Objective:To explore the prognostic value of baseline 18F-FDG PET/CT metabolic parameters in locally advanced cervical cancer (LACC) after concurrent chemoradiotherapy (CCRT). Methods:From September 2015 to October 2021, the clinical data of 180 LACC patients (age: 22-76 years) who underwent 18F-FDG PET/CT before CCRT at Affiliated Cancer Hospital of Shandong First Medical University were analyzed retrospectively. The metabolic tumor volume (MTV), total lesion glycolysis (TLG), SUV max, and SUV mean were computed by using the margin threshold of 42%SUV max. The optimal threshold for predicting progression-free survival (PFS) was obtained by ROC curve analysis. The Kaplan-Meier method was applied for survival analysis, and the log-rank test was applied to compare the survival rate between groups. Multivariate Cox proportional hazard regression was used to analyze progression for PFS. Results:The median follow-up was 19.1 months, and 54 patients (30.0%, 54/180) suffered from disease progression. ROC curve analysis showed that the optimal cut-off value of MTV was 31.145 ml, with the AUC of 0.641. Para-aortic lymph node (PALN) metastasis had the highest AUC value (0.589) among the clinical factors, followed by International Federation of Gynecology and Obstetrics (FIGO) stage (0.581). The 1-year PFS rates of patients with MTV<31.145 ml ( n=88) and MTV≥31.145 ml ( n=92) were 80.68% and 59.78%, respectively ( χ2=13.72, P<0.001). Multivariate Cox analysis demonstrated that pathological type (hazard ratio ( HR)=3.075, 95% CI: 1.370-6.901, P=0.006), FIGO stage ( HR=1.955, 95% CI: 1.031-3.707, P=0.040), PALN metastasis ( HR=2.136, 95% CI: 1.202-3.796, P=0.010) and MTV ( HR=2.449, 95% CI: 1.341-4.471, P=0.004) were the significant predictors for PFS. Conclusions:Pathological type, FIGO stage, PALN metastasis and MTV are independent prognostic risk factors for PFS. MTV as the baseline 18F-FDG PET/CT metabolic parameter, can realize prognostic stratification analysis.

OBJECTIVE To explore the effects of letrozole combined with methylprednisolone on clinical outcomes， ovarian reserve function， serum sex hormones， and safety in infertile patients with polycystic ovary syndrome resistant to clomiphene. METHODS The clinical data of 78 infertile patients with polycystic ovary syndrome resistant to clomiphene in the Department of Gynecology of Qingdao Central Hospital from February 2021 to January 2022 was analyzed retrospectively， and all patients were divided into control group （42 cases） and observation group （36 cases） based on the treatment methods. The control group took letrozole 5 mg/d orally on the 5th to 9th day of the menstrual cycle. Vaginal ultrasound was used to monitor the development of the endometrium and follicles； estradiol valerate was used to correct endometrial thickness， and measures such as inducing ovulation with follicle-stimulating hormone were taken to promote pregnancy. On the basis of treatment in the control group， the observation group began taking methylprednisolone orally at a dose of 4 mg/d starting from the third day of natural menstruation or withdrawal bleeding. Both groups were treated for 6 menstrual cycles. The ovulation and pregnancy within one year， serum levels of sex hormones [estradiol （E2）， luteinizing hormone （LH）， follicle-stimulating hormone （FSH）， testosterone] and anti-Müllerian hormone （AMH）， ovulation indicators （follicle growth time， the number of ovulations， and the number of dominant follicles）， and the occurrence of adverse drug reactions were compared between the two groups. RESULTS After treatment， the biochemical pregnancy rate （72.22%） and clinical pregnancy rate （47.22%） of the observation group were significantly higher than those of control group （47.62%， 19.05%）； the serum levels of E2， LH， FSH， testosterone and AMH were significantly lower than the control group； the follicle growth time was significantly shorter than the control group； the number of ovulation and dominant follicles were significantly higher than the control group （P＜0.05）. There was no statistically significant difference in ovulation rate （94.44% vs. 83.33%） and total incidence of adverse drug reactions （8.33% vs. 9.52%） between the observation group and the control group （P＞0.05）. CONCLUSIONS Compared with letrozole alone， the combination of letrozole and methylprednisolone can significantly improve the pregnancy rate， the sex hormone levels and ovarian reserve function in infertile patients with polycystic ovary syndrome resistant to clomiphene， with high safety profiles.

Objective To explore the prognostic value of serum neutrophils/lymphocytes(NLR)for first-line treatment of patients with advanced gastric cancer using programmed cell death receptor 1(PD-1)inhibitors.Methods A total of 168 patients with advanced gastric cancer who were treated with immunotherapy combined with chemotherapy in the Fourth Hospital of Qinhuangdao from January 2018 to January 2021 were selected as study subjects,and the follow-up period was terminated at January 2023.The patients'data were collected,hematological and tumor markers before the combined treatment were analyzed,and the optimal cut-off value of NLR was calculated using X-tile software.The effect of NLR expression on the survival rate of patients with advanced gastric cancer was analysed by the Kaplan-Meier survival curve.Receiver operating curve(ROC)was used to analyze the predictive value of NLR in patients with advanced gastric cancer.The related factors affecting the disease progression of patients with advanced gastric cancer were screened combined with Cox proportional risk model.Results Among 168 patients,the optimal cut-off value of serum NLR before treatment was 2.41.Patients were divided into high NLR group(NLR＞2.41,n=93)and low NLR group(NLR＜2.41,n=75).NLR was related to tumor differentiation,distant metastasis,composite positive scores of PD-L1,carcinoembryonic antigen and cancer antigen 125(P＜0.05);the effective rate in the low NLR group was significantly higher than that in the high NLR group(P＜0.05);the median progression free survival(PFS)and the overall survival(OS)of patients in the low NLR group were both longer than those in the high NLR group(PFS:P=0.006;OS:P=0.023);ROC analysis showed that the area under the curve of NLR for the prognosis of advanced gastric cancer patients was 0.740,sensitivity was 81.50％,and specificity was 69.70％;in multivariate analysis,except initial NLR value,tumor differentiation degree and distant metastasis were also independent predictors of poor prognosis in patients with advanced gastric cancer(P＜0.05).Conclusion Among patients with advanced gastric cancer who received first-line immunotherapy combined with chemotherapy,pretreatment NLR is correlated with efficacy and PFS/OS,and has high value in predicting the prognosis of immunotherapy for advanced gastric cancer.

Objective:To investigate the effect and molecular mechanism of tumor necrosis factor-α-inducible protein 8-like 2(TIPE2)on lipopolysaccharide(LPS)or interleukin-4(IL-4)-induced phenotypic switch of adipose tissue macrophages(ATM).Methods:The expression levels of TIPE2, inducible nitric oxide synthase(iNOS), monocyte chemoattractant protein 1(MCP-1), CD206, and arginase 1(Arg-1)in the visceral adipose tissue of obese mice, TIPE2-knockout(KO)mice, and control mice were detected by immunohistochemistry, Western blotting, and real-time PCR(RT-qPCR). Peritoneal macrophages isolated from KO and wild-type mice and RAW 264.7 mouse macrophage cell line were cultured, and then stimulated with LPS(100 ng/mL)or IL-4(20 ng/mL)for 6 hours. The expression levels of TIPE2, iNOS, MCP-1, CD206, and Arg-1 were detected by Western blotting and RT-qPCR.Results:Obese mice showed down-regulated TIPE2 expression, up-regulated pro-inflammatory markers iNOS and MCP-1 expressions, and down-regulated anti-inflammatory markers CD206 and Arg-1 expressions. LPS decreased the expression of TIPE2 in RAW 264.7 cells and peritoneal macrophages from mice, increased the expression of the classically activated macrophages(M1 phenotype)markers iNOS and MCP-1, and decreased the expression of the substituting activated macrophages(M2 phenotype)markers CD206 and Arg-1. IL-4 increased the expression of TIPE2 in RAW 264.7 cells and peritoneal macrophages, decreased the expression of iNOS and MCP-1, and increased the expression of CD206 and Arg-1. During the M1 polarization of macrophages, LPS increased toll-like receptor(TLR4)expression as well as nuclear transcription factor κBα suppressor protein(IκBα) and NF-κB phosphorylations in macrophages. Knockout of TIPE2 further increased the expression of the TLR4/IκBα/NF-κB signaling pathway and M1 macrophage markers, and further reduced the expression of the M2 macrophage markers.Conclusion:TIPE2 regulates ATM phenotypic transformation through inhibition of the TLR4/IκBα/NF-κB signaling pathway, which ameliorates adipose tissue inflammation in obese states.

The stem and branch extract of Tripterygium wilfordii (Celastraceae) afforded seven new dihydroagarofuran sesquiterpene polyesters [tripterysines A-G (1-7)] and eight known ones (8-15). The chemical structures of these new compounds were established based on combinational analysis of HR-ESI-MS and NMR techniques. The absolute configurations of tripterysines A-C (1-3) and E-G (5-7) were determined by X-ray crystallographic analysis and circular dichroism spectra. All the compounds were screened for their inhibitory effect on inflammation through determining their inhibitory effect on nitric oxide production in LPS-induced RAW 264.7 cells and the secretion of inflammatory cytokines TNF-α and IL-6 in LPS-induced BV2 macrophages. Compound 9 exhibited significant inhibitory activity on NO production with an IC₅₀ value of 8.77 μmol·L^-1. Moreover, compound 7 showed the strongest inhibitory effect with the secretion of IL-6 at 27.36%.
Tripterygium/chemistry* ; Esters/pharmacology* ; Interleukin-6 ; Lipopolysaccharides/pharmacology* ; Plant Leaves/chemistry* ; Anti-Inflammatory Agents/chemistry* ; Nitric Oxide/analysis* ; Sesquiterpenes/chemistry* ; Molecular Structure

It is still at the initial stage for basic-level military doctors to participate in the standardized residency training. While, their professional backgrounds and training objectives are significantly different from those civilian residents, it is necessary to explore the standardized training methods in line with the military career demands for those basic-level military doctors. Based on the actual needs of grass-roots troops and military medicine, this study makes significant progress in the integration of standardized residency training and field surgery training methods, making the basic-level military doctors achieve the goal of field surgery training in the course of clinical practice of residents. Not only the surgical capability of basic-level military doctors, but also the medical support capability in grass-roots troops has been improved. This article summarizes the application methods and experience of field surgery teaching in the standardized residency training of military medical residents at the grass-roots level.

Aggregatibacter aphrophilus is a member of the normal flora of the human oral cavity and pharynx, a Gram-negative fastidous bacteria, belonging to agglomerates, which is a normal mixed oropharyngeal flora in humans, most commonly colonized on the surface of oral mucosa. This bacterial infection is rare in clinical practice, and it is difficult to culture and identify the bacteria, which is easy to be missed. A patient with intracranial infection was admitted to Huaihe Hospital, who showed fever and headache as the main clinical manifestations, and Aggregatibacter aphrophilus was detected by the metagenomic next-generation sequencing of cerebrospinal fluid. The patient′s symptoms were significantly improved after anti-infection treatment.

Objective:To analyze the clinical characteristics and prognostic factors in patients with new-onset acute heart failure (AHF) and acutely decompensated chronic heart failure (ADCHF).Methods:Patients with heart failure (HF) admitted to Beijing Hospital during January 2009 to December 2017 with follow-up records were retrospectively enrolled. According to the duration of heart failure, the patients were divided into new-onset AHF group (duration of HF<1 month) and ADCHF group (duration of HF ≥1 month). Clinical data were collected and endpoint events (all-cause death and cardiovascular death) were recorded. The Kaplan-Meier survival curve and the log-rank method was used to compare survival between different groups. The multivariate Cox regression model was used to analyze the independent risk factors for the end-point events in patients with new-onset AHF and ADCHF.Results:The study enrolled 562 patients,292 (52.0%) with new-onset AHF and 270 (48.0%) with ADCHF. Patients with new-onset AHF were more likely to have coronary heart disease, acute myocardial infarction, higher diastolic blood pressure and higher troponin I levels(χ2=12.999,15.018, t=-2.088, Z=-2.727; all P<0.05). Patients with ADCHF were more likely to have poor cardiac function, atrial fibrillation, larger left ventricle and left atrium diameter, higher proportion of patients with pulmonary hypertension(χ2=16.565, 15.688, t=2.714, 5.029, χ2=15.274; all P<0.05). There were 205 (36.5%) all-cause deaths and 132 (23.5%) cardiovascular deaths during 28 (14, 60) months of follow-up. All-cause mortality rate [33.2%(97/292) vs. 40.0%(108/270), log-rank P=0.010] and cardiovascular mortality rate [18.8%(55/292) vs. 28.5%(77/270), log-rank P=0.001]were significantly lower in patients with new-onset AHF than those in ADCHF group. Multivariate Cox regression analysis showed that low body mass index (BMI), reduced hemoglobin, reduced resting heart rate, enlarged left atrium, and segmental wall motion abnormalities were independent risk factors for poor prognosis in new-onset AHF patients. It was different with ADCHF patients. Conclusion:Patients with new-onset AHF are more likely to have coronary heart disease; and lower BMI, reduced hemoglobin, acute coronary disease are associated with poor prognosis of patients. It is necessary to identify the underlying diseases early and actively standardize treatment to avoid the deterioration of cardiac function and readmission.

OBJECTIVE：To investiga te main risk factors for adverse drug reactions （ADR）of skin by intravenous injection of iodine contrast agent. METHODS ：From Jan. 2009 to Apr. 2020，the patients suffering from skin ADR after enhanced CT with iodine contrast agent were collected from our hospital. The basic information ，laboratory test results before using iodine contrast agent and ADR related information were collected through hospital information system （HIS）. The use of iodine contrast agent ，main manifestations of skin ADR and drug combination were analyzed statistically. Taking the sex ，age，body mass index （BMI），the dosage of iodine contrast agent ，length of stay ，laboratory examination ，tumor history ，basic disease ，allergy history ，drinking history as independent variables ，the incidence of skin ADR related to iodine contrast agent was analyzed by single factor analysis ，and the variables with statistically significant were selected for multivariate Logistic stepwise regression analysis. RESULTS ：There were 157 cases of skin ADR ，involving 79 males（50.3％）and 78 females（49.7％）. The age ranged from 19 to 86 years old ，being（52.68± 18.73）years old in average. BMI was 14.6-40.7 kg/m2，being（22.5±3.7） kg/m2. 67 cases（42.68％）were treated with iprodione ，34 cases（21.66％）with iodixanol ，31 cases（19.74％）with iohexol and 25 cases（15.92％）with iopamidol ；the dose of iodine contrast agent were 50-100 mL，being（73.06±13.29）mL in average. There was no significant difference among different dosage of 4 kinds of iodine contrast agents （P≤0.05）. Among 4 kinds of iodine contrast agents ，the incidence of skin ADR induced by iopromide was the highest（0.197％）. The skin ADR related to iodine contrast agent was mainly acute （89.2％），the severity was mild （75.2％），and urticaria（38.9％）was the most common. After symptomatic treatment ，135 cases were cured ，13 cases were improved and 9 cases were not improved. Among the patients with iodine contrast agent related skin ADR ，the incidence of ADR induced by combined use of anti infective drugs was the highest （33.1％）；however，the combined use of anti-tumor drugs was the main cause of severe skin ADR. The length of stay ｛11～20 d[OR＝1.21，95％CI（1.07，1.20），P＝0.042]、21～30 d[OR＝1.39，95％CI（1.12，1.52），P＝0.035]、31～40 d[OR＝1.15，95％CI（1.03，1.37），P＝0.008]、＞40 d[OR＝1.33，95％CI（1.28，1.53），P＝0.003]｝，respitatory and circulatory system tumor history[OR ＝1.51，95％CI（1.35，1.61），P＝0.037]，injection allergy history[OR ＝1.50，95％CI（1.37，1.59），P＝0.005] can significantly increase the incidence of iodine contrast agent related skin ADR. CONCLUSIONS ：The main manifestation of skin ADR related to iodine contrast agent was urticaria. The main risk factors of skin ADR related to iodine contrast agent were length of stay （＞ 10 d），respiratory and circulatory system tumor history and injection allergy history.

Objective:To investigate the coverage rate and the adverse reactions of National Immunization Program vaccines in children with spinal muscular atrophy (SMA).Methods:A cross-sectional retrospective cohort study was carried out from July 2016 to June 2019, 192 children (116 boys and 76 girls) with SMA registered by Capital Institute of Pediatrics and 191 healthy children (115 boys and 76 girls) vaccinated in Chaoyang Olympic Village Community Health Service Center from July 2016 to December 2018 were included. Questionnaire survey was designed to investigate the vaccination coverage rate and associated adverse events. The t-test and χ 2 test were used to compare the difference between SMA patients and healthy children. Results:The coverage rate of age-appropriate immunization in SMA children was 62.0% (119/192) in general, and were 52.2% (12/23), 55.7% (68/122), and 83.0% (39/47) for SMA type 1-3 patients, respectively (χ 2=12.23, P=0.002). The vaccination coverage rates of Bacillus Calmette-Guerin (BCG) vaccine, the 3 rd dose of hepatitis B, the 3 rd dose of polio, the 3 rd dose of diphtheria-pertussis-tetanus, the 1 st dose of meningococcal polysaccharide group A, the 1 st dose of measles or measles and rubella vaccine, the 1 st dose of Japanese encephalitis vaccine, hepatitis A, measles-mumps-rubella, and group A+C meningococcal polysaccharide vaccine were 100.0% (192 cases), 94.3% (181 cases), 81.8% (157 cases), 88.5% (170 cases), 83.9% (161 cases), 76.6% (147 cases), 80.2% (154 cases), 68.2% (131 cases), 69.8% (134 cases), 54.7% (105 cases), respectively. Among the 73 patients who did not have their planned immunization completed, 57 cases (78.1%) gave up the vaccination due to parents′ concern of potential aggravation of their disease, and 16 cases (21.9%) had the plan discontinued by the immunization department because of the disease. Fever, local redness and swelling were the most common side-effects after vaccination both in SMA patients and healthy children (19.8% (38/192) vs. 18.8% (36/191) , χ 2=0.055, P=0.815). The main abnormal reactions of vaccination were rash and neurovascular edema, without significant difference between these two groups (2.6% (5/192) vs. 3.7% (7/191), χ 2=0.355, P=0.551). The coverage rate of Influenza and pneumococcal vaccine in SMA patients were 22.4% (43 cases) and 31.8% (61 cases), respectively. The incidence of pneumonia in the SMA patients decreased from 59.0% (23/39) to 41.0% (16/39) after vaccination. And none of the Influenza vaccinated patients had the flu in the year of vaccination. Conclusions:The coverage rate of National Immunization Program vaccines in the SMA children is low, especially in type 1 SMA patients, which is mainly due to their guardians′ concern of potential adverse events, even though the incidence of adverse reactions is similar in SMA patients and healthy children. Influenza and pneumococcal vaccine can reduce the risk of pneumonia and flu in children with SMA effectively.