Objective:To investigate the application value of modified multivisceral trans-plantation (MMT) in chronic intestinal pseudo-obstruction (CIPO) secondary to autoimmune enteril leiomyositis (AEL).Methods:The retrospective and descriptive study was conducted. The clinico-pathological data of a recipient who was admitted to Beijing Tsinghua Changgung Hospital Affiliated to Tsinghua University on February 2022 and underwent MTT for CIPO secondary to AEL were collected. The recipient was a male, aged 29 years old. Results of preoperative histopathological examination showed that there were muscle plexus and ganglion cells in the rectum, sigmoid colon, ascending colon, intrinsic muscle layer of ileum, and a small amount of submucosal layer. There was also a small amount of chronic inflammatory cell infiltration in the muscle, indicating a high possi-bility of diagnosis of neurogenic CIPO.Results:(1) Surgical situations. The operation time was 14 hours and 30 minutes, and the cold ischemia time was 9 hours and 30 minutes. The intra-operative blood product dosage included 14 U of red blood cells, 1 400 mL of fresh frozen plasma, and two therapeutic doses of platelets. (2) Postoperative histopathological examination. Results of postoperative histopathological examination showed chronic inflammation and local erosion of the small intestine and duodenal mucosa, with scattered disappearance of the focal mucosal muscle layer; There is a large infiltration of CD3 + and CD8 + lymphocytes in the lamina propria, especially in the muscularis propria. In severe lesions, there is infiltration of ribbon lymphocytes in the subserosal and muscular layers; Muscle fiber degeneration, reduction, and fibrosis. Deposition of pigment granules in the cytoplasm of smooth muscle cells; No abnormalities were found in the intermuscular, submu-cosal ganglia, and Cajal cells; Fibrosis of the serosal layer with local cellulose exudation; Chronic inflammation of the colonic mucosa, scattered and focal lymphocyte infiltration in the local muscle layer, and myositis related changes. Pathological diagnosis was secondary CIPO induced by AEL. (3) Postoperative immune rejection, recurrence and treatment. Results of colonoscopy and histopatholo-gical examination at postoperative 8 days showed acute cellular rejection. The cell count of reci-pient′s B lymphocytes, CD3 + lymphocytes, CD4 + lymphocytes, and CD8 + lymphocytes were 27.00×10 3, 373.00×10 3, 179.00×10 3 and 142.00×10 3 cell/mL, respectively. Anti-immune rejection treatment was performed using tacrolimus, rabbit anti-human thymocyte immunoglobulin, methylprednisolone mycophenolate mofetil, and monoclonal antibodies against basil. The cell count of recipient′s B lymphocytes, CD3 + lymphocytes, CD4 + lymphocytes, and CD8 + lymphocytes at postoperative 57 days were 0.72×10 3, 239.59×10 3, 89.28×10 3 and 91.53×10 3 cell/mL, respectively. Results of colonoscopy and histopathological examination at postoperative 79 days showed the recurrence of AEL. The cell count of recipient′s B lymphocytes, CD3 + lymphocytes, CD4 + lymphocytes, and CD8 + lymphocytes were 0.32×10 3, 264.92×10 3, 46.95×10 3 and 169.54×10 3 cell/mL, respectively. The tacrolimus and methylprednisolone were used for treatment. Results of colonoscopy and histopathological examina-tion at postoperative 89 days showed AEL recurrence without remission. The cell count of recipient′s B lymphocytes, CD3 + lymphocytes, CD4 + lympho-cytes, and CD8 + lymphocytes were 0.28×10 3, 187.00×10 3, 55.52×10 3 and 92.45×10 3 cell/mL, respec-tively. The tacrolimus and methylprednisolone were used for treatment. Results of colonoscopy and histopathological examination at postoperative 92 days showed the intestinal mucosa had returned to a normal state. (4) Postoperative oral feeding time and time to get rid of parenteral nutrition. The recipient began oral feeding at postoperative 28 days and eliminated parenteral nutrition at postoperative 35 days. (5) Follow-up. The recipient was discharged 114 days after surgery and as of the follow-up deadline, the graft function was good. The recipient maintained a low-fat, high sugar, and high protein diet, completely consumed orally, with a body mass index of 22 kg/m 2, and has returned to normal work. Conclusion:MMT can be used for the treatment of CIPO secondary to AEL.

Objective:To explore the impact of home enteral nutrition (HEN) on the treatment strategy of patients with high position intestinal fistula.Methods:The clinical and follow-up data of 36 patients with high position intestinal fistula requiring HEN treated in Beijing Tsinghua Changgung Hospital from Jan 2021 to Sep 2023 was retrospectively analyzed.Results:Among the 36 cases, 2 had indwelling nasogastric tubes, 12 had indwelling nasojejunal nutritional tubes, and 22 had percutaneous jejunostomy. The incidence of HEN-related complications in patients was 13.9%, and there were no serious catheter complications.During HEN, high position intestinal fistula healed in 19 cases (52.8%), returned to the hospital for the next stage of intestinal fistula treatment in 11 cases (30.6%), needed to return to the hospital for nutritional support in 1 case (2.8%), and intestinal fistula aggravated to terminate HEN in 2 cases (5.6%).Conclusion:Under the management of professional team, HEN via nasogastric/jejunal nutritional tube or percutaneous jejunostomy is safe and feasible in patients with high intestinal fistula.

Combretum indicum can kill insects and benefit the spleen and stomach, which is the most important medicine to treat children's diseases. The classics of materia medica, calendar edition of Chinese Pharmacopoeia, local processing standards and related literature were reviewed to sort out the processing history of Combretum indicum, compare the ancient medicinal parts and processing methods, and summarize the inclusion in national and local standards. The history of the evolution of Combretum indicum was summarized in order to provide ideas for rational drug use in clinical and standard improvement.

Objective:To evaluate the efficacy and safety of non-osteotomy total hip arthroplasty (THA) in the treatment of Crowe IV developmental dysplasia of the hip (DDH).Methods:From Jan 2013 to Sep 2021, 46 patients (46 hips) in our department who underwent total hip arthroplasty without osteotomy for unilateral Crowe IV DDH were retrospectively analyzed, including 6 males and 40 females, with an average age of 41.2±7.2 years (25-61 years). The reduction of the femoral head was achieved successfully through moderate upward-posterior displacement of the movement center, gradual osteotomy of the calcar femorale, proper sinking of the femoral prosthesis and sufficient soft tissue release. The evaluation indexes included the basic condition of the operation (operation time, blood loss, blood transfusion, volume), clinical evaluation (Harris score of hip joint function, patient satisfaction, Trendelenburg sign), imaging evaluation (measurement of limb length and pelvic inclination) and incidence of complications.Results:The mean follow-up time was 72.2±8.8 months (8-101 months). The operation time was 97.2±12 min (84-112 min). The average intraoperative bleeding volume was 550±60 ml (350-850 ml). No patient had periprosthetic infection or fracture, no periprosthetic osteolysis or prosthesis loosening, and no patient needed revision surgery at the last follow-up of all cases. The average HHS score of patients increased from 42.5±12.3 points before surgery to 89.2±10.8 points at the last follow-up, and the difference was statistically significant ( t=19.35, P<0.001). Patient self-rated satisfaction: none was very dissatisfied, 1 patient were less satisfied (2%, 1/46), 4 patients were average (9%, 4/46), 19 patients were relatively satisfied (41%, 19/46), and 22 patients were very satisfied (48%, 22/46). The Trendelenburg sign of 46 cases was positive before operation, and all were negative at the last follow-up. The patients' true leg length discrepancy (LLD) measurement was -2.5±0.6 mm before surgery and 11.5±3.2 mm at the last follow-up ( t=29.17, P<0.05). Patients' perceived LLD was 28.2±5.1 mm before surgery and 3.4±1.4 mm at the last follow-up ( t=32.18, P<0.05). The length of the residual calcar femorale was 3.2±0.4 mm after THA. The limb extended distance of affected limb was 45.2±4.6 mm. The preoperative iliolumbar angle was -6.5°±2.3°, which returned to -0.5°±1.3° at the last follow-up ( F=651.97, P<0.05). Conclusion:For patients with unilateral type IV DDH, non-osteotomy THA is a safe and effective surgical method with simple operation and few complications. It can quickly correct pelvic tilt and lumbar compensatory scoliosis postoperatively.

The bacterial ATP-competitive GyrB/ParE subunits of type II topoisomerase are important anti-bacterial targets to treat super drug-resistant bacterial infections. Herein we discovered novel pyrrolamide-type GyrB/ParE inhibitors based on the structural modifications of the candidate AZD5099 that was withdrawn from the clinical trials due to safety liabilities such as mitochondrial toxicity. The hydroxyisopropyl pyridazine compound 28 had a significant inhibitory effect on Gyrase (GyrB, IC₅₀ = 49 nmol/L) and a modest inhibitory effect on Topo IV (ParE, IC₅₀ = 1.513 μmol/L) of Staphylococcus aureus. It also had significant antibacterial activities on susceptible and resistant Gram-positive bacteria with a minimum inhibitory concentration (MIC) of less than 0.03 μg/mL, which showed a time-dependent bactericidal effect and low frequencies of spontaneous resistance against S. aureus. Compound 28 had better protective effects than the positive control drugs such as DS-2969 ( 5) and AZD5099 ( 6) in mouse models of sepsis induced by methicillin-resistant Staphylococcus aureus (MRSA) infection. It also showed better bactericidal activities than clinically used vancomycin in the mouse thigh MRSA infection models. Moreover, compound 28 has much lower mitochondrial toxicity than AZD5099 ( 6) as well as excellent therapeutic indexes and pharmacokinetic properties. At present, compound 28 has been evaluated as a pre-clinical drug candidate for the treatment of drug-resistant Gram-positive bacterial infection. On the other hand, compound 28 also has good inhibitory activities against stubborn Gram-negative bacteria such as Escherichia coli (MIC = 1 μg/mL), which is comparable with the most potent pyrrolamide-type GyrB/ParE inhibitors reported recently. In addition, the structure-activity relationships of the compounds were also studied.

The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.

Recording the highly diverse and dynamic activities in large populations of neurons in behaving animals is crucial for a better understanding of how the brain works. To meet this challenge, extensive efforts have been devoted to developing functional fluorescent indicators and optical imaging techniques to optically monitor neural activity. Indeed, optical imaging potentially has extremely high throughput due to its non-invasive access to large brain regions and capability to sample neurons at high density, but the readout speed, such as the scanning speed in two-photon scanning microscopy, is often limited by various practical considerations. Among different imaging methods, light field microscopy features a highly parallelized 3D fluorescence imaging scheme and therefore promises a novel and faster strategy for functional imaging of neural activity. Here, we briefly review the working principles of various types of light field microscopes and their recent developments and applications in neuroscience studies. We also discuss strategies and considerations of optimizing light field microscopy for different experimental purposes, with illustrative examples in imaging zebrafish and mouse brains.
Animals ; Mice ; Microscopy/methods* ; Zebrafish ; Neurons/physiology* ; Brain/physiology* ; Neurosciences

Objective:To compare the consistency and difference of non-mydriatic two-field 45° ultra-wide field Optos and Clarus500 fundus imaging in a large-scale diabetic retinopathy (DR) screening.Methods:A diagnostic methodology study. From November 2020 to August 2021, 526 eyes of 277 patients with type 2 diabetes who diagnosed in Department of Ophthalmology, Henan Provincial People's Hospital were included in the study. Among them, there were 175 males with 328 eyes and 102 females with 198 eyes; the age was 53±10 years old. The same experienced technician performed the non-mydriatic dual-field 45° fundus imaging and the non-mydriatic ultra-wide-angle imaging system Optos, Clarus500 single-field fundus imaging examination on the patient on the same day, and obtained the dual-field 45° fundus image and Optos, Clarus500 single-field fundus image. The Optos and Clarus500 single-field fundus images in the same area as the dual-field 45° fundus image were captured by Photoshop software, and the Optos and Clarus500 dual-field fundus images were obtained. Subsequently, two experienced ophthalmologists performed interpretation and DR grading of the 5 groups of images, respectively. Images with inconsistent grading results were interpreted by a third ophthalmologist and used as the final grading result. In order to avoid the mydriatic dual-field 45° imaging interpretation results as the standard, the consistency and detection rate difference of the two ultra-wide-angle imaging systems in the rapid DR screening results were evaluated. The weighted Kappa ( κ) test was used to analyze the consistency of DR diagnosis between dual-field 45° fundus imaging and Optos and Clarus500 fundus imaging; χ2 test was used to compare the detection rates of DR between different imaging systems. Results:Compared with the dual-field 45° fundus image, the Clarus500 single-field had a higher DR detection rate ( χ2=24.965, P<0.001), and the Optos dual-field fundus image had a lower DR detection rate ( χ2=49.559, P<0.001). Compared with the DR detection rate of dual-field 45° fundus image, Optos single-field fundus image, Clarus500 double-field fundus image had no significant difference ( χ2=2.572, 0.649; P=0.109, 0.421). Compared with Optos, Clarus500 single-field and dual-field fundus images DR detection rate, the difference was statistically significant ( χ2=43.214, 61.216; P<0.001). Consistency assessment of DR grading results: dual-field 45° fundus images and Clarus500 dual-field fundus images ( κ value=0.932, 95% confidence interval ( CI) 0.907-0.956) were highly consistent; dual-field 45° fundus images and Optos single-field fundus images [ κ value=0.474, 95% CI 0.417-0.532], Optos dual-field fundus image ( κ value=0.495, 95% CI 0.438-0.551), Optos dual-field fundus image ( κ value=0.495, 95% CI 0.438-0.551) and Clarus500 dual-field fundus image ( κ value=0.452, 95% CI 0.395-0.506) were moderately consistent; dual-field 45°fundus images and Clarus500 single-field fundus images ( κ value=0.354, 95% CI 0.303-0.403) and Optos single-field fundus images and Clarus500 single-field fundus images ( κ value=0.347, 95% CI 0.287-0.393) showed general agreement. Conclusions:Compared with Optos dual-field fundus image, dual-field 45°fundus image and Clarus500 dual-field fundus image have high consistency in the grading results of DR rapid screening. Compared with Optos single-field fundus image, the detection rate of the DR of Clarus500 single-field fundus image is higher.

In causal inference, the concept of temporality (or directionality) has not been fully clarified. Starting from causal thinking, this paper divides the time axis in nature into three time domains and two time points by the occurrence timings of both a real cause and a real effect. This has anchored that causal inference can only be realized in the third domain. The measured temporalities can be divided into five types: cross-first-to-third-domain longitudinal (or experimental temporalities), cross-second-to-third-domain longitudinal, within-domain longitudinal, within-domain reversely longitudinal, and within-domain transversal (or observational temporalities). This new classification encompasses all measurement strategies, either for first or multiple measurements, or timely and delayed measurements. Except that the actual measurement for the cause occurs either before its occurrence (only in experiment) or within the second domain, all other measurements are similar to the act of historical reconstruction or "archaeology" , where the importance of measured temporalities may be inferior to the accuracy of the measurements. From the point of view that research design should integrate bias design, this new classification for measured temporalities based on the time axis in Nature, which has a clear meaning and helps to judge the possible biases in the observation methods, provides a basis for correct causal inferences.

Objective To investigate the efficacy of anti-infective reconstituted bone xenograft (ARBX) combined with external fixation in the treatment of adult infective nonunion of humeral shaft.Methods A retrospective case series study was conducted to analyze the clinical data of 18 patients with infected nonunion of humeral shaft admitted to Xijing Hospital of Air Force Military Medical University from January 2014 to December 2016.There were 10 males and eight females,aged 19-62 years [(36.9 ± 11.8)years].According to Umiarov classification of infective nonunion,there were 11 patients with type Ⅲ and seven with type Ⅳ.All patients were treated with anti-infective reconstituted bone xenograft (ARBX) combined with external fixation.The number of operations,bone healing time,bone healing rate,infection control rate,postoperative weight bearing time,the time of external fixation removal,postoperative complications,erythrocyte sedimentation rate (ESR),and C-reactive protein (CRP) before and after operation were recorded.Fracture healing and functional recovery were evaluated using the Johner-Wruch lower limb function score.Results The patients were followed up for 12-30 months [(21.3 ±5.6)months].The operation was performed for (1.4 ±0.9) times,with time of bone healing for (16.6 ± 5.8)months,bone healing rate of 83％ (15/18),and infection control rate of 94％ (17/18).The postoperative weight bearing time in 15 patients who obtained bone healing was (3.3 ± 1.5)months after operation,and the external fixation removal time was (18.5 ± 4.2) months after operation.There were three patients with nonunion after operation including one with infection recurrence.Five patients were found with nail tract infection.ESR and CRP at postoperative 3 months [(13.1 ± 8.4)mm/h and (5.6 ± 4.6)mg/L] were significantly lower than those before operation [(47.3 ± 19.2)mm/h and (23.4 ± 7.4) mg/L] (P ＜ 0.05).According to Johner-Wruch lower limb function scores,the results were excellent in nine patients,good in four,fair in one,and poor in four,with excellent and good rate of 72％.Conclusion ARBX combined with External fixation can effectively treat infective nonunion of humeral shaft,improve bone healing rate,and promote function recovery.