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.

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 study the pharmacological basis of Schisandra chinensis in the treatment of allergic asthma. METHODS The common components of 10 batches of S. chinensis from different habitats were analyzed by UPLC-Q-TOF-MS/MS. Furthermore， the allergic asthma model was established by intraperitoneal injection of ovalbumin （OVA） and aluminum hydroxide for stimulation combined with atomization exitation； general behavioral observation and the contents of interferon γ （IFN-γ）， interleukin-4 （IL-4） and immunoglobulin E （IgE） in serum were taken as criteria for evaluating the therapeutic effect of S. chinensis from different habitats in the treatment of allergic asthma. Correlation coefficients between common peak area and efficacy evaluation index of each batch of medicinal material were analyzed through grey correlation degree and Pearson correlation analysis. RESULTS A total of 21 common components were identified in 10 batches of S. chinensis from different habitats. After administration of S. chinensis， symptoms such as shortness of breath， sneezing and curling of rats were alleviated. In addition， the content of IFN-γ was significantly increased while the contents of IL-4 and IgE in serum were distinctly decreased （P＜0.01）. Grey correlation analysis showed that 11 common components had high correlation coefficients with IFN-γ， IL-4 and IgE （rˉ＞0.8）. Pearson correlation analysis showed that 8 components were significantly positively correlated with the content of IFN-γ （P＜ 0.05）， and 9， 8 components were significantly negatively correlated with the content of IL-4 and IgE （P＜0.05）. Based on the results of grey correlation degree and Pearson correlation analysis， 7 components such as peak 3， 4， 6， 7， 9， 19 and 20， were highly related to S. chinensis in the treatment of allergic asthma. CONCLUSIONS Schisandrol A， schisandrin B， schisandrin C， gomisin M2， gomisin J， pregomisin and angeloylgomisin H are the potential pharmacodynamic substance basis of S. chinensis in the treatment of allergic asthma.

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.

Iron overload, as a pathological feature of many nervous system diseases, can cause oxidative stress and lead to abnormal iron metabolism and injury of nerve cells. Hypoxia inducible factor (HIF) can participate in brain iron metabolism by regulating brain iron uptake, storage, excretion and intracellular regulation. So, HIF is expected to become a therapeutic target to inhibit brain iron overload in nervous system diseases. This paper reviews the physiological/pathological mechanism of HIF in regulating brain iron metabolism, in order to provide new treatment ideas and methods for nervous system diseases characterized by brain iron overload.

Objective:To compare the anesthetic effects and complications of different concentrations ropivacaine inultrasound-guided axillary brachial plexus block.Methods:From September 2016 to May 2018, 120 patients who underwent forearm or hand surgery in Sichuan Orthopedic hospital were selected as the study objects. According to the principle of random number table, the patients were divided into low-dose group ( n=40), medium dose group ( n=40) and high-dose group ( n=40). Different doses (0.25, 0.5, 0.75 ml/kg respectively) of 0.33% ropivacaine was used for local anesthesia. The anesthesia effect, complication rate, serum cardiac troponin I (cTnI) and creatine kinase myoglobin (CKMB) level and vital signs were compared among the three groups. Results:The onset time of sensory block and motor block in high dose group was shorter than that in low dose group and medium dose group, and the duration was longer than that in low dose group and medium dose group ( P<0.05); there was no significant difference in diastolic blood pressure (DBP), systolic blood pressure (SBP) and heart rate (HR) levels between the three groups at T 0 and T 3 ( P>0.05), and the DBP, SBP and HR levels in the three groups at T 1 were significantly lower than those at T 0 ( P<0.05); the level of DBP, SBP and HR in the low dose group was significantly higher than that in the medium dose group and the high dose group ( P<0.05), and there was no significant difference between the medium dose group and the high dose group ( P>0.05); the overall complication rate in the low dose group was 5.0%, which was significantly lower than that in the medium dose group (20.0%) and the high dose group (25.0%) ( P<0.05); after administration, the serum cTnI and CKMB levels in the low dose group were lower than those in the high dose group and medium dose group ( P<0.05). Conclusions:Three doses of ropivacaine can meet the surgical needs, but low-dose ropivacaine has a stable effect on vital signs and high safety.

Objective:To analyze the application effects of ultrasound-guided fascia illiaca compartment block (FICB) and continuous adductor canal block (CACB) on analgesia after knee arthroplasty.Methods:84 patients undergoing total knee arthroplasty (TKA) in Department of Anesthesiology, Orthopaedic Hospital of Sichuan, from May 2016 to April 2018 were randomly divided into observation group and control group, 42 cases in each group. The observation group was given ultrasound-guided FICB. The control group was given ultrasound-guided CACB. The postoperative analgesia effects [visual analogue scale (VAS) in rest and exercise states], major neurosensory block rate, stress response (cortisol, glucose level), muscle strength of quadriceps femoris and complications in the two groups were compared.Results:There was no significant difference in VAS scores at rest stage between the two groups at any time point after operation ( P>0.05). The VAS scores at exercise state of the observation group were lower than those of the control group at 12 h, 24 h and 48 h after operation ( P<0.01). The block rate of lateral femoral cutaneous nerve in the observation group was higher than that in the control group at 5 min, 10 min, and 30 min after block ( P<0.01). There was no significant difference in the block rates of femoral nerves between the two groups at each above time point ( P>0.05). The levels of blood cortisol and blood glucose in the observation group were significantly lower than those in the control group at 24 h and 48 h after operation ( P<0.05). The muscle strength of quadriceps femoris in the observation group was lower than that in the control group at 24 h and 48 h after operation ( P<0.01). There was no significant difference in the incidence of complications between the two groups ( P>0.05). Conclusions:Both FICB and CACB can significantly improve resting pain and femoral nerves in patients after total knee arthroplasty. FICB has advantages in blocking lateral femoral cutaneous nerve, controlling postoperative exercise pain and reducing stress response, while CACB has better effects on improving muscle strength of quadriceps femoris. The safety of the two groups is comparable. And each has its own advantages and disadvantages.

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.