ObjectiveTo evaluate the effectiveness of stone needle thermocompression and massage compared to flurbiprofen gel patch in relieving chronic musculoskeletal pain in the shoulder and back， and to explore the potential mediating mechanism through muscle elasticity. MethodsA total of 120 patients with chronic musculoskeletal pain in the shoulder and back were randomly assigned to either stone needle group or flurbiprofen group， with 60 patients in each. The stone needle group received stone needle thermocompression and massage for 30 minutes， three times per week； the flurbiprofen group received flurbiprofen gel patch twice daily. Both groups were treated for 2 weeks. Pain improvement， as the primary outcome， was assessed using the Global Pain Scale （GPS） at baseline， after 2 weeks of treatment， and again 2 weeks post-treatment. To explore potential mechanisms， a mediator analysis was conducted by measuring changes in superficial and deep muscle elasticity using musculoskeletal ultrasound at baseline and after the 2-week treatment period. ResultsThe stone needle group showed significantly greater pain relief than the flurbiprofen group 2 weeks post-treatment. After adjusting for confounders related to pain duration， the between-group mean difference was -8.8 ［95% CI （-18.2， -0.7）， P＜0.05］. Part of the therapeutic effect was mediated by changes in deep muscle elasticity， with a mediation effect size of -1.5 ［95% CI （-2.0， -0.9）， P = 0.024］， accounting for 17.9% of the total effect. ConclusionStone needle thermocompression and massage can effectively relieve chronic musculoskeletal pain in the shoulder and back， partly through a mediating effect of improved deep muscle elasticity.

Objective:To observe the clinical effect of Shenfu injection in preventing septic cardiomyopathy (SIC) in septic patients.Methods:From June 2022 to January 2023, patients with sepsis or septic shock who did not develop SIC were randomly divided into treatment group and control group according to the ratio of 1:1. In the treatment group, Shenfu injection (50 mL) was pumped intravenously once every 12 hours for 5 days. In the control group, 50 mL of normal saline was pumped intravenously once every 12 hours, and the course of treatment was 5 days. The primary end point was the incidence of SIC in the first 5 days. The secondary end points were the application time of vasoactive drugs, fluid balance in the previous week, hospitalization time in ICU, total ventilation time and 28-day mortality.Results:112 patients were randomly divided into two groups. Seven patients in the treatment group were excluded twice, and finally 49 patients were included in the analysis, while six patients in the control group were excluded twice and 50 patients included in the analysis. The total incidence of SIC in the treatment group within 5 days was significantly lower than that in the control group (42.9% vs. 64.0%, P = 0.035). Among them, the left ventricular systolic dysfunction in the treatment group was significantly lower than that in the control group (24.5% vs 52.0%, P=0.005), and there was no significant difference in the incidence of left ventricular diastolic dysfunction between the two groups. The incidence of right ventricular dysfunction in the control group was 28.0%, which was significantly higher than 10.2% in the treatment group ( P = 0.025). The duration of using vasoconstrictors in the treatment group was 75(48, 97) hours, which was significantly lower than 97(66, 28) hours in the control group ( P = 0.039). The duration of inotropic drugs use in the treatment group was 32(18, 49) h, which was also significantly shorter than 44(25, 61) h in the control group ( P=0.046). The fluid balance of the control group in the first week was (1 260±850) mL, which was significantly higher than (450±520) mL in the treatment group ( P=0.008). There was no statistical difference in ICU stay, total ventilation time and 28-day mortality between the two groups (all P > 0.05). Conclusion:Early application of Shenfu injection can significantly reduce the incidence of SIC, accompanied by less use of vasoactive drugs and positive fluid balance, which has a good clinical application prospect.

Objective:To investigate the application value of metagenomic next-genera-tion sequencing (mNGS) in pathogenic diagnosis of suspected infected severe acute pancreatitis (SAP).Methods:The prospective study was conducted. The clinical data of 25 patients with suspected infected SAP who were admitted to the Xiangya Hospital of Central South University from May to September 2023 were collected. Upper limb venous blood samples of all the patients were collected for both of mNGS and routine pathogen microbial culture. Observation indicators: (1) grouping situations of the enrolled patients; (2) comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture; (3) results of peripheral blood pathogen microbial testing and peri-pancreatic effusion microbial culture; (4) testing time and cost. Measurement data with normal distribution were represented as Mean± SD, and comparison between groups was conducted using the independent sample t test. Measurement data with skewed distribution were represented as M( Q1, Q3). Count data were expressed as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Results:(1) Grouping situations of the enrolled patients. A total of 25 patients were selected for eligibility. There were 18 males and 7 females, aged 48(40,59)years. The duration of hospital stay of 25 patients was 30(20,50)days. The etiologies of 25 patients included 14 cases of hyperlipidemic pancreatitis, 8 cases of biliary pancreatitis, 1 case of alcohol-induced acute pancreatitis, and 2 cases of pancreatitis caused by other causes. Of the 25 patients, there were 17 cases with infected pancreatic necrosis (IPN) including 7 cases of death, and 8 cases with sterile pancreatic necrosis including no death. (2) Comparison of the diagnostic efficiency of mNGS and routine pathogen microbial culture. The positive rates of mNGS and routine pathogen microbial culture in diagnosis of suspected infected SAP were 72.0%(18/25) and 32.0%(8/25), respectively, showing a significant difference between them ( χ2=8.01, P<0.05). The sensitivity and negative predic-tive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 94.1%(16/17), 35.3%(6/17) and 85.7%(6/7), 35.3%(6/17), showing significant differences between them ( χ2=12.88, 5.04, P<0.05). The specificity and positive predictive value of mNGS and routine pathogen microbial culture in diagnosis of IPN were 75.0%(6/8), 75.0%(6/8) and 88.9%(16/18), 75.0%(6/8), showing no significant difference between them ( χ2=0, 0.82, P>0.05). (3) Results of peripheral blood pathogen microbial testing and peripancreatic effusion microbial culture. Of the 17 patients with IPN, 36 strains of pathogenic bacteria were detected by mNGS, and 6 strains were detected by routine pathogen microbial culture. There were 16 of 17 patients with IPN showing positive mNGS pathogenic testing, of which 13 cases were consistent with the pathogenic testing results of peri-pancreatic effusion microbial culture, showing a consistency rate of 76.5%(13/17). There were 6 pati-ents with IPN showing positive routine pathogen microbial culture, with a consistency rate of 35.3%(6/17) to peripancreatic effusion microbial culture. (4) Testing time and cost. Testing time of mNGS and routine pathogen microbial culture were (43±17)hours and (111±36)hours, showing a signifi-cant difference between them ( t=9.31, P<0.05). Testing cost of mNGS was (2 267±0)yuan/case, accoun-ting for 1.7% of the hospitalization expenses of (133 759±120 744)yuan/case. Testing cost of routine pathogen microbial culture was (240±0)yuan/case, accounting of 0.2% of the hospitalization expenses. Conclusion:mNGS has important value for early pathogenic diagnosis of suspected infected SAP, and has a high timeliness.

Background and Aims:Accurate early pathogen diagnosis is a breakthrough for improving the prognosis of infectious pancreatic necrosis(IPN)patients.However,there is currently a lack of efficient methods for early identification of IPN in clinical settings.This study was performed to assess the application value of next-generation sequencing technology based on metagenomic capture(MetaCAP)in the pathogen diagnosis of IPN. Methods:A prospective study was conducted on 29 patients suspected of having acute necrotizing pancreatitis at Xiangya Hospital of Central South University between January and July 2024.Blood samples were tested using MetaCAP and conventional pathogen culture.The results of peritoneal fluid pathogen culture were used as the gold standard to compare the diagnostic efficacy of the two methods. Results:Due to three cases lacking peritoneal fluid culture results,a total of 26 cases were included in the final analysis.The overall mortality rate was 23.1％(6/26).During hospitalization,9 cases(34.6％)were diagnosed with IPN.The sensitivity and negative predictive value of MetaCAP for diagnosing IPN were significantly higher than those of conventional pathogen culture(77.8％vs.11.1％,P=0.031;86.7％vs.65.2％,P=0.032),while the differences in specificity(76.5％vs.88.2％,P=0.689)and positive predictive value(63.6％vs.33.3％,P=0.347)between the two methods were not statistically significant.The average detection time for MetaCAP was 33(20-49)h,while microbial culture took 125(45-142)h,with a significant difference(P＜0.001).The average cost for blood MetaCAP testing was 2 500 yuan per case,but it accounted for only 1.19％of the average hospitalization cost. Conclusion:MetaCAP has significant value in the early pathogen diagnosis of IPN,with a shorter detection time,good testing efficacy,and health-economic value,demonstrating a promising clinical application prospect.

As a representative chemotherapeutic drug, docetaxel (DTX) has been used for breast cancer treatment for decades. However, the poor solubility of DTX limits its efficacy, and the DTX based therapy increases the metastasis risk due to the upregulation of C-X-C chemokine receptor type 4 (CXCR4) expression during the treatment. Herein, we conjugated CXCR4 antagonist peptide (CTCE) with DTX (termed CTCE-DTX) as an anti-metastasis agent to treat breast cancer. CTCE-DTX could self-assemble to nanoparticles, targeting CXCR4-upregulated metastatic tumor cells and enhancing the DTX efficacy. Thus, the CTCE-DTX NPs achieved promising efficacy on inhibiting both bone-specific metastasis and lung metastasis of triple-negative breast cancer. Our work provided a rational strategy on designing peptide-drug conjugates with synergistic anti-tumor efficacy.

Objective:To compare the efficacy and safety of standard treatment with or without adjuvant chemotherapy in patients with highly malignant non-metastatic prostate cancer.Methods:In this prospective non-randomized controlled study, consecutive non-metastatic prostate cancer patients with pathologically proven Gleason score of 9-10 or Gleason score of 5 admitted to Peking University First Hospital were enrolled. Four to six cycles of chemotherapy using docetaxel ± carboplatin regimen were added or not after standard radical therapy. The primary end point was 5-year event-free survival (EFS), and the secondary end points were distant metastasis-free survival (MFS), overall survival (OS), and treatment-related adverse events. The survival curve was drawn by Kaplan-Meier method. The differences between two groups were analyzed by log-rank test.Results:A total of 176 patients were consecutively enrolled from November 2019 to January 2022 of which 138 patients received only standard radical therapy (control group), and 38 patients received adjuvant chemotherapy after standard radical therapy (chemotherapy group). The median follow-up time was 13.4 (2.0-34.0) months. All patients survived. The 30-month EFS rates in the chemotherapy and control groups were 100% and 85.6%, respectively ( P=0.064). There were no events in the chemotherapy group, while there were 12 cases of events in the control group, including 6 cases of biochemical recurrence and 6 cases of imaging progression. The 30-month MFS rates in two groups were 100% and 91.9%, respectively ( P=0.205). After the 1 vs. 2 propensity score matching, the EFS and MFS rates in two groups were 100% vs. 85.7% ( P=0.056), and 100% vs. 92.2% ( P=0.209), respectively. The incidence rates of grade 2 and above urinary toxicity in the chemotherapy and control groups were 2.6% and 7.2% ( P=0.354), respectively. The incidence rates of grade 2 and above rectal toxicity were 5.3% and 5.1% ( P=0.711), respectively. Grade 3 and above chemotherapy-related toxicity in the chemotherapy group were leukopenia (31.6%), thrombocytopenia (2.6%) and alopecia (13.2%). Conclusion:The addition of adjuvant chemotherapy after standard radical therapy tends to improve the overall EFS of patients with highly malignant prostate cancer, and the adverse effects are tolerable, which should be confirmed by long-term follow-up results.

ObjectiveTo explore the clinical efficacy of compound Wufengcao liquid （CWL） on tuberculous ulcer and the influence on macrophage polarization. Method① Clinical experiment： A total of 145 patients with tuberculous ulcer who were treated in Nanjing Integrated Traditional Chinese and Western Medicine Hospital were randomized into observation group， control group Ⅰ， and control group Ⅱ according to the random number table method. In addition to the basic anti-tuberculosis chemotherapy， CWL， Kangfuxin liquid， and isoniazid solution （local external application） were respectively used in the observation group， control group Ⅰ， and control group Ⅱ. The treatment lasted 4 weeks for each group. The total effective rate in wound healing， traditional Chinese medicine（TCM） syndrome score， and histopathological morphology of wound were observed and the expression of inducible nitric oxide synthase （iNOS） and arginase-1 （Arg-1） in wound tissue was measured. ② Cell experiment： RAW264.7 cells were cultured in DMEM （10% fetal bovine serum， 1% double-antibody solution） in a cell incubator （37 °C， 5% CO₂）. Phorbol 12-myristate 13-acetate （PMA） was used to induce the differentiation of RAW264.7 cells into macrophages. Lipopolysaccharide （LPS） was employed to stimulate polarization of macrophages into M1 type and interleukin-4 （IL-4） to induce the polarization into M2 type. Kangfuxin solution， isoniazid solution， and CWL were respectively applied to the above cell model for 36 h. The cell supernatant was collected and centrifuged. Western blot was used to detect the protein expression of tumor necrosis factor-α （TNF-α）， transforming growth factor-β （TGF-β）， iNOS， and Arg-1， and flow cytometry （FCM） to detect the expression of CD86 and CD206. Result①Clinical experiment： The total effective rate in the CWL group ［98.0% （48/49）］ was higher than that in the control group Ⅰ ［87.5% （42/48）， χ²=3.962， P<0.05］ and control group Ⅱ ［83.3% （40/48）， χ²=6.162， P<0.05］. After 28 days of treatment， compared with control group Ⅰ and control group Ⅱ， CWL decreased the TCM syndrome score （P<0.05） and obviously improved the histopathological morphology of the wound. Immunohistochemistry results showed that the iNOS expression in local focus tissue was lower （P<0.05） and the expression of Arg-1 was higher （P<0.05， P<0.01） in the CWL group than in the control group Ⅰ and control group Ⅱ after 28 days of treatment. ② Cell experiment： Western blot assay showed that the expression of iNOS and TNF-α in LPS group increased compared with that in the M0 group （P<0.01） and the expression in the LPS+ isoniazid group， LPS+ Kangfuxin group， and LPS+CWL group was lower than that in the LPS group （P<0.05）. The expression of iNOS in LPS+Kangfuxin group and LPS+ CWL group was lower than that in the LPS+isoniazid group （P<0.05， P<0.01）， and the expression of TNF-α in LPS+ CWL group was lower than that in LPS+isoniazid group （P<0.01）. The expression of TNF-α in LPS+ CWL group decreased compared with that in the LPS+ Kangfuxin group （P<0.05）. The expression of Arg-1 and TGF-β in IL-4 group was higher than that in the M0 group （P<0.01）， and the expression in the IL-4+isoniazid group， IL-4+Kangfuxin group， and IL-4+ CWL group was higher than that in the IL-4 group （P<0.05）. The expression of Arg-1 and TGF-β in the IL-4+ Kangfuxin group and IL-4+CWL group was higher than that in the IL-4+isoniazid group （P<0.05， P<0.01）， and the expression was higher in the IL-4+CWL group than in the IL-4+Kangfuxin group （P<0.05， P<0.01）. The FCM result showed that the expression of CD86 and CD206 in LPS group and IL-4 group was higher than that in M0 group （P<0.01）. CD86 expression in LPS+isoniazid group， LPS+ Kangfuxin group， and LPS+CWL group was lower than that in the LPS group （P<0.01）. The expression of CD86 in LPS+Kangfuxin group and LPS+ CWL group increased compared with that in the LPS+isoniazid group （P<0.01）， and the expression was higher in the LPS+ CWL group than in the LPS+Kangfuxin group （P<0.01）. CD206 expression in IL-4+ isoniazid group， IL-4+Kangfuxin liquor group， and IL-4+ CWL group was increased compared with that in the IL-4 group （P<0.01）. CD206 expression in IL-4+Kangfuxin liquid group and IL-4+ CWL group was decreased compared with that in the IL-4+isoniazid group （P<0.01）. CD206 expression in IL-4+CWL group was lower than that in the IL-4+ Kangfuxin group （P<0.05）. ConclusionCWL can promote the healing of tuberculous ulcers， and the mechanism is that it inhibits the expression of iNOS， TNF-α， and CD86 and promotes the expression of Arg-1， TGF-β， and CD206， thereby regulating M1/M2 polarization balance.

Objective:To compare the efficacy of high-flow nasal cannula oxygen therapy (HFNC) and non-invasive ventilation (NIV) in the treatment of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) with moderate typeⅡ respiratory failure, to clarify the feasibility of HFNC in the treatment of AECOPD, and to explore the influencing factors of HFNC failure.Methods:This study was a randomized controlled trial of non-inferiority. Patients with AECOPD with moderate type Ⅱ respiratory failure [arterial blood gas pH 7.25-7.35, partial pressure of arterial blood carbon dioxide (PaCO 2)> 50 mmHg] admitted to the Intensive Care Unit (ICU) from January 2018 to December 2021 were randomly assigned to the HFNC group and NIV group to receive respiratory support. The primary endpoint was the treatment failure rate. The secondary endpoints were blood gas analysis and vital signs at 1 h, 12 h, and 48 h, total duration of respiratory support, 28-day mortality, comfort score, ICU length of stay, and total length of stay. Multivariate logistic regression analysis was used to evaluate the failure factors of HFNC treatment. Results:Totally 228 patients were randomly divided into two groups, 108 patients in the HFNC group and 110 patients in the NIV group. The treatment failure rate was 29.6% in the HFNC group and 25.5% in the NIV group. The risk difference of failure rate between the two groups was 4.18% (95% CI: -8.27%~16.48%, P=0.490), which was lower than the non-inferiority value of 9%. The most common causes of failure in the HFNC group were carbon dioxide retention and aggravation of respiratory distress, and the most common causes of failure in the NIV group were treatment intolerance and aggravation of respiratory distress. Treatment intolerance in the HFNC group was significantly lower than that in the NIV group (-29.02%, 95% CI -49.52%~-7.49%; P=0.004). After 1 h of treatment, the pH in both groups increased significantly, PaCO 2 decreased significantly and the oxygenation index increased significantly compared with baseline (all P < 0.05). PaCO 2 in both groups decreased gradually at 1 h, 12 h and 48 h after treatment, and the pH gradually increased. The average number of daily airway care interventions and the incidence of nasal and facial lesions in the HFNC group were significantly lower than those in the NIV group ( P < 0.05), while the comfort score in the HFNC group was significantly higher than that in the NIV group ( P=0.021). There was no significant difference between the two groups in the total duration of respiratory support, dyspnea score, ICU length of stay, total length of stay and 28-day mortality (all P > 0.05). Multivariate logistic regression analysis showed that acute physiology and chronic health evaluation Ⅱ score (≥15), family NIV, history of cerebrovascular accident, PaCO 2 (≥60 mmHg) and respiratory rate (≥32 times/min) at 1 h were independent predictors of HFNC failure. Conclusions:HFNC is not inferior to NIV in the treatment of AECOPD complicated with moderate type Ⅱ respiratory failure. HFNC is an ideal choice of respiratory support for patients with NIV intolerance, but clinical application should pay attention to the influencing factors of its treatment failure.

Objective To screen the epithelial mesenchymal transformation(EMT)-related genes in lung adenocarcinoma,perform functional enrichment analysis and construct protein interaction network(PPI).Ac-cording to the competitive endogenous RNA(ceRNA)hypothesis and the effect of gene expression on the prognosis of patients,the ceRNA network was constructed.Methods The differentially expressed genes be-tween lung adenocarcinoma tissues and normal tissues were screened by gene expression map and tumor ge-nome map database,and the genes were imported into GenClip3 to obtain EMT-related genes.Metascape was used to perform gene ontology and Kyoto encyclopedia of gene and genome enrichment analysis,and STRING database was used to construct PPI and obtain EMT key genes.The relationship between key genes and prog-nosis was analyzed by Kaplan-Meier analysis.Analysis tools such as miRTarbase,miRNet database,and EN-CORI were used to construct ceRNA networks.Results In this study,156 lung adenocarcinoma EMT-related genes and their key genes cadherin 1,interleukin-6,matrix metalloproteinase-9,platelet endothelial cell adhe-sion molecule,cyclin-dependent kinase inhibitor 2A,α1-Ⅰcollagen gene,secreted phosphoprotein 1,TIMP in-hibitor of matrix metalloproteinase-1,caveolin-1 and Zeste homologue enhance core 2(EZH2)-1 were identi-fied.The PPI of key genes was predicted,and the therapeutic drugs targeting these key genes including salvia miltiorrhiza,ginseng lu,ginseng leaf and ginseng flower were also predicted.The prognostic ceRNA regulatory network of EZH2/hsa-miR-101-3p/GSEC was constructed.Conclusion This study describes using bioinfor-matics methods system in the process of EMT gene interactions,according to the lung adenocarcinoma pa-tients clinical data to construct the prognosis of the EMT process related ceRNA network,for the treatment and prognosis of lung adenocarcinoma judgment provides a new way of thinking.

Objective:To evaluate the pancreatic subclinical dysfunction after intensity-modulated radiation therapy (IMRT) for gastric cancer by analyzing biochemical indexes and pancreatic volume changes, and to reduce the dose of pancreas by dosimetric prediction and dose limitation.Methods:30 patients with gastric cancer who received 45 Gy postoperative adjuvant radiotherapy were retrospectively selected. The pancreas was delineated and its dose and anatomical relationship with planning target volume (PTV) were evaluated. Fasting blood glucose, serum lipase and amylase, and pancreatic volume changes before and after radiotherapy were analyzed. The correlation between the changes of biochemical indexes and volume and pancreatic dose was evaluated by Pearson analysis. The threshold of the dosimetric prediction was obtained by receiver operating characteristic (ROC) curve. Finally, the feasibility of dosimetric limitation in IMRT was assessed.Results:The pancreatic volume of 30 patients was 37.6 cm 3, and 89.0% of them were involved in PTV. D mean of the pancreas was 45.92 Gy, and 46.45 Gy, 46.46 Gy and 45.80 Gy for the pancreatic head, body and tail, respectively. The fasting blood glucose level did not significantly change. The serum lipase levels were significantly decreased by 66% and 77%(both P<0.001), and the serum amylase levels were significantly declined by 24% and 38%(both P<0.001) at 6 and 12 months after radiotherapy. Pancreatic volumes of 22 patients was decreased by 47% within 18 months after radiotherapy. ROC curve analysis showed that pancreatic V 45Gy had the optimal predictive value for the decrease by 1/3 of serum lipase and amylase levels at 6 months and serum amylase level at 12 months after radiotherapy, and the cut-off value was V 45Gy<85%. Pancreatic D mean yielded the optimal predictive value for the decrease by 2/3 of serum lipase level at 12 months after radiotherapy, and the cut-off value was D mean<45.01 Gy. After" whole pancreas" and" outside PTV pancreas" dose limit, V 45Gy of the pancreas was decreased by 11% and 7%, D mean of the pancreas was declined by 2% and 2%, and D mean of the pancreatic tail was decreased by 3%, respectively. Conclusions:Serum lipase and amylase levels significantly decline at 6 and 12 months after adjuvant radiotherapy for gastric cancer, and pancreatic volume is decreased significantly within 18 months after radiotherapy. Pancreatic V 45Gy<85% and D mean<45.01 Gy are the dose prediction values for the decrease of serum lipase and amylase levels. The dose can be reduced to certain extent by dosimetric restriction.