Objective To investigate the molecular mechanism by which Lichong Xiaozheng Granules(LCXZ)sensitize ovarian cancer to cisplatin(DDP)treatment.Methods LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage.In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts,the effects of daily gavage of distilled water(control group),intraperitoneal injection of DDP(5 mg/kg)once a week,or both DDP injection and daily LCXZK gavage(15 g/kg)on tumor growth were evaluated.Histopathological changes in the xenografts and kidneys were assessed with HE staining.RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis.The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting.Results A total of 218 blood-borne components of LCXZ were detected by LC-MS.In the tumor-bearing mice,treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3%and 72.6%compared with that in the control group,respectively.Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups.Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3(ANT3)with binding energies below-6 kcal/mol.Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice,and these changes were more pronounced in the combined treatment group.The expression levels of BAX,ANT3,cleaved caspase-3 and cleaved caspase-9 were increased,whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups.Conclusion LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.

OBJECTIVE: To investigate the clinical characteristics and genetic etiology of a Chinese pedigree affected with Hereditary dentin dysplasia type II (DD-II) due to variant of dentin sialophosphoprotein (DSPP) gene. METHODS: A child diagnosed with DD- II at the Third Clinical Division of Peking University Hospital of Stomatology in December 2021 and her family members were selected as study subjects. Clinical data were retrospectively analyzed. Saliva samples were collected from the proband, her parents and sister for genomic DNA extraction. Whole exome sequencing (WES) was carried out. Candidate variant was verified by Sanger sequencing and TOPO-TA cloning sequencing. The candidate variant was also subjected to bioinformatics analysis using Mutation Taster v2021. Secondary and tertiary structures of the wild-type and variant DSPP proteins were predicted with psipred v4.0 and PyMOL v2.3 software, respectively. The pathogenicity of the variant was classified based on the guidelines from American College of Medical Genetics and Genomics (ACMG). This study was approved by the Medical Ethics Committee of Peking University Hospital of Stomatology (Ethics No.: PKUSSIRB-202162021). RESULTS: The proband and her mother and sister had all exhibited typical clinical manifestations of hereditary DD-II. The primary dentition of the proband displayed yellowish brown discoloration, wear, and obliteration in the chamber and root canal, while the permanent teeth of the proband's sister and mother appeared nearly normal in both color and appearance, though with obliteration in the chamber and root canal. Her father showed normal dentition. WES identified a heterozygous c.1915_1918delAAGT, p.(Lys639Glnfs*674) frameshift variant in the DSPP gene. Sanger sequencing and TOPO-TA cloning sequencing confirmed the presence of this variant in the proband, the proband's sister, and the mother, while the proband's father was negative for the variant, indicating an autosomal dominant inheritance pattern. The variant was predicted to be pathogenic by Mutation Taster v2021. Prediction of the secondary structure of the DSPP protein showed that the variant has changed it from coil to helix. The tertiary structure prediction of the DSPP protein showed change of the spatial structure of the variant DSPP, with the loops in the variant region replaced by helices at multiple sites. Based on the guidelines from the ACMG, the variant was classified as pathogenic (PVS1+PM2_Supporting+PP1+PP4). CONCLUSION Phenotypic analysis and genetic testing of this family has clarified the clinical diagnosis of hereditary DD- II. The c.1915_1918delAAGT variant probably underlay the pathogenesis of DD-II in this family. Above results have expanded the phenotypic spectrum of the disease and may contribute to further clinical and genetic research on this disease.
Humans ; Pedigree ; Female ; Extracellular Matrix Proteins/chemistry* ; Male ; Sialoglycoproteins/chemistry* ; Dentin Dysplasia/genetics* ; Asian People/genetics* ; Phosphoproteins/chemistry* ; Child ; Mutation ; China ; Exome Sequencing ; Adult ; East Asian People

Objective To investigate the effect and safety of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy.Methods The subjects of this study,112 female patients who underwent axillary endoscopic thyroidectomy in our hospital from January 2022 to October 2024,were randomly divided into an observation group and a control group,each with 56 cases.All patients were administered with ultrasound-guided cervical plexus block followed by general anesthesia.The observation group was injected with 0.1 mg/kg of esketamine prior to anesthesia induction and continuously pumped with esketamine at a rate of 0.1 mg/(kg·h)during the operation until sutures were completed,while the control group was administered with an equal volume of normal saline following the same procedure.The vital sign indicators[mean arterial pressure(MAP),heart rate(HR)and percutaneous arterial oxygen saturation(SpO2)]immediately after establishing electrocardiogram monitoring(T0),immediately before tracheal intubation(T1),immediately after tracheal intubation(T2),immediately after skin incision(T3)and immediately after the operation(T4)were compared between the two groups.Surgical related indicators such as propofol dosage,remifentanil dosage,and extubation time were also compared between them.Pain visual analogue scale(VAS)scores were performed on patients from the two groups at 1,6,12,and 24 h postoperatively.The 40-item quality of recovery score(QoR-40)was used before the surgeries and 1 d after surgeries to assess the patients.Adverse reactions were also compared.Results The difference was significant in terms of MAP,HR time effect in the two groups(F=24.63,F=20.11,P<0.05)and inter-group MAP,HR values(F=13.54,F=11.49,P<0.05).There were statistically significant differences in the interaction effects of MAP and HR between the two groups(F=4.10,F=3.46,P<0.05).The difference was not statistically significant in time,inter group,and interaction effects of SpO2(P>0.05).The dosage of propofol,remifentanil,and postoperative 1 d drainage in the observation group were less than those in the control group,the differences were statistically significant(P<0.05).The differences were not statistically signiciant in extubation time and awakening time between the two groups(P>0.05).The VAS scores at 1,6,12,and 24 h after operation in the observation groups were lower than those in the control group,the differences were statistically significant(P<0.05).Physical comfort,pain dimension ratings,and total score of the QoR-40 scale:1)those 1 d after operation were lower than those before operation in both groups(P<0.05);2)1 d after operation:those in the control group were lower than those in the observation group(P<0.05).The control group witnessed a remarkable decrease in QoR-40 emotional state rating 1 d after operation than it did before operation(P<0.05),while no significant change was seen by the observation group in this regard(P>0.05).The incidence of coughing after extubation in the observation group was lower than that in the control group(14.29%and 37.50%),the difference was statistically significant(P<0.05).The differences were not statistically signiciant in the incidence of other adverse reactions such as nausea,vomiting,dizziness,headache,respiratory depression,awakening restlessness and awakening delirium between the two groups(P>0.05).The total incidence of adverse reactions in the observation group was significantly lower than that in the control group(25.00%and 66.07%,P<0.05).Conclusion The application of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy can significantly stabilize hemodynamics in patients,reduce postoperative pain,and promote postoperative recovery.It is worthy clinical application.

OBJECTIVES: To investigate the molecular mechanism by which Lichong Xiaozheng Granules (LCXZ) sensitize ovarian cancer to cisplatin (DDP) treatment. METHODS: LC-MS analysis was used to identify the blood components of LCXZ after its administration in mice via gavage. In a BALB/c mouse model bearing subcutaneous ovarian cancer xenografts, the effects of daily gavage of distilled water (control group), intraperitoneal injection of DDP (5 mg/kg) once a week, or both DDP injection and daily LCXZK gavage (15 g/kg) on tumor growth were evaluated. Histopathological changes in the xenografts and kidneys were assessed with HE staining. RNA-seq was performed to identify the differentially expressed genes followed by KEGG pathway analysis. The changes in mitochondrial ultrastructure and expressions of mitochondrial apoptosis-related were examined with transmission electron microscopy and Western blotting. RESULTS: A total of 218 blood-borne components of LCXZ were detected by LC-MS. In the tumor-bearing mice, treatments with DDP and DDP combined with LCXZ redcued the tumor volume by 60.3% and 72.6% compared with that in the control group, respectively. Transcriptomic analysis revealed significantly upregulated ANT3 expression in both the two treatment groups. Molecular docking indicated that the main active components of LCXZ were capable of binding to adenine nucleotide translocator 3 (ANT3) with binding energies below -6 kcal/mol. Transmission electron microscopy showed obvious mitochondrial swelling and outer-membrane damage in the tumor cells in DDP-treated mice, and these changes were more pronounced in the combined treatment group. The expression levels of BAX, ANT3, cleaved caspase-3 and cleaved caspase-9 were increased, whereas BCL-2 expression was decreased significantly in the tumor cells in both the DDP and DDP+LCXZ groups. CONCLUSIONS LCXZ enhances the therapeutic efficacy of cisplatin against ovarian cancer xenografts in mice by promoting mitochondrial dysfunction and activating apoptotic signaling pathways via upregulating ANT3.
Animals ; Female ; Cisplatin/pharmacology* ; Ovarian Neoplasms/metabolism* ; Apoptosis/drug effects* ; Mitochondria/metabolism* ; Drugs, Chinese Herbal/pharmacology* ; Mice, Inbred BALB C ; Mice ; Rats ; Xenograft Model Antitumor Assays ; Humans ; Cell Line, Tumor ; Antineoplastic Agents/pharmacology*

Objective:To investigate the follow-up colonoscopy of patients after colorectal adenoma (CRA) resection, so as to improve colonoscopy quality and reduce missed CRA diagnosis.Methods:A total of 189 patients after CRA resection who underwent follow-up colonoscopy from October 2020 to October 2021 were consecutively recruited. The effect of bowel preparation was evaluated by the Boston bowel preparation scale (BBPS). The location, the number, and gross morphology of adenomas during CRA resection and two colonoscopies during 1 year follow-up after the resection were recorded, and their correlation with major clinicopathologic features were analyzed, and the missed CRA in follow-up colonoscopy were also analyzed.Results:The BBPS scores of the right colon, transverse colon, left colon and total colon in 189 patients who underwent CRA resection were 1.93±0.42, 2.53±0.52, 2.77±0.45, and 7.22±1.03 points at the 1-year follow-up colonoscopy and 2.08±0.35, 2.70±0.46, 2.81±0.40, and 7.57±0.84 points at the time of CRA resection. Except for the left colon segment ( χ 2=0.98, P>0.05), the differences in other colon segments were significantly different ( P<0.05). At the time of CRA resection, 62, 66, 210 and 338 CRAs were detected in the right colon, transverse colon, left colon and total colon segments, respectively. At the 1-year follow-up colonoscopy, 21, 38, 49 and 108 CRAs were missed in the corresponding colon segments and total colon, respectively. CRA missed diagnosis was related to patient age (≥60 years accounting for 54.2%), gender (males accounting for 81.9%), adenoma location (predominantly in the left colon comprising 36.2%) and gross morphology (flat types representing 72.3%) ( P<0.05), but not related to being vegetarian, history of cholecystectomy or appendectomy, smoking or alcohol consumption, number of adenomas or pathological type ( P>0.05). Conclusion:The missed diagnosis of CRA in patients after CRA resection primarily involves the flat type adenomas, which is associated with the age, gender, adenoma location within the colon and the gross morphology.

Objective To investigate the effect and safety of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy.Methods The subjects of this study,112 female patients who underwent axillary endoscopic thyroidectomy in our hospital from January 2022 to October 2024,were randomly divided into an observation group and a control group,each with 56 cases.All patients were administered with ultrasound-guided cervical plexus block followed by general anesthesia.The observation group was injected with 0.1 mg/kg of esketamine prior to anesthesia induction and continuously pumped with esketamine at a rate of 0.1 mg/(kg·h)during the operation until sutures were completed,while the control group was administered with an equal volume of normal saline following the same procedure.The vital sign indicators[mean arterial pressure(MAP),heart rate(HR)and percutaneous arterial oxygen saturation(SpO2)]immediately after establishing electrocardiogram monitoring(T0),immediately before tracheal intubation(T1),immediately after tracheal intubation(T2),immediately after skin incision(T3)and immediately after the operation(T4)were compared between the two groups.Surgical related indicators such as propofol dosage,remifentanil dosage,and extubation time were also compared between them.Pain visual analogue scale(VAS)scores were performed on patients from the two groups at 1,6,12,and 24 h postoperatively.The 40-item quality of recovery score(QoR-40)was used before the surgeries and 1 d after surgeries to assess the patients.Adverse reactions were also compared.Results The difference was significant in terms of MAP,HR time effect in the two groups(F=24.63,F=20.11,P<0.05)and inter-group MAP,HR values(F=13.54,F=11.49,P<0.05).There were statistically significant differences in the interaction effects of MAP and HR between the two groups(F=4.10,F=3.46,P<0.05).The difference was not statistically significant in time,inter group,and interaction effects of SpO2(P>0.05).The dosage of propofol,remifentanil,and postoperative 1 d drainage in the observation group were less than those in the control group,the differences were statistically significant(P<0.05).The differences were not statistically signiciant in extubation time and awakening time between the two groups(P>0.05).The VAS scores at 1,6,12,and 24 h after operation in the observation groups were lower than those in the control group,the differences were statistically significant(P<0.05).Physical comfort,pain dimension ratings,and total score of the QoR-40 scale:1)those 1 d after operation were lower than those before operation in both groups(P<0.05);2)1 d after operation:those in the control group were lower than those in the observation group(P<0.05).The control group witnessed a remarkable decrease in QoR-40 emotional state rating 1 d after operation than it did before operation(P<0.05),while no significant change was seen by the observation group in this regard(P>0.05).The incidence of coughing after extubation in the observation group was lower than that in the control group(14.29%and 37.50%),the difference was statistically significant(P<0.05).The differences were not statistically signiciant in the incidence of other adverse reactions such as nausea,vomiting,dizziness,headache,respiratory depression,awakening restlessness and awakening delirium between the two groups(P>0.05).The total incidence of adverse reactions in the observation group was significantly lower than that in the control group(25.00%and 66.07%,P<0.05).Conclusion The application of esketamine combined with general anesthesia and ultrasound-guided cervical plexus block in axillary endoscopic thyroidectomy can significantly stabilize hemodynamics in patients,reduce postoperative pain,and promote postoperative recovery.It is worthy clinical application.

Objective To explore the diagnostic value of dual-low-dose CT energy spectral imaging combined with adaptive statis-tical iterative reconstruction-Veo(ASIR-V)in distinguishing benign and malignant thyroid nodules.Methods A total of 242 patients with thyroid nodules were included.In part Ⅰ,the initial 90 patients were randomly and equally assigned to the conventional scan group,the low radiation dose group,and the dual-low-dose group.Both subjective and objective image qualities,the radiation dose,and contrast agent dosage in these three groups were evaluated,respectively.In part Ⅱ,the remaining 152 patients underwent dual-low-dose CT energy spectral scanning.Radiographic features of thyroid nodules in benign and malinant groups were observed,fol-lowed by spectral imaging analysis.The iodine concentration(IC)value,normalized iodine concentration(NIC)value,effective atomic number(Eff-Z),and λHU value of benign and malignant nodules were measured and compared,respectively.Results There were significant differences in nodule morphology,sign of edge truncation,enhancement characteristics and nodule boundary enhancement between benign and malignant thyroid nodules(P<0.05).There were statistically significant differences in IC value,NIC value,and λHU value in the venous phase among the three groups(P<0.05).The sensitivity and specificity of IC,NIC,λHU were 81.6%and 60.0%,86.4%and 67.5%,88.8%and 65.0%,respectively.The area under the curve(AUC)of combining the three energy spectral parameters with radiographic fea-tures via binary logistic regression model was 0.905,and the sensitivity and specificity were 82.4%and 87.5%,respectively.The effective dose(ED)in the dual-low-dose group was reduced by 60.13%com-pared to the conventional scan group,and the contrast agent dos-age was reduced by 38.56%.Conclusion The dual-low-dose CT energy spectral imaging combined with ASIR-V significantly reduced the radiation dose and the contrast agent dosage,and might help in distinguishing between benign and malignant thyroid nodules,demonstrating considerable clinical application value.

Objective To explore the diagnostic value of dual-low-dose CT energy spectral imaging combined with adaptive statis-tical iterative reconstruction-Veo(ASIR-V)in distinguishing benign and malignant thyroid nodules.Methods A total of 242 patients with thyroid nodules were included.In part Ⅰ,the initial 90 patients were randomly and equally assigned to the conventional scan group,the low radiation dose group,and the dual-low-dose group.Both subjective and objective image qualities,the radiation dose,and contrast agent dosage in these three groups were evaluated,respectively.In part Ⅱ,the remaining 152 patients underwent dual-low-dose CT energy spectral scanning.Radiographic features of thyroid nodules in benign and malinant groups were observed,fol-lowed by spectral imaging analysis.The iodine concentration(IC)value,normalized iodine concentration(NIC)value,effective atomic number(Eff-Z),and λHU value of benign and malignant nodules were measured and compared,respectively.Results There were significant differences in nodule morphology,sign of edge truncation,enhancement characteristics and nodule boundary enhancement between benign and malignant thyroid nodules(P<0.05).There were statistically significant differences in IC value,NIC value,and λHU value in the venous phase among the three groups(P<0.05).The sensitivity and specificity of IC,NIC,λHU were 81.6%and 60.0%,86.4%and 67.5%,88.8%and 65.0%,respectively.The area under the curve(AUC)of combining the three energy spectral parameters with radiographic fea-tures via binary logistic regression model was 0.905,and the sensitivity and specificity were 82.4%and 87.5%,respectively.The effective dose(ED)in the dual-low-dose group was reduced by 60.13%com-pared to the conventional scan group,and the contrast agent dos-age was reduced by 38.56%.Conclusion The dual-low-dose CT energy spectral imaging combined with ASIR-V significantly reduced the radiation dose and the contrast agent dosage,and might help in distinguishing between benign and malignant thyroid nodules,demonstrating considerable clinical application value.

Objective:To investigate the follow-up colonoscopy of patients after colorectal adenoma (CRA) resection, so as to improve colonoscopy quality and reduce missed CRA diagnosis.Methods:A total of 189 patients after CRA resection who underwent follow-up colonoscopy from October 2020 to October 2021 were consecutively recruited. The effect of bowel preparation was evaluated by the Boston bowel preparation scale (BBPS). The location, the number, and gross morphology of adenomas during CRA resection and two colonoscopies during 1 year follow-up after the resection were recorded, and their correlation with major clinicopathologic features were analyzed, and the missed CRA in follow-up colonoscopy were also analyzed.Results:The BBPS scores of the right colon, transverse colon, left colon and total colon in 189 patients who underwent CRA resection were 1.93±0.42, 2.53±0.52, 2.77±0.45, and 7.22±1.03 points at the 1-year follow-up colonoscopy and 2.08±0.35, 2.70±0.46, 2.81±0.40, and 7.57±0.84 points at the time of CRA resection. Except for the left colon segment ( χ 2=0.98, P>0.05), the differences in other colon segments were significantly different ( P<0.05). At the time of CRA resection, 62, 66, 210 and 338 CRAs were detected in the right colon, transverse colon, left colon and total colon segments, respectively. At the 1-year follow-up colonoscopy, 21, 38, 49 and 108 CRAs were missed in the corresponding colon segments and total colon, respectively. CRA missed diagnosis was related to patient age (≥60 years accounting for 54.2%), gender (males accounting for 81.9%), adenoma location (predominantly in the left colon comprising 36.2%) and gross morphology (flat types representing 72.3%) ( P<0.05), but not related to being vegetarian, history of cholecystectomy or appendectomy, smoking or alcohol consumption, number of adenomas or pathological type ( P>0.05). Conclusion:The missed diagnosis of CRA in patients after CRA resection primarily involves the flat type adenomas, which is associated with the age, gender, adenoma location within the colon and the gross morphology.

Objective:To explore the effects of computer-navigated surgery and traditional surgery on the functional and oncological outcomes of pelvic chondrosarcoma.Methods:Retrospective analysis of 136 cases of pelvic chondrosarcoma surgically treated at Beijing Jishuitan Hospital from January 2000 to December 2017. There were 65 males and 71 females with an average age of 46.07±13.37 years (range 13-73 years). There were 120 primary cases and 16 secondary cases, of which 109 cases were ordinary chondrosarcoma (7 cases with pathological differentiation grade I, 83 cases with grade II. There were 109 cases of common type chondrosarcoma (7 cases of pathological differentiation grade I, 83 cases of grade II, 19 cases of grade III), 21 cases of dedifferentiated chondrosarcoma, 3 cases of mesenchymal type, 2 cases of clear cell type, 1 case of mucinous type; 12 cases of malignant degeneration of multilocular chondrosarcoma of bone; 104 cases of Enneking staging stage IB, 32 cases of stage IIB. According to the pelvis zone classification, there were 14 cases of pelvic zone I, 1 case of zone II, 13 cases of zone III, 16 cases of zone I+II, 16 cases of zone I+IV, 47 cases of zone II+III, 25 cases of zone I+II+III, 25 cases of zone I+II+III, 4 cases of zone I + II + III + IV. All cases were classified as intracapsular, marginal, or wide resection according to the resection boundary classification. There were 45 cases in computer-navigated surgery (navigated group) and 91 cases in non-navigated surgery group. The demographic data, preoperative tumor staging, surgical characteristics, surgical boundary classification, oncological indexes, reconstruction methods, postoperative complications, and bone and soft tissue tumor function score (Musculoskeletal Tumor Society score, MSTS) were compared between the two groups.Results:No surgical complications related to the computerized navigation system occurred in the navigation group. The postoperative follow-up time was 68.56±37.82 months (range 6-197 months) and 76.85±52.60 months (range 5-225 months) for the navigation and non-navigation groups, respectively. The MSTS was 25.43±2.85 and 24.56±4.19 points in the navigation and non-navigation groups, respectively, with no significant difference ( t=1.191, P=0.237). There were 10 cases of marginal resection and 35 cases of wide resection in the navigation group, and 12 cases of intracapsular resection, 32 cases of marginal resection and 47 cases of wide resection in the non-navigation group with significant difference (χ 2=10.977, P=0.004). There were 4 cases (8.9%, 4/45) of local recurrence after surgery in the navigation group and 20 cases (21.9%, 20/91) in the non-navigation group, with significant difference (χ 2=4.040, P=0.046). There were 2 cases of final amputation and 2 cases of re-excision with recurrence in the navigation group and 6 cases of final amputation and 14 cases of re-excision in the non-navigation group. Distant metastases occurred in 3 cases (7%, 3/45) in the navigation group and 18 cases (20%, 18/91) in the non-navigation group wtih significant difference (χ 2=4.478, P=0.034). The five-year postoperative survival rates of the navigation and non-navigation groups were 93.3% and 72.6%, and the three- and five-year progression-free survival rates were 91.1% and 84.4% and 74.8% and 62.7%, respectively, with significant differences (χ 2=5.081, P=0.024; χ 2=6.800, P=0.009). The five-year survival rate of stage IB tumors was 96.7% in the navigation group and 84.5% in the non-navigation group with significant difference (χ 2=3.897, P=0.048); the five-year survival rate of stage IIB tumors was 75.0% in the navigation group and 35.0% in the non-navigation group with no significant difference ( P>0.05). Postoperative complications included 15 cases of postoperative infection, 16 cases of deep vein thrombosis, 14 cases of double lower limb inequality, 2 cases of prosthesis dislocation, 2 cases of lymphedema, 1 case of hernia and 1 case of allograft bone resorption. There was no significant difference of complication rates between the two groups ( P>0.05). Conclusion:Computer navigation-assisted resection of pelvic chondrosarcoma was better in obtaining a safe surgical border of the tumor compared with traditional surgery, reducing the rate of local recurrence of the tumor and thus effectively improved the survival and prognosis of patients.