ObjectiveTo evaluate a third-generation applicator template for intracavitary combined with interstitial brachytherapy （IC-ISBT） suitable for locally advanced cervical cancer， aiming to improve therapeutic outcomes. MethodsA retrospective study was conducted on patients with stage IB3-ⅣB cervical cancer treated at Sun Yat-sen University Cancer Center from January 2023 to October 2023. Magnetic resonance imaging data before and after external beam radiation therapy were collected and analyzed. According to the residual tumor after external beam radiation， high-risk clinical target volumes （HR-CTV） were delineated， based on which a third-generation IC-ISBT applicator template was designed. The dosimetric and therapeutic differences between using this applicator template （template implantation group） and traditional freehand interstitial implantation （freehand implantation group） were further compared. Statistical methods were used to analyze the data from both groups to test the efficacy and safety of the two approaches. ResultsThe third-generation applicator template could accommodate different cervical structures and optimize needle path layout. The tumor volume in the template implantation group was significantly larger than in the freehand implantation group， showing statistical differences. In terms of dosimetric coverage （V_100%）， the template implantation group exhibited significant statistical differences compared with the freehand implantation group， demonstrating superior dose coverage. Additionally， the third-generation template showed advantages in protecting the rectum and sigmoid colon by potentially reducing high-dose points， while there were no significant differences in bladder dosimetry between the two methods. The primary cervical lesion remission rates were similar between the two groups. ConclusionThe third-generation IC-ISBT applicator template is scientifically and rationally designed， especially for patients with larger tumor volumes and later stages. It is easy to operate， highly reproducible， and shows significant advantages in dose distribution and protection of surrounding critical organs. The template has the potential to be widely applied as a routine treatment option.

ObjectiveTo prepare oral nanoemulsions encapsulating essential oil from Alpinia zerumbet fructus（EOFAZ） and to investigate its pro-absorption effect in vitro and distribution in vivo. MethodThe proteoglycan conjugate polysaccharides of vinegar-processed Bupleuri Radix-bovine serum albumin（VBCP-BSA） was prepared by Maillard reaction of VBCP and BSA. Taking VBCP-BSA as emulsifier， vitamin B₁₂（VB₁₂） as absorption enhancer， and medium chain triglycerides mixed with EOFAZ as oil phase， the nanoemulsions loaded with EOFAZ was prepared by high energy emulsification method. The particle size， particle size distribution， surface Zeta potential， EOFAZ content and appearance and morphology of the nanoemulsions were characterized， and fluorescein tracer method was used to investigate the absorption effect of fluorescein-labeled EOFAZ nanoemulsions in vitro and their distribution in vivo. ResultVBCP-BSA was formed by Maillard reaction for 48 h with high grafting rate. Using VBCP-BSA as emulsifier， the homogeneous pink nanoemulsions was prepared and denoted as EOFAZ@VBCP-BSA/VB₁₂. The particle size of the nanoemulsions was less than 100 nm and the particle size distribution was uniform. The surface of the nanoemulsions was a weak negative charge， and the shape was spherical. The encapsulation rate of the nanoemulsions for EOFAZ was greater than 80%， which had a good absorption effect in vitro and could enhance liver accumulation after oral administration. ConclusionThe designed proteoglycan nanoemulsions can effectively load EOFAZ， promote oral absorption and enhance liver distribution， which can provide experimental basis for the development of oral EOFAZ liver protection preparations.

Objective To observe the clinical efficacy of Lingnan Traditional Vesiculating Moxibustion No.4 Recipe(mainly composed of Brassicae Junceae Semen,Euodiae Fructus,and Curcumae Radix)in the treatment of mild depressive disorder(DD),and to provide a novel approach to the treatment of mild DD population.Methods Sixty-one patients with mild DD were randomly divided into 31 cases in the trial group and 30 cases in the control group.The trial group was given medicinal vesiculation treatment with Lingnan Traditional Vesiculating Moxibustion No.4 Recipe,and the control group was given medicinal vesiculation treatment with the placebo of Lingnan Traditional Vesiculating Moxibustion No.4 Recipe.The treatment was performed twice a week and with an interval of 3-4 days between the treatment,and the course of treatment covered 6 weeks.The changes of Hamilton Depression Scale-17(HAMD-17)scores and Patient Health Questionnaire-9(PHQ-9)scores in the two groups were observed before and after the treatment.After treatment,the clinical efficacy and safety of the patients in the two groups were evaluated.Results(1)After 6 weeks of treatment,the total efficacy rate of the trial group was 77.42%(24/31),and that of the control group was 26.67%(8/30).The intergroup comparison(tested by rank sum test)showed that the efficacy of the trial group was significantly superior to that of the control group,and the difference was statistically significant(P＜0.01).(2)After treatment,the HAMD-17 scores and PHQ-9 scores of patients in the two groups were lower than those before treatment(P＜0.01),and the decrease of HAMD-17 and PHQ-9 scores in the trial group was significantly superior to that of the control group,the difference being statistically significant(P＜0.01).(3)During the trial,there were 5 cases of adverse events related to the vesiculating moxibustion treatment,and all 5 cases of adverse events occurred in the trial group,manifested as minor blisters at the acupoint application region.The 5 cases kept on participating in the trial after relevant treatment.Conclusion Lingnan Traditional Vesiculating Moxibustion No.4 Recipe can effectively relieve the clinical symptoms of patients with mild DD,and has high safety.

Objective To investigate the predictive value of new simplified insulin resistance(IR)assessment indexes in identifying subclinical left ventricular systolic function impairment in patients with type 2 diabetes mellitus(T2DM).Methods A total of 150 T2DM patients with preserved left ventricular ejection fraction(LVEF≥50%)who were admitted to Department of Endocrinology of the First Affiliated Hospital of Air Force Medical University from June 2021 to December 2021 were retrospectively analyzed.All patients underwent two-dimensional speckle tracking echocardiography to measure left ventricular global longitudinal strain(GLS).According to GLS value,the subjects were divided into the normal group(GLS≥18%group,n=80)and the impaired group(GLS<18%group,n=70).Some new simplified IR assessment indicators were calculated and compared between the two groups,including body mass index(BMI),TG/HDL-C ratio,triglyceride-glucose(TyG)index,TyG-BMI index,TyG-WHR and metabolic score for IR(METS-IR).Correlation between the GLS and the new simplified IR assessment indexes was analyzed.The receiver operating characteristic(ROC)curve was used to analyze the diagnostic efficacy of different simplified IR assessment indexes,with the area under the curve(AUC)calculated.Furthermore,according to whether the subjects were complicated with hypertension,binary logistics regression analysis was performed to explore the independent correlation between the simplified IR assessment index and GLS<18%.Results Total 150 were included with aged(54.5±13.7)years with 96(64.0%)men and 54(36.0%)women.Compared with the GLS≥18%group,the TG/HDL-C ratio,TyG index,TyG-BMI,and METS-IR of subjects in the GLS<18%group were significantly increased(P<0.05).Pearson correlation analysis showed that TG/HDL-C ratio,TyG index,TyG-BMI,TyG-WHR,and METS-IR were negatively correlated with GLS(P<0.05).ROC analysis showed that TyG index had a certain predictive value for the evaluation of GLS<18%(AUC=0.678,95%CI 0.591-0.765,P<0.001).Stratification based on hypertension and further adjusting for confounding factors,TyG index remains significantly associated with GLS<18%(OR=3.249,95%CI 1.045-10.103,P=0.042).Conclusions The novel simplified insulin resistance evaluation indexes are closely associated with left ventricular subclinical systolic dysfunction in T2DM patients with preserved ejection fraction.TyG index is an effective index to identify left ventricular subclinical dysfunction in these populations.

Objective To explore the efficacy and safety of recombinant human anti-severe acute respiratory syn-drome coronavirus 2(anti-SARS-CoV-2)monoclonal antibody injection(F61 injection)in the treatment of patients with coronavirus disease 2019(COVID-19)combined with renal damage.Methods Patients with COVID-19 and renal damage who visited the PLA General Hospital from January to February 2023 were selected.Subjects were randomly divided into two groups.Control group was treated with conventional anti-COVID-19 therapy,while trial group was treated with conventional anti-COVID-19 therapy combined with F61 injection.A 15-day follow-up was conducted after drug administration.Clinical symptoms,laboratory tests,electrocardiogram,and chest CT of pa-tients were performed to analyze the efficacy and safety of F61 injection.Results Twelve subjects(7 in trial group and 5 in control group)were included in study.Neither group had any clinical progression or death cases.The ave-rage time for negative conversion of nucleic acid of SARS-CoV-2 in control group and trial group were 3.2 days and 1.57 days(P=0.046),respectively.The scores of COVID-19 related target symptom in the trial group on the 3rd and 5th day after medication were both lower than those of the control group(both P＜0.05).According to the clinical staging and World Health Organization 10-point graded disease progression scale,both groups of subjects improved but didn't show statistical differences(P＞0.05).For safety,trial group didn't present any infusion-re-lated adverse event.Subjects in both groups demonstrated varying degrees of elevated blood glucose,elevated urine glucose,elevated urobilinogen,positive urine casts,and cardiac arrhythmia,but the differences were not statistica-lly significant(all P＞0.05).Conclusion F61 injection has initially demonstrated safety and clinical benefit in trea-ting patients with COVID-19 combined with renal damage.As the domestically produced drug,it has good clinical accessibility and may provide more options for clinical practice.

ObjectiveA rapid method for identification of chemical constituents in Baoyuantang reference sample was established in order to clarify the material basis of this formula. MethodBased on ultra-performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS） and self-established database information， the chemical components in Baoyuantang were systematically characterized and identified. The chromatography was performed on a Waters ACQUITY UPLC HSS T3 column（2.1 mm×100 mm， 1.8 μm） with mobile phase of 0.1% formic acid aqueous solution（A）-0.1% formic acid acetonitrile solution（B） for gradient elution（0-3 min， 2%-19%B； 3-8 min， 19%B； 8-8.1 min， 19%-22%B； 8.1-14 min， 22%-29%B； 14-16 min， 29%B； 16-32 min， 29%-45%B； 32-32.1 min， 45%-90%B； 32.1-35 min， 90%-95%B； 35-36 min， 95%-98%B； 36-37 min， 98%-2%B； 37-40 min， 2%B）. Based on electrospray ionization（ESI）， continuum data format was collected in both positive and negative ion modes with a scanning range of m/z 50-1 500. Chemical constituents in the decoction of Baoyuantang were systematically analyzed by UNIFI 1.9.4 software matching， control comparison， The Encyclopedia of Traditional Chinese Medicine（ETCM） database search and literature reports. ResultA total of 229 components were identified under negative ion mode and 181 under positive ion mode， with a total of 322 components after removing duplicates， including 116 triterpene saponins， 66 flavonoids， 19 organic acids， 6 gingerphenols， 6 gingerols， 5 gingerones， 10 amino acids， 7 saccharides， 5 coumarins and 82 other components. Among them， 83， 141， 39， 35 and 38 components were attributed to Ginseng Radix et Rhizoma， Glycyrrhizae Radix et Rhizoma， Astragali Radix， Cinnamomi Cortex and Zingiberis Rhizoma Recens， respectively. ConclusionIn this study， the rapid characterization and identification of multi-class components in Baoyuantang was realized， and it was confirmed that the material basis of this formula was mainly triterpenoid saponins， flavonoids， gingerols and organic acids， and the chemical composition was attributed and analyzed， which provided a reference for the subsequent quality control research.

Objective To evaluate the efficacy and safety of brexpiprazole in treating acute schizophrenia.Methods Patients with schizophrenia were randomly divided into treatment group and control group.The treatment group was given brexpiprozole 2-4 mg·d-1 orally and the control group was given aripiprazole 10-20 mg·d-1orally,both were treated for 6 weeks.Clinical efficacy of the two groups,the response rate at endpoint,the changes from baseline to endpoint of Positive and Negative Syndrome Scale(PANSS),Clinical Global Impression-Improvement(CGI-S),Personal and Social Performance scale(PSP),PANSS Positive syndrome subscale,PANSS negative syndrome subscale were compared.The incidence of treatment-related adverse events in two groups were compared.Results There were 184 patients in treatment group and 186 patients in control group.After treatment,the response rates of treatment group and control group were 79.50％(140 cases/184 cases)and 82.40％(150 cases/186 cases),the scores of CGI-I of treatment group and control group were(2.00±1.20)and(1.90±1.01),with no significant difference(all P＞0.05).From baseline to Week 6,the mean change of PANSS total score wese(-30.70±16.96)points in treatment group and(-32.20±17.00)points in control group,with no significant difference(P＞0.05).The changes of CGI-S scores in treatment group and control group were(-2.00±1.27)and(-1.90±1.22)points,PSP scores were(18.80±14.77)and(19.20±14.55)points,PANSS positive syndrome scores were(-10.30±5.93)and(-10.80±5.81)points,PANSS negative syndrome scores were(-6.80±5.98)and(-7.30±5.15)points,with no significant difference(P＞0.05).There was no significant difference in the incidence of treatment-related adverse events between the two group(69.00％vs.64.50％,P＞0.05).Conclusion The non-inferiority of Brexpiprazole to aripiprazole was established,with comparable efficacy and acceptability.

Programmed cell death 1 ligand 1 (PD-L1) is an important immunosuppressive molecule, which inhibits the function of T cells and other immune cells by binding to the receptor programmed cell death-1. The PD-L1 expression disorder plays an important role in the occurrence, development, and treatment of sepsis or other inflammatory diseases, and has become an important target for the treatment of these diseases. Mesenchymal stem cells (MSCs) are a kind of pluripotent stem cells with multiple differentiation potential. In recent years, MSCs have been found to have a strong immunosuppressive ability and are used to treat various inflammatory insults caused by hyperimmune diseases. Moreover, PD-L1 is deeply involved in the immunosuppressive events of MSCs and plays an important role in the treatment of various diseases. In this review, we will summarize the main regulatory mechanism of PD-L1 expression, and discuss various biological functions of PD-L1 in the immune regulation of MSCs.

Extracting extracts of secondary metabolites from the karst cave fungus Metarhizium anisopliae NHC-M3-2 from the Yilingyan Scenic Area in Guangxi. Ten compounds were isolated and purified from fungal secondary metabolites using thin-layer chromatography and high-performance liquid chromatography. 7-Hydroxy-3-hydroxypropyl-5,6-dimethylisochrome-1-one (1) and 7-hydroxy-3,5,6-trimethyl-isochromen-1-one (2) were new isocoumarin compounds, N-acetyl phenylalanine (3), chaetosumin J (4), 2-one-13-hydroxy-3,5,8,7(11)-eudesmatetraen-12,8-olide (5), 1H-indole-3-carboxaldehyde (6), irpexolaceus B (7), irlactin L (8), cytochalasin K (9), and helvolic acid (10), a total of 8 known compounds. The structure of the compound was determined using methods such as NMR and mass spectrometry. The tumor cytotoxicity of the compound was evaluated using the CCK-8 method. The results showed that the IC₅₀ of compound 2 on HepG2 cells was 29.83 µmol·L^-1, and compound 9 on HCT116 cells was 27.44 µmol·L^-1.

Objective To observe the therapeutic effect and mechanism of acupuncture at Zusanli-Zhongwan combined matching points on rats with exercise-induced stress gastric ulcer.Methods Forty male SD rats were randomly divided into blank group,model group,acupuncture group and Omeprazole group,with 10 rats in each group.Except for the blank group,the rats in the other groups were used to construct the model of exercise stress gastric ulcer by daily exhaustive swimming.After successful modeling,the acupuncture group was intervened by acupuncture at Zusanli(ST36)and Zhongwan(RN12),once a day,10 minutes each time.Rats in the Omeprazole group were given Omeprazole Enteric-Coated Tablets distilled water suspension by gavage two hours before daily swimming.After continuous 7-day intervention,the overall state and behavior of rats were observed,the gastric mucosal injury index was calculated by Guth method,the pathological morphology of gastric mucosa was observed by hematoxylin-eosin(HE)staining,the contents of superoxide dismutase(SOD),glutathione peroxidase(GSH-PX)and malondialdehyde(MDA)in serum were correspondingly determined by WST-1 method,colorimetry and TBA method,respectively,enzyme-linked immunosorbent assay(ELISA)was used to detect the contents of gastrin(GAS),somatostatin(SS),tumor necrosis factor-α(TNF-α),interleukin-1 β(IL-1β),interleukin-6(IL-6)and interleukin-10(IL-10)in serum,the expression levels of epidermal growth factor receptor(EGFR),matrix metalloproteinase 3(MMP3),nuclear factor erythroid-related factor 2(NRF2),heme oxygenase 1(HO-1)and mitochondrial SOD2,TNF-α,IL-1β,IL-6 and IL-10 mRNA in gastric mucosa were detected by real-time fluorescence quantitative polymerase chain reaction(qPCR).Results Compared with the blank group,the body mass of rats in the model group was increased slowly,the activity distance and activity in the open field test were decreased,the gastric mucosal ulcer index was increased significantly,the gastric mucosal function indexes involving GAS level was increased and SS level was decreased in serum,the mRNA expression level of EGFR in gastric mucosa was decreased and the mRNA expression level of MMP3 in gastric mucosa was increased.The serum levels of antioxidant substances SOD and GSH-PX were decreased significantly,and the serum level of oxidation product MDA was increased significantly.The mRNA expression levels of antioxidant genes NRF2,HO-1 and SOD2 in gastric mucosa were significantly decreased.The serum contents and the gastric mucosa mRNA levels of inflammatory factors TNF-α,IL-1α,IL-6 were significantly increased,while the serum content and the gastric mucosa mRNA level of IL-10 were significantly decreased.The differences were statistically significant(P＜0.05 or P＜0.01 or P＜0.001).HE staining showed obvious gastric mucosal injury.Compared with the model group,the above indexes in the acupuncture group and the Omeprazole group were significantly improved(P＜0.05 or P＜0.01 or P＜0.001).HE staining showed that the gastric mucosal injury was significantly reduced.Conclusion Acupuncture at Zusanli-Zhongwan combined matching points can reduce the local oxidative stress and inflammatory response in rats with exercise-induced stress gastric ulcer,reduce gastric mucosal injury,improve the emotional state of rats,and maintain the overall vitality of rats.