Objective To prepare and characterize caspofungin acetate-loaded solid lipid nanoparticles using glycerol monostearate （CAS-SLNs）, and investigate the antifungal effect of potentiation on Candida albicans in vitro and in vivo. Methods A high performance liquid chromatography method was established for the determination of caspofungin acetate （CAS）. CAS-SLNs were prepared by the melt-emulsification method and characterized. The minimum inhibitory concentration （MIC） and the inhibitory effect on Candida albicans biofilm were determined. A systemic infection model of Candida albicans was established in mice, and the growth curve models for body weight and fungal load of kidneys of the animals were investigated after intravenous infection. Results The retention time of CAS was 6.8 min. The calibration curve showed good linearity, and the precision and stability met the requirements of the assay. Transmission electron microscopy revealed that CAS-SLNs were spherical, with a particle size of （135.97±1.73） nm. The Zeta potential was （19.33±0.37） mV, drug loading was （7.55±0.68）%, and encapsulation efficiency was （67.71±1.74）%. CAS-SLNs showed significant in vitro antifungal inhibition with a MIC of 9.78×10⁻⁴ g/ml, which was significantly better than CAS group and the physical mixture group of CAS and GMS, as well as the same biofilm inhibition was observed （P<0.001）. Pharmacodynamic studies demonstrated that CAS-SLNs maintained stable body weight gain compared to the control （P<0.01） and CAS groups in Candida albicans invasive infection model, and that CAS-SLNs significantly reduced renal fungal burden load relative to the CAS group （P<0.05）. In vivo study revealed that a stable body weight was maintained in CAS-SLNs group compared to the control group （P<0.01） in Candida albicans invasive infection model. CAS-SLNs also significantly reduced renal fungal load compared to the CAS group （P<0.05）. Conclusion CAS-SLNs significantly enhanced the antifungal effects of CAS in vitro and in vivo, which provided a valuable insight for the research of new formulation of CAS.

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

ObjectiveTo assess the level of internal exposure to PCP in a community population in Shanghai， to investigate the factors affecting the level of PCP， and to analyze the correlation between the exposure and thyroid hormone levels. MethodsA total of 464 residents of a community in Shanghai were selected as the study subjects. A questionnaire survey was conducted to obtain the demographic information， dietary situation， lifestyle and behavioral habits， and disease history of the individuals， and blood samples were collected. Gas chromatography-electron trap was applied to determine the PCP levels in serum. Multicategorical logistic regression analysis was used to analyze the possible influencing factors of PCP exposure in humans. Thyroid hormone levels were used as the dependent variable and serum PCP as the independent variable. Multiple linear regression analysis was used to assess the association between PCP and thyroid hormones in the community population after controlling the confounding factors such as age， gender， literacy， annual personal income， and chronic diseases. ResultsThe detection rate of serum PCP in 464 subjects was 90.3%， and the median serum PCP level was 0.43 μg·L^-1. The differences in PCP levels among different age groups were statistically significant. There were no significant differences in PCP levels among different gender and BMI groups. The study of PCP exposure factors showed that age， frequency of using plastic products， consumption of freshwater fish， type of occupation， annual income， and consumption of tea or coffee were the potential influencing factors for PCP exposure. Among them， age， frequency of using plastic products， consumption of tea or coffee， and consumption of freshwater fish were positively associated with PCP levels， and annual personal income was negatively associated with it. The results of multiple linear regression analysis showed that among men， PCP levels were positively correlated with TSH （b=0.105， 95%CI：0.017‒0.313） and negatively correlated with FT4 （b=-0.026， 95%CI：-0.057‒0.004）， and among women， PCP levels were positively correlated with TSH （b=0.092， 95%CI：-0.211‒0.904） and FT3 （b=0.017， 95%CI：-0.058‒0.230） and negatively correlated with FT4 （b=-0.013， 95%CI：-0.011‒0.037）. ConclusionSerum PCP detection is common among community residents in Shanghai. Different demographic characteristics or behavioral habits may increase or decrease PCP exposure. PCP exposure then affects human thyroid hormone levels.

Objective:To investigate the clinicopathological features, immunophenotype, molecular characteristics, and differential diagnosis of primary intracranial DICER1-mutant sarcoma in order to better understand this tumor type.Methods:A retrospective analysis was conducted on 7 cases of primary intracranial DICER1-mutant sarcoma diagnosed in the Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China between 2021 and 2023 using next-generation sequencing. At the same time, 10 gliosarcomas, 4 intracranial FET::CREB fusion-positive mesenchymal tumors, 4 malignant meningiomas, 3 malignant solitary fibrous tumors, 3 malignant peripheral nerve sheath tumors, 3 synovial sarcomas and 3 rhabdomyosarcomas (total 30 cases) were selected as control.Results:Among the 7 patients with primary intracranial DICER1-mutant sarcoma, 6 were male and 1 was female, aged 10-32 years (median, 23 years). The tissue morphology was predominantly spindle or pleomorphic sarcoma-like, with 6 cases exhibiting eosinophilic globules, and 3 cases showing rhabdomyoblastic or rhabdomyosarcoma-like cell differentiation. Immunohistochemistry revealed focal desmin expression in 3 cases (3/7), ATRX loss in 3 cases (3/7), and p53 mutant pattern in 4 cases (4/7). Additionally, 4 cases (4/7) showed focal or diffuse SALL4 expression, whereas the control cases (30 cases) did not exhibit SALL4 protein expression, suggesting that SALL4 may possess certain auxiliary diagnostic value. Next-generation sequencing confirmed that all 7 cases of primary intracranial DICER1-mutant sarcoma harbored mutations in the DICER1 gene, with 5 cases having the mutation site at p.E1813D. Until May 2024, all 7 patients were alive.Conclusions:Primary intracranial DICER1-mutant sarcoma is a rare tumor. Understanding its morphological characteristics, immunohistochemical and molecular markers and differential diagnosis is crucial to avoid misdiagnosis and to improve diagnostic accuracy of this tumor.

Intrahepatic cholangiocarcinoma (ICC) is characterized with low incidence, high malignancy and poor prognosis. In China, hepatitis B virus (HBV)-associated ICC is the most common subtype of ICC and its incidence rate is on the rise. The pathogenesis and clinical characteristics of HBV-associated ICC are different from other types of ICC. In recent years, the targeted therapy has brought significant survival benefits for patients. This article reviews the pathogenesis of HBV-associated ICC and the latest research progress of the clinical characteristics and treatments of patients.

Objective:To study the variational trend in disease characteristics of patients with hepatitis B-related primary liver cancer (HBV-HCC) in the past five years.Method:A single-center retrospective cross-sectional analysis was performed to compare patients diagnosed with HBV-HCC from January 2012 to December 2016 (control group) and from January 2017 to December 2021 (observation group). The data of the study variables were extracted from the electronic medical record system of the hospital information system of the Second Hospital of Lanzhou University. The 1:2 propensity score matching was used to adjust potential confounding factors such as gender and age. Multivariate logistic regression analysis was used to study the factors affecting changes in disease characteristics of the HBV-HCC population in the observation group. GraphPad Prism 8.0 software was used to draw forest plots to intuitively display the effect size of the study variables in the logistic regression analysis.The t-test was used to compare normally distributed data between groups. The χ2 test was used for inter-group comparison. Results:A total of 1 717 eligible cases were collected, including 510 in the control group and 1 207 in the observation group. Compared with the control group, the number of newly diagnosed cases in the observation group increased by 2.36 times, and males were still the main onset population (83.3% vs. 82.7%). The median age of onset increased (51.9 vs. 53.5 years, P<0.001). 79.4% of HBV-HCC patients had not received antiviral therapy, and the proportion of HBeAg-negative patients increased (56.4%). The factors affecting HBV-HCC patients included family history of HBV ( OR=1.626, 95% CI: 1.181-2.238), family history of hepatocellular carcinoma ( OR=1.388, 95% CI: 1.013-1.901), hypoviremia ( OR=1.322, 95% CI: 1.046-1.671), abnormal alanine aminotransferase ( OR=1.545, 95% CI: 1.231-1.940), liver fibrosis ( OR=1.478, 95% CI: 1.153-1.894), liver cirrhosis ( OR=1.431, 95% CI: 1.128-1.815), and metabolic-related fatty liver disease ( OR=1.438, 95% CI: 1.116-1.815) after propensity score matching adjustment. The factors affecting HBeAg-positive patients were decreased ( OR=0.390, 95% CI: 0.389-0.617); however, the number of early HBV-HCC diagnoses was increased (12.7% vs. 19.3%, P=0.001). Conclusion:The characteristics of patient disease and occurrence of HBV-HCC are changing over the past five years. The risk of developing hepatocellular carcinoma in middle- to older male patients with chronic hepatitis B is increasing with familial history of HBV and hepatocellular carcinoma, HBeAg negativity, hypoviremia, abnormal alanine aminotransferase, liver fibrosis, cirrhosis, and metabolic-related fatty liver disease.

Objective: To measure the position of the mandibular nerve canal at the mandibular second molar by CBCT image data, analyze the theoretical implantation range of trans-alveolar implantation, and provide a theoretical solution to insufficiency of posterior mandibular bone volume in clinical practice. Methods: Eighty patients with missing mandibular second molars whose vertical bone height of the edentulous area was less than 9 mm were selected for CBCT image measurement, and the distances from the mandibular nerve canal to the buccal cortex, lingual cortex, and alveolar crest were measured to simulate trans-inferior alveolar nerve implantation. The angular range of the buccolingual inclination of the implant was also measured. Results: The distances from the mandibular nerve canal to the buccal cortex, lingual cortex and alveolar crest at the mandibular second molar were(6.913±1.222)mm, (2.859±0.891)mm and (7.991±0.783)mm, respectively. The distance from the mandibular nerve canal to the buccal cortex was significantly greater than that to the lingual cortex. And, 75% of the patients could be implanted by the inferior alveolar nerve. The minimum angle of buccolingual inclination of the simulated implant was 19.360°±7.086°, and the maximum angle was 39.462°±6.924°. Conclusion The mandibular nerve canal at the mandibular second molar is inclined toward the lingual side, which ensures sufficient buccal bone volume. Most patients with severe mandibular atrophy can still adopt implants of conventional length by trans-inferior alveolar nerve implantation to keep a safe distance from the nerve canal.

Objective:To study the effectiveness and safety of PD-1(programmed cell death protein-1,PD-1)inhibitors for the treatment of patients with advanced cancer in real-world in a Chinese cohort. Methods:Data of patients with advanced cancer who were admitted to the Department of Oncology,Renji Hospital affiliated to Shanghai Jiao Tong University School of Medicine between May 2018 and September 2019 and received PD-1 inhibitor alone orcombined with otheranti-cancer therapies were collected.The clinical characteristics,therapeutic efficacy and adverse events were analyzed retrospectively. Results:A total of 75 patients with advanced cancer were included in this study.The cohort consisted of 53 males and 22 females with an average age of 60 years,among whom 60 patients had metastasis.Lung cancer(27 cases)and gastric cancer(12 cases)accounted for the largest proportion.Other cancer types included cancers of the digestive system(colorectal,liver,pancreatic,esophageal,and bile duct cancer),urinary system(kidney,pelvis,ureter,and bladder cancer)and female reproductive system(breast,cervical,and ovarian cancer),malignant melanoma,and head and neck cancer(nasopharyngeal and laryngeal cancer).Among all the patients studied,55 patients(73.3％)received PD-1 inhibitors as first-line and(or)second-line therapy,and 62 patients(82.7％)received PD-1 inhibitors in combination with other anti-cancer therapies.The objective response rate was 1 4.5％,disease control rate was 65.2％,the median progression-free survival was 6.1 months[95％confidence interval(C/):4.356-7.844],and the median overall survival was 1 8.0 months(95％CI:9.565-26.435).Adverse events,mainly grade 1 or grade 2,accured in 5 5 patients.The progression-free survival was 6.3 months in patients treated with PD-1 inhibitors as first-line and(or)second-line therapy,significantly longer than the 3.0-month-long progression-free survival of the patients treated with PD-1 inhibitors as third-line or multiline therapy[hazard ratio(HR)=0.492,95％Cl:0.244-0.992,P=0.048]. Conclusions:Immunotherapy with PD-1 inhibitors was effective and safe for patients with advanced cancer in real-world,especially in those who received PD-1 inhibitor treatment as first-or second-line therapy.

Objective:To evaluate the clinical survival rates and influence factors of different types of resin-bonded fixed partial dentures (RBFPD) used in anterior missing teeth restoration.Methods:Ninety-three RBFPD were delivered to 92 patients [92 patients,43 males and 49 females, average age (46.1±12.8) years] who visited Peking University School and Hospital of Stomatology from January 2006 to December 2021 for restoration of 1 or 2 anterior missing teeth. Altogether 32 cases of glass fiber reinforced RBFPD, 39 cases of glass-based ceramic RBFPD and 22 cases of porcelain-fused-to-metal RBFPD were retrospectively analyzed. The complete survival rate, functional survival rate, patients′ satisfaction and color matching of the restorations were recorded and evaluated every year since the replacement with RBFPD. The Kaplan-Meier survival curve method was used for survival analysis, and the Log-rank analysis was used to compare the effect of the number of missing teeth, position (maxillary or mandibular), cantilever or non-cantilever and gender on the survival rate of the restorations.Results:The overall survival time for the 93 RBFPD was 13.7 years (95% CI: 12.3-15.1 years). There was a decreasing trend in complete survival and functional survival for all three material RBFPD from year to year, but complete and functional survival rates exceeded 90% at year 5 and exceeded 80% at year 10. The complete survival rate of the glass-ceramic RBFPD was higher than the other two during the follow-up period, with a complete survival rate of 90% (35/39) at year 15. The porcelain-fused-to-metal RBFPD had a higher functional survival rate in years 1-8, but the complete and functional survival rates showed a substantial decrease after year 9. The single-factor Log-rank analysis showed that the success rate of porcelain-fused-to-metal RBFPD was significantly higher than that of glass fiber reinforced RBFPD (χ2=7.33, P=0.007), and the success rate of RBFPD with 1 missing tooth restored was significantly higher than that of RBFPD with 2 missing teeth restored (χ2=3.23, P=0.072). The differences in success rates between different restoration positions (maxillary and mandibular), cantilever or non-cantilever, and gender factors were not statistically significant (χ2=2.26, P=0.133; χ2=0.68, P=0.411; χ2=1.07, P=0.300). Conclusions:For the restoration of individual missing anterior teeth, both porcelain-fused-to-metal RBFPD and glass-based ceramic RBFPD achieve a high long-term clinical success rate, with glass-based ceramic RBFPD being more able to ensure long-term restorative result.

The first rate-limiting enzyme of the serine synthesis pathway (SSP), phosphoglycerate dehydrogenase (PHGDH), is hyperactive in multiple tumors, which leads to the activation of SSP and promotes tumorigenesis. However, only a few inhibitors of PHGDH have been discovered to date, especially the covalent inhibitors of PHGDH. Here, we identified withangulatin A (WA), a natural small molecule, as a novel covalent inhibitor of PHGDH. Affinity-based protein profiling identified that WA could directly bind to PHGDH and inactivate the enzyme activity of PHGDH. Biolayer interferometry and LC-MS/MS analysis further demonstrated the selective covalent binding of WA to the cysteine 295 residue (Cys295) of PHGDH. With the covalent modification of Cys295, WA blocked the substrate-binding domain (SBD) of PHGDH and exerted an allosteric effect to induce PHGDH inactivation. Further studies revealed that with the inhibition of PHGDH mediated by WA, the glutathione synthesis was decreased and intracellular levels of reactive oxygen species (ROS) were elevated, leading to the inhibition of tumor proliferation. This study indicates WA as a novel PHGDH covalent inhibitor, which identifies Cys295 as a novel allosteric regulatory site of PHGDH and holds great potential in developing anti-tumor agents for targeting PHGDH.