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.

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.

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 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.

Objective:To investigate the efficacy and safety of radium-223 in combination with new-generation hormonal agents in patients with bone metastases of prostate cancer.Methods:The clinical data of 17 patients (12 from the First Affiliated Hospital of Airforce Military Medical University and 5 from Xi'an International Medical Center Hospital) with metastatic castration-resistant prostate cancer(mCRPC) treated by radium-223 combined with new-generation hormonal agents from January 2021 to June 2022 were retrospectively analyzed. In all cases, the average age was (73.3±8.5) years old. Before treatment, the median prostate-specific antigen (PSA) was 15.7 (3.2, 36.5) ng/ml, the median alkaline phosphatase (ALP) was 131.5 (79.0, 430.7) U/L. All patients had ≥ 2 bone metastases but no visceral or lymph node metastases. The median number of bone scan lesions was 10(8, 15). Bone pain symptom was present in 16(94.1%) patients. There were 9 cases (52.9%) with Eastern Cooperative Oncology Group (ECOG) score of ≥2, 1 case (5.9%) with ECOG score of 1 and 6 cases (35.2%) with ECOG score of 0. All patients were treated with radium-223 (55 kBq/kg, injected every 4 weeks for a maximum of 6 cycles), of which 5 patients were combined with enzalutamide, 8 patients combined with apatamide and 4 patients combined with bicalutamide. PSA response (PSA decreased by ≥30% from baseline and maintained for at least 1 month), ALP response (ALP decreased by ≥30% from baseline and maintained for at least 1 month) and pain relief rates were analyzed. Imaging evaluation was performed before and after treatment to calculate the objective response rate of metastases. The incidence of treatment-related adverse effects and skeletal related event (SRE) were also recorded.Results:Eleven patients completed 6 courses, 3 patients completed 5 courses and 3 patients completed ≥4 courses. The median ALP after 1 month of last treatment was 83.2 (51.5, 126.5) U/L, which was significantly decreased than baseline. 12 patients (70.6%) showed an ALP response and the other 5 (29.4%) showed varying degrees of ALP elevation. PSA response was observed in 4 patients (23.5%), of which 2 (11.8%) had a continuous decrease and 2 (11.8%) had a late-stage increase in PSA. Pain relief was relieved in 15 cases (88.2%) during treatment, 1 case (5.9%) had worsening pain due to disease progression and 1 case (5.9%) had no change during treatment. The ECOG score decreased in 15 (88.2%) patients. The median number of bone metastases in patients decreased to 5 (4, 9). One patient (5.9%) had complete remission during treatment, 11 patients (64.7%) had a partial response, 4 patients (23.5%) were stable, and 1 (5.9%) showed imaging progression after 4 months of treatment. The overall objective remission response rate was 70.5% (12/17). Treatment-related hematologic adverse effects included anemia (1 case, 5.9%, grade 3), thrombocytopenia (1 case, 5.9%, grade 3) and leukopenia (1 case, 5.9%, grade 2). Non-hematologic adverse effects included fatigue (3 cases, 17.6%, 2 cases in grade 1, 1 case in grade 2), gastrointestinal bleeding (1 case, 5.9%, grade 3), diarrhea (1 case, 5.9%, grade 2) and fever (1 case, 5.9%, grade 1). Patients with grades 1 to 2 relieved with symptomatic management. Three cases (17.6%) were discontinued due to intolerance of grade 3 adverse reactions and 1 case (5.9%) terminated on its own. There was no SRE during treatment and follow-up.Conclusions:Radium-223 combined with New-generation hormonal agents has a high objective remission rate in patients with mCRPC, which could provide pain relief and improve quality of life. The incidence of adverse reactions was low and well tolerated.

Objective:To investigate the risk factors for biochemical recurrence after radical prostatectomy.Methods:The clinical data of 558 radical prostatectomy patients admitted to the First Affiliated Hospital of Air Force Military Medical University from January 2010 to December 2020 were retrospectively analyzed. The average age was 67.9 (40-87) years old, and the average body mass index was 24.56 (15.12-35.94) kg/m 2. The average PSA was 41.07 ng/ml, including 48 cases<10 ng/ml, 98 cases 10-20 ng/ml, and 412 cases>20 ng/ml. There were 123, 214, 118, 89, and 14 cases with biopsy Gleason 6-10 score, respectively. The clinical stage : 90 cases in ≤T 2b, 273 cases in T 2c, and 195 cases in ≥T 3 . 558 cases underwent radical prostatectomy, including 528 robotic-assisted laparoscopic surgery, 25 laparoscopic surgery, and 5 open-surgery. The risk factors for postoperative biochemical recurrence were analyzed by Cox regression. Results:A total of 63 patients had postoperative pathological stage pT 2a, 32 patients had pT 2b, 241 patients had pT 2c, and 222 patients had ≥pT 3. A total of 210 cases developed biochemical recurrence after surgery, and the mean time to biochemical recurrence was 33.3 (3-127) months after the radical prostatectomy. The biochemical recurrence rates at 1, 3, and 5 years were 9.7% (54/558), 21.5% (120/558), and 31.7% (177/558), respectively. Among pT 2a and pT 2b patients, 7 (11.1%) and 4 (12.5%) cases developed biochemical recurrence, respectively. Among pT 2c stage patients, 145 (60.17%) cases had positive cut margins, treated with androgen-deprivation therapy (ADT) after surgery. 68 (28.21%) cases of pT 2c stage patients had biochemical recurrence at mean 36.1 (3-106)months after the radical prostatectomy. Among ≥pT 3 patients, 147 patients with positive margins, perineural invasion, seminal vesicle invasion and positive pelvic lymph nodes were treated with postoperative androgen deprivation therapy (ADT) + radiotherapy. 98 of 147 patients (66.67%) had biochemical recurrence, and the average time to biochemical recurrence was 30.6 (24-98) months.75 patients of ≥pT 3 without positive margins, perineural invasion, seminal vesicle invasion or positive pelvic lymph nodes, were treated with postoperative ADT. 33 of them (44%) had biochemical recurrence, and the average time to biochemical recurrence was 32.5 (21-106) months. 5-and 10-year survival rates of 210 patients with biochemical recurrence were 89.05% (187/210) and 78.09% (164/210) respectively, 5- and 10-year tumor-specific survival rates were 92.57% and 87.69%, respectively. 46 of 210 cases died, of which 31 (67.39%) died from prostate cancer, and 15 cases (32.61%) died from cardiovascular and cerebrovascular diseases. Multifactorial Cox regression analysis showed that patient's age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7 were independent risk factors for biochemical recurrence. Conclusions:After radical prostatectomy, patients were treated according to their pathological stage and surgical margins. Patients with positive margins have a higher risk of biochemical recurrence. The independent risk factors for biochemical recurrence included age ≥70 years, initial PSA > 20ng/ml, ≥pT 3 and Gleason score ≥7.

Objective:To study the correlations of cerebrospinal fluid (CSF) routines and biochemical indexes before ventriculoperitoneal shunt with postoperative intracranial infection in adult patients with hydrocephalus.Methods:A retrospective case-control study was conducted on 347 adult patients who underwent ventriculoperitoneal shunt in Department of Functional Neurosurgery, Neurosurgery Center, Zhujiang Hospital of Southern Medical University from January 2016 to December 2021. According to the appearance of postoperative infection or not, these patients were divided into infection group ( n=27) and non-infection group ( n=320). General clinical data and CSF routines and biochemical indexes test results were analyzed and compared between the two groups. The correlations of postoperative intracranial infection with preoperative levels of white blood cells, chlorine, glucose, lactic acids and proteins in the CSF were analyzed by multivariate Logistic regression. Results:There was no significant difference in age, gender, or primary diseases between infection group and non-infection group ( P>0.05). As compared with the non-infection group, the infection group had significantly decreased glucose content and significantly increased lactic acid content in the CSF ( P<0.05). Multivariate Logistic regression analysis showed that glucose content ( OR=21.825, 95%CI: 4.994-95.394, P<0.001) and lactic acid content ( OR=18.430, 95%CI: 6.023-56.391, P<0.001) were independently correlated with infections after ventriculoperitoneal shunt. Risk of patients with glucose content<2.5 to develop intracranial infection after surgery was 21.825 times that of patients with preoperative glucose content≥2.5 mmol/L. Risk of patients with lactic acid content>2.5 mmol/L to develop intracranial infection after surgery was 18.430 times that of patients with preoperative lactic acid content≤2.5 mmol/L. Conclusion:For adult hydrocephalus patients without intracranial infection but only with abnormal CSF (glucose content<2.5 mmol/L or lactic acid content>2.5 mmol/L), ventriculoperitoneal shunt should only be performed after further improvement of CSF indexes to avoid increasing postoperative 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 explore the preoperative 68Ga-PSMA PET/CT examination on the guidance of surgical strategies for high-risk prostate cancer patients and the influence of positive surgical margins after surgery. Methods:The clinical data of 118 patients with high-risk prostate cancer who underwent robot-assisted laparoscopic radical prostatectomy from June 2019 to December 2020 in Xijing Hospital of Air Force Military Medical University was retrospectively analyzed. 47 patients received 68Ga-PSMA PET/CT examination before surgery (study group), and 71 cases without 68Ga-PSMA PET/CT examination before operation ( control group). There was no statistically significant difference in the age [69 (63, 76) vs. 67 (64, 74) years], PSA [PSA≤20ng/ml: 9.91 (6.00, 13.67) vs. 11.64 (8.15, 15.44) ng/ ml, PSA> 20ng/ml: 66.53 (53.66, 195.30) vs. 63.18 (30.08, 148.05) ng/ml], preoperative clinical staging (T 2/≥T 3: 21/26 cases vs. 34/37 cases), and Gleason score [8 (7, 9) vs. 8 (7, 9) points] (all P>0.05) between study group and control group. Both groups underwent robot-assisted laparoscopic radical prostatectomy. The surgical plan was based on the PSMA PET/CT and MRI results in study group and control group respectively. First, ensure that all tumors are removed, and secondly, preserve the patient's urethral length as much as possible to ensure postoperative urinary control.If there is seminal vesicle invasion, expand the scope of resection as needed. If lymph node metastasis is shown, lymph node dissection is performed. For those with negative lymph nodes in imaging studies, if enlarged lymph nodes are found during the operation, lymph node dissection is also performed. After the operation, the perioperative results and surgical margins of the two groups were compared, and the correlation between the PSA value and the SUVmax value of prostate cancer tissue was analyzed. Results:The operations of the two groups were successfully completed, and there was no transfer to open surgery. The operation time of the study group was shorter than that of the control group [175 (155, 205) min vs. 205 (155, 235) min, P=0.003], and the positive rate of resection margin was significantly lower than that of the control group [23.40% (11/47) vs. 45.07%(32/71), P=0.017]. For patients with pathological stage ≥pT 3, the positive rate of surgical margins in the study group was significantly lower than that in the control group [30.77%(8/26) vs. 62.16%(23/37), P=0.014]. In the study group, 11 cases of PSMA-PET showed positive lymph nodes before operation, 10 cases were pathologically positive after operation (90.91%). PSMA-PET showed negative lymph nodes in 1 case, which was pathologically positive after operation. In the control group, 26 cases underwent lymph node dissection, and 16 cases (61.54%) were pathologically positive after operation. The preoperative PSA value of 47 cases in the study group was positively correlated with the SUVmax value of prostate cancer tissue ( r=0.579, P<0.01). Conclusions:Preoperative 68Ga-PSMA PET/CT for high-risk prostate cancer patients can guide the surgeon to optimize the surgical plan, reduce the positive rate of resection margins, and effectively remove the metastatic lymph nodes, which will benefit the patients.

Objective:To investigate the possible role of long non-coding RNA (LncRNA) 00602 in promoting browning in adipocytes induced by adenovirus type 36 (Ad36).Methods:According to Ad36 infection, adipose tissue samples of obese patients were divided into Ad36-negative group and Ad36-infected group. Realtime fluorescent quantitative PCR (qRT-PCR) was used to detect the changes in the expression of LncRNA00602 mRNA in omental adipose tissue of the two groups, and analyze the differences between the two groups. The correlation between waist-to-hip ratio, systolic blood pressure, diastolic blood pressure, fasting blood glucose, triacylglyceride and other indicators of the patients in the group with LncRNA00602 mRNA expression were analyzed. HE staining was used to detect the size of adipocytes in the omental adipose tissue of the Ad36 negative group and the Ad36 infection group. qRT-PCR and Western blotting were used to detect the mRNA and protein expression levels of uncoupling protein 1 (UCP1) and PR domain containing 16 (PRDM16) in omental adipose tissue of two groups of patients. Human adipose-derived stem cells (hADSC) were isolated and cultured, using Ad36 to induce differentiation, and divided into control group and LncRNA00602 knockdown group. On 0, 2, and 4 days after LncRNA00602 knockdown, fluoroboron dipyrrole (BODIPY) and mitochondrial red fluorescence (Mito-Tracker Red) were used to stain intracellular lipid droplets and mitochondria. At the same time, qRT-PCR and Western blotting were used to detect changes in the expression of UCP1 and PRDM16.Results:The expression of LncRNA00602 gene in the Ad36 infection group was higher than that in the Ad36 negative group (all P<0.05). The expression of LncRNA00602 in the Ad36 negative group was not significantly different from the above clinical indicators, while the expression of LncRNA00602 was negatively correlated with serum fasting blood glucose and triacylglyceride ( r=-0.522, -0.486, P<0.05) in the Ad36 infection group; HE staining showed that the average adipocyte area of the Ad36 infection group was smaller than that of the Ad36 negative group. At the same time, UCP1 and PRDM16 gene expression were higher than the negative group (all P<0.05). At the cellular level, on the 2nd and 4th days after knockdown of LncRNA00602, the lipid droplet area of adipocytes in the LncRNA00602 knockdown group was larger than that of the control group, the number of mitochondria decreased compared with the control group, and difference was statistically significant ( P<0.05 or P<0.01); Compared with the control group, there was significantly lower expression of the browning marker genes UCP1, PRDM16, and protein in the adipocytes in the LncRNA00602 knockdown group (all P<0.05). Conclusion:In Ad36-induced adipocyte differentiation, LncRNA00602 may positively regulate the expression of UCP1, PRDM16 and lipid droplet metabolism, and promote the browning of adipocytes.