OBJECTIVE: To investigate the effectiveness of posterior lateral perforator flap in lower limb combined with free fibula for maxillary tissue defect repair. METHODS: Between December 2018 and December 2023, 16 patients with the maxillary malignant tumors were admitted. There were 10 males and 6 females, with an average age of 64.3 years (range, 54-75 years). There were 7 cases of maxillary gingival cancer, 5 cases of hard palate cancer, and 4 cases of maxillary sinus cancer. According to the 2017 American Joint Committee on Cancer (AJCC) TNM stage, there were 8 cases of stage Ⅲ, 6 cases of stage Ⅳa, and 2 cases of stage Ⅳb. After resection of the lesion, the remaining maxillary defects were classified into class Ⅱa in 3 cases, class Ⅱb in 5 cases, and class Ⅲb in 8 cases according to Brown's classification. The size of soft tissue defects ranged from 4 cm×3 cm to 8 cm×6 cm. The posterior lateral perforator flap in lower limb in size of 5 cm×4 cm-9 cm×7 cm were harvested to repair soft tissue defects, and free fibula in length of 6-11 cm were used to repair bone defects. The donor sites of the lower limb were sutured directly (6 cases) or repaired with free skin grafting (10 cases). Six patients with positive lymph node pathology were treated with radiotherapy after operation. At 6 and 12 months after operation, the self-assessment was performed by the University of Washington Quality of Survival Questionnaire Form (QUW-4) in five dimensions (facial appearance, swallowing function, chewing function, speech function, and mouth opening), and swallowing function was evaluated by using the Kubota water swallowing test. RESULTS: Postoperative pathological examination showed that all patients were squamous cell carcinoma. One patient who was treated with radiotherapy developed osteomyelitis and 1 patient developed venous crisis of skin flap. The rest of the flaps and all skin grafts survived, and the wounds healed by first intention. All patients were followed up 1-5 years (mean, 2.8 years). Two patients died of local recurrence of the tumor at the 4th and 5th years after operation, respectively. Except for the chewing function score and total score at 6 months after operation, which showed significant differences compared to preoperative scores ( P<0.05), there was no significant difference in other QUW-4 scale scores between different time points ( P>0.05). The patients' swallowing function evaluated by Kubota water swallowing test reached normal in 4 cases, suspicious in 9 cases, and abnormal in 3 cases at 6 months after operation, and 10, 6, and 0 cases at 12 months after operation, respectively. The swallowing function at 12 months was significantly better than that at 6 months ( Z=-2.382, P=0.017). CONCLUSION The posterior lateral perforator flap in the lower limb combined with free fibula to repair maxillary tissue defects can repair soft and hard tissue defects at the same time, so that the patient's facial appearance, swallowing function, chewing function, speech function, and mouth opening are satisfactorily restored and the mid-term effectiveness is good.
Humans ; Middle Aged ; Male ; Female ; Fibula/surgery* ; Aged ; Perforator Flap ; Plastic Surgery Procedures/methods* ; Maxilla/surgery* ; Maxillary Neoplasms/surgery* ; Free Tissue Flaps/transplantation* ; Lower Extremity/surgery* ; Bone Transplantation/methods* ; Treatment Outcome

OBJECTIVES: To investigate the clinical application of the digital-assisted reconstruction of the mandible and tumors with free fibula transplantation and immediate implantation via the intraoral approach. METHODS: Twelve patients with benign mandibular tumors were collected. Three-dimensional mandibular reconstruction was performed digitally before surgery to simulate mandibular tumor resection, fibula resection and reconstruction, and implant implantation. The intraoperative resection of the mandibular tumor was conducted through the intraoral approach under the guidance of a guide plate, and fibula resection, molding, reconstruction, and oral fixation were immediately performed. Implant implantation was performed during the second phase of implant surgery and denture restoration was performed 1-2 months after surgery. RESULTS: The types of mandibular defects were BrownⅠ (one case), Ⅰc (four cases), Ⅱ (one case), Ⅱc(three cases), and Ⅲ (three cases). The length of the fibular bone was 12-22 cm. The number of fibular molding amputations was as follows: two cases in two segments, six cases in three segments, three cases in four segments, and one case in five segments. All of these cases underwent folding fibular reconstruction of mandibular and alveolar bone defects. A total of 44 implants were implanted, and none failed after operation. CONCLUSIONS The intraoral approach is a reliable method for the resection of mandibular benign tumors, with few postoperative complications and the ability to position and fix accurately the reconstructed folded fibula under digital design. The immediate implantation of the transplanted fibula does not affect the blood supply and has a high success rate. It is an effective and reliable method for the resection and reconstruction of mandibular benign tumors.
Humans ; Fibula/transplantation* ; Mandibular Neoplasms/surgery* ; Mandibular Reconstruction/methods* ; Bone Transplantation/methods* ; Male ; Middle Aged ; Female ; Mandible/surgery* ; Adult ; Free Tissue Flaps ; Surgery, Computer-Assisted

Magnesium and its alloys have been widely studied in the field of orthopaedics for their desirable mechanical properties, biodegradability and biocompatibility. However, the rapid degradation rate of magnesium and its alloys cannot match the healing process of bone itself, and may adversely affect the adhesion, growth and differentiation of surrounding cells, resulting in early loosening of implants, thus limiting their wide clinical application. Surface coating modification is a feasible and promising anti-corrosion solution to solve the problem of uncontrollable corrosion rate of magnesium implants. The surface coating modification technology can optimize the integration of the bone-implant interface by improving the bone induction ability of the implant surface (such as the bio-mimetic coating based on phosphate ceramics) or improving the corrosion resistance (such as the micro-arc oxidation coating with wear resistance and corrosion resistance, and the phytic acid coating with self-healing potential). While optimizing the degradation rate of magnesium implant, it can also realize multiple functions such as promoting osseointegration, drug delivery and photothermal therapy through composite component modification. In this paper, the advantages and disadvantages of different coating modification method on the surface of orthopaedic magnesium implants are comprehensively illustrated, and the key technologies in each preparation process are summarized and the composite modification methods are further discussed, so as to provide references for the preparation of multifunctional magnesium implants that meet the requirements of orthopaedic applications.

OBJECTIVE To optimize the ultrasound-assisted extraction-deep eutectic solvents technology of total flavonoids from Hypericum japonicum， evaluate its hypoglycemic activity in vitro， and analyze its chemical compositions preliminarily. METHODS The most suitable deep eutectic solvent for total flavonoids from H. japonicum was screened using the composition of hydrogen bond acceptor and donor， molar ratio， water content as factors， and the total flavonoid yield as the response value. Using liquid-solid ratio， ultrasonic power， ultrasonic temperature and ultrasonic time as factors， the yield of total flavonoids as response value， the extraction technology of total flavonoids from H. japonicum was optimized by single-factor experiments combined with Box-Behnken response surface method， and the optimum extraction technology was validated. Taking acarbose as the positive control， the inhibitory activities of total flavonoids from H. japonicum on α-amylase and α-glucosidase in vitro were determined. The chemical constituents of total flavonoids from H. japonicum were analyzed by UPLC combined with comparing the reference substances. RESULTS The most suitable deep eutectic solvent was choline chloride-oxalic acid （the molar ratio of 1∶1， the water content of 30%）. The optimum extraction technology was as follows： the ratio of liquid-solid was 52∶1 （mL/g）， the ultrasonic temperature was 54 ℃ ， the ultrasonic power was 240 W， and the ultrasonic time was 42 min； the total extraction yield of total flavonoids from H. japonicum in 3 validation tests was （73.26±2.48） mg/g， the relative error of which with the theoretical value （73.48 mg/g） was －0.30%. The total flavonoids from H. japonicum could inhibit α-amylase and α-glucosidase with IC50 values of 0.73 and 0.44 mg/mL， respectively， which were higher than those of acarbose （0.23 and 0.15 mg/mL）. UPLC analysis showed that the total flavonoids from H. japonicum contained isoquercetin， quercitrin， quercetin-7-O-α-L-rhamnoside and quercetin. CONCLUSIONS The optimized extraction technology of total flavonoids from H. japonicum is stable and feasible， and the extract has certain hypoglycemic activity in vitro and contains isoquercetin， quercitrin and quercetin-7-O-α-L-rhamnoside， etc.

ObjectiveTo investigate the influencing factors for the clinical outcome of patients with drug-induced liver injury （DILI）， and to establish a nomogram prediction model for validation. MethodsA retrospective analysis was performed for the general information and laboratory data of 188 patients with DILI who were admitted to Heilongjiang Provincial Hospital Affiliated to Harbin Institute of Technology from January 2017 to December 2022， and according to their clinical outcome， they were divided into good outcome group with 146 patients and poor outcome group with 42 patients. The independent-samples t test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups； the chi-square test was used for comparison of categorical data between two groups. Univariate and multivariate Logistic regression analyses were used to investigate the independent influencing factors for the clinical outcome of DILI patients. R Studio 4.1.2 software was used to establish a nomogram model， and calibration curve， receiver operating characteristic （ROC） curve， and decision curve analysis （DCA） were used to perform internal validation. ResultsThe univariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI， platelet count， cholinesterase， albumin， prothrombin time activity， IgM， and IgG were associated with adverse outcomes in patients with DILI. The multivariate Logistic regression analysis showed that liver biopsy for the diagnosis of DILI （odds ratio ［OR］=0.072， 95% confidence interval ［CI］： 0.022‍ ‍—‍ ‍0.213， P<0.001）， clinical classification （OR=0.463， 95%CI： 0.213‍ ‍—‍ ‍0.926， P=0.039）， alanine aminotransferase （OR=0.999， 95%CI： 0.998‍ ‍—‍ ‍1.000， P=0.025）， prothrombin time activity （OR=0.973， 95%CI： 0.952‍ ‍—‍ ‍0.993， P=0.011）， and IgM （OR=1.456， 95%CI： 1.082‍ ‍—‍ ‍2.021， P=0.015） were independent influencing factors for clinical outcome in patients with DILI. The nomogram prediction model was established， and after validation， the calibration curve was close to the reference curve. The area under the ROC curve was 0.829， and the DCA curve showed that the model had good net clinical benefit. ConclusionThe nomogram prediction model established in this study has good clinical calibration， discriminative ability， and application value in evaluating the clinical outcome of patients with DILI.

Objective: To investigate the characteristics of newly reported HIV/AIDS cases aged 15 years and older in Shangcheng District, Hangzhou City from 2006 to 2022, so as to provide the basis for improving AIDS prevention and control strategies. Methods: Data of newly reported HIV/AIDS cases aged 15 years and older in Shangcheng District from 2006 to 2022 were collected through HIV/AIDS Comprehensive Control System of Chinese Disease Prevention and Control Information System. Population distribution and transmission routes were analyzed, and changing trends in case number were analyzed using average annual percent change (AAPC) and annual percent change (APC). Results: A total of 4 409 HIV/AIDS cases aged 15 years and older were newly reported in Shangcheng District from 2006 to 2022, including 3 932 males (89.18%). There were 3 447 cases (78.18%) under 50 years old and 962 cases (21.82%) being 50 years and older. Sexual contact was a predominant transmission route, with 4 326 cases accounting for 98.12%, including 2 626 cases (59.56%) with homosexual contact and 1 700 cases (38.56%) with heterosexual contact. The number of HIV/AIDS cases showed an overall upward trend from 2006 to 2022 (AAPC=13.038%, P<0.05), with an upward trend from 2006 to 2015 (APC=42.578%, P<0.05) and a downward trend from 2015 to 2022 (APC=-19.713%, P<0.05). The increase in the number of cases aged 50 years and older group was faster than that of cases aged under 50 years (AAPC=22.641% vs. 11.162%, both P<0.05). The increase in the number of cases with homosexual contact transmission was faster than that of cases with heterosexual contact transmission (AAPC=20.417% vs. 7.455%, both P<0.05). Conclusions The number of newly reported HIV/AIDS cases aged 15 years and older in Shangcheng District performed an overall upward trend from 2006 to 2022. The cases aged 50 years and older and transmitted through homosexual contact increased rapidly, which should be taken seriously.

Objective:Distribution and antibiotic resistance of pathogen isolated from children with intra-abdominal infection (IAI) associated sepsis in the intensive care unit (ICU) were analyzed to provide a reference for the empirical anti-infective treatment of IAI in children.Methods:We retrospectively analyzed the data of 116 children with culture-positive IAI-associated sepsis admitted to Children's Hospital of Zhejiang University School of Medicine from January 2019 to December 2021. Clinical isolation and drug resistance analysis were conducted based on different years of onset, locations of onset, and primary diseases.Results:A total of 186 strains of pathogens causing children with IAI-associated sepsis in ICU were collected. The distribution and antibiotic resistance of pathogen were as follows: the percentages of gram-positive bacteria, gram-negative bacteria, and fungi were 53.2%, 40.9%, and 5.9%, respectively; the top four strains were Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis, accounting for 57.0% of all isolates; Enterococcus faecium(19.9%) and Enterococcus faecalis (10.2%) were the dominating gram-positive bacteria; Escherichia coli (13.4%) and Klebsiella pneumoniae (13.4%) were more common gram-negative bacteria; Fungi were dominated by Candida albicans (3.8%).Fifty-seven strains of gram-positive bacteria were detected in 61 children with infectious diseases, mainly Enterococcus faecium (28 strains). There were 53 gram-negative strains, mainly Klebsiella pneumoniae (21 strains). Thirty-two strains of gram-positive bacteria were detected in 40 children with digestive tract malformation, and Enterococcus faecalis (six strains) were the most common. There were 14 gram-negative strains, mainly Escherichia coli (six strains). In 13 children with malignant tumors of digestive system, nine strains of gram-positive bacteria were cultured, and Enterococcus faecium (four strains) was the most common. There were eight gram-negative strains, mainly Escherichia coli (four strains).In the 46 community-acquired IAI patients,30 gram-positive isolates were cultured,mainly including Enterococcus faecium (12 strains), Staphylococcus epidermidis (seven strains), and Viridans streptococci (six strains); Forty gram-negative isolates mainly contained Escherichia coli (16 strains), Klebsiella pneumoniae (14 strains), and Enterobacter cloacae (five strains). In the 70 hospital-associated IAI patients, 69 gram-positive isolates such as Enterococcus faecium (25 strains), Enterococcus faecalis (17 strains), Enterococcus gallinarum (eight strains), and Staphylococcus aureus (seven strains) were cultured;Tirty-six gram-negative isolates were dominated by Klebsiella pneumoniae (11 strains), Escherichia coli (nine strains), Pseudomonas aeruginosa (four strains), and Acinetobacter baumannii (four strains). The mixed infection rate of clinical pathogens was up to 46.6%, and the overall resistance rate was 43.4%, in which gram-negative bacteria had high sensitivity to piperacillin/tazobactam, cefoperazone/sulbactam, imipenem, and tigecycline.The detection rates of Klebsiella pneumoniae and Escherichia coli producing extended-spectrum β-lactamases were 36.0% and 24.6%, respectively, with 100% sensitivity to tigecycline. Gram-positive bacteria showed 100% sensitivity to vancomycin, linezolid, and tigecycline. Conclusion:Pathogen isolated from children with IAI-associated sepsis in ICU were dominated by Enterococcus faecium, Escherichia coli, Klebsiella pneumoniae, and Enterococcus faecalis,respectively. Before confirmation of pathogenic bacteria, antibacterial agents can be selected according to the infection type. It is important to note that a single broad-spectrum antibacterial agent or combination medication can be considered the initial empirical choice due to the large variety of pathogens, high rates of mixed infections, and high overall resistance.

Pancreatic cancer is among the most malignant cancers,and thus early intervention is the key to better survival outcomes.However,no methods have been derived that can reliably identify early precursors of development into malignancy.Therefore,it is urgent to discover early molecular changes during pancreatic tumorigenesis.As aberrant glycosylation is closely associated with cancer progression,numerous efforts have been made to mine glycosylation changes as biomarkers for diagnosis;however,detailed glycoproteomic information,especially site-specific N-glycosylation changes in pancreatic cancer with and without drug treatment,needs to be further explored.Herein,we used comprehensive solid-phase chemoenzymatic glycoproteomics to analyze glycans,glycosites,and intact glycopeptides in pancreatic cancer cells and patient sera.The profiling of N-glycans in cancer cells revealed an increase in the secreted glycoproteins from the primary tumor of MIA PaCa-2 cells,whereas human sera,which contain many secreted glycoproteins,had significant changes of glycans at their specific glycosites.These results indicated the potential role for tumor-specific glycosylation as disease biomarkers.We also found that AMG-510,a small molecule inhibitor against Kirsten rat sarcoma viral oncogene homolog(KRAS)G12C mutation,profoundly reduced the glycosylation level in MIA PaCa-2 cells,suggesting that KRAS plays a role in the cellular glycosylation process,and thus glycosylation inhibition contributes to the anti-tumor effect of AMG-510.

Objective:To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis.Methods:A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis.Results:The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P＜0.001; 77.78% vs 16.84% for bone metastasis, P＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant ( P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups ( P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage ( HR=2.806, 95% CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH ( HR=1.841, 95% CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS ( HR=2.538, 95% CI:1.169-5.512, P=0.019). Conclusions:Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.

Objective:To investigate the detection of bone marrow tumor cells in small cell lung cancer (SCLC) patients and their relationship with clinical features, treatment response and prognosis.Methods:A total of 113patients with newly diagnosed SCLC from January 2018 to October 2022 at Beijing Chest Hospital were prospectively enrolled. Before treatment, bone marrow was aspirated and separately submitted for tumor cells detection by liquid-based cytology and disseminated tumor cells (DTCs) detection by the substrction enrichment and immunostaining fluorescence in situ hybridization (SE-iFISH) platform. The correlation between the detection results of the two methods with patients' clinical features and treatment response was evaluated by Chi-square. Kaplan-Meier method was applied to create survival curves and the Cox regression model was used for multivariate analysis.Results:The positive rate of bone marrow liquid-based cytology in SCLC was 15.93% (18/113). The liver and bone metastases rates were significantly higher (55.56% vs 11.58% for liver metastasis, P＜0.001; 77.78% vs 16.84% for bone metastasis, P＜0.001) and thrombocytopenia was more common (16.67% vs 2.11%, P=0.033) in patients with tumor cells detected in liquid-based cytology than those without detected tumor cells. As for SE-iFISH, DTCs were detected in 92.92% of patients (105/113), the liver and bone metastasis rates were significantly higher (37.93% vs 11.90% for liver metastasis, P=0.002; 44.83% vs 20.23 % for bone metastasis, P=0.010), and the incidence of thrombocytopenia was significantly increased (13.79% vs 1.19%, P=0.020) in patients with DTCs≥111 per 3 ml than those with DTCs＜111 per 3 ml. The positive rates of bone marrow liquid-based cytology in the disease control group and the disease progression group were 12.00% (12/100) and 46.15% (6/13), respectively, and the difference was statistically significant ( P=0.002). However, the result of SE-iFISH revealed the DTCs quantities of the above two groups were 29 (8,110) and 64 (15,257) per 3 ml, and there was no statistical difference between the two groups ( P=0.329). Univariate analysis depicted that the median progression-free survival (PFS) and median overall survival (OS) of liquid-based cytology positive patients were significantly shorter than those of tumor cell negative patients (6.33 months vs 9.27 months for PFS, P=0.019; 8.03 months vs 19.50 months for OS, P=0.019, P=0.033). The median PFS and median OS in patients with DTCs≥111 per 3 ml decreased significantly than those with DTCs＜111 per 3 ml (6.83 months vs 9.50 months for PFS, P=0.004; 11.2 months vs 20.60 months for OS, P=0.019). Multivariate analysis showed that disease stage ( HR=2.806, 95% CI:1.499-5.251, P=0.001) and DTCs quantity detected by SE-iFISH ( HR=1.841, 95% CI:1.095-3.095, P=0.021) were independent factors of PFS, while disease stage was the independent factor of OS ( HR=2.538, 95% CI:1.169-5.512, P=0.019). Conclusions:Both bone marrow liquid-based cytology and SE-iFISH are clinically feasible. The positive detection of liquid-based cytology or DTCs≥111 per 3 ml was correlated with distant metastasis, and DTCs≥111 per 3 ml was an independent prognostic factor of decreased PFS in SCLC.