ObjectiveTo investigate the change in the activity of hepatitis B virus （HBV）-specific CD8⁺ T cells after pegylated interferon-α-2b （PEG-IFN-α-2b） therapy in HBeAg-negative patients with chronic HBV infection. MethodsA total of 53 HBeAg-negative patients with chronic HBV infection who attended The First Affiliated Hospital of Xinxiang Medical University and Tangdu Hospital of Air Force Mdical University from April 2020 to June 2022 were enrolled and treated with PEG-IFN-α-2b （180 μg/week， subcutaneous injection） antiviral therapy. The study endpoint was HBsAg clearance （course of treatment<48 weeks） or 48 weeks （course of treatment≥48 weeks）. Peripheral blood mononuclear cells were isolated at baseline and study endpoint， and peripheral blood T cell counts were measured. Enzyme-linked immunospot assay was used to measure the frequency of HBV-specific CD8⁺ T cells secreting perforin， granzyme B， and interferon-γ. A total of 17 HLA-A^*02-restricted patients were selected， and CD8⁺ T cells were purified to establish direct- and indirect-contact co-culture systems for HBV-specific CD8⁺ T cells and HepG2.2.15 cells. The level of lactate dehydrogenase in supernatant was measured to calculate the mortality rate of HepG2.2.15 cells， and the levels of HBV DNA， cytotoxic molecules， and cytokines in supernatant were also measured. Flow cytometry was used to measure the expression of apoptosis ligands， and the cytotoxicity of HBV-specific CD8⁺ T cells was evaluated. The independent samples t-test or the paired t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test or the Wilcoxon rank-sum test was used for comparison of non-normally distributed continuous data between two groups. ResultsThe HBsAg clearance rate at study endpoint was 30.19% （16/53）. There were no significant differences in peripheral blood T cell counts （CD3⁺， CD4⁺， and CD8⁺ T cells） between baseline and study endpoint （P>0.05）. At study endpoint， there was a significant increase in the frequency of HBV-specific CD8⁺ T cells secreting perforin， granzyme B， and interferon-γ （U=177.50， t=11.90， U=186.50， all P<0.001）， and the patients with HBsAg clearance had a significantly higher frequency of such HBV-specific CD8⁺ T cells than those without HBsAg clearance （U=120.50， t=2.73， U=121.50， all P<0.01）. In the direct- and indirect-contact co-culture systems at study endpoint， HBV-specific CD8⁺ T cells induced a significant reduction in HBV DNA in the supernatant of HepG2.2.15 cells （all P<0.001） and significant increases in the secretion of interferon-γ and tumor necrosis factor-α （all P<0.05）； in the direct-contact co-culture system， HBV-specific CD8⁺ T cells induced significant increases in the mortality rate of HepG2.2.15 cells （13.62%±3.27% vs 11.39%±2.40%， t=2.27， P=0.030） and the secretion of perforin and granzyme B （t=72.50， U=52.50， both P<0.05）. In the direct- and indirect-contact co-culture systems， compared with HBV-specific CD8⁺ T cells from the patients without HBsAg clearance， the HBV-specific CD8⁺ T cells from patients with HBsAg clearance had a significantly greater reduction in HBV DNA （P<0.05） and significant increases in the secretion of interferon-γ and tumor necrosis factor-α （P<0.05）. ConclusionPEG-IFN-‍α‍-2b therapy can help to achieve a relatively high HBsAg clearance rate in HBeAg-negative patients with chronic HBV infection， and the activity of HBV-specific CD8⁺ T cells is significantly enhanced， which is closely associated with HBsAg clearance.

OBJECTIVE: To investigate the safety and prognostic factors influencing the treatment of upper urinary tract urothelial carcinoma (UTUC) combined with bladder cancer (BCa) by laparoscopic simultaneous radical cystectomy and nephroureterectomy (RCNU). METHODS: The clinical data of patients admitted to Peking University Third Hospital for laparoscopic RCNU surgery from January 2009 to September 2023 were analyzed retrospectively. Based on the same gender, age (±5 years), history of uroepithelial tumors, underlying diseases, T-stage, N-stage, M-stage, American Society of Anesthesiologists (ASA) score, Charlson comorbidity index, and body mass index (BMI) (±5), 34 patients with RCNU were matched 1 ∶1 with patients with bladder cancer who underwent laparoscopic radical cystectomy (RC) alone. Kaplan-Meier survival analysis was used to calculate patient survival, and Cox proportional regression risk model was used to analyze clinical factors affecting prognosis. RESULTS: Of the 68 patients enrolled, the follow-up rate was 100% with a median follow-up time of 27.0 (11.7, 60.2) months. Comparison of intraoperative conditions (including operation time, estimated intraoperative bleeding, intra-operative blood transfusion, etc.) between the two groups of patients showed no significant difference (P>0.05). Comparison of preoperative creatinine and postoperative creatinine between the two groups of patients showed significant differences (P < 0.05). The perioperative Clavien grade Ⅲ-Ⅳ complication rates were 2.9% (1/34) in the RC group and 5.9% (2/34) in the RCNU group. There was no significant difference in terms of perioperative complications between the two groups. Overall survival was significantly lower in the patients receiving RCNU compared with the matched group receiving RC alone (P < 0.05). Cox regression analysis suggested that two factors, high N stage and high postoperative creatinine, were independent risk factors affecting the prognosis of patients in the 2 groups (P < 0.05). CONCLUSION The overall survival prognosis of patients undergoing RCNU surgery was worse compared with laparoscopic RC surgery alone during the same period. There was no clinically significant difference between the two groups in terms of operation time, intraoperative bleeding, and perioperative complications, and there were clinically significant differences in preoperative renal function and post-operative renal function.
Humans ; Laparoscopy/methods* ; Nephroureterectomy/methods* ; Cystectomy/methods* ; Prognosis ; Male ; Retrospective Studies ; Female ; Urinary Bladder Neoplasms/mortality* ; Middle Aged ; Aged

Two novel skeleton sesquiterpenoids (1 and 6), along with four new iphionane-type sesquiterpenes (2-5) and six new cyperane-type sesquiterpenes (7-11), were isolated from the whole plant of Artemisia hedinii (A. hedinii). The two novel skeleton compounds (1 and 6) were derived from the decarbonization of iphionane and cyperane-type sesquiterpenes, respectively. Their structures were elucidated through a comprehensive analysis of spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS) and 1D and 2D nuclear magnetic resonance (NMR) spectra. The absolute configurations were determined using electronic circular dichroism (ECD) spectra, single-crystal X-ray crystallographic analyses, time-dependent density functional theory (TDDFT) ECD calculation, density functional theory (DFT) NMR calculations, and biomimetic syntheses. The biomimetic syntheses of the two novel skeletons (1 and 6) were inspired by potential biogenetic pathways, utilizing a predominant eudesmane-type sesquiterpene (A) in A. hedinii as the substrate. All compounds were evaluated in LX-2 cells for their anti-hepatic fibrosis activity. Compounds 2, 8, and 10 exhibited significant activity in downregulating the expression of α-smooth muscle actin (α-SMA), a protein involved in hepatic fibrosis.
Artemisia/chemistry* ; Sesquiterpenes/chemical synthesis* ; Molecular Structure ; Humans ; Liver Cirrhosis/genetics* ; Biomimetics ; Plant Extracts/pharmacology*

Objective:To investigate functional outcomes and condition-specific quality-of-life (CSQoL) after intersphincteric resection (ISR) in patients with low rectal cancer using traditional and exploratory questionnaires.Methods:A prospective observational study was conducted in the Characteristic Medical Center of the People′s Liberation Army Rocket Force. Patients with low rectal cancer who underwent ISR with ileostomy reversal from May 2020 to April 2023 were enrolled. An electronic self-assessment survey was sent to enrolled patients at 3 to 6, 12, and 24 to 36 months after reversal, and differences in functional and CSQoL results between the 3 groups were analyzed with generalized estimation equations. Functional outcomes were determined by the Wexner incontinence score (WIS) and the low anterior resection syndrome (LARS) score. In line with the five frequency responses ranging from never (score 0) to always (score 4) defined by the WIS, an exploratory survey was used to measure the severity of 16 LARS-specific variables confirmed by the latest international Delphi consensus. Furthermore, CSQoL was evaluated using the fecal incontinence quality-of-life scale (FIQL) and the visual analog scale (VAS).Results:A total of 90 patients were enrolled in the study. There were 64 males and 26 females, aged (58.6±10.4) years (range: 28 to 79 years). The median distance from the distal tumor margin to the anal verge( M(IQR)) was 3.0 (1.5) cm (range: 1.0 to 5.0 cm). There were 55 patients who completed the questionnaires at 3 to 6 months, 59 patients at 12 months, and 40 patients at 24 to 36 months of follow-up, respectively. The summary score of FIQL and VAS improved significantly after reversal (2.33±0.69 vs. 2.40±0.66 vs. 2.79±0.76, χ2=11.703, P=0.003; 5.31±1.65 vs. 5.61±1.90 vs. 6.58±1.92, χ2=12.781, P=0.002), but the differences in the WIS and LARS score did not reach statistical significance (both P>0.05). The survey responses for the LARS-specific variables indicated that “emptying difficulties” and “dissatisfaction with the bowels” were the most frequent symptom and consequence after ISR, respectively. The exploratory severity score for LARS improved significantly among the 3 time periods(34 (14) vs. 31 (13) vs. 23 (17), χ2=13.952, P=0.001). Furthermore, the FIQL summary score was strongly correlated with the LARS severity score ( r s=-0.72, P<0.01). Conclusions:Although a high prevalence of LARS may persist for years, patients reported an improvement in CSQoL and functional outcomes after ISR. The highest priorities recommended by the international consensus might provide better assessments the severity of LARS.

Objective:To explore the impact of CACNA1C rs58619945 genotype on the cortical thickness of attentional networks in patients with Bipolar 1 disorder type (BD-Ⅰ). Methods:From August 2013 and August 2019, a total of 155 BD-Ⅰ patients were recruited from the outpatient and inpatient Departments of the Affiliated Brain Hospital of Guangzhou Medical University, along with 82 healthy controls (HC) from the community and university. Genotype for the CACNA1C rs58619945 locus was determined for all BD-I patients and HC subjects, followed by 3.0 T magnetic resonance imaging scans to measure the cortical thickness in the alert, orienting, and executive control subnetworks. General linear models (GLMs) were used to evaluate the impact of CACNA1C rs58619945 on the cortical thickness of attentional networks. Concurrently, attentional dimension functions were assessed using repeatable battery for the assessment of neuropsychological status (RBANS) and Cambridge neuropsychological test automated battery rapid visual information processing (CANTAB RVP) test. This study was approved by the Medical Ethics Committee of the Affiliated Brain Hospital of Guangzhou Medical University(Ethics No. 2023-056). Results:Compared with the HC group, the BD-Ⅰ patients had shown reduced thickness in bilateral prefrontal cortex, bilateral posterior cingulate cortex, and bilateral superior temporal cortex( P<0.05). A significant interaction between the CACNA1C genotype and the cortical thickness(HC vs.BD) of right prefrontal cortex, right posterior parietal cortex and right superior temporal cortex was noted( P<0.05). Partial correlation analysis has demonstrated a significant correlation between CANTAB RVP and RBANS attention indices and cortical thickness in the right prefrontal cortex, right posterior cingulate cortex( P<0.05), and right superior temporal cortex predominantly among carriers of the BD-Ⅰ G allele. Conclusion:The G allele of CACNA1C rs58619945 is associated with cortical thickness of the right prefrontal cortex, right posterior cingulate cortex, and right superior temporal cortex in BD-Ⅰ, which are part of the alerting and orienting network.

Objective:To investigate functional outcomes and condition-specific quality-of-life (CSQoL) after intersphincteric resection (ISR) in patients with low rectal cancer using traditional and exploratory questionnaires.Methods:A prospective observational study was conducted in the Characteristic Medical Center of the People′s Liberation Army Rocket Force. Patients with low rectal cancer who underwent ISR with ileostomy reversal from May 2020 to April 2023 were enrolled. An electronic self-assessment survey was sent to enrolled patients at 3 to 6, 12, and 24 to 36 months after reversal, and differences in functional and CSQoL results between the 3 groups were analyzed with generalized estimation equations. Functional outcomes were determined by the Wexner incontinence score (WIS) and the low anterior resection syndrome (LARS) score. In line with the five frequency responses ranging from never (score 0) to always (score 4) defined by the WIS, an exploratory survey was used to measure the severity of 16 LARS-specific variables confirmed by the latest international Delphi consensus. Furthermore, CSQoL was evaluated using the fecal incontinence quality-of-life scale (FIQL) and the visual analog scale (VAS).Results:A total of 90 patients were enrolled in the study. There were 64 males and 26 females, aged (58.6±10.4) years (range: 28 to 79 years). The median distance from the distal tumor margin to the anal verge( M(IQR)) was 3.0 (1.5) cm (range: 1.0 to 5.0 cm). There were 55 patients who completed the questionnaires at 3 to 6 months, 59 patients at 12 months, and 40 patients at 24 to 36 months of follow-up, respectively. The summary score of FIQL and VAS improved significantly after reversal (2.33±0.69 vs. 2.40±0.66 vs. 2.79±0.76, χ2=11.703, P=0.003; 5.31±1.65 vs. 5.61±1.90 vs. 6.58±1.92, χ2=12.781, P=0.002), but the differences in the WIS and LARS score did not reach statistical significance (both P>0.05). The survey responses for the LARS-specific variables indicated that “emptying difficulties” and “dissatisfaction with the bowels” were the most frequent symptom and consequence after ISR, respectively. The exploratory severity score for LARS improved significantly among the 3 time periods(34 (14) vs. 31 (13) vs. 23 (17), χ2=13.952, P=0.001). Furthermore, the FIQL summary score was strongly correlated with the LARS severity score ( r s=-0.72, P<0.01). Conclusions:Although a high prevalence of LARS may persist for years, patients reported an improvement in CSQoL and functional outcomes after ISR. The highest priorities recommended by the international consensus might provide better assessments the severity of LARS.

Objective:To investigate the efficacy of Peritoneal interposition flap (PIF) technique in preventing postoperative pelvic lymphocele formation during laparoscopic radical prostatectomy with extended pelvic lymph node dissection (LRP+ ePLND).Methods:A retrospective analysis was conducted on clinical data of 113 patients with locally high-risk or locally advanced prostate cancer who underwent LRP+ ePLND at Shanghai East Hospital, from January 2020 to November 2023. Among them, 27 patients received PIF technique and 86 received traditional LRP+ ePLND. ePLND was carried out as the clearance of external iliac vessels, medial side of the internal iliac artery, and pararectal lymph nodes. The PIF technique was the suturing the peritoneal flap after freeing the bladder to the lateral side of the bladder, pulling the peritoneal edge that follows the bladder's free edge posteriorly to the pubis, curling it onto the lateral surface of the bladder. This could expose the lymph node clearance bed, establishing a pathway from the lymph node clearance bed to the abdominal cavity space, allowing exuded lymphatic fluid to flow into the abdominal cavity for absorption by the peritoneum. There were no statistically significant differences in age [(68.37±6.92)years vs.(70.47±5.72)years], body mass index [(25.47±2.49)kg/m 2vs.(24.46±2.80)kg/m 2], and preoperative PSA [(23.28±13.94)ng/ml vs.(24.81±13.99)ng/ml] between the PIF group and the control group ( P>0.05). Biopsy Gleason score in PIF group: 6 in 2 cases, 7 in 9 cases, 8 in 9 cases, 9-10 in 2 cases. Biopsy Gleason score in control group: 6 in 4 cases, 7 in 35 cases, 8 in 27 cases, 9-10 in 20 cases. Clinic stage in PIF group: T 2 in 18 cases, T 3 in 6 cases, T 4 in 3 cases. Clinic stage in control group: T 2 in 51cases, T 3 in 27 cases, T 4 in 8 cases. The preoperative Gleason scores and TNM staging comparisons between the PIF group and the control group showed no statistically significant differences ( P>0.05). Surgical duration, intraoperative blood loss, lymph node positivity rate, incidence of postoperative lymphocele, and recovery of urinary control were compared between the two groups. Results:All surgeries were completed successfully without intraoperative complications in both groups. There were no statistically significant differences between the PIF group and the control group in terms of surgical duration [(202.96±24.15)min vs.(201.1±29.85)min], intraoperative blood loss [(85.56±32.27)ml vs.(90.7±49.25)ml], and lymph node positivity rate [(4 in PIF group, 14.8%)vs.(25 in control group, 29.1%)]( P>0.05). Urinary catheters were retained for 10-14 days postoperatively. Following catheter removal, there were no statistically significant differences in urinary control rates at 1 month [51.85%(14/27)vs. 48.83%(42/86)]and 2 months[74.07%(20/27) vs. 72.09%(62/86)] between the PIF group and the control group ( P>0.05). At the 2 to 6-month follow-up CT scan, none of the 27 patients in the PIF group developed pelvic lymphocele, whereas 9 patients in the control group did (6 cases bilateral, 3 cases unilateral), showing a statistically significant difference between the two groups ( P=0.002). Postoperatively, 3 patients in the control group experienced symptoms, with 1 case of lymphocele infection causing fever 1 month after surgery. Lymphocysts were found in 2 patients with ipsilateral lower extremity swelling 2 weeks after surgery. Conclusions:The application of PIF technique during laparoscopic radical prostatectomy with extended pelvic lymph node dissection via the abdominal approach could be safe and feasible. It may prevent postoperative pelvic lymphocele formation.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

ObjectiveBased on network pharmacology and molecular docking techniques， the mechanism of essential oil from Chimonanthus nitens leaves （CLO） in the treatment of acute lung injury （ALI） was predicted， and a rat model of ALI was established to verify the mechanism of CLO. MethodThe composition of CLO was determined by gas chromatography-mass spectrometry （GC-MS）. The component targets were obtained from PharmMapper and SwissTargetPrediction databases， ALI-related targets were obtained from GeneCards， Online Mendelian Inheritance in Man （OMIM） and DisGeNET， cross-over analysis with differential expressed genes （DEGs） of ALI obtained from Gene Expression Omnibus （GEO） on the Venny 2.1.0 platform yielded potential anti-ALI targets of CLO. Protein-protein interaction （PPI） analysis of potential targets was carried out by STRING 11.5. The tissue expression profiles of potential targets were obtained from the National Center for Biotechnology Information （NCBI） and the target tissue distribution maps were constructed. Potential targets were analyzed for Gene Ontology （GO） function and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment by RStudio 4.0.0 software. Composition-target-pathway network was constructed by Cytoscape 3.9.1 software， and key components and pathways were screened out and verified by molecular docking. ALI model was established by lipopolysaccharide （LPS） induction， levels of interleukin （IL）-6 and tumor necrosis factor （TNF）-α in serum of rats were measured， the expression levels of IL-17 protein in the lung tissue of ALI rats were analyzed by immunohistochemistry. ResultA total of 19 components of CLO were identified by GC-MS， and 18 potential targets were obtained by target screening. After PPI analysis， 15 target proteins with interaction relationship were obtained， further analysis showed that they were highly expressed in lung and thymus. The network diagram of component-target-pathway was analyzed to obtain the key components， including bornyl acetate， linalool， elemol， geranyl isobutyrate， and the core targets of matrix metalloproteinase 13 （MMP13）， S100 calcium binding protein A9 （S100A9）， spleen tyrosine kinase （SYK）， as well as the main signaling pathways， such as IL-17 and TNF. The results of molecular docking showed that the key components were stably bound to MMP13 and S100A9 of IL-17 signaling pathway. The results of pharmacological experiment confirmed that CLO could significantly inhibit the expression of IL-6 and TNF-α in serum of ALI rats， and decrease the expression of IL-17 protein in lung tissue of ALI rats. ConclusionCLO can achieve the therapeutic effect on ALI and protect lung tissue， the mechanism may be related to the decrease of the expression of IL-6 and TNF-α in serum and the inhibition of the activation of IL-17 signaling pathway in lung tissue of ALI rats.

Interleukin-35 (IL-35) is an immunosuppressive cytokine mainly secreted by regulatory T cells and regulatory B cells and is involved in the pathogenesis of infectious diseases, tumors, and autoimmune diseases. This article summarizes the immunoregulatory role and mechanism of IL-35 in hepatitis B, liver cirrhosis, liver failure, and hepatocellular carcinoma caused by hepatitis B virus (HBV) infection. The analysis shows that IL-35 is a "double-edged sword" in HBV-related diseases, and it can not only promote the chronicity of infection and the progression of hepatocellular carcinoma, but also alleviate liver inflammation and inhibit liver fibrosis.