Neoadjuvant therapy has become the standard treatment for locally advanced resectable esophageal cancer, significantly improving long-term survival compared to surgery alone. Neoadjuvant therapy has evolved to include various strategies, such as concurrent chemoradiotherapy, chemotherapy, immunotherapy, or targeted combination therapy. This enriches clinical treatment options and provides a more personalized and scientific treatment approach for patients. This article aims to comprehensively summarize current academic research hot topics, review the rationale and evaluation measures of neoadjuvant therapy, discuss challenges in restaging methods after neoadjuvant therapy, and identify the advantages and disadvantages of various neoadjuvant therapeutic strategies.

BACKGROUND: The primary limitation to kidney transplantation is organ shortage. Recent progress in gene editing and immunosuppressive regimens has made xenotransplantation with porcine organs a possibility. However, evidence in pig-to-human xenotransplantation remains scarce, and antibody-mediated rejection (AMR) is a major obstacle to clinical applications of xenotransplantation. METHODS: We conducted a kidney xenotransplantation in a brain-dead human recipient using a porcine kidney with five gene edits (5GE) on March 25, 2024 at Xijing Hospital, China. Clinical-grade immunosuppressive regimens were employed, and the observation period lasted 22 days. We collected and analyzed the xenograft function, ultrasound findings, sequential protocol biopsies, and immune surveillance of the recipient during the observation. RESULTS: The combination of 5GE in the porcine kidney and clinical-grade immunosuppressive regimens prevented hyperacute rejection. The xenograft kidney underwent delayed graft function in the first week, but urine output increased later and the single xenograft kidney maintained electrolyte and pH homeostasis from postoperative day (POD) 12 to 19. We observed AMR at 24 h post-transplantation, due to the presence of pre-existing anti-porcine antibodies and cytotoxicity before transplantation; this AMR persisted throughout the observation period. Plasma exchange and intravenous immunoglobulin treatment mitigated the AMR. We observed activation of latent porcine cytomegalovirus toward the end of the study, which might have contributed to coagulation disorder in the recipient. CONCLUSIONS 5GE and clinical-grade immunosuppressive regimens were sufficient to prevent hyperacute rejection during pig-to-human kidney xenotransplantation. Pre-existing anti-porcine antibodies predisposed the xenograft to AMR. Plasma exchange and intravenous immunoglobulin were safe and effective in the treatment of AMR after kidney xenotransplantation.
Transplantation, Heterologous/methods* ; Kidney Transplantation/methods* ; Heterografts/pathology* ; Immunoglobulins, Intravenous/administration & dosage* ; Graft Survival/immunology* ; Humans ; Animals ; Sus scrofa ; Graft Rejection/prevention & control* ; Kidney/pathology* ; Gene Editing ; Species Specificity ; Immunosuppression Therapy/methods* ; Plasma Exchange ; Brain Death ; Biopsy ; Male ; Aged

Objective To observe the effects of electroacupuncture on intestinal flora and serum inflammatory factors in rabbit model with rheumatoid arthritis(RA);To explore the mechanism of its therapeutic effect on RA.Methods RA model rabbits were established by ovalbumin induction combined with Freund's complete adjuvant,and the rabbits after successful modeling were randomly divided into model group,probiotic group and electroacupuncture group,with 6 rabbits in each group.Another 6 rabbits were set as the normal group.The electroacupuncture group received electroacupuncture at the bilateral"Zusanli"and"Dubi"for 30 minutes,the probiotic group was given probiotic capsules solution(14.5 mg/kg)by gavage,once a day,for two consecutive weeks.The knee joint circumference and pain threshold of rabbits were measured,histopathological morphological changes of colonic tissue and synovial tissue ws observed by HE staining,16S rDNA sequencing was used to analyze structural changes of intestinal flora,the contents of TNF-α,IL-1β and IL-6 in serum were detected by ELISA.Results Compared with the normal group,the circumference of knee joint of rabbits in the model group increased significantly,the pain threshold was significantly decreased(P<0.01);the colonic mucosal damage was serious,the goblet cells were missing,a large number of inflammatory cells were infiltrate;the joint capsule synovial surface was rough,the synovial cell layer was hyperplasia and thickening,the synovial tissue inflammatory cell infiltration was obvious;the number and evenness of gut microbiota species decreased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes decreased(P<0.05,P<0.01),the relative abundance of Desulfobacteria increased(P<0.01),while the relative abundance of Campylobacter,Lawsonella,and Pseudomonas increased(P<0.01),while the relative abundance of Heshanomonas and Herbaspirillum decreased(P<0.01);the contents of serum TNF-α,IL-1β and IL-6 increased(P<0.01).Compared with the model group,the knee joint circumference of the probiotic group and the electroacupuncture group decreased,the pain threshold increased(P<0.01,P<0.05);the degree of intestinal mucosal damage was reduced,the goblet cells were basically arranged neatly,the inflammatory cell infiltration was reduced;synovial cells proliferation and thickening decreased,with a small amount of inflammatory cell infiltration;the number and evenness of gut microbiota species increased,while the relative abundance of Proteobacteria,Firmicutes,and Bacteroidetes increased(P<0.05,P<0.01),the relative abundance of Desulfobacteria decreased(P<0.01),while the relative abundance of Campylobacter,Lawsonella and Pseudomonas decreased(P<0.01),the relative abundance of Heshanomonas and Herbaspirillum increased(P<0.05,P<0.01);the contents of serum TNF-α,IL-1β and IL-6 significantly decreased(P<0.01).Conclusion Electroacupuncture can significantly improve the symptoms of RA rabbits and reduce the inflammatory reaction in synovial tissue of joint,and the mechanism may be related to the regulation of intestinal flora structure.

BACKGROUND:Halo gravity traction is a pre-operative traction method recognized by many scholars,but most of them rely on clinical observation and lack finite element analysis. OBJECTIVE:To explore the best traction force of Halo gravity traction on Lenke 3 scoliosis by finite element method and to provide a theoretical basis for clinics from a biomechanical point of view. METHODS:The CT images scanned by patients with scoliosis were processed by reverse modeling,and a finite element model was established.The validity of the model was verified by taking normal segments(T1-T4 vertebral bodies).Five groups of different stress conditions were set on the lumbar-thoracic scoliosis model to simulate the correction of patients under different traction forces.In all five groups,the lower surface of L5 was completely restrained,and different traction forces were applied to the upper surface of T1 along the positive direction of the Z axis(the opposite direction of gravity),which were 50,100,150,200,and 250 N,respectively.The displacement of the scoliosis spine,Cobb angle change of the main bending,elongation of the spine,and Von Mises stress were compared under different traction forces. RESULTS AND CONCLUSION:(1)When the Halo gravity traction force was 150 N to 200 N,the reduction of the Cobb angle of the main bending was 69.4%to 88.9%of the maximum reduction;the elongation of the Z axis was 69.4%to 85.9%,and the stress was 63.6%to 82.9%of the maximum stress.(2)When the traction force was greater than 200 N,the reduction of the Cobb angle and the elongation of the Z axis did not change obviously,but the stress value increased sharply.At this time,the distance from the centroids of T6,T7,and T8 to the vertical line of L5 was the most obvious.(3)When the Halo gravity traction force was 150 N to 200 N,the correction effect on this type of patient was the best—the reduction of Cobb angle and the elongation of the Z axis were better without the sharp increase in stress.(4)It has certain theoretical support for clinical correction and can ensure the safety of patients when scoliosis is corrected to a large extent.

Hepatectomy is the most effective method for the treatment of liver cancer. Asso-ciating liver partition and portal vein ligation for staged hepatectomy (ALPPS) provides resectable opportunities for patients with unresectable or borderline resectable liver cancer. Traditional ALPPS procedures involve a short interval between two stages of the surgery, leading to a higher incidence of perioperative complications and mortality. The authors present a case of two-stage hepatectomy. Initially, laparoscopic ligation of the right hepatic artery and portal vein was performed. To prevent tumor progression after the first stage of surgery, combined immunotherapy and targeted therapy were administered. Three months later, a successful right hemihepatectomy was performed. Postoperative histopathological examination revealed hepatocellular carcinoma with extensive tumor necrosis. A 15-month follow-up showed no tumor recurrence. This indicated that two-stage hepatectomy including simultaneous ligation of the hepatic artery and portal vein, combined with two-stage hepatectomy plus immunotherapy and targeted therapy, showed considerable promise for borderline resectable liver cancer.

Objective To observe the effects of needle-knife tendon-sparing and knot-dissolving technique on NF-κB/Bcl-2 pathway activity and the expression of TNF-α,IL-1β,IL-6,Bax and caspase-3 in synovial tissue of knee joints of rabbits with rheumatoid arthritis(RA)model;To explore the mechanism of its inhibitory effect on RA synovial inflammation.Methods Totally 24 New Zealand white rabbits were randomly divided into normal group,model group,drug group and needle-knife group,with 6 rabbits in each group.Except for the normal group,the other groups were injected with ovalbumin and Freund's complete adjuvant into the knee joint cavity to replicate the RA model,and corresponding interventions were given for 18 consecutive days.The knee pain threshold and knee circumference were measured,ultrasound was used to observe the joint cavity effusion,synovial thickness and internal blood flow signals,the synovial tissue morphology were observed by HE staining,the apoptosis of fibroblast-like synoviocytes(FLS)in synovial tissue was observed by TUNEL staining,the expression of TNF-α,IL-1β and IL-6 in synovial tissue were detected by immunohistochemistry,RT-PCR was used to detect NF-κBp65 and Bcl-2 mRNA expression in synovial tissue,Western blot was used to detect the protein expression of NF-κBp65,p-NF-κBp65,Bcl-2,Bax and caspase-3 in synovial tissue.Results Compared with the normal group,the knee pain threshold decreased,knee circumference increased,ultrasonic score and pathological score of synovial tissue increased in the model group;FLS apoptosis rate decreased,the expression of TNF-α,IL-1β and IL-6 in synovial tissue increased,the expressions of NF-κBp65,Bcl-2 mRNA and protein,and p-NF-κBp65 protein increased,while the expression of Bax,caspase-3 protein decreased,with statistical significance(P<0.05).Compared with the model group,the knee pain threshold increased in the drug group and the needle knife group,the circumference of the knee joint decreased,the ultrasonic score and pathological score of synovial tissue were significantly decreased;the apoptosis rate of FLS increased,the expression of TNF-α,IL-1β and IL-6 in synovial tissue decreased,the expressions of NF-κBp65,Bcl-2 mRNA and protein,and p-NF-κBp65 protein decreased,and the expression of Bax and caspase-3 protein increased,with statistical significance(P<0.05).Conclusion Needle-knife tendon-sparing and knot-dissolving technique may promote FLS apoptosis and reduce TNF-α,IL-1β and IL-6 production,inhibit synovial inflammation in RA,reduce knee joint swelling,and raise pain threshold by reducing the activity of synovial tissue NF-κB/Bcl-2 pathway.

Objective:To evaluate an effective manner to replace the drainage tube due to drainage complications during the irrigation treatment of abdominal infection after pancreaticoduodenectomy (PD).Methods:Clinical data of 39 patients with abdominal infection after PD due to drainage complications who were successfully treated by replacement of the drainage tubes with continued flushing in the Department of Hepatobiliary Surgery, Yuncheng Central Hospital Affiliated to Shanxi Medical University from August 2020 to August 2023 were retrospectively analyzed, including 23 males and 16 females, aged (54.8±9.6) years. According to the fashion of tube replacement, patients were divided into the observation group ( n=21), in which a flushing tube was placed through the original abdominal drainage tube sinus tract combined with external negative pressure suction; and the control group ( n=18), in which two parallel drainage tubes were placed through the original abdominal drainage tube sinus tract for flushing and drainage. The two groups were compared in terms of indicators before tube replacement, including the primary tumor classification, incidence of pancreatic fistula and biliary fistula after PD, complications of abdominal drainage, time from the surgery to tube replacement; and indicators after tube replacement, including total hospital stay, hospitalization cost, continuous abdominal lavage time, fever and elevated white blood cell count, number of dressing changes, etc. Results:There were no significant difference in the primary tumor classification, incidence of pancreatic fistula and biliary fistula after PD, complications of abdominal drainage, and time from PD to tube replacement between the two groups before tube replacement (all P>0.05). After tube replacement, the total hospitalization time(32.7±1.9 vs 44.7±14.5, d), hospitalization cost (67 604±16 052 vs 91 845±19 826, yuan), continuous abdominal lavage time [4.0 (3.0, 5.0) vs 9.0 (8.0, 10.8), d], fever [23.8% (5/21) vs 55.6% (10/18)] and leukocytosis rate [28.6% (6/21) vs 66.7% (12/18)], and times of dressing change times [10.0 (7.0, 13.0) vs 22.0 (18.2, 27.0)] of the observation group were lower than those of the control group (all P<0.05). Conclusion:Inserting a flushing tube through the sinus tract of original abdominal drainage tube combined with external negative pressure drainage is an effective way to manage the abdominal infection after PD surgery due to drainage complications, featuring good irrigation and drainage, short irrigation time, and early control of the abdominal infection.

There remains a significant gap in our quantitative understanding of crosstalk between apoptosis and necroptosis pathways. By employing the SWATH-MS technique, we quantified absolute amounts of up to thousands of proteins in dynamic assembling/de-assembling of TNF signaling complexes. Combining SWATH-MS-based network modeling and experimental validation, we found that when RIP1 level is below ~1000 molecules/cell (mpc), the cell solely undergoes TRADD-dependent apoptosis. When RIP1 is above ~1000 mpc, pro-caspase-8 and RIP3 are recruited to necrosome respectively with linear and nonlinear dependence on RIP1 amount, which well explains the co-occurrence of apoptosis and necroptosis and the paradoxical observations that RIP1 is required for necroptosis but its increase down-regulates necroptosis. Higher amount of RIP1 (>~46,000 mpc) suppresses apoptosis, leading to necroptosis alone. The relation between RIP1 level and occurrence of necroptosis or total cell death is biphasic. Our study provides a resource for encoding the complexity of TNF signaling and a quantitative picture how distinct dynamic interplay among proteins function as basis sets in signaling complexes, enabling RIP1 to play diverse roles in governing cell fate decisions.
Animals ; Apoptosis ; Caspase 8/metabolism* ; GTPase-Activating Proteins/metabolism* ; HEK293 Cells ; Humans ; Mice ; Mice, Knockout ; Necroptosis ; Receptor-Interacting Protein Serine-Threonine Kinases/metabolism*

Objective:To evaluate the effect of dual-tube epidural segmental injection of lidocaine analgesia on the delivery outcome and maternal and infant complications of persistent posterior occipital position postpartum or lateral occipital position postpartum patients with protracted active phase.Methods:The full and single-term primiparas ( n=216, 37 to 42 weeks gestation, 22 to 35 years) diagnosed as persistent posterior or lateral occipital position during the active period were selected from the Department of Obstetrics of Qingdao Municipal Hospital from January 2015 to October 2019. The subjects were randomly assigned into two groups: double-tube epidural block group ( n=108) and single-tube epidural block group ( n=108), 1% lidocaine was used for epidural analgesia respectively under ultrasound guidance. Senior midwife or obstetricians implement new partogram, and guide women to perform position management, and push or rotate the fetal head in a timely manner. Observation indicators: general condition, the use of non-pharmacological analgesic measures, analgesia related conditions and pain visual analogue scale (VAS) score, delivery-related indicator, cesarean section indication, anesthesia-related indicator, maternal and child complications. Results:(1) General condition: the age, weight, height, gestational age, the ratio of persistent lateral or posterior occipital position, cephalic score, and neonatal birth weight between the two groups of women were not statistically significant (all P>0.05). (2) The use of non-pharmacological analgesic measures: the women’s Lamaze breathing method, Doula delivery companionship, percutaneous electrical stimulation, and other measures between two groups were compared, and there were not significant differences (all P>0.05). (3) Analgesia related conditions and VAS scores of women undergoing vaginal delivery: compared with the single-tube epidural block group ( n=40), the second-partum time of the women in the double-tube epidural block group ( n=59) was significantly shortened [(124±44) vs (86±33) minutes, P<0.01]; after 30 minutes of analgesia (4.4±0.5 vs 0.9±0.5, P<0.01), during forced labor in the second stage of labor (5.7±0.6 vs 1.3±0.4, P<0.01), the VAS scores of pain were also significantly reduced ( P<0.01). (4) Labor-related indicators: compared with the single-tube epidural block group, the natural delivery rate (21.3% vs 49.1%) and the delivery experience satisfaction rate (51.9% vs 98.1%) of women in the double-tube epidural block group were significantly increased (all P<0.01), cesarean section rate (63.0% vs 45.4%), instrument assisted rate (15.7% vs 5.6%) decreased significantly (all P<0.05). (5) Cesarean section indications: compared with the single-tube epidural block group, the cesarean section rate caused by prolonged labor or protracted active phase of women in the double-tube epidural block group was significantly reduced (38.0% vs 22.2%； P<0.05), and the fetal distress, intrauterine infection, and social factors caused by cesarean section between the two groups were compared, while the differences were not statistically significant (all P>0.05).(6) Anesthesia related indexes: the block planes of the maternal upper tube administration in the double-tube epidural block group were mostly T7, T8, T9-L2 and L3,While,the block planes in the single-tube epidural block group were mostly T10, T11-S1, S2, S3, and the modified Bromage score were all 0. (7) Maternal and child complications: compared with the single-tube epidural block group, the postpartum hemorrhage rate (18.5% vs 7.4%), the perineal lateral cut rate (20.4% vs 5.6%), the neonatal asphyxia rate (12.0% vs 3.7%), ICU rate of transferred neonates (13.9% vs 4.6%) in the double-tube epidural block group were significantly reduced (all P<0.05). Soft birth canal injury rate, puerperal disease rate and neonatal birth rate between two groups were compared, and there were not statistically significant differences (all P>0.05). Conclusion:Dual-tube epidural segmental injection of lidocaine analgesia could increase the natural delivery rate of women with posterior occipital or lateral occipital position with active stagnation, reduce the rate of cesarean section and the rate of transvaginal instruments, and reduce the complications of mother and child.

Objective: To retrospectively analyze the distribution of non-fermentative bacteria causing bloodstream infection in hospitalized patients in Sichuan Province and their drug susceptibility to common antibiotics for better understanding their epidemiological characteristics. Methods: From January 1, 2015 to December 31, 2017, all of the non-fermentative bacteria isolated from patients with bloodstream infection in nine hospitals in Sichuan Province were collected. Species distribution and drug resistance test results were retrospectively analyzed. Results: A total of 6 291 strains of pathogenic bacteria were isolated, including 3 674 strains of gram-negative bacteria (58.4%) and 2 617 strains of gram-positive bacteria (41.6%). The gram-positive bacteria were 1 895 strains of Staphylococcus (30.1%), 372 strains of Streptococcus (5.9%), 317 strains of Enterococcus (5.1%) and 33 strains of other gram-positive bacteria (0.5%). The gram-negative bacteria were 3 191 Enterobacteriaceae strains (50.7%), 389 non-fermentative strains (6.2%) and 94 other gram-negative strains (1.5%). The isolated non-fermentative bacteria were mainly Pseudomonas aeruginosa (136 strains, 35.0%), Acinetobacter baumannii (126 strains, 32.0%) and Stenotrophomonas maltophilia (33 strains, 8.5%). There were 167 (42.9%), 112 (28.8%) and 82 (21.1%) non-fermentative bacteria isolated in internal medicine departments, ICUs and surgery departments, respectively. The drug resistance rates of Pseudomonas aeruginosa to cefepime, ciprofloxacin and gentamicin were 16.5%, 10.7% and 9.9%, respectively. Carbapenems-resistant Pseudomonas aeruginosa (CR-PA) accounted for 13.6%. No polymyxin-resistant Pseudomonas aeruginosa was found. The resistance rates of Acinetobacter baumannii to all antibiotics were over 30% except for minocycline and polymyxin and 75.7% of carbapenem-resistant Acinetobacter baumannii (CR-AB) were isolated. The drug resistance rates to levofloxacin, trimethoprim/sulfamethoxazole and ceftazidime were 0%, 0% and 37.0% in Stenotrophomonas maltophilia isolates and 10.5%, 4.2% and 19% in Burkholderia cepacia isolates, respectively. Conclusions Non-fermentative bacteria causing 6.2% of bloodstream infection in Sichuan, mainly by Pseudomonas aeruginosa and Acinetobacter baumannii. There were significant differences in the isolation rate of non-fermentative bacteria in different departments and most of the strains were isolated in internal medicine departments. The detection rate of Acinetobacter baumannii with multiple drug resistance was high, while other non-fermentative bacteria had good sensitivity to antibiotics.