ObjectiveTo explore the regulation of hypothalamic-pituitary-gonadal （HPG） axis by modified Erxian decoction in rats with perimenopausal syndrome （PMS） and to further analyze the expression of proteins related to the silent information regulator 1 （SIRT1）/hypothalamic kisspeptin （Kisspeptin）/gonadotropin-releasing hormone （GnRH） signaling pathway in the arcuate nucleus region （ARC） of the hypothalamus， so as to reveal the potential target of action and molecular biological mechanism of modified Erxian decoction for the treatment of perimenopausal syndrome. MethodsAn animal model was established via the incomplete castration method， with successful modeling confirmed by the exfoliated cervical cell smear method. The 48 rats were divided into six groups based on the randomization principle after successful modeling， including a sham operation group， a model group， an estradiol valerate group （0.09 mg∙kg^-1∙d^-1）， high-， medium-， and low-dose modified Erxian decoction groups （7.614， 3.807，1.903 5 g∙kg^-1∙d^-1）， with 8 rats in each group. The estradiol valerate group and the high-， medium- and low-dose modified Erxian decoction groups were continuously administered by gavage for 28 days， and the indicators were detected 24 hours after the last administration. Body weights and uterine indices were measured. The pathological changes of the uterus were observed by hematoxylin-eosin （HE） staining. Enzyme-linked immunosorbent assay （ELISA） was performed to measure the levels of estradiol （E₂）， follicle-stimulating hormone （FSH）， luteinizing hormone （LH）， and gonadotropin-releasing hormone （GnRH）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to determine the expression levels of SIRT1， Kisspeptin， kisspeptin receptor （GPR54）， and GnRH in the ARC region of the hypothalamus and gonadotropin-releasing hormone receptor （GnRH-R） in pituitary. ResultsCompared with the sham operation group， rats in the model group had a significantly increased body weight （P0.01）， reduced wet weight and index of uterus （P0.01）， endometrial thinning or atrophy， glandular atrophy， and a decreasing number of glands. Additionally， serum levels of E₂ and the expression of SIRT1 in the ARC region of the hypothalamus significantly decreased （P0.01）. Serum levels of FSH， LH， and GnRH， the expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus， and GnRH-R in pituitary significantly increased （P0.01）. Compared with the model group， the estradiol valerate group and the high-， medium-dose modified Erxian decoction groups had significantly reduced body weight， serum levels of FSH， LH， and GnRH， and expression of Kisspeptin， GPR54， and GnRH in the ARC region of the hypothalamus and GnRH-R in pituitary （P0.05， P0.01） and significantly increased wet weight and index of uterus， serum level of E₂， and expression of SIRT1 in the ARC region of the hypothalamus （P0.05， P0.01）. In addition， they showed thickened endometrium， increased number of endometrial glands， and improved glandular atrophy. ConclusionModified Erxian decoction regulates the function of the HPG axis through multi-targets， and its mechanism of action may be related to the up-regulation of the expression of SIRT1 in the ARC region of the hypothalamus， the inhibition of the over-activation of the Kisspeptin/GnRH signaling pathway， the regulation of the expression of GnRH-R in the pituitary， the restoration of secretion balance of gonadotropins， and the elevation of the estrogen level. This study provides an experimental basis for the interpretation of the scientific connotation of modified Erxian decoction in the treatment of perimenopausal syndrome and a theoretical reference for the development of a novel therapeutic strategy based on the SIRT1/Kisspeptin/GnRH pathway.

BACKGROUND:Due to the very limited ability of articular cartilage to repair itself,articular cartilage defects caused by natural degeneration or trauma often cannot be repaired on their own,which triggers or aggravates osteoarthritis and even leads to severe disability.Therefore,the repair treatment after articular cartilage injury has become an urgent clinical problem. OBJECTIVE:To summarize the hot research topics and development trends in the field of articular cartilage repair using bibliometric analysis. METHODS:Literature related to articular cartilage repair was searched from the Web of Science Core Collection from 2000 to 2023,and bibliometric and visualization analyses were carried out using VOSviewer,Citespeace and Bibliometrix R-package. RESULTS AND CONCLUSION:The annual publication volume in the field of articular cartilage repair shows an overall increasing trend,with the United States,China,and Germany being the top three countries in terms of publication volume,and the research institutions focus on universities and hospitals,with Harvard University,New York Hospital for Special Surgery,and Shanghai Jiao Tong University being the top three institutions in terms of publication volume.AMERICAN JOURNAL OF SPORTS MEDICINE is the journal that publishes the most research literature in the field,and BIOMATERIALS is the journal with the highest number of citations in the field."Injectable hydrogels for cartilage and bone tissue engineering"is the most cited document published in the last decade,and the author with the most publications is Madry Henning,an active author in the field.The active authors in this field have formed a number of stable research teams with each other,and the cooperation between different teams needs to be further strengthened.Intra-articular injections,high tibial osteotomies,hydrogels,drug delivery,inflammation,cartilage regeneration,and scaffolds are the current hot topics of research in this field,and the application of 3D printing technology,bio-inks,silk proteins,injectable hydrogels,and exosomes in articular cartilage repair may be the frontier of research in this field.Integrating various innovative technologies and methods for more effective,durable and functional cartilage tissue regeneration and repair,and facilitating the clinical translation of the relevant technologies and methods by conducting more high-quality clinical studies may be the future research trend in this field.

Objective:A mouse silicosis model was constructed by injecting silicon dioxide (SiO 2) particles into the trachea to explore the effect and mechanism of Cordyceps cicadae polysaccharides (CCP) on ameliorating pulmonary fibrosis in silicosis mice. Methods:In May 2023, CCP were extracted and isolated, the monosaccharide composition and functional group composition were analyzed by high performance liquid chromatography and Fourier transform infrared spectroscopy. C57BL/6J mice were injected with 50 μl 50 mg/ml SiO 2 suspension to construct silicosis mouse model, which were then randomly divided into model group, CCP intervention groups [low dose group (LCCP group), medium dose group (MCCP group) and high dose group (HCCP group) ], the control group was administered by physiological saline, 8 mice in each group. Mice in the CCP intervention groups received oral gavage administration once daily with CCP solution (100, 200 and 400 mg/kg), while control group and model group received physiological saline, lasted for 30 days. The body weight of mice was recorded and the lung coefficient was calculated. The pathomorphological changes of mouse lung tissue were determined by HE and Masson staining. The contents of fibrosis indexes [hydroxyproline acid (HYP), connective tissue growth factor (CTGF) and matrix metallopeptidase 2 (MMP-2) ] of lung tissue and the pro-inflammatory factors[tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) ] of lung tissue and alveolar lavage fluid were determined by ELISA. The expression level of Collagen Ⅰ was determined by immunohistochemistry. The relative protein expression levels of transforming growth factor-β1 (TGF-β1), P-Smad2, α-smooth muscle actin (α-SMA), Toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κBp65) and myeloid differentiation primary response gene 88 (MyD88) in lung tissue were determined by Western blot. Results:The total sugar content of the CCP was 86.78%, composed of D-mannose, D-rhamnose, D-glucose and D-galactose, with a molar ratio of 12.71∶1.53∶1.00∶12.64. The infrared spectrum indicated the characteristic groups of its polysaccharides. Compared with the control group, the body weight of mice in the model group was decreased, lung coefficient was increased, the contents of HYP, CTGF and MMP-2 in lung tissue were increased, and the contents of TNF-α, IL-1β and IL-6 in lung tissue and alveolar lavage fluid were increased ( P<0.05). The mice lung showed massive inflammatory cell infiltration and collagen fiber deposition, and the silicosis fibrosis was severe. The expression of CollagenⅠin lung tissue of model group was increased, and the proteins expression levels of TGF-β1, P-Smad2/Smad2, α-SMA, TLR4, NF-κBp65 and MyD88 were increased in mouse lung tissue ( P<0.05). Compared with the model group, the body weights of mice in the MCCP and HCCP groups were increased, the lung coefficients were decreased, the contents of HYP, CTGF and MMP-2 in lung tissue were decreased, and the contents of TNF-α, IL-1β and IL-6 in lung tissue and alveolar lavage fluid were decreased ( P<0.05). The inflammatory cell infiltration in the lung was reduced, and the degree of fibrosis was improved to varying degrees. The expression level of CollagenⅠwas down-regulated in the lung tissue of MCCP and HCCP groups, and the protein expression levels of TGF-β1, P-Smad2/Smad2, α-SMA, TLR4, NF-κBp65 and MyD88 were decreased in lung tissue ( P<0.05) . Conclusion:The CCP could reduce the levels of fibrosis-related indicators and pro-inflammatory factors in lung tissue, ameliorating mouse lung inflammation and silicosis fibrosis caused by SiO 2 particles by inhibiting the activation of TGF-β1/Smad pathway and TLR4/nuclear factor kappa-B (NF-κB) pathway.

Objective:A mouse silicosis model was constructed by injecting silicon dioxide (SiO 2) particles into the trachea to explore the effect and mechanism of Cordyceps cicadae polysaccharides (CCP) on ameliorating pulmonary fibrosis in silicosis mice. Methods:In May 2023, CCP were extracted and isolated, the monosaccharide composition and functional group composition were analyzed by high performance liquid chromatography and Fourier transform infrared spectroscopy. C57BL/6J mice were injected with 50 μl 50 mg/ml SiO 2 suspension to construct silicosis mouse model, which were then randomly divided into model group, CCP intervention groups [low dose group (LCCP group), medium dose group (MCCP group) and high dose group (HCCP group) ], the control group was administered by physiological saline, 8 mice in each group. Mice in the CCP intervention groups received oral gavage administration once daily with CCP solution (100, 200 and 400 mg/kg), while control group and model group received physiological saline, lasted for 30 days. The body weight of mice was recorded and the lung coefficient was calculated. The pathomorphological changes of mouse lung tissue were determined by HE and Masson staining. The contents of fibrosis indexes [hydroxyproline acid (HYP), connective tissue growth factor (CTGF) and matrix metallopeptidase 2 (MMP-2) ] of lung tissue and the pro-inflammatory factors[tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β) and interleukin-6 (IL-6) ] of lung tissue and alveolar lavage fluid were determined by ELISA. The expression level of Collagen Ⅰ was determined by immunohistochemistry. The relative protein expression levels of transforming growth factor-β1 (TGF-β1), P-Smad2, α-smooth muscle actin (α-SMA), Toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κBp65) and myeloid differentiation primary response gene 88 (MyD88) in lung tissue were determined by Western blot. Results:The total sugar content of the CCP was 86.78%, composed of D-mannose, D-rhamnose, D-glucose and D-galactose, with a molar ratio of 12.71∶1.53∶1.00∶12.64. The infrared spectrum indicated the characteristic groups of its polysaccharides. Compared with the control group, the body weight of mice in the model group was decreased, lung coefficient was increased, the contents of HYP, CTGF and MMP-2 in lung tissue were increased, and the contents of TNF-α, IL-1β and IL-6 in lung tissue and alveolar lavage fluid were increased ( P<0.05). The mice lung showed massive inflammatory cell infiltration and collagen fiber deposition, and the silicosis fibrosis was severe. The expression of CollagenⅠin lung tissue of model group was increased, and the proteins expression levels of TGF-β1, P-Smad2/Smad2, α-SMA, TLR4, NF-κBp65 and MyD88 were increased in mouse lung tissue ( P<0.05). Compared with the model group, the body weights of mice in the MCCP and HCCP groups were increased, the lung coefficients were decreased, the contents of HYP, CTGF and MMP-2 in lung tissue were decreased, and the contents of TNF-α, IL-1β and IL-6 in lung tissue and alveolar lavage fluid were decreased ( P<0.05). The inflammatory cell infiltration in the lung was reduced, and the degree of fibrosis was improved to varying degrees. The expression level of CollagenⅠwas down-regulated in the lung tissue of MCCP and HCCP groups, and the protein expression levels of TGF-β1, P-Smad2/Smad2, α-SMA, TLR4, NF-κBp65 and MyD88 were decreased in lung tissue ( P<0.05) . Conclusion:The CCP could reduce the levels of fibrosis-related indicators and pro-inflammatory factors in lung tissue, ameliorating mouse lung inflammation and silicosis fibrosis caused by SiO 2 particles by inhibiting the activation of TGF-β1/Smad pathway and TLR4/nuclear factor kappa-B (NF-κB) pathway.

Objective:To investigate the correlation between serum vitamin D and the risk of pre-eclampsia at the early, middle and late stages of pregnancy.Methods:Pregnant women who registered and delivered in Electric Power Teaching Hospital of Capital Medical University from August 2020 to July 2021 were included. Pregnant women with pre-eclampsia during pregnancy were selected as the case group (150 cases), while pregnant women without any complications after delivery were selected as the control group (600 cases) according to the 1∶4 matching principle (age, pre-pregnancy body mass index and last menstruation). The levels of serum vitamin D in differences stages of pregnancy between the two groups were compared. Logistic regression model was used to analyze the association between serum vitamin D levels and the risk of pre-eclampsia.Results:The levels of serum vitamin D at the early, middle and late stages of pregnancy in the case group were lower than those in the control group: (14.32 ± 3.61) μg/L vs. (18.78 ± 4.73) μg/L, (15.06 ± 3.12) μg/L vs. (19.88 ± 4.25) μg/L, (16.04 ± 3.51) μg/L vs. (22.04 ± 5.63) μg/L, there were statistical differences ( P<0.05). Taking pregnant women with adequate serum Vitamin D as a reference, and adjusting for confounding factors such as gain weight and primipara, the risk of pre-eclampsia in early stages pregnant women with serum Vitamin D serious deficiency, middle deficiency and deficiency was increased and the OR and 95% CI were 4.84(1.25 -31.42), 3.09(1.12 - 8.96), 1.48(1.12 - 13.05); the risk of pre-eclampsia in middle stages pregnant women with serum vitamin D serious deficiency, middle deficiency and deficiency was increased and the OR(95% CI) were 4.43(1.23 - 13.55), 2.22(1.05 - 6.78), 1.12(0.45 - 7.73); the risk of pre-eclampsia in late stages pregnant women with serum vitamin D serious deficiency, middle deficiency and deficiency was increased and the OR(95% CI) were 2.13(1.12 - 8.64), 1.76(1.02 - 4.98), 1.22(0.72 - 3.94). Conclusions:The level of serum vitamin D is associated with the risk of pre-eclampsia in pregnant women in the early, middle and late stages of pregnancy, and the risk of pre-eclampsia is significantly increase when the level of serum vitamin D is severely deficient or deficient during pregnancy.

Objective:To investigate the application value of metagenomic next generation sequencing (mNGS) in the diagnosis of spinal infectious diseases except tuberculosis and non-tuberculous mycobacterium infection.Methods:According to the inclusion and exclusion criteria, the clinical data of 171 patients with suspected non-tuberculous infectious diseases of spine from January 2019 to November 2020 were analyzed retrospectively. All patients underwent puncture biopsy of spine or surgery to obtain tissue specimens, then tissue biopsy were measured, and Foci purulent blood or lavage fluid was obtained for routine bacterial and mNGS. The differences of reporting time, sensitivity (positive rate) and specificity (true negative rate) were compared between the two methods. The pathogenic microorganism spectrum of spinal infection was analyzed. The effects of specimen collection method, preoperative antibiotic use and specimen type on the detection of pathogenic microorganisms were analyzed.Results:According to the diagnostic criteria of non-tuberculous infectious diseases of the spine, there were 136 cases of infection, among which 111 cases had specific pathogenic microorganism. The average reporting time of traditional culture and mNGS were 81.67+15.52 h and 36.33+11.92 h. There were 43 positive cases and 5 false positive cases in traditional culture, the sensitivity was 31.62%, and the specificity was 85.71%; There were 76 positive cases and 19 false positive cases in mNGS, the sensitivity was 55.88%, and the specificity was 45.71%. There were significant statistical differences in the sensitivity, specificity and reporting time for detection of pathogenic microorganisms by mNGS. The top 3 pathogens of non-specific infection were Staphylococcus aureus and Staphylococcus, Escherichia coli and Streptococcus. Eleven patients with non-tuberculous specific infection were confirmed, including 2 positive cases with traditional culture, 11 positive cases with mNGS. A higher detection rate for rare specific infections were expressed in mNGS. Logistic regression analysis indicated that the standard antibiotic use 4 weeks before surgery and specimen acquisition methods had significant effects on the traditional culture results, while the specimen acquisition methods had no statistically significant effects on the mNGS.Conclusion:Metagenomic next generation sequencing has a higher sensitivity to the detection of pathogenic microorganisms in the diagnosis of non-tuberculous spinal infectious diseases, especially for the detection of rare pathogenic microorganisms, which has a high diagnostic value.

Objective:To study the clinical effect of different doses of ulinastatin combined with glutamine in treatment of acute severe pancreatitis.Methods:70 patients with acute severe pancreatitis patients admitted in our hospital from Jan. 2017 to Oct. 2019 were enrolled. According to the different dosage of ulinastatin, these patients were divided into 200 000 IU ulinastatin combined with glutamine group (200 000 IU combination group) , 400 000 IU ulinastatin combined with glutamine group (400000 IU combination group) , and 600 000 IU ulinastatin combined with glutamine group (600 000 IU combination group) . The study compared the 1-week mortality rate, abdominal pain relief time, respiratory frequency and heart rate back to normal time, blood amylase, glucose, C-reactive protein, procalcitonin levels, and white blood cell (WBC) count among the different groups.Results:The mortality of 400 000 IU combined group and 600 000 IU combined group were 4.35% and 5.56% respectively, which were significantly lower than 31.58% and 35% of the control group and 200 000 IU combined group ( P< 0.05) . The time of abdominal pain relief, respiratory rate and heart rate returning to normal in the 400 000 IU combined group were (7.21±1.25) d, (8.54±1.83) d and (9.54±2.23) d respectively, and (7.52±1.83) d, (8.13±1.75) d and (9.37±2.31) d in the 600 000 IU combined group, which were significantly lower than (9.12±2.78) d, (9.85± 3.16) d and (10.86±2.68) d in the control group and (8.76±1.96) d, (8.76±1.96) d and (10.62±1.43) d in the 200 000 IU combined group ( P<0.05) , There was no significant difference between the control group and the 200 000 IU combination group ( P>0.05) . Compared with the control group, there were significant differences in blood glucose, CRP and leukocyte count in different doses of ulinastatin+ glutamine treatment group ( P<0.05) ; However, there was no significant difference in blood glucose and CRP levels between different doses of ulinastatin+ glutamine treatment group ( P>0.05) , but compared with 200 000 IU combination group and 400 000 IU combination group, the leukocyte level of 600 000 combination group was significantly higher ( P<0.05) . Conclusion:ulinastatin combined with glutamine can significantly improve the clinical prognosis of patients with severe acute pancreatitis, but the clinical effect varies with the dose of ulinastatin. Conclusion Ulinastatin combined with glutamine can significantly improve the clinical prognosis of patients with acute severe pancreatitis, but the clinical effect varies with the dose of ulinastatin.

Objective:To examine the role of the number of lymph nodes examined(NLNE) on the prognosis of patients with curatively resected gallbladder carcinoma(GBC).Methods:The clinicopathological data and prognosis of 401 patients with GBC who underwent radical surgery from six institutions of China from January 2013 to December 2017 were analyzed retrospectively. There were 153 males(38.2%) and 248 females(61.8%), with age of (62.0±10.5) years (range: 30-88 years). Fifty-three patients(22.2%) were accompanied by jaundice. All patients underwent radical resection+regional lymphadenectomy.R0 or R1 resection was confirmed by postoperative pathological examination.The different cut-off values of NLNE were determined by the X-tile software, the optimal cut-off values were identified by analyzing the relationship between different cut-off values of NLNE with survival rate. Kaplan-Meier method was used for survival analysis. Univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:Among the 401 patients enrolled, 135 cases (33.6%) had lymphatic metastasis, of which 98 cases were in N1 stage(24.4%) and 37 cases were in N2 stage(9.2%).A total of 2 794 NLNE were retrieved, with a median count of 6 (5).The median positive lymph nodes count was 0 (1), and the median positive lymph nodes ratio was 0 (IQR, 0-0.2). Since the 12 and 15 were determined as the cut-off values by X-tile, all patients were divided into three groups of 1-11, 12-15 and ≥16.The 3-year survival rate of the three groups was 45.2%, 74.5%, 12.0% respectively, with statistically significant difference between three groups (χ 2=10.94, P<0.01). The results of multivariate analysis showed that NLNE was an independent prognostic factor for overall survival ( P<0.05). Further analysis was performed specifically for subgroup of T stages. For T1b patients, the prognosis of the NLNE with 1-7 group was significantly better than that of the ≥8 group(χ 2=4.610, P<0.05). For T2 patients, the prognosis of the TLNE ≥7 group was significantly better than that of 1 -6 group (χ 2=4.287, P<0.05). For T3 and T4 patients, the prognosis of the TLNE with 12 - 15 group was significantly better than that of 1 -11 group (χ 2=5.007, P<0.01) and ≥16 group (χ 2=10.158, P<0.01). Conclusions:The NLNE is an independent factor affecting the prognosis of patients with GBC.For patients with stage T1b,8 lymph nodes should be retrieved; for patients with stage T2,extensive dissection of more than 6 lymph nodes can significantly improve the prognosis.For advanced patients (stages T3 and T4), extensive dissection with 12-15 lymph nodes is recommended. However, it fails to get more survival benefits by dissecting more than 16 lymph nodes.

Objective:To examine the role of the number of lymph nodes examined(NLNE) on the prognosis of patients with curatively resected gallbladder carcinoma(GBC).Methods:The clinicopathological data and prognosis of 401 patients with GBC who underwent radical surgery from six institutions of China from January 2013 to December 2017 were analyzed retrospectively. There were 153 males(38.2%) and 248 females(61.8%), with age of (62.0±10.5) years (range: 30-88 years). Fifty-three patients(22.2%) were accompanied by jaundice. All patients underwent radical resection+regional lymphadenectomy.R0 or R1 resection was confirmed by postoperative pathological examination.The different cut-off values of NLNE were determined by the X-tile software, the optimal cut-off values were identified by analyzing the relationship between different cut-off values of NLNE with survival rate. Kaplan-Meier method was used for survival analysis. Univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.Results:Among the 401 patients enrolled, 135 cases (33.6%) had lymphatic metastasis, of which 98 cases were in N1 stage(24.4%) and 37 cases were in N2 stage(9.2%).A total of 2 794 NLNE were retrieved, with a median count of 6 (5).The median positive lymph nodes count was 0 (1), and the median positive lymph nodes ratio was 0 (IQR, 0-0.2). Since the 12 and 15 were determined as the cut-off values by X-tile, all patients were divided into three groups of 1-11, 12-15 and ≥16.The 3-year survival rate of the three groups was 45.2%, 74.5%, 12.0% respectively, with statistically significant difference between three groups (χ 2=10.94, P<0.01). The results of multivariate analysis showed that NLNE was an independent prognostic factor for overall survival ( P<0.05). Further analysis was performed specifically for subgroup of T stages. For T1b patients, the prognosis of the NLNE with 1-7 group was significantly better than that of the ≥8 group(χ 2=4.610, P<0.05). For T2 patients, the prognosis of the TLNE ≥7 group was significantly better than that of 1 -6 group (χ 2=4.287, P<0.05). For T3 and T4 patients, the prognosis of the TLNE with 12 - 15 group was significantly better than that of 1 -11 group (χ 2=5.007, P<0.01) and ≥16 group (χ 2=10.158, P<0.01). Conclusions:The NLNE is an independent factor affecting the prognosis of patients with GBC.For patients with stage T1b,8 lymph nodes should be retrieved; for patients with stage T2,extensive dissection of more than 6 lymph nodes can significantly improve the prognosis.For advanced patients (stages T3 and T4), extensive dissection with 12-15 lymph nodes is recommended. However, it fails to get more survival benefits by dissecting more than 16 lymph nodes.

Objective To investigate the application value of choledochoscopy and imaging examination in the diagnosis and treatment of residual bile duct stones.Methods The retrospective descriptive study was conducted.The clinical data of 618 patients who underwent choledochoscopy and imaging examination after operation of hepatolithiasis in the First Affiliated Hospital of Zhengzhou University between April 2014 and September 2018 were collected,including 300 males and 318 females,aged from 19 to 89 years,with an average age of (58 ± 12)years.Observation indicators:(1) situations of residual bile duct stones diagnosed by choledochoscopy and imaging examination;(2) stone extraction situations of patients with hepatolithiasis.Measurement data with normal distribution were represented as Mean±SD,and measurement data with skewed distribution were described as M (range).Count data were represented as absolute number or percentage,and analyzed using the chi-square test or Fisher exact propability.Results (1) Situations of residual bile duct stones diagnosed by choledochoscopy and imaging examination:all the 618 patients underwent choledochoscopy,and 505 of them underwent the imaging examination before choledochoscopy.① Of patients undergoing single imaging examination,72 received ultrasonography,with false-negative rate of 29.17％ (21/72);37 received CT examination,with false-negative rate of 10.81％(4/37);33 received T-tube cholangiography,with false-negative rate of 39.39％ (13/33).② Of patients undergoing combined two imaging examinations,61 received ultrasonography + CT,with false-negative rate of 8.20％ (5/61);129 received ultrasonography + T-tube cholangiography,with false-negative rate of 12.40％ (16/129);52 received CT + T-tube cholangiography,with false-negative rate of 5.77％(3/52).③ There were 121 receiving ultrasound+CT+T-tube cholangiography,with false-negative rate of 7.44％ (9/121).There were statistically significant differences in the false-negative rates of combined two or three examinations of ultrasound + CT+ T-tube cholangiography and single imaging examination (x2=40.83,P＜0.05).The further analysis showed a statistically significant difference among the single imaging examination (x2=7.70,P＜0.05).There was no statistically significant difference among the combined two of imaging examinations (x2=2.10,P＞0.05).There were statistically significant differences in the combined three examinations of ultrasound +CT+T-tube cholangiography and ultrasound and T-tube cholangiography examination respectively (x2=16.23,21.62,P＜0.05).There was no statistically significant difference in the combined three of imaging examinations and CT examination and combination of CT+T-tube cholangiography respectively (P＞ 0.05).There was no statistically significant difference in the combined three of imaging examinations and combination of ultrasound+CT examinations and combination of ultrasound+T-tube cholangiography (x2=0.33,1.71,P＞0.05).Seventy-one patients without residual bile duct stone by preoperative imaging examination were detected residual bile duct stones by intraoperative choledochoscopy,and residual bile duct stones of 36,31 and 4 patients are respectively distributed around the distal common bile duct,small intrahepatic bile duct,left and right hepatic ducts,common hepatic duct and remaining common bile duct.(2) Stone extraction situations of patients with hepatolithiasis:of 618 patients,cases with 1,2,3,4,5,6,7,8,9 and 10 times of residual bile duct stones clearance were respectively 392,116,48,39,9,6,3,2,2 and 1.Residual bile duct stones clearance frequency of patients was an average of 1.73 times.There were 63.43％(392/618) and 96.28％(595/618) of patients had stone clearance with once and ≤ 4 times of stone extraction,respectively.Conclusion The negative results of preoperative imaging examinations cannot be as standards of bile duct stone clearance before choledochoscopy,and the best choice is to detect whether there are residual bile duct stones and remove the stones combined with choledochoscopy.