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.

The study explores the traditional Chinese medicine （TCM） diagnostic and treatment approach to coronary microvascular disease （CMVD） from the perspective of "disharmony of blood collaterals and dysfunction of qi transformation". It is proposed that the core pathogenesis of CMVD lies in these two mechanisms. From an integrative medicine perspective， different CMVD types are analyzed based on their specific pathogenesis. Through clinical practice， four targeted treatment methods， i.e. warming， unblocking， tonifying， and activating， are formulated. CMVD caused by atherosclerosis is primarily associated with myocardial ischemia， myocardial infarction， and coronary revascularization， with corresponding pathological mechanisms of latent pathogenic obstruction， toxic accumulation in the collaterals， and deficiency with collateral stasis. The disease progression exhibits characteristics of correlation， staging， and transformation. Accordingly， treatment principles include warming to assist qi transformation， unblocking obstruction and dispelling turbidity， activating to disperse toxic stasis and invigorate collaterals， and tonifying to eliminate stasis and nourish collaterals. For CMVD unrelated to atherosclerosis， attention should be paid to the underlying disease， analyzing the main syndromes of blood and collateral disharmony. An approach combining disease-syndrome differentiation with blood and collateral regulation is emphasized for precise treatment.

OBJECTIVE To analyze the clinical characteristics of aplastic anemia （AA）/pure red cell aplasia （PRCA） induced by pembrolizumab， and provide reference for clinical safe drug use. METHODS Using search terms as “pembrolizumab”， “keytruda”， “anemia” and “aplastic anemia” in both Chinese and English， the literature related to AA/PRCA induced by pembrolizumab were retrieved from PubMed， Embase， CNKI， Wanfang and VIP databases， and then analyzed descriptively and statistically. RESULTS A total of 10 patients were included from 10 literature； among these 10 patients， there were 5 males and 5 females， with 5 patients being aged 65 or above. The primary disease was mainly metastatic melanoma （4 cases）. AA/PRCA occurred 13 d-3 years after the first dose of pembrolizumab. The main clinical manifestations included fatigue， dyspnea， oral/nasal bleeding， diffuse purpura， etc.； 8 cases developed moderate anemia and 2 cases developed severe anemia. After discontinuation and receiving supportive therapy， 5 cases improved， 1 case worsened in anemia， and 4 cases died. CONCLUSIONS When using pembrolizumab in clinical practice， blood routine should be regularly monitored. When AA/PRCA and other related symptoms occur， pembrolizumab should be stopped in time and a therapy regimen should be formulated according to the patient’ condition， to ensure the safety of medication.

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: To investigate the influencing factors of overactive bladder (OAB) in college freshmen and the impacts of OAB on their mental health, quality of life and social interaction. Methods: An epidemiological questionnaire survey was conducted in an anonymous manner on the prevalence of OAB among 5300 freshmen aged 17 to 22 years enrolled in the 2023—2024 academic year in Xinxiang Medical University and Sanquan College of Xinxiang Medical University.The questionnaire included questions on basic information, history of urinary tract infection, constipation, smoking, history of alcohol consumption, history of coffee/strong tea drinking, history of carbonated beverage drinking, redundant prepuce, phimosis, holding urine, chronic insomnia, self-rating anxiety scale (SAS), quality of life score (QoL), and social avoidance and distress scale (SADS).The influencing factors of OAB were analyzed with multivariate logistic regression analysis.The subjects were grouped according to whether they had OAB, and the differences in SAS, QoL and SADS between the OAB group and non-OAB group were compared.The impacts of OAB on the anxiety level, quality of life, and social interaction were analyzed with multiple linear regression analysis. Results: The overall prevalence rate of OAB was 4.9% (244/5018).Multivariate logistic regression analysis showed that the history of urinary tract infection (OR=0.177), constipation (OR=0.636), smoking (OR=0.582), alcohol consumption (OR=0.685), coffee/strong tea drinking (OR=0.387), carbonated beverage drinking (OR=0.631), redundant prepuce (OR=0.673), phimosis (OR=0.311), urine holding (OR=0.593), and chronic insomnia (OR=0.256) were influencing factors for the occurrence of OAB (P＜0.05).The OAB group had higher SAS score [(41.18±6.54) vs. (38.61±6.36)], QoL score [(3.65±1.20) vs. (2.79±0.95)], social avoidance score [(6.25±1.86) vs. (5.86±1.51)], social distress score [(6.27±1.59) vs. (5.97±1.32)], and total SADS score [(12.51±2.35) vs. (11.84±2.01)] than the non-OAB group (P＜0.05).The results of multiple linear regression analysis showed that OAB could independently affect the scores of QoL, SAS, and SADS.The OAB group had higher scores of QoL, SAS, and SADS compared with the non-OAB group (P＜0.001). Conclusion: History of urinary tract infection, constipation, smoking, alcohol consumption, coffee/strong tea drinking, carbonated beverage drinking, redundant prepuce, phimosis, urine holding, and chronic insomnia are influencing factors for the occurrence of OAB in male college students.Moreover, OAB has negative impacts on their mental health, quality of life, and social interaction.

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.

ObjectiveTo investigate the influence of triglyceride （TG）/high-density lipoprotein cholesterol （HDL-C） ratio on the onset of primary liver cancer. MethodsA prospective cohort study was conducted. Physical examination data were collected from 99 750 cases of on-the-job and retired employees of Kailuan Group who participated health examination from July 2006 to December 2007， and they were followed up till December 31， 2021 to observe the onset of primary liver cancer. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Kruskal-Wallis H test was used for comparison of continuous data with skewed distribution between multiple groups； the chi-square test was used for comparison of categorical data between groups. According to the tertiles of TG/HDL-C ratio， the subjects were divided into Q1， Q2， and Q3 groups， and the incidence density of primary liver cancer was calculated for each group. The Kaplan-Meier method was used to calculate the cumulative incidence rate of primary liver cancer in each group， and the log-rank test was used to compare the difference in cumulative incidence rate between groups. The Cox proportional hazards model was used to analyze the influence of TG/HDL-C ratio on the onset of primary liver cancer. ResultsThere were significant differences between the three groups in age， proportion of male subjects， waist circumference， body mass index， fasting blood glucose， systolic pressure， diastolic pressure， triglyceride， total cholesterol， HDL-C， low-density lipoprotein cholesterol， alanine aminotransferase， high-sensitivity C-reactive protein， chronic liver diseases， hypertension， diabetes， the family history of malignant tumor， drinking， smoking， physical exercise， and educational level （P<0.05）. During the mean follow-up time of 14.06±2.71 years， there were 484 cases of new-onset liver cancer， among whom there were 446 male subjects and 38 female subjects. The incidence density of primary liver cancer was 0.39/1 000 person-years in the Q1 group， 0.35/1 000 person-years in the Q2 group， and 0.30/1 000 person-years in the Q3 group， and the cumulative incidence rates of primary liver cancer in the three groups were 6.03‰， 5.28‰， and 4.49‰， respectively， with a significant difference between the three groups based on the long-rank test （χ²=6.06， P=0.048）. After adjustment for the confounding factors considered， the Cox proportional hazards model showed that compared with the Q3 group， the Q1 group had a hazard ratio of 2.04 （95% confidence interval ［CI］： 1.61‍ ‍—‍ ‍2.58， P_{for trend}<0.05）， and the Q2 group had a hazard ratio of 1.53 （95%CI： 1.21‍ ‍—‍ ‍1.92， P_{for trend}<0.05）. ConclusionThe reduction in TG/HDL-C ratio is associated with an increase in the rask of primary liver cancer， especially in people with chronic liver diseases.

Objective:To investigate the effects of unilateral ureteral obstruction on renal pelvic peristalsis and pacemaker cells in neonatal rats.Methods:An animal experimental study.Thirty-six 2-day-old newborn SD rats were randomly divided into the partial unilateral ureteral obstruction (PUUO) group, complete unilateral ureteral obstruction (CUUO) group, and sham operation group, with 12 rats in each group.One week after surgery, all rats were subjected to renal pelvic pressure (RPP) measurement by puncture.After measurement, the rats were euthanized, and their left renal pelvis and ureter were removed and fixed for histological examination.Parameters such as RPP, peristaltic wave frequency and amplitude at different perfusion speeds were recorded and compared, and the changes in pacemaker cells (atypical smooth muscle cells and Cajal-like interstitial cells) were also compared.The independent samples t-test was used for comparison between 2 groups, and the one-way ANOVA of variance was used for comparison among 3 groups. Results:In the sham operation group, the RPP increased gradually with the increase of perfusion speed; the frequency of peristaltic waves rose rapidly and then dropped after reaching the highest level with the increase of perfusion speed; similarly, the amplitude of peristaltic waves first increased and then decreased as the perfusion speed increased.In the PUUO group, the RPP increased rapidly with the increase of perfusion speed, higher than that in the sham operation group; the frequency of peristaltic waves was higher than that in the sham operation group, and it was relatively constant under the perfusion speed of 40 mL/h, but when the perfusion speed increased again, the frequency began to decline; the amplitude of peristaltic waves increased quickly and then declined at a faster rate than the sham operation group with the increase of perfusion speed.In the CUUO group, the basic RPP was 12 cmH 2O(1 cmH 2O=0.098 kPa); at the perfusion speed of 5 mL/h, the RPP rose gradually, and no plateau appeared; when the RPP reached 73 cmH 2O, the perfusate retrograded from the side of the puncture needle, then the RPP slightly decreased and then balanced, and no regular peristaltic waves were observed in the renal pelvis throughout the whole perfusion process.Immunofluorescence staining analysis showed the pacemaker cells were all located in the smooth muscle of the renal pelvic wall.The sham operation group had the highest positive rate, followed by the PUUO group and then the CUUO group. Conclusions:Ureteral obstruction has a significant impact on the peristalsis of the renal pelvis, and its impact on the peristaltic wave frequency and amplitude and RPP can be predicted.The reduction of pacemaker cells in the renal pelvis may be involved in the changes of renal pelvic peristalsis caused by ureteral obstruction, but further research is needed on how pacemaker cells regulate the peristalsis of the renal pelvis and ureter.

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.

Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.