression of Nrf2 and HO-1 in lung tissue was decreased，and the relative mRNA expression of Keap1 was elevated (P＜0. 05) ．Compared with the FA group，the lung injury of rats in the MT group was improved ; the levels of GSH and SOD in the lung tissue were increased (P＜0. 05) ，and the level of 8-OHdG was decreased (P＜0. 05) ; the levels of TNF-α , IL-6，and IL-1 β in the alveolar lavage fluid were de- creased (P＜0. 05) ; and the expression levels of the Nrf2 and HO-1 proteins in the lung tissue were increased (P ＜0. 05) ．p-NF-κB protein expression level was decreased (P ＜0. 05) ; the relative mRNA expression levels of Nrf2 and HO-1 in lung tissues were increased (P＜0. 05) ，and the relative mRNA expression level of Keap1 was decreased (P＜0. 05) in lung tissues，and all of them were in a dose-dependent manner． Conclusion MT can al- leviate oxidative stress and inflammatory responses and mitigate FA exposure-induced acute lung injury by regula- ting the Nrf2 / Keap1 / HO-1 signaling pathway.

Objective:To evaluate the reliability and validity of the Chinese version of HEMO-FISS-QoL(HF-QoL) questionnaire (HF-QoL-C) in the Chinese population with hemorrhoids.Methods:From November 2021 to November 2022, a self-constructed general information questionnaire, HF-QoL-C, and the 36-item short form health survey (SF-36), Goligher classification, and Giordano severity of hemorrhoid symptom questionnaire (GSQ) were used to conduct a questionnaire survey on 760 hemorrhoid patients in the anorectal department of six hospitals. The data was analyzed for reliability and validity using SPSS 21.0 and AMOS 26.0 software.Results:The Cronbach's α coefficient of HF-QoL-C and its dimension ranged from 0.831 to 0.960, and the split coefficient was 0.832-0.915. Four common factors were extracted through principal component exploratory factor analysis. Confirmatory factor analysis indicated acceptable structural validity( χ2/ df=8.152, RSMEA=0.097, CFI=0.881, IFI=0.881, NFI=0.867). HF-QoL-C was correlated with SF36 and GSQ( r=-0.694, 0.501, both P<0.01). There were differences in the total score and dimensional scores of HF-QoL-C between surgical and drug treated patients, different grades of Goligher classification for hemorrhoidal disease, and different ranges of hemorrhoid prolapse (all P<0.001). No ceiling effect was found in the total score and the scores of each dimension(0.3%-2.0%). There was a floor effect in both psychological function and sexual activity dimensions (16.7%, 35.1%). Conclusion:HF-QoL-C has good reliability and validity, which can be used to measure the quality of life of Chinese hemorrhoid patients.