The use of off-label drugs， which accompanies the approval system for new drugs entering the market， is widespread in clinical practice in China， and the resulting medical damage liability is also controversial in theory and practice. Based on 129 judicial cases from 2014 to 2023， this paper conducted a quantitative analysis of medical damage liability caused by off-label drug use. Through sorting out， it was found that the cases of off-label drug use presented obvious characteristics in types and regional distribution， and their damage consequences and appeal rates were far higher than those of general medical damage cases， which need to attract more attention. Based on the liability reasons， this paper further categorized the cases into three types： no liability， single liability， and multiple liabilities. The number and liability ratio of off-label drug use under different liability types were analyzed， and the key factors affecting the establishment of medical damage liability for off-label drug use were sorted out and analyzed in depth. These key factors included the existence of off-label drug use and a clear causal relationship between off-label drug use and medical damage， inadequate informed consent， and lack of sufficient and solid evidence-based medical support. Additionally， it was confirmed that a medical ethics review is not a prerequisite for the legality of off-label drug use. Finally， recommendations for off-label drug use in clinical practice were proposed， such as ensuring timeliness， adequacy， and formality of informed consent， adhering to a clear causal relationship construction， as well as sorting out the scope and effectiveness level of evidence-based medicine to establish industry self-consistency.

Objective To analyze the correlation between serum circular RNA-ATAD1(circ-ATAD1)and microRNA-140-3p(miR-140-3p)expression and the prognosis of cervical cancer patients.Methods From March 2018 to March 2020,a total of 146 patients with cervical cancer(study group),146 patients with benign uterine lesions(benign uterine lesions group),and 146 healthy people who underwent the physical examina-tion(control group)in Cangzhou Hospital of Integrated TCM-WM·Hebei were selected as the research sub-jects.Real-time quantitative PCR was used to detect serum levels of miR-140-3p and circ-ATAD1.The Kap-lan-Meier method was used to analyze the correlation between serum circ-ATAD1 and miR-140-3p expression and the prognosis of cervical cancer patients.Multivariate Cox regression model was used to analyze the influ-encing factors of prognosis of cervical cancer patients.Results The serum circ-ATAD1 level in the study group was significantly higher than those in the control group and benign uterine lesion group(P＜0.05),and miR-140-3p was significantly lower than those in the control group and benign uterine lesion group(P＜0.05).The proportions of patients with low expression of miR-140-3p and high expression of circ-ATD1 in the cervical cancer patients with vaginal infiltration,lymph node metastasis,and FIGOstage Ⅲ-Ⅳ were higher than those in the cervical cancer patients with no vaginal infiltration,no lymph node metastasis,and FIGO stage Ⅰ-Ⅱ(P＜0.05).The 3-year survival rate of cervical cancer patients with high circ-ATD1 expression was lower than that of patients with low circ-ATD1 expression(30.14％vs.64.38％,P＜0.001).The 3-year survival rate of cervical cancer patients with high miR-140-3p expression was higher than that of patients with low miR-140-3p expression(61.64％vs.32.88％,P＜0.001).FIGO stage,circ-ATAD1,lymph node metas-tasis and miR-140-3p were factors affecting the prognosis of cervical cancer patients(P＜0.05).Conclusion The serum level of circ-ATAD1 in patients with cervical cancer is significantly increased and the level of miR-140-3p is significantly decreased,the two are closely related to lymph node metastasis and FIGO stage in patients with cervical cancer,and are influencing factors for the prognosis of cervical cancer patients.

Objective:To explore the clinical efficacy of percutaneous balloon compression (PBC) in the treatment of trigeminal neuralgia (TN) based on the double difference (DID) model.Methods:A retrospective case - control study method was adopted to analyze the general data of 130 patients with trigeminal neuralgia (TN) who were treated in the Department of Neurosurgery of Hebei General Hospital from January 2022 to October 2023. Among them, 49 were males and 81 were females. The age was (53.28±11.67) years, ranging from 25 to 80 years old. According to different treatment methods, the patients were divided into an experimental group ( n=63) and a control group ( n=67). Patients in the experimental group were given percutaneous balloon compression (PBC) treatment, while those in the control group were treated with conservative drug therapy. Propensity score matching method was used for 1∶1 matching. After matching, there were 52 cases in each group. The general data of the two groups were compared. The visual analogue scale (VAS), 36-item short form health survey (SF-36) score, Hamilton depression rating scale (HAMD) score, Hamilton anxiety rating scale (HAMA) score, 5-hydroxytryptamine, neuropeptide P, inflammatory factor interleukin-1 (IL-1), tumor necrosis factor-α (TNF-α) before and after treatment, as well as the clinical efficacy of the two groups of patients were comparatively analyzed. Meanwhile, the incidence of postoperative complications in the two groups was compared. The generalized estimating equation (GEE) model was used to analyze the influencing factors of clinical efficacy, and the difference-in-differences (DID) model was used to evaluate the efficacy before and after treatment. Measurement data conforming to the normal distribution were expressed as mean±standard deviation ( ± s), and the t-test was used for comparison between groups; the chi- square test was used for comparison between count data. Results:After treatment, the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, and TNF-α level in the experimental group were (2.98±0.83) points, (75.56±1.18) points, (7.2±0.83) points, (7.15±0.85) points, (76.34±5.47) ng/mL, (50.95±11.01) pg/mL, (29.45±7.08) ng/L, and (21.18±3.55) ng/L respectively. In the control group, there were (3.63±0.95) points, (73.23±1.13) points, (7.98±0.80) points, (8.04±0.84) points, (186.31±11.61) ng/mL, (86.52±13.32) pg/mL, (34.47±6.58) ng/L, and (26.36±5.80) ng/L, respectively. The differences between the two groups were statistically significant ( P<0.05).The cure rate and the total incidence of postoperative complications in the experimental group were 55.77% and 13.46% respectively, while in the control group, they were 40.38% and 30.77% respectively. The differences between the two groups were statistically significant ( P<0.05).The results of the GEE model analysis showed that age, course of disease, VAS, SF-36 score, HAMA score, HAMD score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, TNF-α level, treatment method, and the long - diameter ratio of FO significantly affected the clinical efficacy of patients ( P<0.05).The results of the DID model showed that the experimental group was superior to the control group in improving the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine level, neuropeptide P level, IL-1 level, and TNF-α level( P<0.05). Conclusion:PBC can significantly improve the VAS, SF-36 score, HAMD score, HAMA score, 5-hydroxytryptamine, neuropeptide P, IL-1, TNF-α, and incidence of complications in patients with TN. It can also improve the psychological status and quality of life of patients.

Objective:To investigate the synergistic effect of physical intervention and chemotherapeutic drug therapy on tumor growth by blocking tumor microvessels and injecting chemotherapy drug Endostar (ecombinant human vascular endostatin injection) to inhibit tumor neovascularization by low intensity ultrasound induced microbubble cavitation combined with hemocoagulase.Methods:Seventy-five male NU/NU mice bearing human-derived lung adenocarcinoma, weighing 25-30 g, were randomly divided into microbubble-enhanced ultrasonic cavitation+ Endostar group (MEUC+ Endostar), microbubble-enhanced ultrasonic cavitation+ hemocoagulase+ Endostar group (MEUC+ HC+ Endostar), microbubble-enhanced ultrasonic cavitation (MEUC), Endostar group (Endostar) and sham group. Fifteen mice in each group were given the corresponding treatment intervention for 4 consecutive days followed by 4 days of aseptic feeding. Two-dimensional ultrasound and contrast-enhanced ultrasound (CEUS) were performed before intervention, immediately after intervention and 4 days after intervention, respectively. Tumor tissues were obtained for vascular endothelial growth factor immunofluorescence staining, and microvessel density (MVD) was observed.Results:There was no difference in tumor volume between the groups before the intervention ( P>0.05). Immediately after the intervention, filling defects were observed in MEUC+ Endostar group, MEUC+ HC+ Endostar group and MEUC group, while filling was good in Endostar group and sham group; 4 days after the intervention, filling defects were observed in MEUC+ Endostar group and MEUC+ HC+ Endostar group. The filling defect was still present in Endostar group, while partial recovery of perfusion was performed in MEUC group, and PI and AUC were still significantly lower in MEUC+ HC+ Endostar group than in the other groups ( P<0.05). When tumor tissues were obtained 4 days after the intervention, the MVD in MEUC+ HC+ Endostar group was significantly lower than that in the remaining groups, and the difference of MVD in tumor tissue was statistically significant ( P<0.05). Conclusions:Low intensity ultrasound induced microbubble cavitation combined with hemocoagulase and Endostar can produce a synergistic effect in blocking tumor microvessels and inhibiting tumor angiogenesis, which can more effectively inhibit tumor growth.

Frailty denotes a nonspecific clinical condition characterized by a decrease of physiological reservation in multiple systems, which makes individuals extremely vulnerable to stressors. Frailty increases the incidence of adverse outcomes and death of patients. However, frailty is reversible and preventable. Therefore, this article reviews theoretical models, assessment tools and influencing factors of frailty in elderly patients with hematologic maligilancy, so as to provide references for medical staff to carry out frailty management and related research in elderly patients with hematologic maligilancy.

Objective:To investigate the effects of mixed probiotics on food allergy and the underlying mechanism.Methods:BALB/c mice on the 15 th day of pregnancy were randomly (random number table method) classified into the control group, food allergy model group and mixed probiotics group.Mice in the food allergy model and mixed pro-biotics group were subjected to ovalbumin (OVA) sensitization after birth, and those in the mixed probiotics group were then given probiotic solution by gavage from day 21 to day 35.Mice in control group were similarly given 9 g/L saline.Twenty-four hours after the last OVA sensitization, intestinal histopathological sections were prepared to observe intestinal pathological changes.Blood smears were prepared to detect eosinophil count.In addition, serum samples were collected to measure cytokine levels and OVA specific antibodies.The number of dendritic cells (DCs) and regulatory T cells (Tregs) in mouse mesenteric lymph nodes was calculated.Differences among 3 groups were compared by the One- Way ANOVA or Kruskal- Wallis H test. Results:Compared with those of food allergy model group, diarrhea score, the ratio of eosinophils and serum levels of interleukin(IL)-4, IL-5, IL-13, mast cell protease 1 (MCPT-1), and OVA specific antibodies IgE and IgG were significantly lower in mixed probiotics group[(2.00±0.71) points vs.(3.22±0.97) points, (2.28±1.61)% vs.(10.99±2.26)%, (413.68±22.81) ng/L vs.(708.78±27.66) ng/L, (36.64±3.74) ng/L vs.(46.05±4.95) ng/L, (201.37±65.61) ng/L vs.(495.22±96.66) ng/L, (31 924.15±1 177.77) ng/L vs.(36 175.77±618.29) ng/L, (9.10±8.08) ng/L vs.(19.69±0.84) ng/L, (30.50±8.81) ng/L vs.(190.32±6.40) ng/L], while IL-10 level was significantly higher[(164.12±3.88) ng/L vs.(123.90±7.31) ng/L] ( t=3.37, 8.72, 16.07, 3.90, 7.40, 7.95, 3.91, 44.00 and 7.76, respectively, all P<0.01). Compared with those of food allergy model group, programmed cell death ligand 1 (PD-L1) level on the surface of CD 103+ DCs and CD 103+ CD 80-CD 40-DCs, the proportion of Tregs in CD4 + T cells, and the level of programmed cell death 1 (PD-1) on the surface of Tregs were significantly higher in mixed probiotics group[(75.59±0.45)% vs.(45.60±4.73)%, (67.56±1.87)% vs.(37.12±6.07)%, (8.24±0.69)% vs.(6.20±0.66)%, (11.25±3.12)% vs.(4.08±2.33)%]( t=7.88, 4.48, 3.63 and 3.71, all P<0.01). Conclusions:Mixed probiotics can alleviate the symptoms of food allergy and inflammatory response of young rats through mediating Tregs via the PD-1/PD-L1 pathway.

Objective:To investigate the clinical efficacy of different grade transoral atlantoaxial release for the treatment of irreducible atlantoaxial dislocation.Methods:From January 2010 to December 2019, 297 patients with irreducible atlantoaxial dislocation treated by different grade releases were retrospectively analyzed, including 132 males and 165 females, aged 42.3±12.14 years (range, 10-63 years). All cases were treated by different grade releases, Grade I (196, 66.0%), Grade II (54, 18.2%), Grade III (28, 9.4%) and Grade IV (19, 6.4%). The American Spinal Injury Association (ASIA) grade and Japanese Orthopedic Association (JOA) score were recorded as the clinical evaluation index. The clivus-canal angle (CCA) and cervico-medullary angle (CMA) were measured to evaluate the reduction. The surgery time, blood loss, duration of bony fusion and complications were also analyzed.Results:The follow-up time was 14.8±10.2 months (range, 9-36 months). The surgery time of Grade I-IV were 2.02±0.35 min, 3.00±0.36 min, 4.07±0.96 min and 5.24±0.83 min, respectively ( F=385.43, P<0.001), blood loss was 84.08±27.21 ml, 153.61±31.36 ml, 268.93±48.94 ml and 444.21±109.51 ml, respectively ( F=582.39, P<0.001). The preoperative ASIA motor score of Grade I-IV were 83.85±6.68, 84.06±5.47, 84.07±5.99 and 85.00±4.11, respectively. The last follow-up were 98.34±2.38, 98.67±1.79, 98.86±1.58 and 98.32±2.11, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative JOA score of Grade I-IV were 11.44±1.73, 11.59±1.72, 11.61±1.47 and 11.32±1.80, respectively. The last follow-up were 16.22±1.00, 16.28±1.02, 16.14±1.04 and 16.16±1.07, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative CCA of Grade I-IV were 110.19°±8.76°, 112.48°±7.66°, 106.61°±6.54° and 109.05°±7.79°, respectively. The last follow-up were 140.22°±8.04°, 141.86°±7.04°, 142.35°±8.62° and 140.15°±6.49°, respectively, with statistically significant differences from preoperative ( P<0.05). The preoperative CMA of Grade I-IV were 113.48°±9.54°, 116.03°±8.38°, 109.55°±7.13°, and 112.46°±8.33°, respectively. The last follow-up were 144.28°±7.75°, 146.40°±6.98°, 145.81°±8.27° and 143.24°±6.36°, respectively, with statistically significant differences from preoperative ( P<0.05). Solid bony fusion was obtained except for 3 cases, the fusion time was 9.71±2.55 months (range 3-14 months). Altogether 33 complications occurred in all cases (11.1%), including 3 fusion failure, 3 cerebrospinal leak, 3 wound infection, 2 death (1 case caused by cerebrospinal leak), 11 pharyngeal discomfort, 4 postoperative pain surrounding iliac crest, and 8 malunion of iliac crest. Conclusion:Transoral stepped atlantoaxial release theory could provide guidelines for atlantoaxial dislocation treatment, and make the transoral release technique more effective and safer.

Objective:To evaluate the clinical application value of endoscopic ultrasonography (EUS) in the etiological diagnosis of patients initially diagnosed with idiopathic acute pancreatitis (IAP).Methods:Clinical data of 128 patients who underwent further EUS and magnetic resonance cholangiopancreatography (MRCP) after initial diagnosis of IAP at the Gastrointestinal Endoscopy Center of the First Affiliated Hospital of Naval Medical University between January 2015 and February 2022 were collected and divided into a single-episode group (single-episode group, 51 cases) and a multiple-episode group (recurrent group, 77 cases) based on the number of AP episodes. The data and the diagnosis of the etiology of IAP in the two groups by EUS were analyzed and compared with the etiological diagnosis results of MRCP.Results:The differences on basic information such as gender, age, history of smoking, history of alcohol consumption, family history of pancreatic disease, history of cholecystectomy, abnormality of liver function, and severity of pancreatitis between the single-episode group and recurrent group of IAP patients were not statistically significant. The etiology was clarified in 79 (62%) IAP patients after EUS examination, of which 55 (43%) cases had biliary disease (gallstones, microlithiasis, biliary sludge) and 24 (19%) cases had pancreatic disease (chronic pancreatitis, pancreatic divisum, pancreatic interstitial or pancreatic ductal changes). The percentage of patients with biliary disease as the cause of IAP was significantly higher in the single-episode group than in the recurrent group (59% vs 32%), while the percentage of patients with pancreatic disease as the cause of IAP was higher in the recurrent group than in the single-episode group (25% vs 10%), with statistically significant differences ( P values=0.004 and 0.035, respectively). The performance of EUS in diagnosing the etiology of IAP was significantly higher than that of MRCP (62% vs 19%, P=0.032), where EUS was more accurate in detecting biliary microlithiasis or biliary sludge (43% vs 9%, P<0.01). EUS was also superior to MRCP in identifying subtle changes in chronic pancreatitis lesions (small pancreatic nodules, patchy hyperechogenicity, etc.) and intraductal papillary mucinous neoplasms(17% vs 7%, P<0.05), but was inferior to MRCP in identifying pancreatic divisum (2 cases vs 4 cases). Conclusions:In view of high diagnostic accuracy and safety of EUS in diagnosing biliary diseases, and based on the fact that most IAPs in China are due to biliary diseases, EUS based management strategy can be considered to be a reasonable approach for evaluation of IAP patients. The MRCP can be used as a supplement to the EUS to identify a controversial etiology.

Objective:To retrieve, evaluate, and summarize the best evidence for the assessment of gastrointestinal function in critically ill patients by bedside ultrasound.Methods:Guidelines, evidence summaries, group standards, expert consensus, systematic reviews, and randomized controlled trials on the assessment of gastrointestinal function in critically ill patients by bedside ultrasound were retrieved by computer on domestic and foreign guideline websites, society websites and databases based on evidence-based nursing. The search period was from January 1, 2010 to April 30, 2021. The quality of the article was independently assessed by two researchers using the Appraisal of Guidelines for Research and Evaluation Ⅱ and the critical appraisal tool of the Joanna Briggs Institute (JBI) in Australia (2016) . Combined with the judgment of the research team, the data from the article that met the criteria were extracted and the evidence was graded and recommended according to the JBI quality level of evidence system (2014 Edition) .Results:A total of 22 articles were included, involving 5 guidelines, 1 evidence summary, 1 group standard, 6 expert consensuses, 4 systematic reviews, and 5 randomized controlled trials. A total of 33 pieces of evidence were summarized from 6 aspects, namely, the feasibility of nurses applying bedside ultrasound, fundamentals of ultrasound assessment of gastrointestinal tract, ultrasound assessment of gastric contents, ultrasound assessment of gastric motility, ultrasound assessment of bowel, ultrasound guided enteral nutrition program.Conclusions:Nurses who have been systematically trained can use ultrasound to assess gastrointestinal function in critically ill patients in real time. Ultrasound-guided enteral nutrition for critically ill patients needs to be standardized and improved, and many studies need to be carried out.

Objective:To evaluate diagnostic value of contrast-enhanced harmonic endoscopic ultrasonography (CEH-EUS) for pancreatic cystic lesions.Methods:Endoscopic and clinical follow-up data of patients with pancreatic cystic lesions diagnosed by EUS in Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University with CEH-EUS video from March 2013 to April 2020 was retrospectively analyzed.Results:A total of 36 patients were included. There were 16 cases of serous cystadenomas (SCA), 10 cases of mucinous cystic neoplasm (MCN), 5 cases of intraductal papillary mucinous neoplasms (IPMN, 3 with complex type, 2 with main pancreatic duct type) and 5 cases of pancreatic pseudocyst (PPC). 87.5%(14/16) of SCA and 86.7%(13/15) of MCN+ IPMN had hyperenhanced cystic wall with obvious peak and similar washout as surrounding tissue, whereas only 20%(1/5) PPC had hyperenhanced cystic wall. The hyperenhancing effect of PPC was significantly lower than that of SCA and MCN+ IPMN ( P=0.0035 and P=0.0048, respectively ). Mural nodules were detected in 17 cases of pancreatic cystic lesions by EUS, of which 3 cases had hyperenhanced mural modules and 14 cases had hypoenhanced mural nodules by CEH-EUS. Patients showing hyperenhanced mural modules were all finally diagnosed as pancreatic malignancy (1 IPMN, 2 MCN), and the accuracy was 100%. Conclusions:CEH-EUS can have a obvious advantage of differentiating pseudocyst and other pancreatic cystic lesions, while not very useful for differentiating SCA and MCN. Pancreatic cystic lesions showing hyperenhanced mural nodules under CEH-EUS may imply malignancy potential.