This study reports the diagnosis and treatment of a 26-year-old pregnant woman with severe malnutrition combined with acute pyelonephritis causing sepsis, refractory septic shock and multiple organ failure. A female patient, 26 years old, was admitted to hospital mainly due to "menelipsis for more than 19 weeks, nausea and vomiting for 20 days, fever with fatigue for 3 days". At the end of 19 weeks of intrauterine pregnancy, the patient presented with fever accompanied by urinary tract irritation. Laboratory tests showed elevated inflammatory indicators, and ultrasonography showed bilateral pelvicalyceal dilation. She was diagnosed with acute pyelonephritis, sepsis, acute kidney injury (AKI) and severe malnutrition. After a whole-hospital consultation, the patient was treated with meropenem and vancomycin as antimicrobial therapy, and bilateral nephrostomy drainage was performed simultaneously. After that, the patient suffered a sudden decrease in blood pressure, blood oxygen saturation, and rapid heart rate. Septic shock with multiple organ dysfunction was considered, and she was transferred to intensive care unit (ICU) immediately. After the patient was transferred to ICU, emergency tracheal intubation and ventilator-assisted ventilation were performed. Rapid fluid resuscitation was administered for the patient. While pulse indicator continuous cardiac output (PICCO) monitoring was performed, norepinephrine, terlipressin, and methylene blue were administered to maintain peripheral vascular resistance. Since the patient developed septic cardiomyopathy and cardiogenic shock later, levosimendan and epinephrine were admi-nistered to improve cardiac function. While etiological specimens were delivered, meropenem, teicoplanin and caspofungin were given as initial empiric antimicrobial therapy. Unfortunately, the intrauterine fetal death occurred on the night of admission to ICU. On the 3rd day of ICU admission, a still-born child was delivered vaginally with 1/5 defect of the fetal membrane. On the 6th day of ICU admission, the patient had fever again with elevated inflammatory indicators. After excluding infection in other parts, intrau-terine infection caused by incomplete delivery of fetal membrane was considered. Then emergency uterine curettage was performed and the infection gradually improved. Later the laboratory results showed that the nephrostomy drainage was cultured for Escherichia coli and uterine, cervical and vaginal secretions were cultured for Candida albicans. Due to severe infection and intrauterine incomplete abortion, the patient developed disseminated intravascular coagulation (DIC). Active antimicrobial therapy and blood product supplement were given. However, the patient was critically ill with significant decrease in hemoglobin and platelets combined with multiple organ failure. Thrombotic microangiopathy (TMA) was not excluded yet, so plasma exchange was performed for the patient in order not to delay treatment. The patient underwent bedside continuous renal replacement therapy (CRRT) for AKI. The patient was complicated with acute liver injury, and the liver function gradually returned to normal after liver protection, antimicrobial therapy and other treatments. Due to the application of large doses of vasoactive drugs, the extremities of the patient gradually developed cyanosis and ischemic necrosis. Local dry gangrene of the bilateral toes remained at the time of discharge. In general, the patient suffered from septic shock, cardiogenic shock, combined with DIC and multiple organ dysfunction. After infection source control, antimicrobial therapy, uterine curettage, blood purification treatment, nutritional and metabolic support, the patient was discharged with a better health condition.
Humans ; Female ; Pyelonephritis/complications* ; Pregnancy ; Adult ; Multiple Organ Failure/etiology* ; Shock, Septic/etiology* ; Sepsis/etiology* ; Pregnancy Complications ; Pregnancy Complications, Infectious ; Malnutrition/complications*

Glioma is difficult to treat due to the unique tumor microenvironment and blood-brain barrier. (13aS)-3-Hydroxyl-6,7-dimethoxyphenanthro[9,10-b] indolizidine (PF403), a phenanthroindolizidine alkaloid, has been identified as a promising therapeutic agent for the treatment of glioma. However, the anti-glioma mechanism of PF403 in vivo has not been conclusively verified and must be further elucidated. Hence, a strategy without chemical modification was applied to identify the target of PF403. In this study, we identified nicotinamide phosphoribosyl transferase (NAMPT) as the target of PF403 by using thermal proteome profiling (TPP). Moreover, microscale thermophoresis (MST), surface plasmon resonance (SPR), and isothermal titration calorimetry (ITC) experiments confirmed that NAMPT exhibits good affinity for PF403. Direct and indirect enzyme activity assays revealed that PF403 inhibited the catalytic activity of NAMPT, leading to a decrease in the concentration of nicotinamide adenine dinucleotide (NAD⁺) in U87 cells. X-ray diffraction and amino acid spot mutation experiments revealed that PF403 primarily relies on the formation of pi-pi interactions with residue Tyr188 to maintain binding with NAMPT (PDB code 8Y55). After NAMPT was knocked down with lentivirus, PF403 lost or partially lost its antitumor activity at the cellular and animal levels. These findings suggest that PF403 exerts antitumor activity by directly targeting NAMPT.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

The incidence and mortality of venous thromboembolism (VTE) are high in critically ill patients, and there is still a risk of VTE and bleeding after the use of fixed-dose low molecular weight heparin (LMWH) for prophylaxis. The level of anti-factor Ⅹa is not up to standard after LMWH prophylaxis in patients with surgery or trauma. The condition of critically ill patients is complicated, and the proportion of patients with low antithrombin Ⅲ is high, which can affect the prophylactic efficacy of LMWH and contribute to VTE occurrence. There is currently no consensus on whether adjusting LMWH dose according to anti-factor Ⅹa levels can reduce VTE occurrence in critically ill patients. High-quality multicenter randomized controlled studies are needed in the future to establish new approaches for precise prevention of VTE in critically ill patients.

Venous thromboembolism(VTE)includes deep venous thrombosis(DVT)and pulmonary embolism(PE).Patients in intensive care unit(ICU)are often at a high risk of VTE due to combining many risk factors.Prevention strategies of VTE in critically ill patients are crucial,including identification of risk factors,the risk as-sessment of thrombosis and bleeding,mechanical prophylaxis and drug prophylaxis,effect monitoring,and quality control.Since the risk of VTE in ICU patients is high,the risk of bleeding should not be ignored.It is a challenge for ICU physicians to comprehensively evaluate the risk of thrombosis and bleeding in critically ill patients and im-plement effective preventive and monitoring measures in time.This article reviews the relevant research progress on prevention strategies of VTE in critically ill patients in order to provide clinical evidence for the prophylaxis of VTE in critically ill patients.

Objective:To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application.Methods:This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis.Results:The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group ( χ2=5.560, P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group ( χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion:SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.

In the field of plastic and reconstructive surgery, the loss of organs or tissues caused by diseases or injuries has resulted in challenges, such as donor shortage and immunosuppression. In recent years, with the development of regenerative medicine, the decellularization-recellularization strategy seems to be a promising and attractive method to resolve these difficulties. The decellularized extracellular matrix contains no cells and genetic materials, while retaining the complex ultrastructure, and it can be used as a scaffold for cell seeding and subsequent transplantation, thereby promoting the regeneration of diseased or damaged tissues and organs. This review provided an overview of decellularization-recellularization technique, and mainly concentrated on the application of decellularization-recellularization technique in the field of plastic and reconstructive surgery, including the remodeling of skin, nose, ears, face, and limbs. Finally, we proposed the challenges in and the direction of future development of decellularization-recellularization technique in plastic surgery.
Tissue Engineering/methods* ; Tissue Scaffolds/chemistry* ; Surgery, Plastic ; Regenerative Medicine/methods* ; Extracellular Matrix

Objective:To evaluate superior mesenteric artery preferential approach in the borderline resectable pancreatic head cancer.Methods:The clinical and follow-up data of 90 patients with borderline resectable pancreatic head cancer who underwent radical pancreatoduodenectomy at Beijing Chaoyang Hospital,Capital Medical University from Jan 2015 to Dec 2021 were analyzed.Results:After exploring the superior mesenteric artery in the lower colon area to confirm the vascular invasion meet the resection criteria, the blood supply is cut off first, then the tumors were resected en bloc, with the invaded vessels resected and reconstructed or replaced. All 90 patients successfully completed the operation without perioperative death. Pathology established pancreatic ductal adenocarcinoma. The 1-year, 2-year, and 3-year disease-free survival rates of patients in the arterial priority approach group were 68.2%, 60.4%, and 54.3%, while the 1-year, 2-year, and 3-year disease-free survival rates of patients by conventional approach were 58.4%, 26.4%, and 11.7% ( P=0.001). Conclusion:The superior mesenteric artery preferential approach in the inferior colon region can prolong the survival time of patients after surgery, and reduce the recurrence.

Background: The emergence of the severe acute respiratory syndrome coronavirus 2 omicron variant has been triggering the new wave of coronavirus disease 2019 (COVID-19) globally. However, the risk factors and outcomes for radiological abnormalities in the early convalescent stage (1 month after diagnosis) of omicron infected patients are still unknown. Methods: Patients were retrospectively enrolled if they were admitted to the hospital due to COVID-19. The chest computed tomography (CT) images and clinical data obtained at baseline (at the time of the first CT image that showed abnormalities after diagnosis) and 1 month after diagnosis were longitudinally analyzed. Uni-/multi-variable logistic regression tests were performed to explore independent risk factors for radiological abnormalities at baseline and residual pulmonary abnormalities after 1 month. Results: We assessed 316 COVID-19 patients, including 47% with radiological abnormalities at baseline and 23% with residual pulmonary abnormalities at 1-month follow-up. In a multivariate regression analysis, age ≥ 50 years, body mass index ≥ 23.87, days after vaccination ≥ 81 days, lymphocyte count ≤ 1.21 × 10 -9 /L, interleukin-6 (IL-6) ≥ 10.05 pg/mL and IgG ≤ 14.140 S/CO were independent risk factors for CT abnormalities at baseline. The age ≥ 47 years, presence of interlobular septal thickening and IL-6 ≥ 5.85 pg/mL were the independent risk factors for residual pulmonary abnormalities at 1-month follow-up. For residual abnormalities group, the patients with less consolidations and more parenchymal bands at baseline could progress on CT score after 1 month. There were no significant changes in the number of involved lung lobes and total CT score during the early convalescent stage. Conclusion The higher IL-6 level was a common independent risk factor for CT abnormalities at baseline and residual pulmonary abnormalities at 1-month follow-up. There were no obvious radiographic changes during the early convalescent stage in patients with residual pulmonary abnormalities.

Objective:To evaluate the correlation between brain-derived neurotrophic factor (BDNF) and inflammatory markers in rheumatoid arthritis (RA) patients with depressive symptoms.Methods:This study was a cross-sectional study. RA patients' medical history were recorded and disease activity was evaluated. Serum BDNF, interleukin (IL)-6, tumor necrosis factor (TNF)-α were tested and clinical inflammatory indicators such as C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen (FIB), serum amyloid A (SAA) were recorded. RA patients were instructed to fill in the patient health Questionnaire-9 (PHQ-9) scale by themselves. Patients with a score greater than or equal to 5 were included in the RA with depressive symptoms group, and patients with a score of 4 or less were included in the RA without depressive symptoms group. The changes in BDNF and inflammatory indexes were compared between the two groups. Correlation analysis of PHQ-9, BDNF, inflammatory markers and DAS28 was performed. Logistic regression analysis was performed to find the risk factors of depression in RA.Results:A total of 140 RA patients were enrolled in this study, and 66 patients (47.1%) with a PHQ-9 score greater than or equal to 5 were included in the RA with depressive symptoms group. Compared with the RA without depressive symptoms group, RA patients with high disease activity, single and living alone, poor economic self-awareness and unemployed were more likely to have depressive symptoms. The serum level of BDNF[(2 276±333) pg/ml vs (1 367±431) pg/ml, t=13.91, P<0.001], IL-6[(39±28) pg/ml vs (27±8) pg/ml, t=3.66, P<0.001], TNF-α[(9.0±7.2) pg/ml vs (6.6±3.9)pg/ml, t=2.43, P=0.035], CRP[(25±13) mg/L vs (17±11) mg/L, t=3.94, P<0.001], ESR[(48±18) mm/1 h vs (34±21) mm/1 h, t=4.14, P=0.024], Fib[(3.8±1.1) g/L vs (3.0±0.5) g/L, t=5.92, P=0.023], SAA[(64±39) mg/L vs (37±19) mg/L, t=5.32, P<0.001] in RA with depressive symptoms group were significantly higher than those in RA without depressive symptoms group. Serum BDNF was significantly positively correlated with PHQ-9 score ( r=0.66, P<0.001), IL-6( r=0.20, P=0.019), TNF-α ( r=0.14, P=0.090), CRP ( r=0.32, P<0.001), ESR ( r=0.20, P= 0.001), Fib ( r=0.28, P=0.001), SAA( r=0.28, P=0.001) and DAS28 ( r=0.37, P<0.001) . BDNF [ OR (95% CI) =1.578(1.257, 2.354), P=0.001], IL-6[ OR (95% CI) =1.073(1.012, 1.075), P=0.006], CRP[ OR(95% CI)=1.085(1.045, 1.178), P=0.001], SAA[ OR(95% CI)=1.125(1.004, 1.198), P=0.018] and unemployment were risk factors for depressive symptoms in RA. Conclusion:Serum BDNF is positively correlated with PHQ-9 scores, inflammatory markers and disease activity in RA patients. BDNF, IL-6, CRP, SAA and unemployment are risk factors for depressive symptoms in RA. Effective treatment of RA can reduce the occurrence of depression symptoms.