Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective To retrospectively analyze multicenter data from domestic sources, aiming to explore the link between intrahepatic cholangiocarcinoma (ICC) tumor size and prognosis, establishing a classification system based on tumor size. Methods Between December 2011 and September 2018, 280 ICC patients from 13 hospitals were included. The tumor size prognosis cutoff was identified by the minimum P-value method, and the classification's overall survival related effectiveness was assessed by Kaplan-Meier analysis. Results All 280 patients were divided into the group of tumor maximum diameter ≤4 cm and >4 cm. Tumor size was confirmed as an independent prognosis factor by multivariate COX regression analysis (HR=2.110, 95% CI: 1.358-3.280). Conclusions The tumor size dichotomy classification system based on the Chinese patient group can expediently predict ICC prognosis and offers an important basis for selecting post-operative individualized adjuvant therapy and follow up plans.

Objective:To evaluate the alveolar ridge preservation effect of immediate implantation at extraction site with the im-proved CBCT measuring method.Methods:Eighty patients with extraction site were divided into test group A,B,C and control group.The patients were treated by means of immediate implant placement combined with large flap surgery,guided bone regener-ation(GBR)using mass Bio-Oss bone particles in the group A(the thickness of facial bone wall＜1 mm);The patients were trea-ted by means of immediate implant placement combined without flap surgery and bone graft in the group B(the thickness of facial bone wall ≥1 mm and＜2 mm)and C(the thickness of facial bone wall ≥2 mm),the CGF was implanted in the jumping space only when the thickness of jumping space was＞2 mm.In the control group,the alveolar sockets healed naturally without any in-tervention or treatment.CBCT was taken before surgery,immediately after surgery,and 6 months after surgery to evaluate the height and width of alveolar bone,the thickness of facial bone wall and jumping space.Results:The reduction of alveolar ridge height in group A,B,C and control group was(0.41±0.13,0.94±0.18,0.59±0.12,1.31±0.19)mm,The reduction of alveolar ridge width in group A,B,C and control group was(0.93±0.10,1.48±0.21,1.12±0.17,1.66±0.16)mum.The re-sults of four groups were statistically different(F=177.0,P＜0.001;F=125.3,P＜0.001).The alveolar ridge thickness of facial bone wall in group A,B,C and con-trol group was(0.98±0.25,2.39±0.28)mm,(1.43±0.52,2.10±0.33)mm,(2.17±0.41,2.79±0.27)mm before surgery and six months after immediate implantation.The results of each group were statistically different between before surgery and six months after immediate implantation(t=16.45,P＜0.001;t=7.357,P＜0.001;t=5.488,P＜0.001).Patients in three test groups had the thickness of jumping space＞2 mm and ≤2 mm,and the reduction of alveolar ridge width was(0.78±0.18,0.88±0.17)mm.The results were statistically different(t=17.18,P=0.018).Conclusion:The alveolar ridge preservation was obtained by means of immediate implant placement combined with large flap surgery,guided bone regeneration(GBR)using mass Bio-Oss bone particles at extraction site with the thickness of facial bone wall＜1 mm;The alveolar ridge preservation was obtained without flap surgery and GBR at extraction site with the thickness of facial bone wall≥1 mm.The preservation of soft and hard tissue was better in the axial palatal side of immediate implantation with the thickness of jumping space＞2 mm than that with the thickness of jumping space≤2 mm.

Background and Aims:Intrahepatic cholangiocarcinoma(ICC)is a highly malignant liver tumor,with an increasing incidence worldwide,particularly in Asia.Although radical surgical resection is currently the only potentially curative treatment,the high recurrence rate and low postoperative overall survival(OS)rate of ICC remain major clinical challenges.Adjuvant therapy(AT)and neoadjuvant therapy(NAT)are important strategies to reduce postoperative recurrence and prolong OS.Several studies have shown certain efficacy of these treatments.However,the specific efficacy and safety of combined NAT and AT in ICC treatment require further validation.This study was conducted to evaluate the value of combining NAT and AT in improving the therapeutic outcomes of ICC patients through a multicenter retrospective analysis,so as to provide scientific evidence for optimizing treatment strategies.Methods:The clinicopathologic data of 576 patients with ICC who underwent radical resection and were pathologically confirmed from 13 hospitals in China between December 2011 and December 2017 were retrospectively collected.Patients were grouped based on their treatment modality:NAT+AT group,AT group,and non-NAT/AT group.The three patient groups were matched pairwise in a 1∶1 ratio using propensity score matching(PSM)to balance baseline data.The Kaplan-Meier method was used to analyze OS and disease-free survival(DFS),and subgroup analyses were conducted according to the 8th edition of the AJCC TNM staging system.Results:A total of 395 ICC patients were included in the final analysis,with 42 patients(10.6%)in the NAT+AT group,62 patients(15.7%)in the AT group,and 291 patients(73.7%)in the non-NAT/AT group.Before PSM,significant differences were observed between groups in terms of CA19-9,liver function Child-Pugh classification,intraoperative blood loss,surgical margin,differentiation grade,vascular invasion,ECOG score,and lymph node dissection ratio(all P<0.05).After PSM,there were no significant differences in baseline characteristics between the groups(all P>0.05).After matching,the median OS and DFS in the NAT+AT group were significantly better than in the AT and non-NAT/AT groups(both P<0.05),while there were no significant differences in OS and DFS between the AT and non-NAT/AT groups(both P>0.05).Subgroup analysis showed that in TNM stage I patients,DFS in the NAT+AT group was significantly better than in the non-NAT/AT group(P<0.05),but OS was not significantly different(P>0.05).In TNM stage Ⅱ and Ⅲ patients,both OS and DFS in the NAT+AT and AT groups were significantly better than in the non-NAT/AT group(both P<0.05),and DFS in the NAT+AT group was significantly better than in the AT group in TNM stage Ⅲ patients(P<0.05).Conclusion:NAT combined with AT provides better survival benefits for patients with locally advanced ICC,but its benefit for early-stage ICC patients is limited.However,the retrospective design and sample size limitations of this study may affect the stability of the results,and future large-sample,multicenter,prospective studies are needed for further validation.

Objective:To evaluate the alveolar ridge preservation effect of immediate implantation at extraction site with the im-proved CBCT measuring method.Methods:Eighty patients with extraction site were divided into test group A,B,C and control group.The patients were treated by means of immediate implant placement combined with large flap surgery,guided bone regener-ation(GBR)using mass Bio-Oss bone particles in the group A(the thickness of facial bone wall＜1 mm);The patients were trea-ted by means of immediate implant placement combined without flap surgery and bone graft in the group B(the thickness of facial bone wall ≥1 mm and＜2 mm)and C(the thickness of facial bone wall ≥2 mm),the CGF was implanted in the jumping space only when the thickness of jumping space was＞2 mm.In the control group,the alveolar sockets healed naturally without any in-tervention or treatment.CBCT was taken before surgery,immediately after surgery,and 6 months after surgery to evaluate the height and width of alveolar bone,the thickness of facial bone wall and jumping space.Results:The reduction of alveolar ridge height in group A,B,C and control group was(0.41±0.13,0.94±0.18,0.59±0.12,1.31±0.19)mm,The reduction of alveolar ridge width in group A,B,C and control group was(0.93±0.10,1.48±0.21,1.12±0.17,1.66±0.16)mum.The re-sults of four groups were statistically different(F=177.0,P＜0.001;F=125.3,P＜0.001).The alveolar ridge thickness of facial bone wall in group A,B,C and con-trol group was(0.98±0.25,2.39±0.28)mm,(1.43±0.52,2.10±0.33)mm,(2.17±0.41,2.79±0.27)mm before surgery and six months after immediate implantation.The results of each group were statistically different between before surgery and six months after immediate implantation(t=16.45,P＜0.001;t=7.357,P＜0.001;t=5.488,P＜0.001).Patients in three test groups had the thickness of jumping space＞2 mm and ≤2 mm,and the reduction of alveolar ridge width was(0.78±0.18,0.88±0.17)mm.The results were statistically different(t=17.18,P=0.018).Conclusion:The alveolar ridge preservation was obtained by means of immediate implant placement combined with large flap surgery,guided bone regeneration(GBR)using mass Bio-Oss bone particles at extraction site with the thickness of facial bone wall＜1 mm;The alveolar ridge preservation was obtained without flap surgery and GBR at extraction site with the thickness of facial bone wall≥1 mm.The preservation of soft and hard tissue was better in the axial palatal side of immediate implantation with the thickness of jumping space＞2 mm than that with the thickness of jumping space≤2 mm.

Objective:To analyze the impact of lymph node dissection on textbook outcomes (TO) and the prognosis of intrahepatic cholangiocarcinoma (ICC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 376 ICC patients who underwent hepatectomy in 4 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from December 2011 to December 2017 were collected. There were 242 males and 134 females, aged 57(range, 48-63)years. According to the criteria of TO, patients were classified as two cate-gories, including patients achieving TO and not achieving TO. Measurement data with normal distri-bution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M(range) or M( Q1, Q3), and comparison between groups was conducted using the Mann-Whitney U test. Count data were represented as absolute numbers, and comparison between groups was conducted using the chi-square test, Yates adjusted chi-square test or Fisher exact probability. Comparison of ordinal data was conducted using the non-parameter rank sum test. Univariate and multivariate analyses were conducted using the Logistic regression model. The Kaplan-Meier method was used to draw survival curve. Survival analysis was conducted using the Log-rank test. Results:(1) TO situations. Of the 376 ICC patients who underwent hepatectomy, 199 cases achieved TO, including 40 cases with lymph node dissection and 159 cases without lymph node dissection, 177 cases did not achieve TO, including 76 cases with lymph node dissection and 101 cases without lymph node dissection. (2) Influencing factors for TO after hepatectomy of ICC patients. Results of multivariate analysis showed that lymph node dissection, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL were independent risk factors for achieving TO after hepatec-tomy of ICC patients ( odds ratio=2.22, 2.95, 3.58, 4.09,95% confidence interval as 1.34-3.69, 1.43-6.07, 1.40-9.17, 1.35-12.43, P<0.05). Of the 116 patients with lymph node dissection, 40 cases achieved TO, 103 cases achieved R 0 resection, 38 cases had postoperative complications, 67 cases had delayed hospital stay. The above indicators were 159, 255, 41, 65 of 260 patients without lymph node dissection. There were significant differences in the above indicators between patients with and without lymph node dissection ( χ2=22.90, 15.16, 13.95, 37.78, P<0.05). (3) Follow-up. All the 376 patients were followed up for 19(range, 1-74)months. Of 199 patients achieving TO, the 1-, 2-and 3-year survival rates of 40 patients with lymph node dissection were 54.0%, 36.6% and 26.1%, respectively, versus 67.7%, 42.7% and 34.4% of 159 patients without lymph node dissection, showing no significant difference between them ( χ2=1.89, P>0.05). Of 177 patients not achieving TO, the 1-, 2-and 3-year survival rates of 76 cases with lymph node dissection were 58.9%, 25.7% and 10.3%, respectively, versus 53.0%, 28.5% and 17.2% of 101 cases without lymph node dissection, showing no significant difference between them ( χ2=0.25, P>0.05). Conclusions:Lymph node dissec-tion, microvascular invasion, nerve invasion and the volume of intraoperative blood loss >800 mL are independent risk factors for achieving TO after hepatectomy of ICC patients. Lymph node dissec-tion may increase the postoperative complication rate, prolong the hospital stay and decrease the rate of achieving TO. However, it does not affect the prognosis of patients.

Objective:To study the effects of cathepsin K(CTSK)on the healing process of tooth extraction socket and type H blood vessel angiogenesis in mice.Methods:Ctsk knockout(Ctsk-/-)mice were generated by CRISPR/Cas9 technology,and genotype sequen-cing,general observation,Micro-CT and immunohistochemistry were performed to confirm successful knockout of Ctsk.Then 8 week-old WT and Ctsk-/-mice were used to establish the tooth extraction modle by extracting the left maxillary first molars,and the mice were sac-rificed at the day 7,10,14,21,28 and 35 respectively(n=3)after tooth extraction.Then samples were subjected to stereo microscope and Micro-CT examination.Immunofluorescence staining was used to study the effect of Ctsk knockout on type H blood vessel angiogene-sis.Results:Ctsk knockout did not affect the soft tissue healing of tooth extraction socket,but significantly promoted the bone healing process,and Ctsk deficency significantly enhanced type H blood vessel angiogenesis in the tooth extraction socket.Conclusion:Ctsk knockout can enhance type H vessel angiogenesis,and promote bone healing process of tooth extraction socket in mice.

Objective To establish and validate a Nomogram model for predicting the overall survival(OS)of the patients with intrahepatic cholangiocarcinoma(ICC)based on domestic multicenter data,and screen the beneficiaries of adjuvant chemotherapy based on the prediction model.Methods From December 2011 to December 2017,the data of 278 patients with postoperative pathological diagnosis of ICC from 4 medical centers in our country were collected retrospectively COX regression model was used to screen the independent risk factors of OS and constructed a Nomogram model.This model was used to stratify the risk of OS for all patients and to screen the beneficiaries of adjuvant chemotherapy.Results A total of 278 patients were enrolled,and 23 cases(8.3%)received adjuvant chemotherapy.COX multivariate analysis showed that drinking history,ECOG score,method of hepatectomy,lymph node status,number of tumors,and tumor differentiation were independent risk factors for postoperative OS.The Nomogram model had a C-index of 0.690(95%CI:0.646-0.734)in the training cohort and 0.740(95%CI:0.863-0.617)in the validation cohort.According to risk stratification by Nomogram model,in the high-risk group there was a statistically significant difference in survival between adjuvant chemotherapy and non-adjuvant chemotherapy(P=0.033),whereas in the low-risk group,there was no significant difference in survival(P=0.59).Conclusions Nomogram model based on independent risk factors of OS demonstrated excellent predictive capability for survival and could be used to screen,and identify the patients with ICC who benefit from adjuvant chemotherapy.

To promote the development of extracellular vesicles of herbal medicine especially the establishment of standardization, led by the National Expert Committee on Research and Application of Chinese Herbal Vesicles, research experts in the field of herbal medicine and extracellular vesicles were invited nationwide with the support of the Expert Committee on Research and Application of Chinese Herbal Vesicles, Professional Committee on Extracellular Vesicle Research and Application, Chinese Society of Research Hospitals and the Guangdong Engineering Research Center of Chinese Herbal Vesicles. Based on the collation of relevant literature, we have adopted the Delphi method, the consensus meeting method combined with the nominal group method to form a discussion draft of "Consensus statement on research and application of Chinese herbal medicine derived extracellular vesicles-like particles (2023)". The first draft was discussed in online and offline meetings on October 12, 14, November 2, 2022 and April and May 2023 on the current status of research, nomenclature, isolation methods, quality standards and research applications of extracellular vesicles of Chinese herbal medicines, and 13 consensus opinions were finally formed. At the Third Academic Conference on Research and Application of Chinese Herbal Vesicles, held on May 26, 2023, Kewei Zhao, convenor of the consensus, presented and read the consensus to the experts of the Expert Committee on Research and Application of Chinese Herbal Vesicles. The consensus highlights the characteristics and advantages of Chinese medicine, inherits the essence, and keeps the righteousness and innovation, aiming to provide a reference for colleagues engaged in research and application of Chinese herbal vesicles at home and abroad, decode the mystery behind Chinese herbal vesicles together, establish a safe, effective and controllable accurate Chinese herbal vesicle prevention and treatment system, and build a bridge for Chinese medicine to the world.

Objective:To observe the efficacy of hypertonic dextrose injection(prolotherapy)at retrodiscal tissue in the treatment of chronic joint pain in patients with temporomandibular disorders(TMD).Methods:From June 2012 to March 2022,244 patients(aged 16 to 75 years)underwent the treatment were included and classified according to DC/TMD.The treatment started from an anesthetic in-jection of 2％lidocaine(1.5-2 mL)into the retrodiscal tissue.The patients were then instructed to perform mandibular condylar exercise for 5-10 min,prior to the therapeutic injection of 50％dextrose(1-1.5 mL)by using the same method.Assessment of TMJ pain and jaw function was performed at 2 weeks,2,6 and 12 months after injection.Results:By March 2022,221 cases completed the final sur-vey(the rate of loss of follow-up was 9.4％),the average follow-up time was(75.7±25.1)months.2 weeks after treatment,there was significant relief of joint pain,and mandibular function was significantly improved in most patients by 2 month after treatment.Of these,186 cases achieved profound pain relief and faily normal jaw function,17 cases with recurrence of joint pain and jaw dysfunction and op-ted for occlusal splint treatment due to fear of injection,16 cases claimed no obvious therapeutic effect but rejected any further tratment,2 cases subsequently accepted TMJ surgery.There was no worsening of TMD or other complication as a result of the treatment.Conclu-sion:Hypertonic dextrose injection in retrodiscal tissue attachment is straightforward,safe and effective in the treatment of chronic joint pain and TMD.