Objective To explore the efficiency improvement in segmenting neural network with the application of Transformer + U-Net artificial intelligence (AI) and modeling with the application of Python scripts in three-dimensional (3D) printing brachytherapy. Methods A Transformer + U-Net AI neural network model was constructed, and Adam optimizer was used to ensure rapid gradient descent. Computed tomography or magnetic resonance imaging data of patients were standardized and processed as self-made data sets. The training set was used to train AI and the optimal result weight parameters were saved. The test set was used to evaluate the AI ability. Python programming language was used to write an automated script to obtain the output segmentation image and convert it to the STL file for import. The source applicator and needle could be automatically modeled. The time of automatic segmentation and modeling and the time of manual segmentation and modeling were entered by two people, and the difference was verified by paired t-test. Results Dice similarity coefficient (DSC), mean intersection over union (MIOU), and Hausdorff distance (HD95) were used for evaluation. DSC was 0.9341, MIOU was 0.8762, and mean HD95 was 2.516. The mean time of manual segmentation was 1187 s, and the mean time of AI segmentation was 145 s (P < 0.01). The mean time of manual modeling was 321 s, and the mean time of modeling with Python automated scripts was 18 s (P < 0.01). Conclusion The application of Transformer + U-Net automatic segmentation and Python automated scripts can effectively improve work efficiency in the 3D printing brachytherapy for cervical cancer.

Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

OBJECTIVES: To investigate the inhibitory effect of pirfenidone (PFD) on growth of bladder cancer xenograft and its regulatory effect on Treg cells in tumor-bearing mice. METHODS: Thirty-two C57BL/6 mice bearing ectopic bladder tumors were randomized into control and PFD groups (n=16). In PFD group, PFD was administered orally at the daily dose of 500 mg/kg, and tumor growth and survival of the mice were monitored. After treatment for 21 days, the tumors and vital organs were harvested for analysis. Immunohistochemistry was used to assess CD3, CD4, CD8, and FOXP3 expressions in the tumors. Flow cytometry and RT-qPCR were used to analyze the percentage of CD4⁺CD25⁺FOXP3⁺ Treg cells and IL-2, IL-10, and IL-35 expressions in the tumors and spleens; organ damage of the mice was examined with HE staining. RESULTS: Compared with the control group, the PFD-treated mice exhibited significantly lower tumor growth rate with smaller tumor volumes at day 21, along with improved survival at day 28. Immunohistochemistry revealed no significant differences in the infiltration of CD3⁺ and CD8⁺ cells between the two groups, but the percentages of CD4⁺ and FOXP3⁺ cells were significantly lower in the tumors of PFD-treated mice. Flow cytometric analysis confirmed a decrease in CD4⁺CD25⁺FOXP3⁺ Treg cells in the tumors from PFD-treated mice, which also had reduced expression levels of IL-2, IL-10 and IL-35 mRNAs in the tumors. No significant differences were found in Treg cell populations or cytokine expressions in the spleen tissues between the two groups. HE staining showed obvious organ damage in neither of the groups. CONCLUSIONS PFD inhibits bladder cancer growth and enhances survival of tumor-bearing mice possibly by suppressing Treg cells in the tumor microenvironment.
Animals ; Urinary Bladder Neoplasms/drug therapy* ; Mice ; T-Lymphocytes, Regulatory/metabolism* ; Mice, Inbred C57BL ; Interleukins/metabolism* ; Interleukin-10/metabolism* ; Cell Line, Tumor ; Interleukin-2/metabolism* ; Xenograft Model Antitumor Assays ; Female

Objective To investigate the efficacy and safety of subretinal fluid extraction combined with intravitreal conbercept and gas injection in treating polypoidal choroidal vasculopathy(PCV)complicated with serous retinal pigment epithelium detachment(sPED).Methods From July 2019 to February 2021,13 patients(13 eyes)with PCV complicated with sPED who were treated with subretinal fluid extraction combined with intravitreal injection of conbercept and gas in the Weifang Eye Hospital were selected.All affected eyes received at least 3 times(once a month)of intravitreal anti-vas-cular endothelial growth factor(VEGF)(ranibizumab)injections before the surgery,and the treatment was ineffective.The changes in best corrected visual acuity(BCVA),central retinal thickness(CRT),macular foveal PED height and width before and 1 week,1 month,3 months and 6 months after the operation were observed,and the intraoperative and postop-erative complications were recorded.Results The BCVA of the affected eyes 1 week after operation was better than that before operation,and the difference was statistically significant(Z=-3.237,P=0.001).The CRT of the affected eyes at 1 week,1 month,3 months and 6 months after the operation were thinner than that before the operation,and the differ-ence was statistically significant(Z=-3.180,-3.180,-3.110 and-3.180,P=0.001,0.001,0.002 and 0.001).The height and width of PED at 1 week,1 month,3 months and 6 months after the operation were lower than those before the operation,and the differences were statistically significant(all P＜0.05).Thirteen eyes received an average of(4.15±1.40)intravitreal injections(ranibizumab)before the surgery,and the treatment duration was(5.92±3.95)months(equivalent to one injection every 6 weeks).During the 6-month follow-up,13 eyes received an average of(2.31±1.97)intravitreal injections(conbercept)(equivalent to once every 10 weeks).Partial correlation analysis showed a weak positive correla-tion between the increase in BCVA and the decrease in CRT 6 months after operation(r=0.416,P=0.203).There was no significant correlation between the increase in BCVA and the changes in PED height and width 6 months after operation(r=0.218,0.209,P=0.520,0.538).At 1 month after the operation,9 eyes had PED recurrence or different degrees of retinal nerve subepithelial effusion,and PED improved after repeated intravitreal injection of conbercept.At 6 months after opera-tion,subfoveal PED completely disappeared in 3 eyes,and the retina was completely reattached.There was still active exu-dation in the retina of 1 eye.No systemic or severe ocular complications occurred in 13 eyes during the follow-up period.Conclusion Subretinal fluid extraction combined with intravitreal injection of conbercept and gas in the treatment of PCV complicated with sPED can safely and effectively reduce CRT,improve PED,and reduce the damage to the retina caused by long-term PED,but it has no significant effect on the improvement of BCVA at 6 months after the operation.

Visceral leishmaniasis is a zoonotic parasitic disease caused by viscerotropic Leishmania species and transmitted by bites of infected phlebotomine sandflies, which is predominantly prevalent in the Indian subcontinent, eastern Africa and South America. Currently, visceral leishmaniasis is the second most fatal parasitic disease in the world. Because of climate changes, urban development and individual conditions, there are changes in the density of visceral leishmaniasis vector sandflies and the likelihood of contact with humans, resulting in a visceral leishmaniasis transmission risk. The review summarizes natural, social and biological factors affecting the transmission of visceral leishmaniasis, so as to provide insights into formulation of targeted control measures for visceral leishmaniasis.

Objective:To summarize the successful diagnosis and treatment experience of two patients with peritoneal dialysis complicated with cholangiolithiasis and cholangitis who received endoscopic retrograde cholangiopancreatography (ERCP).Methods:A retrospective analysis was conducted on the clinical data of two patients with peritoneal dialysis combined with bile duct stones at Peking University Third Hospital who underwent ERCP combined with endoscopic sphincterotomy and were successfully transferred out of the hospital. Observe successful removal of bile duct stones and adverse events related to surgery, such as pancreatitis, summarize experience, and conduct literature review.Result:The overall success rate of stone removal in 2 patients was 100%, and they recovered well after treatment without severe postoperative bleeding. One patient developed postoperative pancreatitis and secondary peritonitis after ECRP, and active anti infection treatment did not affect peritoneal function. Regular peritoneal dialysis was maintained during the perioperative period, and postoperative close follow-up and flexible adjustment of peritoneal dialysis dose and concentration were carried out to ensure a smooth transition of patients to regular and stable peritoneal dialysis.Conclusion:ERCP is a feasible treatment for PD patients combined with choledocholithiasis, and can be well tolerated by them. The treatment of peritoneal dialysis patients requires long-term follow-up and management, and multidisciplinary cooperation is required when acute complications occur.

Objective:To investigate the changes and clinical significance of multiple cytokine levels in exhaled breath condensate (EBC) in patients undergoing tracheotomy with severe inhalation injury.Methods:A prospective study was conducted. A total of 32 patients with severe burn combined with severe inhalation injury admitted to the department of burns and plastic surgery of Affiliated Suzhou Hospital of Nanjing Medical University from May 2021 to August 2022 were enrolled. Twenty healthy volunteers from the same period were served as controls. EBC of patients at 12 hours after burn and the samples of healthy controls were collected. The levels of 27 cytokines in EBC, including tumor necrosis factor-α (TNF-α) and interleukins (IL-1β, IL-6, IL-8, IL-10, and IL-17), were determined by liquid phase chip technology. Meanwhile, plasma of patients at 12 hours after burn and the plasma of volunteers were collected, and the levels of inflammatory cytokines were detected by liquid chip technology, and the differences between the levels in plasma and those in EBC were analyzed. Plasma and EBC of patients with aspiration injury were collected at 12 hours and 3, 7, 14 and 21 days after burn, and TNF-α levels were determined by enzyme-linked immunosorbent assay (ELISA).Results:Finally, 32 patients were enrolled, and the total burned area was (40±16)% of total body surface area (TBSA). The time of admission was (4.2±2.3) hours after injury. ① Twenty-seven cytokines in EBC: 18 kinds of cytokines including macrophage inflammatory protein-1β (MIP-1β), IL-6, IL-5, IL-2, IL-1β, IL-8, IL-10, IL-15, IL-9, interferon-γ (IFN-γ), IL-1 receptor antagonist (IL-1ra), TNF-α, chemotactic factor for eosinophil (Eotaxin), basic fibroblast growth factor (bFGF), platelet derived growth factor-BB (PDGF-BB), interferon-inducible protein-10 (IP-10), monocyte chemoattractant protein-1 (MCP-1), granulocyte colony-stimulating factor (G-CSF) were significantly increased in patients with severe aspiration injury compared with health controls. Eotaxin was not detected in EBC of healthy controls. Five cytokines, granulocyte-macrophage colony-stimulating factor (GM-CSF), chemokine ligand 5 (CCL5/RANTES), IL-13, IL-4 and MIP-1α, were not detected in EBC of severe inhalation injury patients and healthy controls. Vascular endothelial growth factor (VEGF) and IL-12 p70 in EBC of severe aspiration injury patients were slightly decreased as compared with healthy controls, while IL-7 and IL-17 were slightly increased, but the differences were not statistically significant. ② Six inflammatory cytokines in plasma: the levels of IL-6 and IL-8 in the severe aspiration injury group were significantly increased as compared with healthy controls [IL-6 (ng/L): 18.51 (10.87, 26.21) vs. 0.22 (0.10, 0.36), IL-8 (ng/L): 10.75 (8.58, 18.79) vs. 1.06 (0.81, 2.14), both P < 0.01]. The plasma levels of TNF-α, IL-1β and IL-10 were slightly increased in patients with severe aspiration injury as compared with healthy controls, and IL-17 was slightly decreased, but the difference was not statistically significant. In the EBC collected during the same period, five inflammatory cytokines, including TNF-α, IL-1β, IL-6, IL-8 and IL-10, in patients with severe inhalation injury were significantly increased as compared with healthy controls [TNF-α (ng/L): 16.42 (12.57, 19.21) vs. 7.34 (6.11, 8.69), IL-1β (ng/L): 15.57 (10.53, 20.25) vs. 0.99 (0.67, 1.41), IL-6 (ng/L): 13.36 (9.76, 16.54) vs. 0.70 (0.42, 0.85), IL-8 (ng/L): 1 059.29 (906.91, 1 462.37) vs. 10.36 (8.40, 12.37), IL-10 (ng/L): 2.69 (1.54, 3.33) vs. 1.54 (1.18, 2.06), all P < 0.05]. ③ Dynamic changes of TNF-α in plasma and EBC: the level of TNF-α in EBC of patients with severe aspiration injury was lower than that in plasma. Plasma TNF-α level was increased gradually with the extension of time after injury, and was significantly higher than that of healthy controls on day 3 [ng/L: 30.38 (24.32, 39.19) vs. 22.94 (17.15, 30.74), P < 0.05], and reached the peak on day 14, then fell back. The level of TNF-α in EBC at 12 hours after injury was significantly higher than that in healthy controls [ng/L: 15.34 (11.75, 18.14) vs. 6.99 (6.53, 7.84), P < 0.01], and reached the peak on 3 days after injury, and then gradually decreased. Conclusion:There are changes in the expression of multiple cytokines in EBC of patients with severe inhalation injury, and the changes of many inflammatory cytokines including TNF-α are more sensitive than those in plasma, which can be used to monitor and evaluate the condition of patients with inhalation injury.

Objective:To explore the effect of enhanced recovery after surgery (ERAS) protocols in patients undergoing laparoscopic radical cystectomy (LRC) and intracorporeal urinary diversion (ICUD).Methods:A total of 83 patients who received LRC+ ICUD in Beijing Chaoyang Hospital from March 2014 to September 2020, were divided into 2 groups based on different perioperative management, including 29 ERAS cases and 54 conventional recovery after surgery (CRAS) cases. The ERAS group included 26 males and 3 females , with an average age of (62.07 ± 9.26) years. There were 26 patients with ASA class Ⅰ-Ⅱ, 3 patients with ASA class Ⅲ, 4 patients received neoadjuvant chemotherapy, and 7 patients had a history of abdominal surgery in ERAS group. The CRAS group included 44 males and 10 females , with an average age of (61.59 ± 10.16) years. There were 50 patients with ASA class Ⅰ-Ⅱ, 4 patients with ASA class Ⅲ, 9 patients received neoadjuvant chemotherapy, and 10 patients had a history of abdominal surgery in CRAS group. There were no statistically significant differences in the baseline characteristics between the two groups. The patients in both groups underwent LRC+ ICUD procedures. The perioperative results and complications between the two groups were compared.Results:In the ERAS group, there were 20 patients who underwent Bricker ileal conduit surgery and 9 patients who underwent Studer orthotopic ileal neobladder surgery. Pathological staging included 3, 3, 7, 7, 5 and 4 cases in stage T a, T is, T 1, T 2, T 3 and T 4a, respectively. There were 23, 2, 3 and 1 patient with pathological stage N 0, N 1, N 2 and N 3, respectively. Pathological diagnosis included 3 cases of low-grade urothelial carcinoma, 24 cases of high-grade urothelial carcinoma, and 2 cases of other histological subtypes. In the CRAS group, there were 31 patients who underwent Bricker ileal conduit surgery and 23 patients who underwent Studer orthotopic ileal neobladder surgery. Pathological staging included 5, 3, 12, 9, 15 and 10 patients in stage T a, T is, T 1, T 2, T 3 and T 4a, respectively. There were 35, 6, 7 and 6 patients with pathological stage N 0, N 1, N 2, and N 3, respectively. Pathological diagnoses included 6 cases of low-grade urothelial carcinoma, 45 cases of high-grade urothelial carcinoma, and 3 cases of other histological subtypes. There were no statistically significant differences ( P>0.05) in surgical methods, pathological staging, or pathological types between the ERAS and CRAS groups. ERAS group presented less albumin loss [(25.73±8.63)% vs. (32.63±9.05)%, P=0.001], shorter hospital stay [9(7, 13)d vs. 12(9, 16)d, P=0.006], less 30-day overall complications [55.2% (16/29) vs. 83.3% (45/54), P=0.009]. In multivariable analysis, maximum albumin loss≥20% was independently associated with 30-day minor complications ( P=0.049), and maximum albumin loss ≥25% was independently associated with hospital of stay≥10 days ( P=0.038), respectively. Conclusions:For patients who received LRC+ ICUD, ERAS was associated with reduced perioperative albumin loss, shorter length of stay, less 30-day complications, accelerated recovery time, improved clinical outcome and less albumin injection.

Background/Aims: The aim of this study was to analyze the chronological changes in postoperative complications in surgical ulcerative colitis patients over the past decade in China and to investigate the potential parameters that contributed to the changes. Methods: Ulcerative colitis patients who underwent surgery during 2008–2017 were retrospectively enrolled from 13 hospitals in China. Postoperative complications were compared among different operation years. Risk factors for complications were identified by logistic regression analysis. Results: A total of 446 surgical ulcerative colitis patients were analyzed. Fewer short-term complications (24.8% vs. 41.0%, P=0.001) and more laparoscopic surgeries (66.4% vs. 25.0%, P<0.001) were found among patients who received surgery during 2014–2017 than 2008–2013. Logistic regression suggested that independent protective factors against short-term complications were a higher preoperative body mass index (odds ratio [OR], 0.870; 95% confidence interval [CI], 0.785–0.964; P=0.008), laparoscopic surgery (OR, 0.391; 95% CI, 0.217–0.705; P=0.002) and elective surgery (OR, 0.213; 95% CI, 0.067–0.675; P=0.009). The chronological decrease in short-term complications was associated with an increase in laparoscopic surgery. Conclusions Our data revealed a downward trend of short-term postoperative complications among surgical ulcerative colitis patients in China during the past decade, which may be due to the promotion of minimally invasive techniques among Chinese surgeons.

Polymyxin B and polymyxin E (colistin) are presently considered the last line of defense against human infections caused by multidrug-resistant Gram-negative organisms such as carbapenemase-producer Enterobacterales, Acinetobacter baumannii, and Klebsiella pneumoniae. Yet resistance to this last-line drugs is a major public health threat and is rapidly increasing. Polymyxin S₂ (S₂) is a polymyxin B analogue previously synthesized in our institute with obviously high antibacterial activity and lower toxicity than polymyxin B and colistin. To predict the possible resistant mechanism of S₂ for wide clinical application, we experimentally induced bacterial resistant mutants and studied the preliminary resistance mechanisms. Mut-S, a resistant mutant of K. pneumoniae ATCC BAA-2146 (Kpn2146) induced by S₂, was analyzed by whole genome sequencing, transcriptomics, mass spectrometry and complementation experiment. Surprisingly, large-scale genomic inversion (LSGI) of approximately 1.1 Mbp in the chromosome caused by IS26 mediated intramolecular transposition was found in Mut-S, which led to mgrB truncation, lipid A modification and hence S₂ resistance. The resistance can be complemented by plasmid carrying intact mgrB. The same mechanism was also found in polymyxin B and colistin induced drug-resistant mutants of Kpn2146 (Mut-B and Mut-E, respectively). This is the first report of polymyxin resistance caused by IS26 intramolecular transposition mediated mgrB truncation in chromosome in K. pneumoniae. The findings broaden our scope of knowledge for polymyxin resistance and enriched our understanding of how bacteria can manage to survive in the presence of antibiotics.