Background/Aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients. Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development. Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients. Conclusions Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

A dry suspension of Indigo Naturalis (IN) based on lactose-IN composite particles was designed by powder modification technology to meet the clinical needs of IN. The contact angle was used as an evaluation index to investigate the effects of the type of modifier lactose, the amount of lactose, and the co-grinding time of lactose and IN on the hydrophilicity of IN. The difference between IN before and after modification was compared through physical properties such as particle size and scanning electron microscope, as well as hydrophilic properties such as surface free energy and multiple light scattering. The optimal process of lactose-IN composite particles is as follows: after lactose is ground alone for 2 minutes, it is co-ground with IN at a ratio of 1∶1 for 6 minutes. The results of the investigation of powder properties show that the particle size d_0.9 of IN is reduced from 112.75 μm to 87.30 μm after modification. The BET and Langmuir specific surface areas decreased by 8.661 m²·g^-1 and 12.512 m²·g^-1, respectively. SEM shows that lactose is attached to the surface of modified IN (MIN); surface element analysis shows that Si, Ca, and Mg elements of MIN are smaller than IN, and O elements are larger. The infrared spectrum shows that the MIN possesses the characteristic peaks of both IN and lactose. Compared MIN with IN, the contact angle and the non-polar surface free energy decreased by 35.1° and 9.975 mJ·m^-2, respectively; the polar surface free energy and the surface free energy increased by 36.956 and 26.950 mJ·m^-2, respectively. The results of multiple light scattering showed that the light transmittance of MIN was 35% lower than that of IN, and the backscattered light intensity was increased by about 25%. Only one excipient was used to successfully prepare IN dry suspension with good wettability and suspending property, which provided a basis for the development of new preparations of IN.

Objective: To explore the application and efficacy of paclitaxel liposome in the treatment of advanced breast cancer among Chinese population in the real world. Methods: The clinical characteristics of patients with advanced breast cancer who received paclitaxel liposome as salvage treatment from January 1, 2016 to August 31, 2019 in 11 hospitals were collected and retrospectively analyzed. The primary outcome was progression free survival (PFS), and the secondary outcome included objective response rate (ORR) and safety. The survival curve was drawn by Kaplan-Meier analysis and the Cox regression model were used for the multivariate analysis. Results: Among 647 patients with advanced breast cancer who received paclitaxel liposome, the first-line treatment accounted for 43.3% (280/647), the second-line treatment accounted for 27.7% (179/647), and the third-line and above treatment accounted for 29.1% (188/647). The median dose of first-line and second-line treatment was 260 mg per cycle, and 240 mg in third line and above treatment. The median period of paclitaxel liposome alone and combined chemotherapy or targeted therapy is 4 cycles and 6 cycles, respectively. In the whole group, 167 patients (25.8%) were treated with paclitaxel liposome combined with capecitabine±trastuzumab (TX±H), 123 patients (19.0%) were treated with paclitaxel liposome alone (T), and 119 patients (18.4%) were treated with paclitaxel liposome combined with platinum ± trastuzumab (TP±H), 108 patients (16.7%) were treated with paclitaxel liposome combined with trastuzumab ± pertuzumab (TH±P). The median PFS of first-line and second-line patients (5.5 and 5.5 months, respectively) were longer than that of patients treated with third line and above (4.9 months, P<0.05); The ORR of the first line, second line, third line and above patients were 46.7%, 36.8% and 28.2%, respectively. Multivariate analysis showed that event-free survival (EFS) and the number of treatment lines were independent prognostic factors for PFS. The common adverse events were myelosuppression, gastrointestinal reactions, hand foot syndrome and abnormal liver function. Conclusion: Paclitaxel liposomes is widely used and has promising efficacy in multi-subtype advanced breast cancer.
Humans ; Female ; Breast Neoplasms/chemically induced* ; Paclitaxel/adverse effects* ; Liposomes/therapeutic use* ; Retrospective Studies ; Treatment Outcome ; Trastuzumab/therapeutic use* ; Capecitabine/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects*

OBJECTIVE: To evaluate the effect of transcutaneous acupoint electrical stimulation (TEAS) at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy. METHODS: A total of 66 patients of primary lung cancer undergoing thoracoscopic lobectomy were divided to an observation group (33 cases, 1 case discontinued) and a control group (33 cases). In the observation group, TEAS at Neiguan (PC 6) was used 30 min before anesthesia induction till the end of surgery. The surgery time, maximum value of partial pressure of end-tidal carbon dioxide (P_ETCO₂) and minimum value of oxygen saturation (SpO₂) of the two groups were recorded. The dosage of propofol, sufentanil, remifentanil and dexmedetomidine were analyzed. Separately, before induction (T₀), at the start of surgery (T₁), thoracic exploration (T₂) and lobectomy (T₃), as well as 30 min (T₄) and 60 min (T₅) after lobectomy, the mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), serum cortisol (Cor) and norepinephrine (NE) were measured. The time of post anesthesia care unit (PACU) stay, ambulation, flatus, chest drainage and the incidence of nausea and vomiting were compared between the two groups. RESULTS: The maximum value of P_ETCO₂, the dosage of propofol and remifentanil in the observation group were lower than those in the control group (P < 0.05, P < 0.01), the minimum value of SpO₂ in the observation group was higher than that of the control group (P < 0.01). At T₁-T₅, the MAP, HR, serum Cor and NE levels in the observation group were all lower than those in the control group (P < 0.05). The ambulation time, the time for the flatus, chest drainage time, and the incidence of nausea and vomiting in the observation group were all lower than those in the control group (P<0.001, P < 0.01). CONCLUSION For the general anesthesia under preserving spontaneous breathing in thoracoscopic surgery, TEAS at Neiguan (PC 6) relieves stress response, reduces opioids dosage and promotes postoperative recovery.
Humans ; Acupuncture Points ; Carbon Dioxide ; Flatulence ; Propofol ; Remifentanil ; Anesthesia, General ; Nausea ; Norepinephrine ; Electric Stimulation

Objective: To examine the application value of 3D Slicer software assisted domestic frameless stereotactic robot in biopsy of intracranial lesions. Methods: A retrospective analysis was performed on 80 patients who admitted consecutively and underwent intracerebral lesions biopsy with the domestic frameless stereotactic robot at Department of Neurosurgery, Aerospace Central Hospital from January 2019 to December 2021. There were 36 males and 44 females, with a mean age of (38.5±18.0) years (range: 6 to 71 years). Before surgery only enhanced T1-weighted three-dimensional magnetization prepared gradient echo sequences and diffusion tensor imaging scans were performed. Self-reconstruction of intracranial lesions, cerebral cortex and blood vessels was carried out using 3D Slicer software system after the DICOM format imaging data of 80 patients were collected. These imaging data were merged to the workstation of the domestic frameless stereotactic robot for preoperative surgical planning and the surgical puncture path was designed to avoid blood vessels in the brain functional area, cerebral cortex and sulcus. Results: All frameless stereotactic biopsy were successfully performed. Postoperative pathological diagnosis included 50 cases of diffuse astrocytic and oligodendroglioma, 15 cases of lymphoma, 5 cases of metastatic tumors, 5 cases of inflammatory demyelinating disease, 2 cases of inflammatory granuloma, 1 case of hemangioma, 1 case of acute lymphoblastic leukemia intracranial invasion and 1 case of seminoma. The positive diagnosis rate was 100% (80/80). Postoperative imaging confirmed that the puncture path and target were accurately implemented according to the preoperative planning, and the target error was (1.32±0.44) mm (range: 0.55 to 1.99 mm). One case of puncture-related bleeding occurred at the target after surgery and improved after treatment. Conclusion: The three-dimensional multimodal images reconstructed by the 3D Slicer software before operation could help the surgeons make the preoperative planning and reduce the risk of stereotactic brain biopsy.
Male ; Female ; Humans ; Child ; Adolescent ; Young Adult ; Adult ; Middle Aged ; Aged ; Brain Neoplasms/pathology* ; Diffusion Tensor Imaging ; Retrospective Studies ; Robotics ; Biopsy ; Software ; Stereotaxic Techniques

Objectives: To examine the short-term and mid-term effects of surgical treatment of obstructive hypertrophic cardiomyopathy (HCM) in one center. Methods: The perioperative data and short-term follow-up outcomes of 421 patients with obstructive HCM who received surgical treatment at Department of Cardiac Surgery, Zhongshan Hospital, Fudan University from January 2017 to December 2021 were analyzed retrospectively. There were 207 males and 214 females, aged (56.5±11.7) years (range: 19 to 78 years). Preoperative New York Heart Association (NYHA) classification included 45 cases of class Ⅱ, 328 cases in class Ⅲ, and 48 cases in class Ⅳ. Fifty-eight patients were diagnosed with latent obstructive HCM and 257 patients had moderate or more mitral regurgitation with 56 patients suffering from intrinsic mitral valve diseases. All procedures were completed by a multidisciplinary team, including professional echocardiologists involving in preoperative planning for proper mitral valve management strategies and intraoperative monitoring. A total of 338 patients underwent septal myectomy alone, and 59 patients underwent mitral valve surgery along with myectomy. A single transaortic approach was used in 355 patients, and a right atrial-atrial septal/atrial sulcus approach was used in 51 other patients. Long-handled minimally invasive surgical instruments were used for the procedures. Student t test, Wilcoxon rank sum test, χ² test or Fisher exact test were used to compare the data before and after surgery. Results: The aortic cross-clamping time of septal myectomy alone was (34.3±8.5) minutes (range: 21 to 94 minutes). Eighteen patients had intraoperative adverse events and underwent immediate reoperation, including residual obstruction (10 patients), left ventricular free wall rupture (4 patients), ventricular septal perforation (3 patients), and aortic valve perforation (1 patient). Four patients died during hospitalization, and 11 patients developed complete atrioventricular block requiring permanent pacemaker implantation. After discharge, 384 (92.1%) patients received a follow-up visit with a median duration of 9 months. All follow-up patients survived with significantly improved NYHA classifications: 216 patients in class Ⅰ and 168 patients in class Ⅱ (χ²=662.73, P<0.01 as compared to baseline). At 6 months after surgery, follow-up echocardiography showed that the thickness of the ventricular septum ((13.6±2.5) mm vs. (18.2±3.0) mm, t=23.51, P<0.01) and the peak left ventricular outflow tract gradient ((12.0±6.3) mmHg vs. (93.4±19.8) mmHg, 1 mmHg=0.133 kPa, t=78.29, P<0.01) were both significantly lower than baseline values. Conclusion: The construction of the surgical team (including echocardiography experts), proper mitral valve management strategies, identification and management of sub-mitral-valve abnormalities, and application of long-handled minimally invasive surgical instruments are important for the successful implementation of septal myectomy with satisfactory short-and medium-term outcomes.
Male ; Female ; Humans ; Retrospective Studies ; Atrial Fibrillation ; Treatment Outcome ; Cardiomyopathy, Hypertrophic/surgery* ; Mitral Valve Insufficiency/surgery* ; Ventricular Septum

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ²=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ²=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ²=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.
Female ; Male ; Humans ; Child, Preschool ; Infant ; Child ; Critical Illness ; Pulmonary Surfactants/therapeutic use* ; Retrospective Studies ; Risk Factors ; Respiratory Distress Syndrome/therapy*

The anatomical studies of intersphincteric resection (ISR) have made remarkable progress in recent years. The anatomy of internal, external sphincter and hiatal ligament has been further understood. In this paper, the generation and functional mechanism of ISR related anatomy are described from the embryonic development process, and then the influence of hiatal ligament and internal sphincter on ISR surgery is analyzed respectively according to the anatomical characteristics. Finally, the correlation analysis of anatomical factors on the common problems of mucosal bleeding and instrument anastomosis in ISR is carried out. The objective of this paper is to improve the safety of ISR surgery by providing detailed anatomical explanations.
Humans ; Anal Canal/surgery* ; Rectal Neoplasms/surgery* ; Clinical Relevance ; Anastomosis, Surgical

Echinococcosis is a zoonotic parasitic disease caused by Echinococcus infections, and this disorder may cause fibrosis of multiple vital organs, which may further progress into cirrhosis. Early-stage hepatic fibrosis is reversible, and unraveling the mechanisms underlying hepatic fibrosis induced by Echinococcus infections is of great significance for the prevention and treatment of early-stage hepatic fibrosis. Recently, the studies pertaining to hepatic fibrosis associated with Echinococcus infections focus on cytokines and immune cells. This review summarizes the advances in the mechanisms underlying host immune cells- and cytokines-mediated hepatic fibrosis in humans or mice following Echinococcus infections.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment