Animal experiments are an essential component of life sciences and medical research. However, the external validity and reliability of individual animal studies are frequently challenged by inherent limitations such as small sample sizes, high design heterogeneity, and poor reproducibility, which impede the effective translation of research findings into clinical practice. Systematic reviews and meta-analysis represent a key methodology for integrating existing evidence and enhancing the robustness of conclusions. Currently, however, the application of systematic reviews and meta-analysis in the field of animal experiments lacks standardized guidelines for their conduct and reporting, resulting in inconsistent quality and, to some extent, diminishing their evidence value. To address this issue, this paper aims to systematically delineate the reporting process for systematic reviews and meta-analysis of animal experiments and to propose a set of standardized recommendations that are both scientific and practical. The article's scope encompasses the entire process, from the preliminary preparatory phase [including formulating the population， intervention， comparison and outcome （PICO） question, assessing feasibility, and protocol pre-registration] to the key writing points for each section of the main report. In the core methods section, the paper elaborates on how to implement literature searches, establish eligibility criteria, perform data extraction, and assess the risk of bias, based on the Preferred Reporting Items for Systematic Reviews and Meta-analysis （PRISMA) statement, in conjunction with relevant guidelines and tools such as Animal Research： Reporting of in Vivo Experiments （ARRIVE) and a risk of bias assessment tool developed by the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE). For the presentation of results, strategies are proposed for clear and transparent display using flow diagrams and tables of characteristics. The discussion section places particular emphasis on how to scientifically interpret pooled effects, thoroughly analyze sources of heterogeneity, evaluate the impact of publication bias, and cautiously discuss the validity and limitations of extrapolating findings from animal studies to clinical settings. Furthermore, this paper recommends adopting the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology to comprehensively grade the quality of evidence. Through a modular analysis of the entire reporting process, this paper aims to provide researchers in the field with a clear and practical guide, thereby promoting the standardized development of systematic reviews and meta-analysis of animal experiments and enhancing their application value in scientific decision-making and translational medicine.

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

ObjectiveTo investigate the protective effect and mechanism of action of flavonoid combination of Alpiniae Officinarum Rhizoma （A. officinarum） against Helicobacter pylori （H. pylori） gastritis in mice. MethodsAfter acclimatization for one week， 56 SPF-grade healthy C57BL/6J mice were gavaged with mixed antibiotics for three consecutive days. They were randomly divided into a normal group， model group， positive drug group （triple therapy group）， and low- and high-dose groups （100， 200 mg·kg^-1） of flavonoid combination of A. officinarum. The H. pylori gastritis mice model was established by gavage with H. pylori bacterial suspension in each group except for the normal group. After successful modeling， mice were administrated with corresponding drugs once a day for two weeks. Hematoxylin-eosin （HE） staining was used to observe the pathological changes in gastric tissue. Rapid urease test paper was used to detect the positive rate of H. pylori. Silver staining was used to observe the H. pylori adherence on the surface of gastric tissue. Immunohistochemistry was used to detect the protein expression of interleukin-8 （IL）-8 and myeloid differentiation factor （MyD88） in gastric tissue. The serum levels of IL-6， tumor necrosis factor-α （TNF-α）， IL-8， and IL-1β were detected by enzyme-linked immunosorbent assay （ELISA）. The expressions of phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） protein were detected by Western blot. ResultsCompared with those in the normal group， mice in the model group had lower gastric weight coefficients， higher pH of gastric juice， 100% H. pylori infection rate， and significantly changed gastric histopathology. The expressions of IL-8 and MyD88 proteins in the gastric tissue of mice in the model group were significantly elevated， and the serum levels of inflammatory factors IL-6， TNF-α， IL-8， and IL-1β were significantly up-regulated in mice. Compared with that in the model group， the gastric weight coefficient of mice in each treatment group of the flavonoid combinations of A. officinarum was elevated （P<0.01）， and the pH of gastric juice was reduced （P<0.01）. The infection rate of H. pylori was reduced. The expressions of IL-8 and MyD88 proteins in the gastric tissue of mice in the treatment groups were significantly reduced （P<0.01）， and the serum levels of inflammatory factors IL-6， TNF-α， IL-8， and IL-1β were significantly reduced in a dose-dependent manner （P<0.01）. The flavonoid combinations of A. officinarum down-regulated the expression of PI3K and Akt proteins in H. pylori gastritis-infected cells （P<0.01）. ConclusionThe protective effect of flavonoid combinations of A. officinarum against H. pylori gastritis is associated with the inhibition of H. pylori infection rate and regulation of PI3K/Akt signaling pathway， resulting in inhibiting the release of inflammatory factors.

Objective:To explore the acupoint selection law of acupuncture and moxibustion in the treatment of broca aphasia after stroke.Methods:RCT articles about acupuncture and moxibustion treatment for broca aphasia after stroke were retrieved from CNKI, VIP, Wanfang Data, China Medical Journal Full-text Database, SinoMed, PubMed, Web of Science and Embase database from the establishment of the databases to May 31, 2024. Excel 2021, SPSS Statistics 27.0, SPSS Modeler 18.0 and Cytoscape 3.9.1 software were used to analyze the frequency of acupoint, clustering, association rules and core co-occurrence network.Results:A total of 87 articles were included, involving 100 acupuncture and moxibustion prescriptions and 101 acupoints/acupoint area, involving 6 types, including Lianquan (CV 23) (35 times), Jinjin (EX-HN12) (35 times) and Yuye (EX-HN13) (34 times). The selected acupoints were mainly distributed in the head, face, neck and lower limbs, and the meridians were mainly Governor Vessel and Conception Vessel; the specific acupoints were mainly original acupoints, followed by collaterals acupoints, and scalp acupuncture was used most frequently in special acupuncture (88 times). According to the clustering analysis of high-frequency acupoints/acupoint area, there were five effective groups, such as "Jinjin (EX-HN12)-Yuye (EX-HN13)-Lianquan (CV 23)-Baihui (GV 20)-Yamen (GV 15)". The core co-occurrence network analysis showed that the acupoints used most frequently were Lianquan (CV 23) and Jinjin (EX-HN12), and the highest correlation between the two acupoints was Jinjin (EX-HN12)-Yuye (EX-HN13).Conclusions:Acupuncture and moxibustion for the treatment of broca aphasia after stroke is often based on "awakening the brain as the outline, benefiting the marrow as the foundation, and resuscitation". Under the guidance of the theory of Zang-fu meridians and collaterals, through dredging the meridians and collaterals, tonifying the brain and opening and closing the sound, the recovery of language function can be achieved.

Objective To investigate the correlations of serum dual-specific phosphatase 1(DUSP1)and soluble cluster of differentiation 93(sCD93)with severity of disease,lung function and airway inflammation in children with acute-phase bronchial asthma(BA).Methods A total of 100 children with acute-phase BA(acute-phase group),100 children with remission-phase BA(remis-sion-phase group),and 100 healthy children(control group)in the Xingyuan Hospital of Yulin from January 2021 to January 2023 were selected,and the acute-phase group was further divided into mild subgroup(n=47),moderate subgroup(n=36)and severe subgroup(n=17)according to the se-verity of the disease.Serum DUSP1,sCD93 levels and lung function indexes[peak expiratory flow(PEF),percentage of forced expiratory volume in the first second compared to the expected value(FEV1％pred)],and airway inflammation indexes[eosinophil(EOS)count,fractional exhaled nitric oxide(FeNO)]were measured.Pearson's method was used to analyze the correlations of serum DUSP1 and sCD93 levels with PEF,FEV1％pred,EOS and FeNO in children with acute-phase BA.Results The levels of serum DUSP1,PEF,and FEV1％pred in the acute-phase group were signifi-cantly lower than those in the remission-phase group and the control group,while the levels of sCD93,EOS count and FeNO were significantly higher than those in the remission-phase group and the control group(P＜0.01).The levels of serum DUSP1,PEF and FEV1％pred in the severe subgroup were significantly lower than those in the moderate and mild subgroups,while the levels of sCD93,EOS count and FeNO were significantly higher than those in the moderate and mild sub-groups(P＜0.01).PEF and FEV1％pred were positively correlated with serum DUSP1 level,but negatively correlated with sCD93 level in children with acute-phase BA(P＜0.01).EOS count and FeNO were negatively correlated with serum DUSP1 level,but positively correlated with sCD93 level(P＜0.01).Conclusions The decreased serum DUSP1 level and increased sCD93 level in chil-dren with acute-phase BA are closely related to the aggravation of the disease,the decrease of lung function,and airway inflammation,which may become new targets for the treatment of children with acute-phase BA.

Objective:To explore the correlation between intrahepatic cholestasis of pregnancy(ICP)and ad-verse pregnancy outcomes.Methods:A total of 511 singleton pregnant women with ICP treated at The Third Affili-ated Hospital of Guangzhou Medical University from August 2017 to January 2024 were selected as the study sub-jects.Among them,patients were divided into the adverse pregnancy outcome group(n=49)and the control group without adverse pregnancy outcomes(n=462).The general and clinical data of the two groups were com-pared and analyzed.Results:①General situation:The number of pregnancies and deliveries,ICU transfer rate,total hospital stay,and total hospitalization costs were significantly higher in the adverse pregnancy outcome group compared to the control group(P<0.05).The number of prenatal check-ups,diagnostic gestational weeks,and gestational weeks at delivery were significantly lower compared to the control group(P<0.05).②Clinical symp-toms:The incidence of itching in the adverse pregnancy outcome group was lower compared to the control group(10.2%vs.26.6%,P<0.05),while other symptoms such as rash,fatigue,jaundice,and gastrointestinal symp-toms showed no significant difference between the two groups(P>0.05).③Laboratory examinations:Compared with the control group,patients in the adverse pregnancy outcome group had significantly the increased levels of alanine aminotransferase,aspartate aminotransferase,uric acid,urea nitrogen,and triglycerides,and significantly the decreased levels of alkaline phosphatase and fasting blood glucose,with statistical significance(P<0.05).Other biochemical indicators showed no significant difference between the two groups(P>0.05).④ICP grading and complications:The proportion of early-onset ICP,severe and very severe ICP in the adverse pregnancy out-come group was significantly higher compared to the control group(P<0.001);the proportion of adverse preg-nancy outcome group with pregnancy-induced hypertension was significantly higher compared to the control group;the incidence of preterm birth,fetal growth restriction,meconium-stained amniotic fluid,and fetal distress in the adverse pregnancy outcome group was significantly higher compared to the control group(P<0.001).⑤Neo-natal outcomes:The neonatal Apgar scores(1 min,5 min,10 min)and neonatal weight in the adverse pregnancy outcome group were lower compared to the control group(P<0.001),and the incidence of mild neonatal asphyx-ia was significantly higher,with a statistically significant difference(P<0.001).Conclusions:The severity of ICP is closely related to the occurrence of adverse pregnancy outcomes.Therefore,it is clinically necessary to pay at-tention to the grading of ICP,closely monitor the levels of total bile acids and liver enzymes,and try to avoid ad-verse pregnancy outcomes,especially intrauterine fetal death.

Objective:To explore the correlation between intrahepatic cholestasis of pregnancy(ICP)and ad-verse pregnancy outcomes.Methods:A total of 511 singleton pregnant women with ICP treated at The Third Affili-ated Hospital of Guangzhou Medical University from August 2017 to January 2024 were selected as the study sub-jects.Among them,patients were divided into the adverse pregnancy outcome group(n=49)and the control group without adverse pregnancy outcomes(n=462).The general and clinical data of the two groups were com-pared and analyzed.Results:①General situation:The number of pregnancies and deliveries,ICU transfer rate,total hospital stay,and total hospitalization costs were significantly higher in the adverse pregnancy outcome group compared to the control group(P<0.05).The number of prenatal check-ups,diagnostic gestational weeks,and gestational weeks at delivery were significantly lower compared to the control group(P<0.05).②Clinical symp-toms:The incidence of itching in the adverse pregnancy outcome group was lower compared to the control group(10.2%vs.26.6%,P<0.05),while other symptoms such as rash,fatigue,jaundice,and gastrointestinal symp-toms showed no significant difference between the two groups(P>0.05).③Laboratory examinations:Compared with the control group,patients in the adverse pregnancy outcome group had significantly the increased levels of alanine aminotransferase,aspartate aminotransferase,uric acid,urea nitrogen,and triglycerides,and significantly the decreased levels of alkaline phosphatase and fasting blood glucose,with statistical significance(P<0.05).Other biochemical indicators showed no significant difference between the two groups(P>0.05).④ICP grading and complications:The proportion of early-onset ICP,severe and very severe ICP in the adverse pregnancy out-come group was significantly higher compared to the control group(P<0.001);the proportion of adverse preg-nancy outcome group with pregnancy-induced hypertension was significantly higher compared to the control group;the incidence of preterm birth,fetal growth restriction,meconium-stained amniotic fluid,and fetal distress in the adverse pregnancy outcome group was significantly higher compared to the control group(P<0.001).⑤Neo-natal outcomes:The neonatal Apgar scores(1 min,5 min,10 min)and neonatal weight in the adverse pregnancy outcome group were lower compared to the control group(P<0.001),and the incidence of mild neonatal asphyx-ia was significantly higher,with a statistically significant difference(P<0.001).Conclusions:The severity of ICP is closely related to the occurrence of adverse pregnancy outcomes.Therefore,it is clinically necessary to pay at-tention to the grading of ICP,closely monitor the levels of total bile acids and liver enzymes,and try to avoid ad-verse pregnancy outcomes,especially intrauterine fetal death.

Objective The objective of this study was to analyze the incidence and mortality of malignant tumors in Fuqing city in 2019,as well as and the trend changes from 2015 to 2019.Methods The data of tumor registration in Fuqing city in 2019 were collected and organized.The crude incidence and mortality of tumor,China age-standardized rates,world standard rates and cu-mulative rate(0-74 years old),age-specific rate,and the top 10 malignant tumor incidence and mortality order were calculated.The China age-standardized rate and World age-standardized rate were calculated based on the Chinese standard population from the 2000 National Population Census(ASRC)and Segi′s World standard population(ASRW),respectively.The Joinpoint software was used to calculate the annual percentage change(APC)of incidence/mortality from 2015 to 2019.Results In 2019,the crude incidence of new malignant tumors in Fuqing city was 343.76/100,000(346.30/100,000 for male and 341.06/100,000 for females),ASRC rate was 255.78/100,000,ASRW rate was 244.91/100,000,and the cumulative rate(0-74 years old)was 27.75%.In 2019,the crude mortality of malignant tumors in Fuqing city was 163.63/100,000(212.26/100,000 for male and 111.95/100,000 for female),AS-RC rate was 110.82/100,000,ASRW rate was 107.82/100,000,and the cumulative rate(0-74 years old)was 12.07%.The top 10 incidence of cancers were lung cancer,thyroid cancer,female breast cancer,liver cancer,stomach cancer,colorectum cancer,cervix cancer,esophagus cancer,prostate cancer and brain tumors,accounting for about 80.96%of all cancers.The top 10 mortality of canc-ers were lung cancer,liver cancer,stomach cancer,esophageal cancer,colorectal cancer,female breast cancer,prostate cancer,brain tumors,pancreas cancer and cervix cancer,accounting for about 81.03%of all cancer deaths.From 2015 to 2019,the overall inci-dence of malignant tumors in Fuqing city showed a fluctuating upward trend(APC=1.41%,P>0.05),and the overall mortality showed a slight downward trend(APC=-0.8%,P>0.05),but the changing trends were not statistically significant.Conclusion The overall incidence and mortality of malignant tumors in Fuqing city are at a high level.Lung cancer,thyroid cancer and digestive system malignant tumors are the key malignant tumors endangering the health of residents in Fuqing city,and monitoring and prevention should be strengthened.

Objective To screen the anti-Helicobacter pylori gastritis active components of the ethyl acetate extract of Alpinia officinarum Hance.Methods The"knock-out"strategy combined with high-performance liquid chromatography(HPLC)detection was developed to separate the components of the ethyl acetate extract of A.officinarum while obtaining the negative samples without the components.A human gastric epithelial cell(GES-1)model of H.pylori gastritis was established,and the levels of interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),interleukin-8(IL-8)and interleukin-1β(IL-1β)in the supernatant of the cells were determined by enzyme-linked immunosorbent assay(ELISA).Results The total flavonoid fraction,the negative fraction without total diphenylheptanoids,the negative fraction without 5-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-phenyl-3-heptanone(DHPA),and galangin significantly reduced IL-6 levels in the supernatant of H.pylori infected GES-1 cells at a concentration of 8 μg·mL-1 with 24 h incubation.The total flavonoid fraction strongly inhibited the release of IL-6,TNF-α,IL-8,and IL-1β from H.pylori gastritis GES-1 cells at a concentration of 16 μg·mL-1.Conclusions The total flavonoid fraction is the major anti-H.pylori gastritis active component of the ethyl acetate extract of A.officinarum.The results lay the foundation for further elucidation of the material basis of A.officnarum against H.pylori gastritis.

[Purpose]To analyze the epidemic characteristics and survival trends of upper gas-trointestinal cancer in Fujian cancer registration areas from 2011 to 2020.[Methods]Cancer regi-stration data in Fujian Province was collected to calculate the crude incidence and mortality rate,age-standardized incidence/mortality rates by Chinese standard population(ASIRC,ASMRC)and by world standard population(ASIRW,ASMRW)and cumulative rate of 0～74 years old of upper gastrointestinal cancer(including esophageal and gastric cancers)as well as the corresponding temporal trends from 2011 to 2020.Using the Joinpoint software to calculate the annual percent-age change(APC)and average annual percentage change(AAPC)to analyze the trends.The data were divided into two time periods(2011-2015 and 2016-2020)to compare the 5-year relative survival rates of upper gastrointestinal cancer.[Results]From 2011 to 2020,there were 26 286 new cases of upper gastrointestinal cancer in Fujian cancer registration areas,accounting for 20.28％of all malignant tumors.The incidence rate,ASIRC and ASIRW of upper gastrointestinal cancer was 56.52/105,42.55/105,and 42.75/105,respectively,and the cumulative incidence rate(0～74 years old)was 5.32％.Incidence of upper gastrointestinal cancer was higher in men than that in women.The incidence of upper gastrointestinal cancer showed an decreasing trend from 2011 to 2020,with an AAPC of ASIRC of-4.7％(95％CI:-6.6％～-2.9％).There were 11 680 new cases of esophageal cancer in Fujian cancer registration areas,the crude incidence,ASIRC,ASIRW and cumulative incidence(0～74 years old)of esophageal cancer were 25.12/105,18.67/105,18.97/105,and 2.32％,respectively.There were 14 606 gastric cancer new cases in Fujian cancer registration areas during 2011-2020,the crude mortality,ASMRC,ASIRW and cumulative mortality(0～74 years old)of gastric cancer were 31.41/105,23.88/105,23.78/105,and 3.00％,respectively.There were 20 133 upper gastrointestinal cancer deaths during 2011-2020 in Fujian cancer registration areas,accounting for 26.05％of all cancer deaths.The crude mortality,ASMRC and ASMRW of upper gastrointestinal cancer was 43.29/105,31.95/105,and 31.89/105,respectively,the cumu-lative mortality rate(0～74 years old)was 3.84％.The mortality of upper gastrointestinal cancer was higher in men than that in women.The mortality rate of upper gastrointestinal cancer showed a trend of first increase and then decrease,with an APC of 3.5％(95％CI:-0.5％～11.3％)from 2011 to 2014 and-5.2％(95％CI:-8.4％～3.7％)from 2014 to 2020.There were 9 643 deaths of esophageal cancer during 2011-2020 in Fujian cancer registration areas.The crude mortality,ASMRC,ASMRW and cumulative mortality rate(0～74 years old)of esophageal cancer was 20.74/105,15.20/105,15.35/105,and 1.83％,respectively.There were 10 490 deaths of gastric cancer dur-ing 2011-2020 in Fujian cancer registration areas.The crude mortality,ASMRC,ASMRW and cumulative mortality rate(0～74 years old)of gastric cancer was 22.56/105,16.75/105,16.54/105,and 2.00％,respectively.The 5-year relative survival rate for upper gastrointestinal cancer patients during 2011-2015 and 2016-2020 were 24.74％(95％CI:23.92％～25.56％)and 25.49％(95％CI:24.65％～26.34％),respectively.The 5-year relative survival rate for esophageal cancer patients during 2011-2015 and 2016-2020 were 17.15％(95％CI:16.10％～18.22％)and 18.72％(95％CI:17.59％～19.88％),respectively.The 5-year relative survival rate for gastric cancer patients during 2011-2015 and 2016-2020 were 30.90％(95％CI:29.71％～32.10％)and 30.76％(95％CI:29.56％～31.97％),respectively.There was a decreasing trend in 5-year survival of upper gastroin-testinal patients with increasing age,with lower survival rate in patients over 65 years old.[Con-clusion]The incidence and mortality of upper gastrointestinal cancer in Fujian cancer registration areas showed an overall decreasing trend,and the 5-year relative survival rate improved slightly,while the disease burden of upper gastrointestinal cancer remains heavy.Incidence and mortality of upper gastrointestinal cancer of men were higher than those of women,and the elderly patients with upper gastrointestinal cancer had a poorer prognosis.Fujian should pay close attention to the prevention and control of gastric cancer among key groups,and strengthen its comprehensive pre-vention and control ability of upper gastrointestinal cancer.