OBJECTIVE To confirm trigger items for adverse drug reaction （ADR） induced by bevacizumab， to identify and analyze the occurrence of related ADR， and to establish a predictive model for severe adverse reaction （SAR） caused by this drug. METHODS Based on the global trigger tool （GTT） theory， and referencing the GTT White Paper， drug package inserts and relevant literature， trigger items for bevacizumab-related ADR were confirmed using a single-round Delphi method. Utilizing these established items， electronic medical records of relevant patients at Guilin People’s Hospital from January 2020 to September 2024 were actively screened via the China Hospital Pharmacovigilance System. Pharmacists then identified and tallied the occurrence of bevacizumab-induced ADR. Data from patients with any positive trigger item served as the study subjects （divided into training and test sets at a ratio of 7∶3）， candidate feature variables were selected from 39 related variables using the Boruta algorithm， and the multivariable Logistic regression analysis was performed with the occurrence of SAR as the dependent variable. Based on these candidate features， Logistic Regression， Extreme Gradient Boosting， Light Gradient Boosting Machine， Random Forest， and Categorical Boosting models were constructed. Model performance was evaluated using metrics including the area under the curve （AUC） of receiver operating characteristic curve and recall rate. The Shapley Additive exPlanations （SHAP） method was applied to analyze and interpret the contribution of each variable. A nomogram was constructed based on the optimal model. RESULTS A total of 38 trigger items for active monitoring of bevacizumab-related ADR were determined， comprising 17 laboratory indicators， 13 clinical manifestations， and 8 intervention measures. In total， 483 patients with positive trigger items were included， and 318 patients with bevacizumab-induced ADR were identified， including 83 SARs. The positive predictive values for the trigger items and cases were 43.57% （708/1 625） and 63.84% （318/483）， respectively. Bevacizumab-induced ADR involved 7 systems/organs， with the hematological system being the most frequently involved （64.15%）. The Boruta algorithm selected 7 vari ables： serum potassium， hematocrit， albumin-to-globulin ratio， prealbumin， hypertension history， age and red blood cell count. Multivariable Logistic regression showed that elevated serum potassium levels were associated with a decreased risk of bevacizumab-induced SAR （OR＝0.234， P ＝0.002）， while a history of hypertension （OR＝2.642， P ＝0.006） and increased age （OR＝1.040， P ＝0.025） were associated with an increased risk. The Logistic Regression model demonstrated superior performance with higher AUC， F1 score and recall rate （0.761， 0.447， 0.607）， compared to other models. SHAP evaluation results indicated that variables such as serum potassium， hematocrit， and age ranked highest in importance. CONCLUSIONS Totally 38 trigger entries have been successfully identified for active screening of bevacizumab-related ADR. Elevated serum potassium levels are a protective factor against bevacizumab-induced SAR， whereas the hypertension history and increased age are risk factors. The Logistic Regression model is the optimal predictive model.

Objective:To explore the causal relationship between human immune cells and hypertrophic scar (HS) using two-sample bidirectional Mendelian randomization (MR) method.Methods:This study was based on two-sample MR method, and the datasets of 731 immune cells and HS were obtained from the genome-wide association study (GWAS) catalog database and Finngen database, respectively. A significance threshold was established to discern single nucleotide polymorphism (SNP) significantly correlated with immune cells or HS, thereby eliminating the impact of weak instrumental variable bias. The inverse variance weighted (IVW) method (meanwhile, the Benjamini-Hochberg (BH) procedure of false discovery rate (FDR) to adjust P values) was used for preliminary detection of the causal relationship between immune cells and HS and screen the immune cells that had a significant causal relationship with HS. Further, the causal relationship between the selected immune cells and HS was detected through five two-sample MR methods: IVW method, weighted median method, simple mode method, weighted mode method, and MR-Egger method, and the scatter plot was drawn. SNPs conformed to the hypothesis were subjected to Cochran Q test for heterogeneity assessment, MR-Egger regression coupled with MR-PRESSO to eliminate horizontal pleiotropic effects, and a leave-one-out analysis was also conducted to determine if significant results were driven by individual SNP. Finally, the IVW method contained in the two-sample MR analysis was utilized to inversely examine the causal relationship between HS and immune cells. Results:The number of SNPs in 731 immune cells reaching the significance threshold varied from 7 to 1 786, while in HS, 119 SNPs met the significance threshold, with the F values of all SNPs being greater than 10, suggesting a low likelihood of bias from weak instrumental variables. The IVW method revealed that 60 types of immune cells potentially had a causal relationship with HS (with all P values <0.05), and after adjustment using the BH method, only CD45RA and CD39 positive regulatory T cell (Treg) maintained a potentially strong causal relationship with HS ( PFDR<0.05). The IVW method (with odds ratio of 1.16 and 95% confidence interval of 1.08-1.24, P<0.05, PFDR<0.05), weighted median method (with odds ratio of 1.16 and 95% confidence interval of 1.05-1.28, P<0.05), weighted mode method (with odds ratio of 1.14 and 95% confidence interval of 1.02-1.27, P<0.05), and MR-Egger method (with odds ratio of 1.18 and 95% confidence interval of 1.07-1.30, P<0.05) of scatter plot all suggested a causal relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS, only simple mode method of scatter plot suggested a not obvious relationship between the 14 SNPs of CD45RA and CD39 positive Treg and risk of HS ( P>0.05). Cochran Q test indicated no heterogeneity in the causal relationship between CD45RA on CD39 positive Treg and HS ( P>0.05). MR-Egger regression and MR-PRESSO analyses showed that there was no horizontal pleiotropy in the significant causal relationship between CD45RA and CD39 positive Treg and HS ( P>0.05). Leave-one-out analysis confirmed that the significant causal relationship between CD45RA and CD39 positive Treg and HS remained stable after sequentially removing individual SNP. Reverse two-sample MR analysis showed that HS had no potential causal relationship with any of the 731 types of immune cells ( P>0.05). Conclusions:From the perspective of genetics, it is revealed that immune cells CD45RA and CD39 positive Treg may increase the risk of HS.

Objective:To study the risk factors of unplanned reoperation within 30 days after laparoscopic pancreaticoduodenectomy (LPD).Methods:The clinical data of 207 patients who underwent LPD in the Lihuili Hospital Affiliated to Ningbo University from February 2017 to October 2022 were retrospectively analyzed. There were enrolled 118 males and 89 females, aged (65.1±11.1) years old. Patients were divided into the reoperation group ( n=15) and non-reoperation group ( n=192) based on whether unplanned reoperation was performed within 30 days after LPD. The risk factors of unplanned reoperation were analyzed with univariate and multivariate logistic regression analysis. Results:The rate of unplanned reoperation within 30 days after LPD was 7.2%(15/207). The unplanned reoperation group exhibited a higher incidence of complications 80% (12/15), mortality 13.3% (2/15), and extended hospital stay (32.9±20.1)d compared to the non-reoperation group, which incidences of complications, mortality and extended hospital stay were 40.1% (77/192)( χ2=9.04, P=0.003), 0.5%(1/192)( χ2=8.28, P=0.004), and (17.9±8.6)d ( t=-2.79, P=0.014), respectively. Unplanned reoperation was associated with diabetes, intraoperative bleeding >130 ml, preoperative serum prealbumin <0.15 g/L, pancreatic texture and pancreatic duct diameter (all P<0.05). Multivariate logistic regression analysis identified diabetes ( OR=4.991, 95% CI: 1.431-17.415), preoperative serum prealbumin <0.15 g/L ( OR=4.06, 95% CI: 1.178-14.043), soft pancreatic texture ( OR=3.900, 95% CI: 1.146-13.272) and pancreatic duct diameter ≤3 mm ( OR=3.449, 95% CI: 1.009-11.789) as independent risk factors for unplanned reoperation within 30 days. Conclusion:Preoperative diabetes, preoperative serum prealbumin levels <0.15 g/L, soft pancreatic texture and pancreatic duct diameter ≤3 mm were independent risk factors for unplanned reoperation within 30 days after LPD.

The incidence of osteoporotic thoracolumbar vertebral fracture (OTLVF) in the elderly is gradually increasing. The kyphotic deformity caused by various factors has become an important characteristic of OTLVF and has received increasing attention. Its clinical manifestations include pain, delayed nerve damage, sagittal imbalance, etc. Currently, the definition and diagnosis of OTLVF with kyphotic deformity in the elderly are still unclear. Although there are many treatment options, they are controversial. Existing guidelines or consensuses pay little attention to this type of fracture with kyphotic deformity. To this end, the Lumbar Education Working Group of the Spine Branch of the Chinese Medicine Education Association and Editorial Committee of Chinese Journal of Trauma organized the experts in the relevant fields to jointly develop Clinical guidelines for the diagnosis and treatment of osteoporotic thoracolumbar vertebral fractures with kyphotic deformity in the elderly ( version 2024), based on evidence-based medical advancements and the principles of scientificity, practicality, and advanced nature, which provided 18 recommendations to standardize the clinical diagnosis and treatment.

Objective:To summarize experience of managing adult Langerhans cell histiocytosis(LCH) in hypothalamic-pituitary region(HPR) from Shanghai Huashan Hospital.Methods:Adult HPR-LCH patients diagnosed at oar endocrinology department from January 2013 to February 2022 were included. Clinical characteristics and treatment response were retrospectively analyzed.Results:A total of 27 adult HPR-LCH patients were included, with 14 cases involving the hypothalamus(H group) and 13 cases without(group NH). The common radiological findings included thickening of the pituitary stalk(25/27, 92.6%). At the time of diagnosis, 14 cases(51.9%) presented with panhypopituitarism, and 19 cases(70.4%) exhibited metabolic abnormalities. The group H had higher proportions of adrenal insufficiency, central hypothyroidism, panhypopituitarism, and diabetes compared to group NH(78.6% vs 23.1%; 78.6% vs 23.1%; 92.9% vs 30.8%, 35.7% vs 0%, respectively, all P<0.05). Hypothalamus syndrome was identified in 71.4%(10/14) of group H. The inital diagnosis rate was 79.2%(19/24), with 48.1% and 51.9% through biopsy of sellar and extrasellar lesions, respectively. Repeated biopsies confirmed the diagnosis in 25.9%(7/27) of cases. The peripheral lesions included bone, thyroid, lung, lymph node, thymus and liver. Out of 20 cases treated with chemotherapy, the objective response rate was 85% at 12 weeks. Four cases received local therapy, one case received traditional Chinese medicine treatment, one case abandoned treatment, and one case was lost to follow-up. The median follow-up time was 28(range 15 to 54) months. During this period, there were 3 deaths in group H and 1 death in group NH. Conclusion:Adult HPR-LCH patients presented with diabetes insipidus and high prevalences of hypopituitarism, hypothalamus syndrome and metabolic abnormalities. Typical imaging features were pituitary stalk thickening. A solitary mass in the HPR was usually very small, posing a great challenge for early diagnosis. Systemic evaluation would help to clarify the diagnosis. Patients with hypothalamus involvement had a higher mortality rate, suggesting the hypothalamus as a risk organ with poor prognosis.

Objective:To investigate the incidence and prothrombotic risk factors of postoperative venous thromboembolism(VTE) in Cushing′s disease and to further develop an assessment model to identify those at high risk of postoperative VTE events.Methods:A retrospective study was performed in 82 patients who were admitted to Huashan Hospital, Fudan University during January 2019 and January 2020 and diagnosed with Cushing′s disease. These patients underwent the evaluation about their clinical, hormonal, and coagulation parameters, as well as ultrasonography and pulmonary angio-CT when necessary. The least absolute shrinkage and selection operator(LASSO) regression analysis was used to screen independent risk factors, and a nomogram model for postsurgical VTE risk assessment in Cushing′s disease was initially established, and Bootstrap method was used for internal verification. Finally, the predictive model was evaluated for calibration and clinical applicability in the study cohort.Results:Nineteen patients(23.17%) developed VTE events, with 14 cases occurring after endoscopic transsphenoidal surgery. Compared to patients without VTE, those in the VTE group were older( P<0.001), had longer postoperative bed rest, higher rates of current infection, higher HbA 1C levels, and more severe glucose tolerance impairment(all P<0.05). Through LASSO regression analysis, two independent risk factors for postoperative VTE were identified: Age and current infection. Then a VTE risk assessment nomogram model was established to predict the patients at high risk of VTE. In the nomogram model for VTE risk assessment, the area under the receiver operating characteristic curve was 0.868(95% CI 0.787-0.949), with the calibration curve closely aligning with the ideal diagonal line and the clinical decision curve exceeding the two extreme curves. Conclusions:Advanced perioperative assessment needs to be taken to screen those with high VTE risks in patients diagnosed with Cushing′s disease. Additionally, during the perioperative period, patients with Cushing′s disease should undergo mandatory physical activity or prophylactic anticoagulant therapy.

Objective:To explore the correlations of neurological function recovery and intraoperative bone window parameters with intracranial pressure (ICP) changes at perioperative period in patients with large hemispheric infarction (LHI) after standard large bone flap decompression.Methods:Forty LHI patients accepted standard large bone flap decompression in Department of Neurosurgery, People's Hospital of Zhengzhou University from December 2020 to December 2023 were enrolled. ICP was measured before decompression, at the time of bone flap removal, during dural opening, and 24 h after decompression. Correlations of National Institutes of Health Stroke Scale (NIHSS), Extended Glasgow Outcome Scale (GOSE) and Glasgow Coma Scale (GCS) score changes, length and area of the bone window, bone window area/cranial bone area, infarct brain tissue volume/brain tissue volume with ICP changes were analyzed by Pearson's correlation. Length and area of bone window in patients with good neurological function recovery (NIHSS score decreased by≥5, GOSE score increased by≥3, or GCS score increased by≥3 before and after decompression) were calculated.Results:ICP at the time of bone flap removal, during dural opening, and 24 h after decompression was significantly lower than that before decompression ( P<0.05); ICP at the time of bone flap removal was higher than that at 24 h after decompression and during dural opening. Reduction between ICP before decompression and that during dural opening was more obvious than ICP reduction before and 24 h after decompression and ICP reduction before decompression and at the time of bone flap removal, with significant differences ( P<0.05). Postoperative NIHSS scores were significantly lower than preoperative ones ( P<0.05), and both postoperative GOSE and GCS scores were significantly higher than preoperative ones ( P<0.05). Decrease of NIHSS score, increase of GOSE and GCS scores before and after decompression were positively correlated with ICP reduction before and 24 h after decompression ( r=0.386, P=0.018; r=0.411, P=0.033; r=0.319, P=0.037); length and area of the bone window were positively correlated with ICP reduction before and 24 h after decompression ( r=0.461, P=0.028; r=0.536, P=0.034); bone window area/cranial bone area was positively correlated with ICP reduction before and 24 h after decompression ( r=0.438, P=0.027), while infarct brain tissue volume/brain tissue volume was negatively correlated with ICP reduction before and 24 h after decompression ( r=-0.371, P=0.031). Of the 40 patients, 25 had good neurological function recovery after decompression, with length of the bone window ranged 12.3-16.7 cm and area of the bone window ranged 54.5-91.9 cm 2. Conclusion:Standard large bone flap decompression can reduce ICP and improve prognosis in LHI patients; intraoperative bone window parameters are obviously correlated with ICP reduction before and 24 h after decompression; length of the bone window ranged 12.3-16.7 cm and area of the bone window ranged 54.5-91.9 cm 2 are suggested for decompression.

Objective:To investigate the efficacy of acellular allogeneic dermal matrix (ADM) combined with autologous razor-thin scalp grafts in scar rehabilitation.Methods:A retrospective study was conducted on patients who underwent skin grafts transplantation to repair scar in the Department of Burns and Plastic Surgery of the First People’s Hospital of Chenzhou from July 2015 to December 2021. All the patients were divided into the observation group and the control group according to surgical methods. The observation group was treated with ADM combined with autologous razor-thin scalp grafts to repair the wound after scar resection, and the control group was treated with split-thickness skin grafts (STSGs) to repair the wound. Efficacy evaluation: On the 1st, 7th and 14th day after surgery, the patients in the two groups scored the pain degree of the donor sites through the visual analogue scale (VAS), with a score of 0 indicating no pain and a score of 10 indicating severe pain. The grid method was used to measure the surviving area of the skin and calculate the surviving proportion of the skin grafts. The wound healing time in donor and recipient sites were recorded. The postoperative complication was recorded, and the incidence of complications was calculated. Scars in donor and recipient sites were observed at the 3rd, 6th, 9th and 12th month after surgery, and the scars in recipient sites were scored by the Vancouver scar scale (VSS), with a total score of 0-13 points, and the higher the score, the more serious the scars were. SPSS 22.0 software was used for statistical analysis of the data. The normally distributed continuous data were represented as Mean±SD, and analyzed by t-test, and the non-normally distributed continuous data were represented as M ( Q1, Q3), and the Wilcoxon rank-sum test was used for comparison between groups. Enumeration data were expressed as examples and (or) percentages, and chi-square test was used for comparison between groups. The differences were considered statistically significant for probability values P<0.05. Results:A total of 50 patients, including 28 males and 22 females, aged (38.5±13.9) years, were enrolled in the observation group, and the wound area caused by scar resection and release was (70.4±17.7) cm 2. The scars were on upper limb in 16 cases, lower limb in 15 cases, trunk in 11 cases, neck in 8 cases. The control group included 50 patients, 30 males and 20 females, aged (34.8±14.6) years, and the wound area caused by scar resection and release was (66.2±16.5) cm 2. The scars were on upper limb in 15 cases, lower limb in 11 cases, trunk in 13 cases, neck in 11 cases. There was no significant difference in gender composition, age, skin graft site and the wound area caused by scar resection and release between these two groups ( P > 0.05). On the 1st, 7th and 14th day after surgery, the VAS scores of the observation group were 6.35 (5.11, 7.67) points, 4.95 (3.63, 6.46) points and 0.73 (0.18, 1.39) points, while the control group were 8.25 (7.14, 9.19) points, 7.00 (5.45, 8.06) points and 0.80(0.20, 1.55)points, respectively. The VAS score of the observation group was lower than that of the control group on the 1st and 7th day after surgery ( Z=-4.53, -3.86, both P < 0.001), and there was no significant difference in VAS score between the two groups on the 14th day after surgery ( P > 0.05). There was no significant difference between the two groups in terms of the survival ratio of skin grafts [(95.6±2.1) % vs. (95.8±2.3) %] ( P>0.05) and the postoperative incidence of complications [18% (9/50) vs. 10% (5/50)] ( P>0.05). The wound healing time in the donor sites in both groups were (6.80±0.88) days, (13.30±1.83) days ( t=-22.70, P<0.001), while the wound healing time in the recipient sites in both groups were 14.33 (12.73, 15.76) days and 8.91 (7.76, 10.67) days ( Z=-7.31, P<0.001). The average follow-up time was 21.8 months, the observation group had no scar formation at the donor site, while the control group had different degrees of scar hyperplasia. There was no significant difference in VSS scores between the two groups at the 3rd and 6th month after surgery ( P>0.05), while the VSS scores of the observation group at 9th and 12th month after surgery were 5.96 (4.81, 7.15) points and 5.85 (4.81, 6.75) points, which were significantly lower than those of in the control group [7.04(5.93, 8.14)points, 6.92(5.81, 8.06)points] ( Z=-2.82, P=0.005; Z=-3.54, P<0.001). Conclusion:The use of ADM combined with autologous razor-thin scalp graft to repair the wound after scar resection can effectively improve the appearance and function of the repair area, and reduce the pain and avoid scar hyperplasia in the donor sites.

Objective:To investigate the efficacy of acellular allogeneic dermal matrix (ADM) combined with autologous razor-thin scalp grafts in scar rehabilitation.Methods:A retrospective study was conducted on patients who underwent skin grafts transplantation to repair scar in the Department of Burns and Plastic Surgery of the First People’s Hospital of Chenzhou from July 2015 to December 2021. All the patients were divided into the observation group and the control group according to surgical methods. The observation group was treated with ADM combined with autologous razor-thin scalp grafts to repair the wound after scar resection, and the control group was treated with split-thickness skin grafts (STSGs) to repair the wound. Efficacy evaluation: On the 1st, 7th and 14th day after surgery, the patients in the two groups scored the pain degree of the donor sites through the visual analogue scale (VAS), with a score of 0 indicating no pain and a score of 10 indicating severe pain. The grid method was used to measure the surviving area of the skin and calculate the surviving proportion of the skin grafts. The wound healing time in donor and recipient sites were recorded. The postoperative complication was recorded, and the incidence of complications was calculated. Scars in donor and recipient sites were observed at the 3rd, 6th, 9th and 12th month after surgery, and the scars in recipient sites were scored by the Vancouver scar scale (VSS), with a total score of 0-13 points, and the higher the score, the more serious the scars were. SPSS 22.0 software was used for statistical analysis of the data. The normally distributed continuous data were represented as Mean±SD, and analyzed by t-test, and the non-normally distributed continuous data were represented as M ( Q1, Q3), and the Wilcoxon rank-sum test was used for comparison between groups. Enumeration data were expressed as examples and (or) percentages, and chi-square test was used for comparison between groups. The differences were considered statistically significant for probability values P<0.05. Results:A total of 50 patients, including 28 males and 22 females, aged (38.5±13.9) years, were enrolled in the observation group, and the wound area caused by scar resection and release was (70.4±17.7) cm 2. The scars were on upper limb in 16 cases, lower limb in 15 cases, trunk in 11 cases, neck in 8 cases. The control group included 50 patients, 30 males and 20 females, aged (34.8±14.6) years, and the wound area caused by scar resection and release was (66.2±16.5) cm 2. The scars were on upper limb in 15 cases, lower limb in 11 cases, trunk in 13 cases, neck in 11 cases. There was no significant difference in gender composition, age, skin graft site and the wound area caused by scar resection and release between these two groups ( P > 0.05). On the 1st, 7th and 14th day after surgery, the VAS scores of the observation group were 6.35 (5.11, 7.67) points, 4.95 (3.63, 6.46) points and 0.73 (0.18, 1.39) points, while the control group were 8.25 (7.14, 9.19) points, 7.00 (5.45, 8.06) points and 0.80(0.20, 1.55)points, respectively. The VAS score of the observation group was lower than that of the control group on the 1st and 7th day after surgery ( Z=-4.53, -3.86, both P < 0.001), and there was no significant difference in VAS score between the two groups on the 14th day after surgery ( P > 0.05). There was no significant difference between the two groups in terms of the survival ratio of skin grafts [(95.6±2.1) % vs. (95.8±2.3) %] ( P>0.05) and the postoperative incidence of complications [18% (9/50) vs. 10% (5/50)] ( P>0.05). The wound healing time in the donor sites in both groups were (6.80±0.88) days, (13.30±1.83) days ( t=-22.70, P<0.001), while the wound healing time in the recipient sites in both groups were 14.33 (12.73, 15.76) days and 8.91 (7.76, 10.67) days ( Z=-7.31, P<0.001). The average follow-up time was 21.8 months, the observation group had no scar formation at the donor site, while the control group had different degrees of scar hyperplasia. There was no significant difference in VSS scores between the two groups at the 3rd and 6th month after surgery ( P>0.05), while the VSS scores of the observation group at 9th and 12th month after surgery were 5.96 (4.81, 7.15) points and 5.85 (4.81, 6.75) points, which were significantly lower than those of in the control group [7.04(5.93, 8.14)points, 6.92(5.81, 8.06)points] ( Z=-2.82, P=0.005; Z=-3.54, P<0.001). Conclusion:The use of ADM combined with autologous razor-thin scalp graft to repair the wound after scar resection can effectively improve the appearance and function of the repair area, and reduce the pain and avoid scar hyperplasia in the donor sites.

Objective By assessing the uncertainty of the determination results for the concentration of ambroxol hydrochloride injection,the reliability of the concentration measurement results is improved,ensuring the safety and efficacy of high-risk dosage form medications.Methods The uncertainty assessment of the content determination results by HPLC external standard method was conducted using both the TOP-DOWN method and the GUM method in the past.The TOP-DOWN method evaluated after synthesizing two components:the combined bias uncertainty component and the intermediate precision uncertainty component.The GUM method analyzed six sources of uncertainty based on the experimental process and evaluated after synthesizing the uncertainty.Results When the confidence level was 95％,the expanded uncertainty assessed by the TOP-DOWN method and the GUM method was 1.84％and 2.36％respectively(K=2).Conclusion The results from both assessments indicated that the determination of ambroxol hydrochloride injection content was reliable,ensuring the safety and efficacy of the drug.