OBJECTIVE To investigate the impact of Netupitant and palonosetron hydrochloride capsules （NEPA） on the pharmacokinetics of Paclitaxel for injection （albumin bound） （i. e. albumin-bound paclitaxel） under different intestinal microenvironment conditions. METHODS Male SD rats were divided into a normal group and a model group （n＝16）. Rats in the model group were intragastrically administered vancomycin solution to establish an intestinal disorder model. The next day after modeling， intestinal microbiota diversity was analyzed， and the mRNA expressions of cytochrome P450 3A1 （CYP3A1） and CYP2C11 in small intestine and liver tissues as well as those protein expressions in liver tissue were measured. Male SD rats were grouped as described above （n＝16）. The normal group was subdivided into the TP chemotherapy group （TP-1 group） and the TP chemotherapy+NEPA group （TP+NEPA-1 group）； the model group was subdivided into the TP chemotherapy group （TP-2 group） and the TP chemotherapy+NEPA group （TP+NEPA-2 group） （n＝8）. Rats in the TP+NEPA-1 and TP+NEPA-2 groups received a single intragastric dose of NEPA suspension （25.8 mg/kg， calculated by netupitant）. One hour later， all four groups received a single tail vein injection of albumin-bound paclitaxel and cisplatin. Blood samples were collected at different time points after the last administration. Using azithromycin as the internal standard， plasma paclitaxel concentrations were determined by liquid chromatography-tandem mass spectrometry. The main pharmacokinetic parameters were calculated using DAS 2.0 software and compared between groups. RESULTS Compared with the normal group， the model group showed significantly decreased Chao1 and Shannon indexes （P＜0.05）， significant alterations in microbiota composition and relative abundance， and significantly downregulated expressions of CYP3A1 mRNA in liver tissue and CYP2C11 mRNA in both small intestine and liver tissues （P＜0.05）. Compared with the TP-1 group， the AUC0－t， AUC0－∞， MRT0－t of paclitaxel in the TP-2 group， the cmax， AUC0－t， AUC0－∞ of paclitaxel in the TP+NEPA-1 group and TP+NEPA-2 group were significantly increased or prolonged； CL of paclitaxel in the TP-2 group， Vd and CL of paclitaxel in the TP+NEPA-1 group and the TP+NEPA-2 group were significantly decreased or shortened （P＜0.05）. Compared with the TP-2 group， cmax of paclitaxel in the TP+NEPA-2 group was significantly increased， and Vd and MRT0－t were significantly decreased or shortened （P＜0.05）. CONCLUSIONS Intestinal microbiota disorder affects the mRNA expressions of CYP3A1 and CYP2C11， leading to decreased clearance and increased systemic exposure of paclitaxel. Concomitant administration of NEPA under normal intestinal microbiota condition increases paclitaxel exposure. However， under conditions of intestinal microbiota disorder， concomitant administration of NEPA has a limited impact on paclitaxel systemic exposure.

Objective:To explore the cutting scheme and clinical application effects of ultrathin thoracodorsal artery perforator flap assisted by color Doppler ultrasound.Methods:This study was a retrospective historical control study. From February 2017 to October 2019, 20 patients who were admitted to the Third Department of Orthopedics of Xingtai General Hospital of North China Medical and Health Group (hereinafter referred to as our department), met the inclusion criteria, and underwent repair of skin and soft tissue defects of extremities with ultrathin thoracodorsal artery perforator flap designed and harvested based on the surgeon's clinical experience were selected as control group, including 16 males and 4 females, aged (37±5) years. From November 2019 to December 2022, 21 patients who were admitted to our department, met the inclusion criteria, and underwent repair of skin and soft tissue defects of extremities with ultrathin thoracodorsal artery perforator flap designed and harvested under the assistance of color Doppler ultrasound were selected as ultrasound-assisted group, including 15 males and 6 females, aged (38±6) years. After debridement, the area of skin and soft tissue defects of extremities ranged 5.0 cm×4.0 cm to 19.0 cm×8.0 cm, and the area of thoracodorsal artery perforator flaps ranged 6.0 cm×5.0 cm to 20.0 cm×9.0 cm. The wounds in flap donor sites were closed directly. For patients in ultrasound-assisted group, the time and cost required for color Doppler ultrasound examination were recorded, and the number, type, and location of thoracodorsal artery perforator vessels detected by preoperative color Doppler ultrasound were compared with those of intraoperative actual detection. The time required for complete flap harvest of patients in 2 groups was recorded. On postoperative day (POD) 1, 3, 5, 7, and 14, the blood perfusion of flaps in the 2 groups of patients was assessed using a flap perfusion assessment scale. On POD 14, flap survival of patients in 2 groups was observed, and the percentage of flap survival area was calculated. In postoperative 6 months, satisfaction of patients with the treatment outcome in the 2 groups was assessed using 5-grade Likert scale, and the satisfaction rate was calculated.Results:For patients in ultrasound-assisted group, the time required for preoperative color Doppler ultrasound examination was (10.5±2.3) min, and the cost was 120 yuan; 21 thoracodorsal artery perforator vessels were detected and marked using preoperative color Doppler ultrasound, including 8 (38.10%) type 1 perforator vessels, 10 (47.62%) type 2 perforator vessels, and 3 (14.29%) type 3 perforator vessels; the number, type, and location of thoracodorsal artery perforator vessels detected preoperatively were consistent with those detected intraoperatively. The time required for complete flap harvest of patients in ultrasound-assisted group was (41±10) min, which was significantly shorter than (63±12) min in control group ( t=6.32, P<0.05). On POD 1, 3, 5, 7, and 14, the blood perfusion scores of flaps of patients in ultrasound-assisted group were significantly better than those in control group (with t values of 6.67, 7.48, 8.03, 8.75, and 7.99, respectively P<0.05). On POD 14, only one patient in ultrasound-assisted group had partial flap necrosis and 6 patients in control group had complete or partial necrosis of the flap; the percentage of flap survival area of patients in ultrasound-assisted group was (99±8)%, which was significantly higher than (87±8)% in control group ( t=4.57, P<0.05). In postoperative 6 months, there was no significant difference in the satisfaction rate of patients with the treatment outcome between the two groups ( P>0.05). Conclusions:Preoperative color Doppler ultrasound is highly accurate in detecting the number, type, and location of perforator vessels. The cutting scheme of ultrathin thoracodorsal artery perforator flaps can be designed according to the different types of perforator vessels, with shorted flap cutting time and improved flap survival rate.

Tumor-associated macrophages(TAMs)are the predominant cell group in the tumor microenvironment(TME)and are the most important regulatory cells of immune system suppression and tumor cell proliferation in TIME.Src homology-2 domain-containing protein tyrosine phosphatase 2(SHP-2)is a non-receptor protein tyrosine phosphatase that plays an important role in the transmission of signals from the cell surface to the nucleus.SHP-2 is a key intracellular regulatory factor mediating cell proliferation and differentiation and is involved in a variety of growth factor and cytokine signaling pathways linking the cell surface to the nucleus.Recent studies have shown that SHP-2 is a key enzyme in determining the function of TAMs,but because of its variable function,it plays different or even opposite roles in different solid TMEs.This paper reviews the function of SHP-2 in TAMs and related solid tumors to provide a comprehensive reference for tumor immunity and targeted therapy research.

Objective:To explore the clinical application of three-dimensional CT angiography (3D-CTA) in repair of limb wounds with free lateral thoracic perforator flaps.Methods:A retrospective study was conducted to analyze the clinical data of 61 patients with limb soft tissue defects who had been treated at The Third Department of Orthopedics, Xingtai General Hospital of North China Medical and Health Group from January 2018 to September 2022. There were 37 males and 24 females with an age of (43.9±12.0) years. Thirty-three left and 28 right sides were injured. Soft tissue defects ranged from 4.0 cm × 3.0 cm to 17.0 cm × 8.0 cm, and flap areas from 5.0 cm × 4.0 cm to 18.0 cm × 9.0 cm. The patients were divided into 2 groups according to the different preoperative vascular exploration methods: an ultrasound group of 30 cases subjected to ultrasound Doppler examination and a 3D-CTA group of 31 cases subjected to 3D-CTA examination. The preoperative findings were compared with those of intraoperative exploration in the 2 groups. The operation time, flap survival rate, patient satisfaction with trauma repair, sensory recovery of the flap area, and the excellent and good rate of the donor area were also compared between the 2 groups.Results:The differences in preoperative general data between the 2 groups were not statistically significant, indicating the 2 groups were comparable ( P>0.05). In the ultrasound group, the inraoperative classification of the lateral thoracic perforator flaps showed a low concordance with preoperative classification (Kappa coefficient of 0.104, P=0.088). In the 3D-CTA group, the classification of lateral thoracic perforator flaps was consistent with the preoperative 3D-CTA examination (Kappa coefficient of 1.00, P<0.001). The preoperative measurements in the 3D-CTA group found that the diameter at the origin of the lateral thoracic artery was (1.2±0.3) mm, the vascular pedicle length (8.1±2.1) cm, and the diameter at the perforator exit (0.6±0.2) mm; the preoperative surface positioning at the perforator exit found that the perforator exit was (1.6±0.3) cm above the horizontal line of the subscapular angle and (5.3±1.4) cm outside the vertical line of the subscapular angle. These measurements were similar to the intraoperative ones [(1.1±0.3) mm, (8.3±2.4) cm, (0.7±0.2) mm, (1.5±0.4) cm, and (5.2±1.5) cm], showing no significant differences ( P>0.05). In contrast, the preoperative measurements of the above indexes in the ultrasound group did not coincide with the actual intraoperative measurements, and the differences were all statistically significant ( P<0.05). The operation time, flap survival rate, rate of patient satisfaction with wound repair, rate of sensory recovery in the flap area, and the excellence and good rate of the donor area in the 3D-CTA group were (52.9±16.7) min, 100.0% (31/31), 96.8% (30/31), 83.9% (26/31), and 87.1% (27/31), respectively, which were significantly better than those in the ultrasound group [(76.3±21.4) min, 86.7% (26/30), 76.7% (23/30), 60.0% (18/30), 63.3% (20/30)] ( P<0.05). Conclusions:As preoperative 3D-CTA examination can clarify the types and anatomical characteristics of the lateral thoracic artery and its perforators, it helps the design and harvest of the lateral thoracic perforator flaps. Compared with the ultrasound Doppler examination, preoperative 3D-CTA examination shortens operation time, raises survival rate of the flaps, and facilitates recovery of the appearance and function of the limb wounds, and leads to little impact on the donor site.

Cholangiocarcinoma is a malignant tumor with biliary epithelial features.The early diagnosis of cholangiocarcinoma is currently difficult and the treatment outcomes are poor.Its microenvironment includes abundant fibrotic mesenchyme and a variety of cell types,which promote the development and metastasis of cholangiocarcinoma by interacting with tumor cells through mechanisms such as facilitating migration,suppressing the immune response,and inducing angiogenesis and lymphangiogenesis.Immunotherapy is an important tumor treatment approach,and immunotherapy for cholangiocarcinoma has made some progress.This article reviews the characteristics of the immune microenvironment of cholangiocarcinoma,its relationship with immunotherapy,and cutting-edge therapeutic strategies.

Objective:To compare the efficacy between deep continuous irrigation combined with vacuum sealing drainage (VSD) and routine dressing change in treating multidrug-resistant bacterial infections at the surgical wound site in patients with major vascular injury.Methods:A retrospective cohort study was conducted to analyze the clinical data of 28 patients with surgical wound infections by multidrug-resistant bacteria after major vascular injury treated at the First Affiliated Hospital of Henan University of Science and Technology from March 2015 to December 2021. There were 15 males and 13 females, aged 15-65 years [(41.8±12.9)years]. All patients received vascular graft surgery after major vascular injury. Postoperative microbiological culture indicated that the wound infections were caused by Carbapenem-resistant organisms (CRO) or vancomycin- resistant Enterococci (VRE), with no available sensitive antibiotics for treatment. The patients received surgical debridement every five days after vascular graft surgery and were divided into two groups to receive the subsequent treatments including a routine dressing change (routine dressing group, 14 patients) or a deep continuous irrigation combined with VSD (irrigation combined with VSD group, 14 patients). On the first day post-operation and then every 3 days, inflammatory indicators [white blood cell count, neutrophils, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and procalcitonin] were observed in the two groups (repeat tests when a patient′s condition changed). Microbiological cultures were applied with patient samples every 5 days to observe the wound and infection control. Comparisons were made between the two groups regarding the duration to normal levels of inflammatory indicators, duration to negative CRO or VRE cultures, visual analogue score (VAS) before and at 1, 2 and 3 hours after changing the irrigation fluid (changing the dressing), conditions of wound skin grafting or flap repair, and incidences of anastomotic fistula.Results:All patients were followed up for 12-24 months [(14.3±2.4)months], during which no wound redness, rupture, purulent discharge or infection recurrence was noted. The duration to normal levels was (9.4±2.4)days for white blood cells, (9.6±2.8)days for neutrophils, (9.8±3.1)days for CRP, (12.2±3.6)days for ESR, and (7.6±1.9)days for procalcitonin in the irrigation combined with VSD group, significantly shorter than those in the routine dressing group [(15.2±3.1)days, (13.6±3.4)days, (14.2±3.9)days, (19.9±3.3)days, and (12.9±4.1)days, respectively] (all P<0.01). The duration to negative CRO or VRE cultures was (13.9±3.1)days in the irrigation combined with VSD group, significantly shorter than that in the routine dressing group [(19.2±6.9)days] ( P<0.05). The VAS before and at 1, 2 and 3 hours after changing the irrigation fluid was (4.2±0.7)points, (4.1±0.9)points, (4.2±0.9)points and (4.1±0.8)points in the irrigation combined with VSD group, respectively, and was (4.3±0.6)points, (6.9±0.7)points, (5.4±0.9)points and (4.5±0.9)points in the routine dressing group, respectively. The VAS score in the irrigation combined with VSD group was significantly lower than that in the routine dressing group at 1 hour and 2 hours after changing the irrigation fluid (all P<0.01), while no significant differences were found before and at 3 hours after changing the irrigation fluid (all P>0.05). After infection control, 5 patients (35.7%) in the irrigation combined with VSD group required skin grafting or flap repair at the wound site, lower than 11 patients (78.6%) in the routine dressing group ( P<0.01). The incidence of anastomotic fistula was 7.1% (1/14) in the irrigation combined with VSD group, lower than 42.9% (6/14) in the routine dressing group ( P<0.05). Conclusion:When multidrug-resistant bacterial infections occur at the surgical wound site after major vascular injury, deep continuous irrigation combined with VSD performs better than routine dressing change in controlling infection as well as in reducing pain, rate of wound skin grafting or flap repair and incidence of anastomotic fistula, without reliance on antibiotics.

Objective:To evaluate the radiological and clinical outcomes of the aged patients with unstable proximal humeral fracture (UPHF) treated with a locking plate and an intramedullary titanium mesh.Methods:A retrospective study was conducted to analyze the 43 aged patients with UPHF who had been admitted to Department of Orthopedics, Zhongda Hospital Affiliated to Southeast University from January 2017 to July 2019. There were 13 males and 30 females with an age of (71.3±10.3) years (from 60 to 83 years). All patients were treated with a locking plate and an intramedullary titanium mesh to support. The postoperative imaging measurements included changes in humeral head height (HHH) and neck-shaft angle (NSA) (the difference between 3 years after surgery and the second day after surgery, taken as an absolute value); the postoperative clinical measurements included visual analogue scale (VAS), range of shoulder motion, Constant-Murley shoulder functional score (Constant score), American Shoulder and Elbow Surgeons (ASES) score, and incidence of complications.Results:All patients were followed up for (39.2±2.3) months after surgery. The change in HHH at 3 years after surgery was (1.5±1.1) mm, and the change in NSA at 3 years after surgery 3.3°±2.6°. At 3 years after surgery, the VAS score was (2.2±1.3) points, the Constant score (79.2±9.1) points, and the ASES score (78.9±9.2) points; the range of forward extension was 143.2°±20.8°, the range of outward extension 139.3°±23.1°, and the range of outward rotation 55.1°±4.7°. Complications after surgery were found in 6 patients, including humeral head necrosis in 2 cases, ectopic ossification in 1 case, and infection in 3 cases.Conclusion:In the treatment of the aged patients with UPHF, a locking plate combined with an intramedullary titanium mesh can help to restore the medial column support, leading to fine radiological and clinical outcomes.

Objective:To analyze the different clinicopathological features of intrahepatic cholangiocarcinoma with and without viral hepatitis.Methods:The clinicopathological data of 79 intrahepatic cholangiocarcinoma cases from Mar 2012 to Sep 2018 at Henan Provincial People's Hospital were retrospectively analyzed.Results:Twenty-five of the 79 patients with intrahepatic cholangiocarcinoma were accompanied by viral hepatitis. Those with viral hepatitis had a lower mean age at onset than those without [(53±11) years vs. (60±11) years, P=0.011], higher proportion of male patients (80% vs. 52%, P=0.017), higher AFP positive rate (40% vs. 19%, P=0.041), lower CA19-9 positive rate (48% vs. 72%, P=0.036), tend to occur in the right liver lobe (76% vs. 44%, P=0.009), a lower rate of bile duct invasion (16% vs. 41%, P=0.03), and were more likely to be mass type (mass type proportion 96% vs. 72%, P=0.032). Conclusions:Viral hepatitis is common in intrahepatic cholangiocarcinoma. Intrahepatic cholangiocarcinoma with and without viral hepatitis differ in clinicopathology. Intrahepatic cholangiocarcinoma with viral hepatitis is more likely to have the characteristics of hepatocellular carcinoma, while intrahepatic cholangiocarcinoma without viral hepatitis is more likely to have the characteristics of cholangiocarcinoma.

Objective:For tympanosclerosis patients with ossicular chain fixation, we use ossicular chain bypass technique and evaluate its long-term effects. Methods:From June 2017 to June 2019, 147 patients with tympanosclerosis who underwent middle ear surgery with otoscopy in Yinchuan First People's Hospital were reviewed. The subjects were divided into three groups according to the implemented operation plan, 51 cases in the ossicular chain mobilization group（OCM）, 56 cases in the ossicular chain bypass reconstruction group（OCB）, and 40 cases in the malleus-incus complex resection reconstruction group（MICR）. Through a three-year follow-up, the medium and long-term effects of different operation plans were compared and analyzed. Results:There was no significant difference among the three groups in the incidence of tympanic membrane perforation, delayed facial nerve palsy, and the dispatch and displacement of PORP. The incidence of tympanic membrane retraction pocket or cholesteatoma after operation in OCB group（0） was significantly lower than that in OCM group（11.76%） and MICR group（7.5%）（P<0.05）. At 12 months after operation, ΔABG of OCB group and MICR group were better than that in the OCM group（P<0.05）. At 36 months after operation, ΔABG of OCB group was better than that in the OCM group（P<0.05）, and there was no significant difference between OCB group and MICR group. The audiological performance of patients with epitympanic sclerosis（ETS） at 12, 24 and 36 months after operation was better than that of patients with posterior tympanosclerosis（PTS） and total tympanosclerosis（TTS）（P<0.05）. Conclusion:Compared with patients undergoing ossicular chain mobilization and malleus-incus complex resection for ossicular chain reconstruction, patients with tympanosclerosis undergoing bypass technique have better and stable hearing prognosis in medium and long term. This technique can effectively prevent the formation of retracted pocket and cholesteatoma in patients with tympanosclerosis after operation.
Humans ; Tympanosclerosis ; Ear Ossicles/surgery* ; Ear, Middle ; Malleus/surgery* ; Cholesteatoma ; Retrospective Studies ; Ossicular Prosthesis ; Treatment Outcome

Objective:To investigate the distribution of allergens in patients with allergic rhinitis （AR） in Ningxia, and provide theoretical data for the prevention and treatment of AR in this region. Methods:A total of 1664 patients diagnosed with AR in the Otorhinolaryngology Head and Neck Surgery Department of Yinchuan First People's Hospital Outpatient Clinic from January 2018 to December 2021 were retrospectively collected. Use the allergen sIgE antibody detection kit （immunoblotting method） to detect inhalation and ingestion allergens in patients.Results: ①Among all AR patients, 1 158 cases were detected positive, resulting in the detection rate was 69.59%; ②The detection rate of inhalation allergen was 65.87%, and the detection rate of ingestion allergen was 19.83%; ③Mugwort was the most sensitive allergen, and 76.32% of the patients having a positive grade ≥3; ④Out of the patients, 294 cases （25.39%） were allergic to only one allergen, 244 cases （21.07%） were allergic to two allergens, and 620 cases （53.54%） were allergic to three or more allergens; ⑤During different seasons, the highest number of positive allergens detected was in the summer, with 968 cases （83.59%）. Mugwort was the main allergen during this season （69.01%）. After the COVID-19 epidemic, the total positive rate of sIgE tests in AR patients decreased compared to before, and the difference was statistically significant （P<0.001）; ⑥Mugwort, dog epithelium, mold combination, egg, peanut, soybean, Marine fish combination and fruit combination all showed statistically significant differences between different gender groups （P<0.05）; ⑦Common ragweed, mugwort, dust mite combination, cockroach, egg, milk, Marine fish combination, shrimp, fruit combination and nut combination all showed statistically significant differences among different age groups （P<0.05）; ⑧There were statistically significant differences in hay dust among different ethnic groups （P<0.05）. Conclusion:Artemisia argyi is the main allergen in Ningxia, and the distribution characteristics of different allergens are influenced by treatment season, the COVID-19 epidemic, gender, age, ethnicity, and other factors, showing certain distribution patterns and rules.
Allergens ; Artemisia ; COVID-19 ; Retrospective Studies ; Rhinitis, Allergic ; Skin Tests ; Humans ; Male ; Female