Objective To investigate the prescription patterns and potential therapeutic mechanisms of traditional Chinese medicine(TCM)in treating laryngopharyngeal reflux disease(LPRD)based on data mining and network pharmacology.Methods The clinical data from 1 016 LPRD patients treated at the Guangdong Provincial Hospital of Chinese Medicine between February 1,2012,and December 30,2023 were collected.Frequency analysis,property and flavor analysis,meridian tropism analysis,efficacy classification,association rule mining,and cluster analysis were performed on the effective TCM prescriptions to identify medication rules.Core herbs were screened,and their therapeutic mechanisms were explored using network pharmacology.Results A total of 1 976 prescriptions involving 139 medicinals(23 644 medicinal frequencies)were analyzed.The top five most frequently-used medicinals were Glycyrrhizae Radix et Rhizoma(Gancao),Poria(Fuling),Citri Reticulatae Pericarpium(Chenpi),Bombyx Batryticatus(Jiangcan),and Galli Gigerii Endothelium Corneum(Jineijin).The herbs predominantly exhibited sweet flavor and neutral property,with a primary affinity for the lung meridian.The most common therapeutic categories were deficiency-tonifying herbs and phlegm-resolving herbs.The herb combination"Gancao-Chenpi-Fuling"was identified as the core prescription for LPRD.Network pharmacology analysis of this combination revealed 11 shared targets between the core herbs and LPRD,including three key targets.The core herbs may alleviate LPRD by modulating the interleukin-17(IL-17)signaling pathway,tumor necrosis factor(TNF)signaling pathway,and cancer-related pathways.Conclusion TCM treatment for LPRD should primarily target the lung,and employs herbs with mild-sweet properties and tonifying effects,supplemented by phlegm-resolving herbs.The core combination"Gancao-Chenpi-Fuling"may exert therapeutic effects by regulating key targets such as IL-1B,TNF,and IL-6,thereby modulating the IL-17 signaling pathway,TNF signaling pathway,and cancer-related pathways to mitigate inflammatory responses in LPRD.

Objective　To explore the application of time series models based on meteorological factors in the population density of Aedes albopictus in Hainan Province, and to provide a scientific basis for the prevention and control of dengue fever in Hainan Province. Methods　The density of Aedes albopictus in different habitats in 18 cities and counties of Hainan Province from 2017 to 2022 was monitored monthly using the double-mosquito net trapping index and the Breteau index. Mann-Kendall trend test was used to analyze the temporal trends of the two density indices; Spearman's correlation analysis was employed to assess the correlation strength between each meteorological factor and the two indexes, eliminating unrelated variables, and further selecting the final variables through the full-subset regression method. Three time-series models were constructed for the two density indices, with root mean square error (RMSE), mean absolute error (MAE), and other accuracy metrics used to determine the optimal model; predictions for the density indices for 2023-2024 were made. All statistical analyses were performed in R (4.3.1). Results　The net trapping and Breteau indices showed an overall decrease over the years (Z-values of Mann-Kendall trend test were -6.15 and -4.03, respectively, and P<0.05). The meteorological factor most strongly associated with the trap index was the monthly average minimum temperature; monthly mean minimum temperature and monthly mean relative humidity were strongly correlated with the Breteau index. Based on various evaluation indicators, the multivariate time series model demonstrated the highest accuracy. The study predicts one to two peaks in both the trap index and Breteau Index for the years 2023 and 2024, with peak periods occurring between June to September and May to September, respectively. The predicted value for 2023 aligns with the measured value, demonstrating outstanding predictive accuracy. Conclusions　This study has introduced meteorological factors into the seasonal time series model, allowing for more accurate predictions of the density of Aedes albopictus in Hainan Province from 2023 to 2024, providing a model framework for the prevention and control of dengue fever in Hainan Province.

Objective To explore the safety and efficacy of neoadjuvant chemotherapy(NAC)combined with immunotherapy before radical cystectomy plus pelvic lymph nodes dissection(RC-PLND)for muscle-invasive bladder cancer(MIBC).Methods The clinical data of 101 patients with MIBC who underwent neoadjuvant therapy followed by RC-PLND in the Department of Urology,the First Affiliated Hospital of Xi'an Jiaotong University during Jan.2019 and Dec.2023 were retrospectively analyzed,including 71 patients(70.3％)who received NAC(NAC group)and 30(29.7％)who received NAC combined with immunotherapy(NAC combine immunotherapy group).The clinical and pathological data and adverse events during neoadjuvant therapy were compared.Logistic regression analysis was used to explore the independent predictors of pathological complete response(pCR)and pathological partial response(pPR).Results There were no significant differences in the baseline data between the two groups(P＞0.05).However,the proportion of multiple tumors in patients receiving NAC before surgery was significantly higher than that in the NAC combined immunotherapy group(69.0％vs.46.7％,P=0.034).Compared with NAC group,NAC combined with immunotherapy group had significantly improved rate of pathological downstaging and pPR(60.6％vs.83.3％,P=0.026;45.1％vs.70.0％,P=0.022).Furthermore,the rate of pCR in patients undergoing NAC combined immunotherapy was higher than those undergoing NAC,but the difference was not significant(53.3％vs.33.8％,P=0.067).Logistic regression analysis revealed that clinical T-stage and tumor diameter were independent predictors of pCR and pPR(P＜0.05).In addition,the most common adverse events during neoadjuvant therapy were anemia,decreased white blood cells,nausea,and vomiting,but most of them were grade 1-2 and could be relieved through symptomatic treatment.Conclusion NAC combined with immunotherapy is safe and effective,which can improve the rate of pathological downstaging,pPR and pCR,without increasing the incidence of adverse reactions.

Objective:To analyze the effects of a novel type of polydopamine (PDA)-coated porous titanium alloy scaffolds loaded with zoledronic acid-gelatin nanoparticles (ZOL-GNPs) for topical sustained drug release on osteoclasts in vitro. Methods:After porous titanium alloy scaffolds were fabricated using electron beam melting technique and ZOL-GNPs with different ZOL concentrations (0, 1, 10, 50, 100, 500 μmol/L) were prepared by desolvation method, PDA-coated porous titanium alloy scaffolds loaded with ZOL-GNPs were constructed by combining the two. The characteristics of the scaffolds were analyzed. The biomechanics of 3 different scaffolds (bare porous titanium alloy scaffolds, PDA-coated porous titanium alloy scaffolds, and PDA-coated porous titanium alloy scaffolds loaded with ZOL-GNPs) were investigated. Drug release detection was carried out by high performance liquid chromatography on the 1st, 4th, 7th, 14th, 21st, and 28th days respectively. The osteoclasts were inoculated into the novel scaffolds with different ZOL concentrations. The expression of osteoclast-related genes was detected by real-time quantitative (RT)-polymerase chain reaction (PCR); the expression of osteoclast-related proteins was detected by Western-blot.Results:The PDA-coated porous titanium alloy scaffolds loaded with ZOL-GNPs were successfully constructed. Electron microscope scanning showed that the GNPs were well spheroidized, smooth in surface, and uniformly dispersed, with a particle size of (243.6±63.4) nm. The ZOL-GNPs were uniformly compounded on the surface and in the pores of the scaffolds, and the spheres were regular in shape with no adhesion. The biomechanical experiments showed that the elastic moduli of the porous titanium alloy scaffolds under 3 different conditions were (1.81±0.12) GPa, (1.80±0.23) GPa and (1.81±0.15) GPa, showing no significant difference ( P> 0.05). The drug release percentage in the porous titanium alloy scaffolds was obviously high on the first day, and increased gradually and slowly in the subsequent 27 days. In the scaffolds with a low concentration ZOL, more osteoclasts adhered and proliferated; in the 50 μmol/L scaffolds, spheroid cells appeared; the spheroid cells increased and even apoptosis occurred with an increase in the ZOL concentration. RT-PCR showed that the expression of Ctsk gene and TRAP gene increased with the increased ZOL concentration, peaked in the 50 μmol/L scaffolds, and then decreased with the increased concentration, showing statistically significant differences ( P < 0.05). Western-blot showed that the expression pattern of Ctsk and TRAP was similar to that of their related genes. Conclusions:The novel PDA-coated porous titanium alloy scaffolds loaded with ZOL-GNPs demonstrate good mechanical properties and an anti-osteoporosis effect via their topical sustained drug release. The scaffolds with a ZOL concentration of 50 μmol/L may exert the best effect on inhibition of osteoclasts.

Objective:To examine the prognosis factors of postoperative cardiac complications in colorectal cancer patients co-morbidated with coronary artery disease.Methods:Clinical data of 449 patients colorectal cancer patients co-morbidated with coronary artery disease accepted redical surgery from April 2013 to April 2020 at Department of General Surgery, Peking Union Medical College Hospital were analyzed retrospectively. There were 306 males and 143 females, aging (68.7±8.9) years (range: 44 to 89 years). Postoperative acute coronary syndrome, new-onset arrhythmia and heart failure that causes clinical symptoms were recorded as cardiac complications. t test, χ 2 test and Fisher exact test were used for univariate analysis of prognosis factors of postoperative cardiac events. The variables with P<0.05 were included in the multivariate Logistic regression was used to determine the independent prognosis factors. Results:After surgery, 44 patients (9.8%) suffered from at least one cardiac event, including 30 patients with acute coronary syndrome, 19 patients with new-onset arrhythmia and 9 patients with heart failure. There were 3 deaths in the cohort within 30 days after surgery. Two patients died from cardiac-related complications, and one from septic shock due to postoperative anastomotic leaks. On Univariate analysis showed that cardiac complications were associated with age ≥80 years, co-morbidated diabetes, emergency surgery, re-operation, anastomotic leakage, intestinal flora disorder and elevation of preoperative neutrophil-lymphocyte ratio (χ 2: 4.308 to 12.219, all P<0.05). Multivariate Logistic regression analysis identified age ≥80 years ( OR=3.195, 95% CI: 1.379 to 7.407, P=0.007), co-morbidated diabetes ( OR=2.551, 95% CI: 1.294 to 5.025, P=0.007), emergency surgery ( OR=4.717, 95% CI: 1.052 to 20.833, P=0.043), and elevated preoperative neutrophil-lymphocyte ratio ( OR=1.114, 95% CI: 1.018 to 1.218, P=0.018) as independent prognosis factors for cardiac complications. Conclusions:Emergency surgery, advanced age, co-morbidated type 2 diabetes and elevated preoperative neutrophil-lymphocyte ratio may increase the risk of postoperative cardiac complications in colorectal cancer patients with coronary artery disease. Surgeons should strictly master surgical indications, pay attention to preoperative assessment, perioperative monitoring, and diagnosis and treatment of postoperative complications in order to reduce the risk of complications.

Objective:To examine the prognosis factors of postoperative cardiac complications in colorectal cancer patients co-morbidated with coronary artery disease.Methods:Clinical data of 449 patients colorectal cancer patients co-morbidated with coronary artery disease accepted redical surgery from April 2013 to April 2020 at Department of General Surgery, Peking Union Medical College Hospital were analyzed retrospectively. There were 306 males and 143 females, aging (68.7±8.9) years (range: 44 to 89 years). Postoperative acute coronary syndrome, new-onset arrhythmia and heart failure that causes clinical symptoms were recorded as cardiac complications. t test, χ 2 test and Fisher exact test were used for univariate analysis of prognosis factors of postoperative cardiac events. The variables with P<0.05 were included in the multivariate Logistic regression was used to determine the independent prognosis factors. Results:After surgery, 44 patients (9.8%) suffered from at least one cardiac event, including 30 patients with acute coronary syndrome, 19 patients with new-onset arrhythmia and 9 patients with heart failure. There were 3 deaths in the cohort within 30 days after surgery. Two patients died from cardiac-related complications, and one from septic shock due to postoperative anastomotic leaks. On Univariate analysis showed that cardiac complications were associated with age ≥80 years, co-morbidated diabetes, emergency surgery, re-operation, anastomotic leakage, intestinal flora disorder and elevation of preoperative neutrophil-lymphocyte ratio (χ 2: 4.308 to 12.219, all P<0.05). Multivariate Logistic regression analysis identified age ≥80 years ( OR=3.195, 95% CI: 1.379 to 7.407, P=0.007), co-morbidated diabetes ( OR=2.551, 95% CI: 1.294 to 5.025, P=0.007), emergency surgery ( OR=4.717, 95% CI: 1.052 to 20.833, P=0.043), and elevated preoperative neutrophil-lymphocyte ratio ( OR=1.114, 95% CI: 1.018 to 1.218, P=0.018) as independent prognosis factors for cardiac complications. Conclusions:Emergency surgery, advanced age, co-morbidated type 2 diabetes and elevated preoperative neutrophil-lymphocyte ratio may increase the risk of postoperative cardiac complications in colorectal cancer patients with coronary artery disease. Surgeons should strictly master surgical indications, pay attention to preoperative assessment, perioperative monitoring, and diagnosis and treatment of postoperative complications in order to reduce the risk of complications.

Objective:To explore the clinical manifestations and surgical outcomes of pediatric epilepsy patients with epileptic spasms (ES) as the main form of seizure, so as to analyze the correlative factors with prognosis and improve the understanding of the operation and preoperative positioning for such patients.Methods:The clinical data of patients with ES who underwent surgery therapy from June 2014 to December 2015 in Pediatric Epilepsy Center, Peking University First Hospital were collected and retrospectively analyzed.Demographic characteristics, seizure forms, etiology, electroencephalogram (EEG), cranial magnetic resonance imaging (MRI), operative methods, pathological findings as well as surgical outcomes evaluated by Engel classification during follow-up of the subjects were collected.Correlative factors with the prognosis were explored by comparing the data between patients with optimal outcome (Engel Ⅰ) and those with poor outcomes (Engel Ⅱ-Ⅳ).Results:A total of 25 pediatric patients were enrolled, including 16 males (64.0%) and 9 females (36.0%). The age of onset was (0.81±0.68) years, the age at operation was (2.98±1.63) years, and the course of disease was (2.17±1.48) years.Besides, 84.0% (21/25 cases) of the ES patients had multiple forms of seizures and partial seizure (19 cases) was the most common.MRI of the heads of all the children showed definite lesions, including 11 patients (44.0%) with lesions limited to one brain lobe and 14 patients (56.0%) involving multiple brain lobes or hemisphere.The most common etiology was focal cortical dysplasia (13 cases), followed by intracranial developmental tumors (3 cases). All patients underwent resection surgery, including resection of lesion (3 cases), single brain lobe resection (9 cases), multiple brain lobe dissection (3 cases) and hemisphere dissection (10 cases). During a follow-up period of 4.0 to 5.5 years, 1 patient was lost.Among the remaining 24 cases, 18 (75.0%) cases achieved good outcomes and wee classified as EngelⅠ, 2 cases (8.3%) and 4 cases(16.7%) were classified as Engel Ⅱand Ⅳ, respectively.The univariate comparison between the good epilepsy prognosis group and the poor epilepsy prognosis group showed that, patients whose EEG abnormalities are consistent with the anatomical lesions during the inter ictal tend to have good prognosis( P=0.006). Conclusions:(1) Optimal therapeutic effects were observed in ES patients with definite lesions treated by surgical therapy.(2) Interictal EEG consistent with the lesion side may suggest a good prognosis for surgical treatment.(3) Structural causes should be screened as soon as possible if a patient with ES is drug-refractory and presents clues of focal origin.

Objective:To design 3D printed prosthesis in an individualized way and explore the short-term clinical efficacy of reconstruction of segmental defect after resection of bone tumor in lower extremities with 3D-printed prosthesis.Methods:From January 2017 to June 2019, 6 patients with lower limb bone tumor who met the inclusion criteria were recruited, including 3 males and 3 females, aged 8.67±1.11 years (range 6-11 years). All 6 cases were primary bone tumors, and the Enneking stages were all IIB, including 3 cases of left tibial tumors, 2 cases of right tibial tumors, and 1 case of right femoral tumor. These 3D-printed prostheses were designed based on the preoperative imaging data. The mechanical stability of the prosthesis was evaluated by three-dimensional finite element analysis. After tumor resection, the 3D-printed prosthesis was installed and fixed to reconstruct the segmental bone defect. All patients were clinically followed up and evaluated by imaging regularly after operation. The functional status was assessed by the Musculoskeletal Tumor Society (MSTS) score. Oncology results and complications were recorded in detail.Results:All operations were successfully performed, including 3 cases underwent left tibial tumor resection, 2 cases underwent right tibial tumor resection, and 1 case underwent right femoral tumor resection. The length of the bone defect after tumor resection was 18.19±3.74 cm, the average operation time was 165.83±54.17 min, and the average intraoperative bleeding was 233.33±133.33 ml. These finite element analysis data show that the overall stress of these prostheses are lower than the maximum mechanical strength of the corresponding materials. These 3D printed prostheses match well with the excision defect and meet the expected effect. There were no adverse reactions during the operation. The mean follow-up period was 16.83±7.17 months. At the last follow-up, all patients survived without tumor recurrence or metastasis. Postoperative imaging results showed that all the implants were stable without complications such as peripheral infection, aseptic loosening, prosthesis fracture. These 3D-printed prostheses composite resulted in substantial bone integration at follow-up. The average MSTS score was 83.67%±9.11%.Conclusion:The individualized 3D printed prosthesis can be used to reconstruct the bone defect after the resection of osteosarcoma in the lower extremities, and the clinical efficacy was satisfactory in the short-term follow-up.

Objective To discuss the correlations amongst the count,molecular and clinicopathological characteristics of circulating tumor cells (CTCs),and the feasibility of using CTC as an aid to judge the metastasis of osteosarcoma,evaluate the therapeutic effect,and predict the prognosis of patients.Methods Retrospective analysis of 30 patients with newly diagnosed osteosarcoma diagnosed from January 2015 to June 2016,there were 17 males and 13 females.The average age was 13.77±4.31 years old (ranged from 7 to 21 years).There were 21 cases of Ennecking stage Ⅱ,including 2 cases of ⅡA,19 cases of ⅡB,and 9 cases of Ennecking Ⅲ.Peripheral blood of all patients was obtained and processed using CanPatrolTM System at baseline,pre-and post-operation.Multiplex RNA-in situ hybridization (RNA-ISH) assay was used to characterize the molecular markers.Combined with clinical data,the relationship between peripheral blood CTC counts,count changes,molecular characteristics,tumor metastasis,chemotherapy effects,and prognosis of patients with osteosarcoma was analyzed and compared.Results The CTC count in peripheral blood was 10.44±5.70 in Ennecking stage Ⅲ patients and 4.76±3.56 in stage Ⅱ patients.The increase or decrease in CTC counts was associated with good or poor neoadjuvant chemotherapy (P=0.002).In patients with good chemotherapy effect,the CTC count in peripheral blood was decreased after chemotherapy.The mean progression-free survival time was 11.85±4.93 months for patients with CTC number ≥7,and the average progression-free survival time was 15.53±4.09 months for patients with CTC number ＜ 7 (P=0.012).The proportion of interstitial CTC in Ennecking stage Ⅲ was 40.42％,which was higher than that of Ennecking ⅡB stage 23.00％.The difference was statistically significant (P=0.010).The positive rate of metastasis-associated gene 1 (MTA1) in interstitial CTC was 85.50％,and the positive rate of other types of CTC was 66.67％.The difference was statistically significant (P=0.000).Conclusion The counting and typing of peripheral blood CTC in osteosarcoma patients can be used as a complement to the commonly used imaging examinations,and they can play an auxiliary role in judging tumor metastasis,curative effect observation and prediction of poor prognosis.

Objective To analyze clinical efficacy of artificial prosthesis in giant cell tumor in distal femur,and to investigate risk factors affecting prosthesis failure and functional outcomes.Methods 42 patients with giant cell tumor of bone in distal femur,who had undergo prosthesis replacement from January 2002 to May 2015,were enrolled in this study.There were 24 males and 18 females,with an average age of 38.53± 12.87 years.There were 28 primary patients and 14 relapsed patients,including 11 cases of recurrence once and 3 cases of twice.Three-dimensional finite element model was used to analyze the effect of different angles of deviation of the spinal needle on the deformation of the bone wall.The correlations between the factors such as age,sex,occupation,prosthesis type,and other factors on prosthesis loosening were compared.Biomechanical effect of lower limbs caused by prosthesis offset angle was analyzed through gait analysis.Analyzed the effects of primary tumor or recurrence,prosthesis service status,and length of surgical osteotomy on joint function.Results A total of 42 patients were followed up by 20-158 months,with an average of 68.7 months.The 3 year survival rate of prosthesis was 83.33％ for 3 years and 57.14％ for 5 years.The major reason of prosthesis failure was loose (18/42,42.8％).X-ray films showed 19 cases of prosthetic intramedullary nail and sagittal bias of medullary force line angle ＞ 3° in the first follow-up.Osteotomy length (OR=0.132,P=0.0027) and offset angle of needle (OR=25.000,P=0.000) were significantly correlated to prosthesis loose.A length more than 12 cm and angle more than 3° were easier to result in prosthesis loose.There were no significant correlation between prosthesis failure and patients age,gender,occupation and prosthesis type.Gait analysis shows that the unsuitable bias angle of the prosthesis can significantly change the joint force of the prosthesis.The average score of MSTS 93 function evaluation was 25.43±4.256,excellent in 33 cases,good in 7 cases and poor in 2 cases.Function of patients with primary GCT were better than that of recurrent ones.Patients with one 1 times recurrence were better than that of recurrence twice (P=0.003).Patients without prosthesis loosening and revision were better than that with loosening (P=0.001).Patients with an osteotomy length less than 12 cm had a poorer function than that with more than 12 cm (P=0.002).Conclusion The main factors affecting distal femoral prosthesis replacement therapy of GCT is loosening,which was caused by broach and medullary cavity mismatch,osteotomy length,prosthesis rotation,prosthesis position.The function of the prosthesis is mainly affected by operation times,prosthesis status,osteotomy length and low patella.