Non-clinical reproductive toxicity studies typically employ mammals like rats, rabbits, and cynomolgus monkeys, with animal pregnancy being a key challenge in such testing. This article focuses on the difficulties encountered in the animal pregnancy process and potential countermeasures. Rats can be used for fertility and early embryonic development toxicity studies (Segment Ⅰ), embryo-fetal development toxicity studies (Segment Ⅱ), and perinatal toxicity studies (Segment Ⅲ). The estrous cycle of female rats can be determined by vaginal smear, and mating behavior is confirmed through copulatory plug checks the following day after pairing one female with one male in the same cage. Rabbits are commonly used in embryo-fetal development toxicity studies (Segment Ⅱ). Mating behavior between male rabbits and estrous females is observed to determine the time of conception. However, challenges such as atypical estrus of female rabbits, large variations in estrus between batches, and mating failure often occur in reproductive toxicity testing, which may be addressed through prolonged light exposure, increased protein supplementation, optimized mating strategies, and environmental modifications like female and male rabbits are raised adjacent to each other. Non-human primates (NHPs) are typically employed in perinatal toxicity studies (Segment Ⅲ), where one of the key challenges lies in accurately determining sexual maturity in males - a critical factor for reproductive toxicity testing, which can be assessed through comprehensive evaluation of age, body weight, and testicular volume. Generally, male macaques are considered sexually mature when they meet the following criteria: age >4.5 years, body weight >4.5 kg, single testis volume >10 mL, and combined testicular volume >20 mL. For pregnancy confirmation, ultrasound examination demonstrating visible gestational sacs is required, though this necessitates experienced veterinary clinicians to establish standardized ultrasound examination protocols. In conclusion, reproductive toxicity studies should employ species-appropriate detection methods and evaluation criteria based on anatomical characteristics of the reproductive system to ensure successful mating and proper study execution.

Objective To construct large medical model named by "Huaxi HongYi"and explore its application effectiveness in assisting medical record generation. Methods By the way of a full-chain medical large model construction paradigm of "data annotation - model training - scenario incubation", through strategies such as multimodal data fusion, domain adaptation training, and localization of hardware adaptation, "Huaxi HongYi" with 72 billion parameters was constructed. Combined with technologies such as speech recognition, knowledge graphs, and reinforcement learning, an application system for assisting in the generation of medical records was developed. Results Taking the assisted generation of discharge records as an example, in the pilot department, after using the application system, the average completion times of writing a medical records shortened (21 min vs. 5 min) with efficiency increased by 3.2 time, the accuracy rate of the model output reached 92.4%. Conclusion It is feasible for medical institutions to build independently controllable medical large models and incubate various applications based on these models, providing a reference pathway for artificial intelligence development in similar institutions.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

ObjectiveThis paper aims to verify the therapeutic effect of Cranial Painkiller pills' extract powder prepared by the new process on the rat's trigeminal neuralgia model caused by infraorbital injection of Talci Pulvis， evaluate its potential clinical application value， and compare the therapeutic effect with that of Cranial Painkiller granules， so as to provide data support for the application of the Cranial Painkiller pills' extract powder and precise treatment. MethodsThe rat's trigeminal neuralgia model was constructed by infraorbital injection of Talci Pulvis， and the rats were randomly divided into the normal group， model group， carbamazepine group （60 mg·kg^-1）， Cranial Painkiller granules group （2.70 g·kg^-1）， and low， medium， and high dosage groups of Cranial Painkiller pills' extract powder （1.35， 2.70， 5.40 g·kg^-1） according to the basal mechanical pain thresholds， and there were 10 rats in each group. The drug was administered by gavage to each group 2 h after modeling， and distilled water was given by gavage to the normal and model groups under the same conditions once a day for 10 d. Von Frey brushes were used to measure mechanical pain thresholds in rats. Hematoxylin-eosin （HE） staining was used to detect pathological changes in the trigeminal ganglion， and enzyme-linked immunosorbent assay （ELISA） was used to detect the inflammatory factors interleukin-1 （IL-1）， interleukin-6 （IL-6）， interleukin-8 （IL-8）， and tumor necrosis factor-α （TNF-α） levels in rat serum， as well as neuropeptide substance P （SP） and β-endorphin （β-EP） levels in rat brain tissue. Western blot technique was used to detect the levels of NLRP3， ASC， Caspase-1， and OTULIN proteins in rat brain tissue. ResultsCompared with the normal group， the pain threshold of rats in the model group showed a continuous significant decrease （P<0.01）. The pathological damage of brain tissue was significant （P<0.01）， and the inflammatory levels of IL-1， IL-6， IL-8， and TNF-α in serum were significantly elevated （P<0.01）. The level of the SP in the brain tissue was significantly elevated （P<0.01）， and the level of β-EP was significantly reduced （P<0.01）， while the level of OTULIN was significantly reduced， and NLRP3， ASC， and Caspase-1 protein levels were significantly elevated （P<0.01）. After administration of the drug， compared with the model group， the pain threshold of each dose group of the Cranial Painkiller pills' extract powder and the Cranial Painkiller granules group significantly increased （P<0.01）. The inflammatory levels of IL-1， IL-6， IL-8， and TNF-α and SP levels significantly decreased （P<0.01）， and the β-EP levels were significantly elevated （P<0.01）， while the levels of OTULIN protein were significantly elevated （P<0.05， P<0.01）， and the levels of NLRP3， ASC proteins were decreased （P<0.01）in high dose Cranial Painkiller pills' extract powder. Meanwhile， compared with those in the model group， the trigeminal ganglion lesions of rats in the Cranial Painkiller pills' extract powder and Cranial Painkiller granules groups showed different degrees of improvement （P<0.05， P<0.01）. ConclusionThe Cranial Painkiller pills' extract powder has significant therapeutic effects on the rat model of trigeminal neuralgia induced by infraorbital injection of Talci Pulvis， and its mechanism is related to the improvement of OTULIN-regulated neuroinflammation.

Objective To investigate the efficacy of antibiotic cement column combined with iliac bone graft in the treat-ment of open fracture with bone defect of distal femur.Methods From October 2014 to March 2021,16 patients of open frac-ture bone defect of distal femur were treated with antibiotic bone cement column and iliac bone graft,including 12 males and 4 females.The age ranged from 28 to 68 years old.There were 11 cases of traffic accident injury,5 cases of falling injury,3 cases as Gustilo type Ⅰ,5 cases as type Ⅱ and 8 cases as type Ⅲ A.AO classification was used:9 cases of C2 type and 7 cases of C3 type.The time from injury to final bone grafting ranged from 4 to 119 days.The length of bone defect ranged from 2 tol0 cm.Fractures healing time,complications and knee function Merchan score were recorded.Results All the 16 patients were fol-lowed up from 9 to 29 months.The incisions of 16 patients healed in one stage without postoperative infection,plate fracture,limb shortening and valgus and varus deformity.The healing time randed from 4 to 10 months.Knee joint function according to the Merchant scoring standard,showed that 8 cases were excellent,4 cases were good,3 cases were fair,and 1 case was poor.Conclusion The use of antibiotic bone cement column combined with iliac bone graft in the treatment of open and complex bone defects of distal femur is an effective surgical method to prevent infection,assist fracture reduction,increase fixation strength and significantly reduce the amount of bone grafting.

Objective:To investigate the correlation between impulse oscillometry system examination indicators and conventional pulmonary ventilation function.Methods:The pulmonary ventilation function data of 10 883 patients from January 1, 2020 to December 31, 2022 at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were included. The one-second rate [ratio of forced expiratory volume in the first second (FEV 1) to forced vital capacity (FVC)] measured as a percentage of the predicted value was ≥92% for the control group ( n=3 478) and <92% for the pulmonary obstruction group ( n=7 405). The obstruction group was subdivided into five groups according to the degree of pulmonary dysfunction: mild group ( n=3 938),moderate group ( n=1 142),oderate-severe group ( n=917),severe group ( n=737),and extremely severe group ( n=671). Conventional pulmonary ventilatory function FVC, FEV 1, one-second rate, and forced expired flow at 50% of FVC (MEF50%), forced expired flow at 75% FVC (MEF25%), maximal mid-expiratory flow (MMEF), peak expiratory flow (PEF), and pulsed oscillation pulmonary function test were detected in both groups of patients. Impedance at 5 Hz (Z5) means total respiratory resistance, resistance at 5 Hz (R5) means total airway resistance, reactance at 5 Hz (X5) indicates the elastic recoil of the peripheral airways, and resistance at 20 Hz (R20) represents resistance of the central airways. R5-R20 reflects resistance in the small airways. Additionally, peripheral resistance (Rp), respiratory resonance frequency (Frex), and area under the reactance curve (Ax) were also measured. Correlation between the indicators of the two groups and the sensitivity and specificity of the impulse oscillometry system parameters for the diagnosis of obstructive pulmonary ventilation dysfunction were analyzed. Results:Pulmonary function force expiratory volume in the first second as a percentage of predicted value (FEV 1%Pre) [80.10 (54.95,97.10)%],one-second rate [62.43(48.67, 67.02)%],MEF50% [1.33 (0.62,1.97)L/s],MEF25% [0.28 (0.17,0.41)L/s], MMEF [0.85 (0.43,1.29)L/s],and PEF [5.64 (3.73,7.50)]L/s in the obstruction group were significantly lower than those in the control group ( P<0.05). The differences within the subgroups of the obstruction group were also significant ( P<0.05). Pulsed oscillation Z5 [0.42 (0.33,0.55)kPa·L -1·s -1],Rp [0.25 (0.20,0.45)kPa·L -1·s -1], R5 [0.39 (0.31,0.49)kPa·L -1·s -1], R20 [0.28 (0.24,0.34)kPa·L -1·s -1], R5-R20 [0.09 (0.05,0.17)kPa·L -1·s -1],Frex [16.32 (13.07,20.84)Hz], and Ax [0.67 (0.28,1.64)] indices in the obstruction group were significantly higher than those in the control group. X5 [-0.14 (-0.23, -0.10)kPa·L -1·s -1] was significantly lower than that in the control group ( P<0.05). Z5, Rp, X5, R5, R5-R20, Frex, and Ax were statistically significant between different degrees of obstruction in the obstruction group ( P<0.05). The impulse oscillometry system parameters Z5, Rp, R5, R20, R5-20, Frex, and Ax were negatively correlated with the indices of conventional pulmonary ventilation ( r=-0.21-0.68, P<0.05), and the parameter X5 was positively correlated with the indices of conventional pulmonary ventilation ( r=0.41-0.68, P<0.05). The pulsed oscillation pulmonary function test parameters X5 (58.60%-95.68%) and Ax (57.08%-98.06%) presented the best sensitivity; X5 (86.29%-98.82%), Frex (86.69%-94.71%), and Ax (88.10%-98.53%) displayed the best specificity; and R20 presented the worst sensitivity and specificity. The sensitivity and specificity were slightly better in female patients than in male patients. Conclusion:The technical parameters of the impulse oscillometry system showed significant correlation with relevant indices of conventional pulmonary ventilation function detection. These well reflect the changes of different degrees of pulmonary ventilation function and have greater significance for reference in evaluating the degree of pulmonary function impairment.

Objective:To investigate the clinical application value of injection of indocyanine green(ICG)via vasopuncture in fluorescence laparoscopic radical prostatectomy(FLRP).Methods:We retrospectively analyzed the clinical data on 50 cases of PCa treated by injection of ICG via vasopuncture in FLRP.The patients were aged(70.60±5.67)years old,with an average PSA value of(18.42±2.69)μg/L.During the operation,we injected ICG at 0.5 ml by vasopuncture through the vas deferens at each side of the scrotum,observed the visualized images of the vas deferens and seminal vesicles using normal high-definition,black-and-white fluorescence,green fluorescence,and color fluorescence respectively,and then isolated the adherent seminal vesicles under the laparoscope.Results:A total of 93 injections of ICG were completed,86 bilaterally,4 on the right and 3 on the left.The vas defer-ens and seminal vesicles were visualized in 41 cases(60 sides,64.52%),19 bilaterally,7 on the right and 15 on the left.Spillage of the fluorescent agent occurred in 9 cases during the incision of the bladder neck and adhesion of the seminal vesicles was found intra-operatively in 10 cases,in which the seminal vesicles were all quickly located by fluorescence visualization.No rectal injury occurred during the surgery.Mild scrotal subcutaneous bruises were observed in 2 cases,with a postoperative pathological Gleason's score of 7.44±0.88.Conclusion:Injection of ICG by vasopuncture is minimally invasive and safe.ICG-mediated near-infrared imaging and real-time fluorescence imaging of the vas deferens and seminal vesicles can achieve precise positioning and removal of the seminal vesicles and prostate gland without causing rectal injury.

AIM To investigate the renal protective effects of Shiwei Ruxiang Powder on gouty nephritis in rats based on mitophagy.METHODS Rats were randomly divided into the blank group,the model group,the low-dose,medium-dose,and high-dose Shiwei Ruxiang Powder groups(200,400,800 mg/kg)and allopurinol group(10 mg/kg).The rat model of gouty nephropathy was established by gavage of potassium oxyzinate(750 mg/kg)and uric acid(300 mg/kg).The rats had their levels of UA,SCr,BUN,XOD,SOD,MDA,ROS measured by automatic biochemical analyzer,ELISA and chemical fluorescence method;their renal pathological changes observed by HE staining;their apoptosis of renal tissue cells observed by TUNEL staining;and their mRNA and protein expressions of IL-1β,TNF-α,Bax,Bcl-2,caspase-3,caspase-9,PINK1,Parkin and LC3-Ⅱ detected by RT-qPCR and Western blot.RESULTS Compared with the model group,Shiwei Ruxiang Powder groups displayed dose-dependently decreased serum levels of UA,BUN and SCr,renal deposition of urate crystal and apoptosis(P<0.05);decreased renal levels of ROS and inflammatory factors IL-1β and TNF-α(P<0.05);and increased renal expressions of mitochondrial autophagy-related proteins PINK1,Parkin and LC3-Ⅱ(P<0.01).CONCLUSION Shiwei Ruxiang Powder may relieve gouty kidney injury in rats by reducing the uric acid level,the renal oxidative stress and inflammatory response,and activating mitophagy pathway as well.

Outpatient humanistic care refered to providing a full process of caring medical services to outpatients. In order to standardize the human caring services for outpatients in medical institutions, promote the comprehensive service level of outpatient services, and improve the patient′s medical experience, Chinese Association for Life Care issued the group standard of Management Norms for Human caring of Outpatients in April 2023. This standard clarified the relevant terms and definitions of human caring for outpatients, specified the basic requirements for human caring, the humanistic quality and care responsibilities of outpatient staff, the outpatient care environment and facilities, the outpatient care process and measures, and quality management. It designed standardized and personalized full process care service norms, providing references for medical institutions at all levels to promote the development of human caring for outpatients.

Objective:To explore the diagnosis and treatment strategy of complex post-sternotomy mediastinitis with exposure of artificial implants (hereinafter referred to as implants).Methods:This study was a retrospective observational study. From January 2016 to January 2023, 16 patients with complex mediastinal infection with implant exposure after thoracotomy who met the inclusion criteria were admitted to Peking University First Hospital, including 9 males and 7 females, aged from 21 to 74 years. The infected wounds were subjected to multiple thorough debridement and negative-pressure wound therapy until the infection was controlled, and contrast-enhanced magnetic resonance imaging (MRI) examination was used to guide the operation after every debridement. During the operation, 5 cases of deep mediastinal pacing lead exposure, 1 case of deep mediastinal pacing lead exposure combined with pericardial patch exposure, 5 cases of pericardial patch exposure, 3 cases of artificial blood vessel exposure, and 2 cases of artificial blood vessel exposure combined with pericardial patch exposure were observed. Partial or complete implants were removed during debridement, therefore 8 patients who completely removed the middle mediastinum implants during the operation were included in the implant complete removal group. Then, according to the defects of the sternum and its surrounding soft tissue, unilateral or bilateral pectoralis major muscle flaps were used for chest wall reconstruction. The remaining 8 patients whose implants could not be completely removed were included in the implant partial removal group. The greater omentum flaps were used to cover the implants and fill the mediastinal defects. Two weeks later, the thigh medium-thickness skin grafts were transplanted on the surface of the greater omentum flaps. After debridement, the wound area was 20 cm×6 cm to 35 cm×10 cm. The area of pectoralis major muscle flap ranged from 15 cm×8 cm to 20 cm×10 cm, and the area of greater omentum flap ranged from 30 cm×15 cm to 40 cm×25 cm. The bacterial culture and high throughput sequencing test results of wound tissue samples of all patients were counted in the first debridement surgery. The hospitalization time, the time for C reactive protein (CRP) to decrease to normal level, and the number of operations were counted for all patients, and the above indexes of the two groups of patients were compared. During the follow-up, the wound recurrence of the patients was observed.Results:The positive ratio of bacterial culture in wound tissue samples was 14/16 in the first debridement surgery, and the positive ratio of high throughput sequencing test was 16/16, with staphylococcus aureus as the bacteria causing most infection among patients. Except for one patient who died during the treatment (a patient in implant partial removal group), the hospitalization time was (56±5) d, the time for CRP to decrease to normal level was (18.9±2.2) d, and the number of operations was (4.5±0.5) times in the remaining patients. Compared with those in implant partial removal group, the length of hospital stay and the time for CRP to decline to normal level of patients in implant complete removal group were significantly shorter (with t values of 3.12 and 3.12, respectively, P<0.05), and the number of operations of patients in implant complete removal group was significantly decreased ( t=3.38, P<0.05). All 15 surviving patients were followed up for more than 6 months, and no recurrence of mediastinitis was observed. Conclusions:The treatment of complex mediastinal infection with exposed implants after thoracotomy is difficult, especially the wounds when the implants cannot be completely removed during debridement. The application of contrast-enhanced MRI examination combined with transplantation of tissue flap such as greater omentum flap and pectoralis major muscle flap can achieve good repair effect.