Fever of unknown origin(FUO)is a difficulty in clinical diagnosis and treatment.Patients with FUO come to seek medical consultation usually with fever as the main complaint,and the accompanying symptoms and signs are generally atypical.The pathogenesis of FUO remains conflicting in the field of modern western medicine,and its treatment is still focused on empirical anti-inflammatory management,which has the deficiency of delayed diagnosis,limited therapeutic options,poor therapeutic effects,and obvious adverse reactions.In the field of traditional Chinese medicine(TCM),FUO generally results from the dysfunction of zang-fu organs and the imbalance of yin and yang,and has the clinical features of long duration of illness,unknown etiology,complexity of illness,recurrent attacks,and difficult to be cured.Based on the six-meridian syndrome differentiation,Chief Physician LI Chuang-Peng pointed out that the pathogenesis of FUO is characterized by the combined disease of shaoyin and yangming,and put forward the therapeutic principle of warming shaoyin and unblocking yangming.He proposed the use of Dahuang Fuzi Decoction(mainly composed of Rhei Radix et Rhizoma and Aconiti Lateralis Radix Praeparata)plus Yiyi Fuzi Baijiang Powder(mainly composed of Coicis Semen,Aconiti Lateralis Radix Praeparata and Patriniae Herba)to subside fever and eliminate pathogen,together with Asari Radix et Rhizoma for guiding the medicine directly to the shaoyin.Moreover,therapies of strengthening and activating spleen and stomach,nourishing yin to produce fluid,and unblocking the blood vessels can be used for eliminating the pathogen and supporting the healthy qi.

BACKGROUND:Diabetic foot patients with wound infections constitute a large patient population,and there is currently no satisfactory treatment approach. OBJECTIVE:To investigate the clinical efficacy of a modified tibial cortex transverse transport combined with antibiotic-loaded bone cement for treating refractory diabetic foot ulcers. METHODS:A total of 46 diabetic foot ulcers patients,27 males and 19 females,with an average age of 64.37 years,were selected from Beijing Chaoyang Hospital,Capital Medical University and Beijing Chaoyang Integrative Medicine Rescue and First Aid Hospital from January 2020 to January 2023.All of them underwent the modified tibial cortex transverse transport combined with antibiotic-loaded bone cement treatment.Ankle-brachial index,WIFi(Wound/Ischemia/Foot infection)classification,pain visual analog scale score,and ulcer area were recorded before and 3 months after surgery. RESULTS AND CONCLUSION:(1)The mean ulcer healing time for the 46 patients was(58.07±24.82)days.At 3 months postoperatively,there were significant improvements in ankle-brachial index,pain visual analog scale score,ulcer area,and WIFi classification in 46 patients,as compared to the preoperative values,with statistically significant differences(P<0.05).Two patients experienced pin-tract infections,without infection or ulcer recurrence during the follow-up period.(2)These findings indicate that the modified tibial cortex transverse transport combined with antibiotic-loaded bone cement effectively alleviates patients'pain,improves lower limb circulation,controls infections,and promotes ulcer healing.

Objective To observe the clinical efficacy and safety of olanzapine tablets combined with magnesium valproate sustained-release tablets in the treatment of adolescent depressed patients.Methods Adolescents with depression were divided into control group and treatment group by simple random method.The control group was treated with oral olanzapine tablets with 5 mg·d-1 as the starting dose.After 1 week of treatment,the drug dose was adjusted according to the symptoms and kept within 20 mg·d-1.The treatment group was given oral magnesium valproate sustained-release tablet combined treatment on the basis of the control group,with 0.5 g as the initial dose,and the maximum dose was adjusted according to clinical symptoms after 1 week of treatment,and the maximum dose was no more than 1 g·d-1.Both groups were treated for 12 weeks.The clinical efficacy,excitatory amino acid(EAA),connectin level,intestinal fatty acid binding protein(Ⅰ-FABP),Hamilton depression scale(HAMD),Bech-Rafaelsen Mania Rating Scale(BRMS)and safety of the two groups were compared.Results Sixty-three cases were included in the treatment group and control group,respectively.After treatment,the total effective rates of the treatment group and the control group were 92.06％(58 cases/63 cases)and 79.37％(50 cases/63 cases),respectively,and the difference was statistically significant(P＜0.05).After treatment,the levels of EAA in the treatment group and the control group were(29.98±3.44)and(27.97±3.88)μg·mL-1;the levels of zonulin were(189.45±19.56)and(182.33±19.89)ng·mL-1;the levels of Ⅰ-FABP were(99.27±9.13)and(103.84±9.36)pg·mL-1,respectively;the HAMD scores of the treatment group and the control group were 9.88±1.03 and 10.74±1.95;the BRMS scores were 5.08±0.32 and 5.32±0.51,respectively.Compared with the control group,the differences of above indexes in the treatment group were statistically significant(all P＜0.05).The main adverse drug reactions in the two groups were weight gain,dry mouth,and drowsiness.The total incidences of adverse drug reactions in the treatment group and the control group were 12.70％and 15.87％,respectively,and the difference was not statistically significant(P＞0.05).Conclusion Olanzapine tablets combined with magnesium valproate sustained-release tablets can effectively increase plasma Ⅰ-FABP,EAA,and zonulin levels in adolescent depressed patients,and improve HAMD and BRMS scores,with good safety.

Objective:To construct a diabetes foot prediction model for adult patients with type 2 diabetes based on retrospective cohort study using data from a regional health data platform.Methods:Using Yinzhou Health Information Platform of Ningbo, adult patients with newly diagnosed type 2 diabetes from January 1, 2015 to December 31, 2022 were included in this study and divided randomly the train and test sets according to the ratio of 7∶3. LASSO regression model and bidirectional stepwise regression model were used to identify risk factors, and model comparisons were conducted with net reclassification index, integrated discrimination improvement and concordance index. Univariate and multivariate Cox proportional hazard regression models were constructed, and a nomogram plot was drawn. Area under the curve (AUC) was calculated as a discriminant evaluation indicator for model validation test its calibration ability, and calibration curves were drawn to test its calibration ability.Results:No significant difference existed between LASSO regression model and bidirectional stepwise regression model, but the better bidirectional stepwise regression model was selected as the final model. The risk factors included age of onset, gender, hemoglobin A1c, estimated glomerular filtration rate, taking angiotensin receptor blocker and smoking history. AUC values (95% CI) of risk outcome prediction at year 5 and 7 were 0.700 (0.650-0.749) and 0.715(0.668-0.762) for the train set and 0.738 (0.667-0.801) and 0.723 (0.663-0.783) for the test set, respectively. The calibration curves were close to the ideal curve, and the model discrimination and calibration powers were both good. Conclusions:This study established a convenient prediction model for diabetic foot and classified the risk levels. The model has strong interpretability, good discrimination power, and satisfactory calibration and can be used to predict the incidence of diabetes foot in adult patients with type 2 diabetes to provide a basis for self-assessment and clinical prediction of diabetic foot disease risk.

Objective:To develop a prediction model for the risk of diabetic retinopathy (DR) in patients with newly diagnosed type 2 diabetes mellitus (T2DM).Methods:Patients with new diagnosis of T2DM recorded in Yinzhou Regional Health Information Platform between January 1, 2015 and December 31, 2022 were included in the study. The predictor variables were selected by using Lasso-Cox proportional hazards regression model. Cox proportional hazards regression models were used to establish the prediction model for the risk of DR. Bootstrap method (500 resamples) was used for internal validation, and the performance of the model was assessed by C-index, the receiver operating characteristic curve and area under the curve (AUC), and calibration curve.Results:The predictor variables included in the final model were age of T2DM onset, education level, fasting plasma glucose, glycated hemoglobin A1c, urinary albumin, estimated glomerular filtration rate, and history of lipid-lowering agent and angiotensin converting enzyme inhibitor uses. The C-index of the final model was 0.622, and the mean corrected C-index was 0.623 (95% CI: 0.607-0.634). The AUC values for predicting the risk of DR after 3, 5, and 7 years were 0.631, 0.620, and 0.624, respectively, with a high degree of overlap of the calibration curves with the ideal curves. Conclusion:In this study, a simple and practical risk prediction model for DR risk prediction was developed, which could be used as a reference for individualized DR screening and intervention in newly diagnosed T2DM patients.

Objective:To construct a risk prediction model for diabetes kidney disease (DKD).Methods:Patients newly diagnosed with type 2 diabetes mellitus (T2DM) between January 1, 2015, and December 31, 2022, were selected as study subjects from the Yinzhou Regional Health Information Platform in Ningbo City. The Lasso method was used to screen the risk factors, and the DKD risk prediction model was established using Cox proportional hazard regression models. Bootstrap 500 resampling was applied for internal validation.Results:The study included 49 706 subjects, with an median ( Q1, Q3) age of 60.00 (50.00, 68.00) years old, and 55% were male. A total of 4 405 subjects eventually developed DKD. Age at first diagnosis of T2DM, BMI, education level, fasting plasma glucose, glycated hemoglobin A1c, urinary albumin, past medical history (hyperuricemia, rheumatic diseases), triglycerides, and estimated glomerular filtration rate were included in the final model. The final model's C-index was 0.653, with an average of 0.654 after Bootstrap correction. The final model's area under the receiver operating characteristic curve for predicting 4-year, 5-year, and 6-year was 0.657, 0.659, and 0.664, respectively. The calibration curve was closely aligned with the ideal curve. Conclusions:This study constructed a DKD risk prediction model for newly diagnosed T2DM patients based on real-world data that is simple, easy to use, and highly practical. It provides a reliable basis for screening high-risk groups for DKD.

Background Cognitive behavioral therapy(CBT)is a widely used and empirically supported psychotherapy method.In recent years,the localization of CBT related to culture has received increasing attention from Chinese scholars.However,there is still a lack of systematic research on the localization of CBT using idioms as materials.Objective To explore whether idioms reflect the mutual influence between the two core therapeutic elements of CBT(cognition and emotion)and to use them as CBT treatment tools among college students,so as to provide references for the localization of CBT.Methods Using the Xinhua Idiom Dictionary(second edition)published by the Commercial Press,a three-round manual screening method was used to select idioms that reflected the mutual influence between cognition and emotion in CBT.Based on the selected idioms,a survey questionnaire titled"survey on idiom understanding level"was developed.From August to October,2022,stratified sampling was conducted among college students from different majors and universities,and 815 valid questionnaires were obtained through the Questionnaire Star platform.By analyzing the understanding of each idiom among college students,idioms that could be used as CBT treatment tools were identified.Results In the Xinhua Idiom Dictionary(second edition),there were 13 idioms that reflected the influence of cognition on emotion and 5 idioms that reflected the influence of emotion on cognition.12 idioms could be used as CBT treatment tools,including 8 idioms that reflected the influence of cognition on emotion and 4 idioms that reflected the influence of emotion on cognition.Conclusion There may be idioms that reflect the mutual influence between the two core therapeutic elements of CBT(cognition and emotion)and these idioms can be attempted as a therapeutic tool for CBT among college students.

Objective　To collect data of fungi isolated from a fungus monitoring network in Hainan Province from 2013 to 2022, and analyze the drug resistance characteristics of Candida and the results of serological tests, with an aim to provide a basis for clinical diagnosis and treatment. Methods　In accordance with the National Fungal Drug Resistance Monitoring Network technical scheme, the qualifying fungal data were extracted from the microbial identification system database using SQL language, and the data information was then analyzed, with statistical processing done using SPSS 26.0 software. Results　Among 5 503 fungal isolates from clinical specimens between 2013 and 2022, cervical orifice secretions accounted for 30.37%(1 671 strains), mid-stream urine for 23.55%(1 296 strains), lower respiratory tract specimens for 25.24% (1 389 strains)[(sputum for 20.37%(1 121 strains) and alveolar lavage fluid for 4.87%(268 strains)], wound pus for 9.59%(528 strains), ascites for 5.60%(308 strains), blood for 3.67%(202 strains), cerebrospinal fluid for 0.38%(21 strains), and joint fluid for 0.04%(2 strains), with the highest number of strains isolated in 2022 and the lowest in 2013, the 2022 figure is about 2.6 times that of 2013. Among yeast-like fungi, Candida albicans had the highest proportion with 3 312 strains accounting for 60.2%; The highest resistance rate of Candida albicans was to fluconazole at 16.7%, with 2.5% being non-wild type (NWT) for amphotericin B; Candida tropicalis had the highest rate of resistance to fluconazole at 36.0%, with NWT at 41.1% for fluconazole and 3.1% for amphotericin B; Candida glabrata had a resistance rate to fluconazole of 2.8%, dose-dependent susceptibility (SDD) of 97.2%, NWT of 15.5% for fluconazole, and NWT of 8.6% for itraconazole; Candida parapsilosis had the highest resistance rate to fluconazole at 15.7% and and NWT of 8.3% for amphotericin B; Candida krusei had a 0.0% resistance rate to caspofungin; and Candida dubliniensis was 100.0% NWT to fluconazole. Of 70 cases of blood culture-positive specimens, 64 cases were detected by G test and 25 cases by Mn test, and the positive blood cultures were statistically significant when compared with the G test and Mn test, respectively (P<0.01). Conclusions　 Fungal serological test can make up for the deficiency of blood culture and distinguish fungal invasion and colonization, thus providing a basis for the effective control of fungal infection in clinical practice.

Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.

Atherosclerosis(AS)is a chronic inflammatory disease of large and medium-sized arteries that leads to ischemic heart disease,stroke,and peripheral vascular disease.Despite the current treatments,mortality and disability still remain high.Sonodynamic therapy(SDT),a non-invasive and localized methodology,has been developed as a promising new treatment for inhibiting atherosclerotic progression and sta-bilizing plaques.Promising progress has been made through cell and animal assays,as well as clinical trials.For example,the effect of SDT on apoptosis and autophagy of cells in AS,especially macrophages,and the concept of non-lethal SDT has also been proposed.In this review,we summarize the ultrasonic parameters and known sonosensitizers utilized in SDT for AS;we elaborate on SDTs therapeutic effects and mechanisms in terms of macrophages,T lymphocytes,neovascularization,smooth muscle cells,lipid,extracellular matrix and efferocytosis within plaques;additionally,we discuss the safety of SDT.A comprehensive summary of the confirmed effects of SDT on AS is conducted to establish a framework for future researchers.