Tacrolimus-Induced Hepatic Vein Occlusive Disease After Deceased Donor Liver Transplantation: A Case Report.

Advancements in surgical techniques and the optimization of immunosuppression have boosted organ transplant survival rates; however, liver transplant recipients still risk complications such as hepatic vein occlusive disease (HVOD), also called sinusoidal obstruction syndrome. Rare but potentially fatal HVOD damages endothelial cells due to factors like chemotherapy, stem cell transplantation, and certain medications such as azathioprine and tacrolimus. Typically, HVOD presents with distinct clinical symptoms, including ascites, jaundice, and significant weight gain. Herein, we present the case of a 66-year-old male with decompensated liver cirrhosis due to hepatitis C virus infection. The patient underwent a deceased donor liver transplantation at our center. Unfortunately, 4 months after the transplant, he experienced progressive dyspnea and developed right pleural effusion. Abdominal computed tomography and a liver biopsy confirmed the diagnosis of HVOD, likely induced by tacrolimus. After stopping tacrolimus, we observed a significant decrease in ascites and remission of the patient's clinical symptoms of abdominal distention and dyspnea; subsequently, we introduced cyclosporine. In this report, we describe this specific patient's case and discuss HVOD, including its diagnosis and management.

Combination of bone marrow mesenchymal stem cells and moxibustion restores cyclophosphamide-induced premature ovarian insufficiency by improving mitochondrial function and regulating mitophagy.

BACKGROUND: Premature ovarian insufficiency (POI) is a major cause of infertility. In this study, we aimed to investigate the effects of the combination of bone marrow mesenchymal stem cells (BMSCs) and moxibustion (BMSCs-MOX) on POI and evaluate the underlying mechanisms. METHODS: A POI rat model was established by injecting different doses of cyclophosphamide (Cy). The modeling of POI and the effects of the treatments were assessed by evaluating estrous cycle, serum hormone levels, ovarian weight, ovarian index, and ovarian histopathological analysis. The effects of moxibustion on BMSCs migration were evaluated by tracking DiR-labeled BMSCs and analyzing the expression of chemokines stromal cell-derived factor 1 (Sdf1) and chemokine receptor type 4 (Cxcr4). Mitochondrial function and mitophagy were assessed by measuring the levels of reactive oxygen species (ROS), mitochondrial membrane potential (MMP), ATP, and the mitophagy markers (Drp1, Pink1, and Parkin). Furthermore, the mitophagy inhibitor Mdivi-1 and the mitophagy activator CCCP were used to confirm the role of mitophagy in Cy-induced ovarian injury and the underlying mechanism of combination therapy. RESULTS: A suitable rat model of POI was established using Cy injection. Compared to moxibustion or BMSCs transplantation alone, BMSCs-MOX showed improved outcomes, such as reduced estrous cycle disorders, improved ovarian weight and index, normalized serum hormone levels, increased ovarian reserve, and reduced follicle atresia. Moxibustion enhanced Sdf1 and Cxcr4 expression, promoting BMSCs migration. BMSCs-MOX reduced ROS levels; upregulated MMP and ATP levels in ovarian granulosa cells (GCs); and downregulated Drp1, Pink1, and Parkin expression in ovarian tissues. Mdivi-1 significantly mitigated mitochondrial dysfunction in ovarian GCs and improved ovarian function. CCCP inhibited the ability of BMSCs-MOX treatment to regulate mitophagy and ameliorate Cy-induced ovarian injury. CONCLUSIONS: Moxibustion enhanced the migration and homing of BMSCs following transplantation and improves their ability to repair ovarian damage. The combination of BMSCs and moxibustion effectively reduced the excessive activation of mitophagy, which helped prevent mitochondrial damage, ultimately improving ovarian function. These findings provide a novel approach for the treatment of pathological ovarian aging and offer new insights into enhancing the efficacy of stem cell therapy for POI patients.

20 potentially new compounds and 11 new bioactive constituents found in Smilacis Glabrae Rhizoma utilizing HPLC-DAD-ESI-IT-TOF-MSn.

INTRODUCTION: Smilacis Glabrae Rhizoma (SGR) is rich in chemical constituents with a variety of pharmacological activities. However, in-depth research has yet to be conducted on the chemical and pharmacodynamic constituents of SGR. MATERIALS AND METHODS: In this study, the chemical constituents of SGR were analyzed using liquid chromatography-mass spectrometry, and the pharmacodynamic compounds responsible for the medicinal effects of SGR were elucidated through a literature review. RESULTS: In total, 20 potentially new compounds, including 16 flavonoids (C19, C20, and C27-C40) and four phenylpropanoids (C107, C112, C113, and C118), together with 161 known ones were identified in the ethanol extract of SGR using liquid chromatography-mass spectrometry, and 25 of them were unequivocally identified by comparison with reference compounds. Moreover, 17 known constituents of them were identified in the plants of genus Smilax for the first time, and 16 were identified in the plant Smilax glabra Roxb. for the first time. Of 161 known compounds, 84 constituents (including isomers) have been reported to have 17 types of pharmacological activities, covering all known pharmacological activities of SGR; among these 84 bioactive constituents, six were found in the plants of genus Smilax for the first time and five were found in S. glabra for the first time, which are new bioactive constituents found in the plants of genus Smilax and the plant S. glabra, respectively. CONCLUSION: The results provide further information on the chemical composition of SGR, laying the foundation for the elucidation of the pharmacodynamic substances of SGR.

Using extracorporeal membrane oxygenation in donations after cardiac death or brain death: A single-center experience and long-term outcome.

Aims: The use of extended criteria donors is a routine practice that sometimes involves extracorporeal membrane oxygenation (ECMO) in donations after cardiac death or brain death. Methods: We performed a retrospective study in a single center from January 2006 to December 2019. The study included 90 deceased donor liver transplants. The patients were divided into three groups: the donation after brain death (DBD) group (n = 58, 64.4%), the DBD with ECMO group (n = 11, 12.2%) and the donation after cardiac death (DCD) with ECMO group (n = 21, 23.3%). Results: There were no significant differences between the DBD with ECMO group and the DBD group. When comparing the DCD with ECMO group and the DBD group, there were statistically significant differences for total warm ischemia time (p < 0.001), total cold ischemia time (p = 0.023), and split liver transplantation (p < 0.001), and there was significantly poor recovery in regard to total bilirubin level (p = 0.027) for the DCD with ECMO group by repeated measures ANOVA. The 5-year survival rates of the DBD, DBD with ECMO, and DCD with ECMO groups were 78.1%, 90.9%, and 75.6%, respectively. The survival rate was not significantly different when comparing the DBD group to either the DBD with ECMO group (p = 0.435) or the DCD with ECMO group (p = 0.310). Conclusions: Using ECMO in donations after cardiac death or brain death is a good technology, and it contributed to 35.6% of the liver graft pool.

Blast injuries with contrasting outcomes treated by military surgery strategies: A case report.

The treatment strategy for blast injuries is closely linked to the clinical outcome of blast injury casualties. However, the application of military surgery experience to blast injuries caused by production safety accidents is relatively uncommon. In this study, the authors present 2 cases of blast injuries caused by one gas explosion, both cases involved individuals of the same age and gender and experienced similar degree of injury. The authors highlight the importance of using a military surgery treatment strategy, specifically emphasizing the need to understand the concept of damage control and disposal. It is recommended that relevant training in this area should be strengthened to improve the clinical treatment of such injuries. This study provides a valuable reference for healthcare professionals dealing with blast injuries.

Racial and ethnic disparities in untreated patients with hepatitis C virus-related hepatocellular carcinoma but not in those with sustained virologic response.

BACKGROUND: Racial and ethnic disparities exist for hepatitis C virus (HCV) treatment and hepatocellular carcinoma (HCC) survival. AIM: To evaluate the impact of HCV treatment on such disparities. METHODS: In a retrospective cohort study, we analysed 6069 patients with HCV-related HCC (54.2% Asian, 30.1% White, 8.5% Black, and 7.3% Hispanic) from centres in the United States and Asia. RESULTS: The mean age was 61, 60, 59 and 68, respectively, for White, Black, Hispanic and Asian patients. Black patients were most likely to have Barcelona Clinic Liver Cancer stage D, vascular invasion and distant metastasis (23% vs. 5%-15%, 20% vs. 10%-17% and 10% vs. 5%-7%, respectively; all p < 0.0001). Treatment rate with direct-acting antiviral agents (DAA) was 35.9% for Asian, 34.9% for White, 30.3% for Hispanic (30.3%), and 18.7% for Black patients (p < 0.0001). Among those untreated or without sustained virologic response (SVR), 10-year survival rates were 35.4, 27.5, 19.3 and 14.0, respectively, for Asian, Hispanic, White and Black patients (p < 0.0001). There were no statistically significant differences among those with SVR (p = 0.44). On multivariable analysis adjusted for relevant confounders, there was no statistically significant association between survival and being Hispanic (aHR: 0.68, p = 0.26) or Black (aHR: 1.18, p = 0.60) versus White. There was a significant association between being Asian American and survival (aHR: 0.24, p = 0.001; non-U.S. Asian: aHR: 0.66, p = 0.05), and for SVR (aHR: 0.30, p < 0.0001). CONCLUSION: DAA treatment rates were suboptimal. Racial and ethnic disparities resolved with HCV cure. Early diagnosis and improved access to HCV treatment is needed for all patients with HCV infection.

The role of Roux-en-Y hepaticojejunostomy for the management of biliary complications after living donor liver transplantation.

INTRODUCTION: Post living donor liver transplantation (LDLT) biliary complications can be troublesome over the post-operative course of patients, especially those with recurrent cholangitis or choledocholithiasis. Thus, in this study, we aimed to evaluate the risks and benefits of Roux-en-Y hepaticojejunostomy (RYHJ) performed after LDLT as a last option to deal with post-LDLT biliary complications. METHODS: Retrospectively, of the 594 adult LDLTs performed in a single medical center in Changhua, Taiwan from July 2005 to September 2021, 22 patients underwent post-LDLT RYHJ. Indications for RYHJ included choledocholithiasis formation with bile duct stricture, previous intervention failure, and other factors. Restenosis was defined if further intervention was needed to treat biliary complications after RYHJ was performed. Thereafter, patients were categorized into success group (n = 15) and restenosis group (n = 4). RESULTS: The overall success rate of RYHJ in the management of post-LDLT biliary complications was 78.9% (15/19). Mean follow-up time was 33.4 months. As per our findings, four patients experienced recurrence after RYHJ (21.2%), and mean recurrence time was 12.5 months. Three cases were recorded as hospital mortality (13.6%). Outcome and risk analysis presented no significant differences between the two groups. A higher risk of recurrence tended to be related to patients with ABO incompatible (ABOi). CONCLUSION: RYHJ served well as either a rescue but definite procedure for recurrent biliary complications or a safe and effective solution to biliary complications after LDLT. A higher risk of recurrence tended to be related to patients with ABOi; however, further research would be needed.

[Protective effect of moxibustion preconditioning in rats with premature ovarian insufficiency].

OBJECTIVE: To observe the effects of moxibustion preconditioning on ovarian function, fertility and ovarian granulosa cell apoptosis in rats with premature ovarian insufficiency (POI), so as to investigate its underlying mechanism in improving POI. METHODS: Forty-two female SD rats with two complete estrous cycles were randomly divided into control group, model group and pre-moxibustion group, with 14 rats in each group. The pre-moxibustion group was pretreated with mild moxibustion for 14 days before POI model establishment at 1) "Guanyuan" (CV4) and "Zhongwan" (CV12) and 2) bilateral "Shenshu" (BL23) as two sets of acupoints on alternate days, once each day, for 10 min each acupoint. After 14-day mild moxibustion intervention, 75 mg·kg-1·d-1 tripterygium glycoside tablet suspension was administered to rats in the pre-moxibustion group and the model group by gavage, for 14 consecutive days, while equivalent saline was given to rats in the control group in the same way. After modeling, the effect of moxibustion preconditioning on ovarian reserve function was evaluated by the estrous cycles, pregnancy rate and embryo number, morphological changes of ovaries, and serum sex hormone levels. TUNEL staining was used to detect the rate of granulosa cell apoptosis in ovaries. Immunohistochemistry and real time quantitative PCR were used to detect the relative expression of Caspase-3 and Caspase-9 proteins and mRNA levels in ovaries. RESULTS: Compared with the control group, the estrous cycles were disturbed; the pregnancy rate and number of embryos, the wet weight of ovary and ovarian index, the number of total follicles and different level of follicles, serum Estradiol (E2) and anti-mullerian hormone (AMH) levels were all significantly decreased (P<0.01,P<0.05), while the number of atretic follicles, serum follicule-stimulating hormone (FSH) and luteinizing hormone (LH) levels, the number of TUNEL-positive granulosa cells, the expression of ovarian Caspase-3 and Caspase-9 proteins and mRNAs were significantly increased (P<0.01) in the model group. Compared with the model group, the disordered estrous cycles were improved; the pregnancy rate, the embryo numbers, the wet weight of ovary, and the total follicle number and primary follicle number, serum AMH level were significantly increased (P<0.01，P<0.05), while the number of atretic follicles, serum FSH level, the number of TUNEL-positive granulosa cells, expression of ovarian Caspase-3 and Caspase-9 proteins and mRNAs were all significantly decreased (P<0.01,P<0.05) in the moxibustion group. CONCLUSION: Moxibustion preconditioning could improve ovarian function and improve fertility of POI rats, which may be associated with reducing the apoptosis of ovarian granulosa cells.

Proteasomal inhibitors induce myeloma cell pyroptosis via the BAX/GSDME pathway.

Proteasomes are overexpressed in multiple myeloma (MM) and proteasomal inhibitors (PIs) have been widely used for the treatment of MM. PIs are reported to induce MM cell apoptosis but impair necroptosis. In the present study, we found that PIs MG132 and bortezomib induce MM cell pyroptosis, a novel type of cell death, in a GSDME-dependent manner. Lack of GSDME totally blocks PI-induced pyroptosis. Interestingly, we found that Caspase-3/6/7/9 are all involved in pyroptosis triggered by PIs because the specific inhibitor of each caspase ablates GSDME activation. PIs markedly reduce mitochondrial membrane potential. Moreover, PIs disrupt the interaction of Bcl-2 and BAX, induce cytochrome c release from mitochondria to cytosol and activate GSDME. Furthermore, we found that overexpression of an N-terminal portion of GSDME suffices to release cytochrome c from mitochondria and to activate Caspase-3/9, suggesting N-GSDME might penetrate the mitochondrial membrane. Consistent with Bcl-2 inhibition, BAX can induce MM cell pyroptosis in a GSDME-dependent manner. In accordance with these findings, inhibition of Bcl-2 synergizes with PIs to induce MM cell pyroptosis. Therefore, the present study indicates that PIs trigger MM cell pyroptosis via the mitochondrial BAX/GSDME pathway and provides a rationale for combined treatment of MM with Bcl-2 and proteasome inhibitors to increase therapeutic efficiency via induction of pyroptosis.

Deep vein thrombosis after open hepatectomy or other major upper abdominal surgery in Taiwan: A prospective and cross-sectional study relevant to the issue of pharmacological thromboprophylaxis.

BACKGROUD/PURPOSE: Venous thromboembolism, including deep vein thrombosis (DVT) and pulmonary embolism (PE), is an important complication in patients who underwent open hepatic surgery as well as other major upper abdominal surgery. This study aims to investigate the occurrence of postoperative DVT without pharmacological thromboprophylaxis in such cohorts in Taiwan. METHODS: This is a prospective, cross-sectional cohort study conducted from March 2010 to December 2011. Patients who underwent major upper abdominal surgery, including open hepatectomy, were enrolled. Color duplex compression ultrasonography (CUS) was used to detect DVT. Symptomatic PE was excluded if there were no suggestive respiratory symptoms or sudden death. Relevant clinicopathological and surgical information of each patient was collected and analyzed. RESULTS: 195 patients (118 male and 77 female) were enrolled, with a median age of 63.6 years. The majority (169/195, 88.7%) were treated for active malignancy. Totally 147 patients received open hepatectomy. Only one asymptomatic and distal postoperative DVT event was identified by CUS, which occurred on a 73-year-old female patient who received a left lateral segmental hepatectomy for removing the advanced hepatocellular carcinoma (pathologic stage, T3aN0M0). No cases of symptomatic PE or sudden death were observed. No correlation between DVT and precipitating factor was demonstrated in our cohort. CONCLUSION: Without pharmacological thromboprophylaxis, a low rate of postoperative DVT among patients undergoing open hepatectomy (0.7%, 1/147) or major upper abdominal surgery (0.5%, 1/195) in Taiwan was reported. A distinctively regional role of pharmacological thromboprophylaxis for hepatic surgery was also suggested by our data.

Using 3D Microscope for Hepatic Artery Reconstruction in Living Donor Liver Transplant.

INTRODUCTION: This study compares the intraoperative process of hepatic artery anastomosis using conventional microscope and novel 3D digital microscope and discusses our technique and operative set-up. METHOD: A retrospective comparative cohort study with 46 hepatic artery reconstructions in living donor liver transplant patients. Either an operational microscope (control group) or a 3D digital microscope Mitaka Kestrel View II (study group) was used for hepatic artery anastomosis. We then discuss and share our institution's experience of improving surgical training. RESULTS: Both operation instruments provide effective and comparable results. There was no statistical difference regarding operational objective results between conventional microscope and exoscope. Both instruments have no hepatic artery size limit, and both resulted in complete vessel patency rate. CONCLUSIONS: There was no statistical differences regarding hepatic artery anastomosis between microscope and exoscope cohorts. Microsurgeons should perform hepatic artery anastomosis efficiently with the instruments they are most proficient with. Yet, exoscope provided better ergonomics in the operation room and lessened musculoskeletal strain, allowing surgeons to work in a more neutral and comfortable posture while allowing the first assistant to learn and assist more effectively. Using exoscope with micro-forceps and modified tie technique make artery reconstruction easier.

Effects of acupuncture treatment on microRNAs expression in ovarian tissues from Tripterygium glycoside-induced diminished ovarian reserve rats.

Acupuncture is widely used to improve ovarian function. Previously, we demonstrated that acupuncture can improve oxidative stress in rats with tripterygium glycoside tablet suspension (TG)-induced diminished ovarian reserve (DOR). Herein, we aimed to explore the antioxidation mechanism of acupuncture for ameliorating the ovarian reserve in DOR rats. We performed microRNA sequencing and bioinformatics analysis to screen differentially expressed miRNAs (DE miRNAs) in ovarian tissues. In total, 1,172 miRNAs were identified by miRNA sequencing, of which 28 DE miRNAs were detected (including 14 upregulated and 14 downregulated) in ovarian tissues from the acupuncture group when compared with the DOR model rats. Based on functional enrichment analysis, the target genes of DE miRNAs were significantly enriched in GO-biological process (BP) terms associated with biological processes, positive regulation of transcription by RNA polymerase II, signal transduction, regulation of transcription, DNA-templated processes, and oxidation-reduction processes. In the Kyoto Encyclopedia of Genes and Genomes analysis, the main pathways were the MAPK signaling pathway, hepatitis B, proteoglycans in cancer, human cytomegalovirus infection, and the Ras signaling pathway. Finally, reverse transcription-quantitative PCR results confirmed that rno-miR-92b-3p, mdo-miR-26b-5p_R+1_1ss10TC, and bta-miR-7857-3p_R-1 were downregulated in the acupuncture group. The results revealed the impact of acupuncture on miRNA profiling of ovarian tissues from DOR rats, suggesting that rno-miR-92b-3p, mdo-miR-26b-5p_R+1_1ss10TC, and bta-miR-7857-3p_R-1 might provide relevant cues to relieve DOR-mediated oxidative stress.

Risk-adapted stereotactic body radiotherapy for patients with cervical spinal metastases.

Owing to the complex anatomical structure and biomechanics, the current standard palliative treatments for cervical spinal metastases are associated with a high risk of recurrence and complications. Stereotactic body radiotherapy (SBRT) can provide radical dose to tumors while protecting normal organs to the maximum extent. However, the efficacy and safety of SBRT for cervical spinal metastases is not well characterized. Data from 71 patients with cervical spine metastases who were treated with SBRT using CyberKnife between 2006 and 2021 were obtained from our prospectively maintained database. Primary endpoint was pain response at 12 weeks following SBRT completion; secondary endpoints included local control (LC), overall survival (OS), and adverse events. Standard-risk patients were planned to receive 30 Gy (range 21-36) with median fractions of 3 (range 1-3) and high-risk patients 35 Gy (range 24-50) with median fractions of 5 (range 4-5) according to the spinal cord and esophagus dose constraints. The median follow-up time was 17.07 months (range 3.1-118.9). After 12 weeks of SBRT completion, 54 (98.2%) of 55 patients with baseline pain achieved pain response and 46 (83.6%) achieved complete pain response. LC rates were 93.1% and 90% at 1 year and 2 year, respectively. The 1-year and 2-year OS rates were 66.2% and 37.4%, respectively. Eight patients experienced grades 1-4 adverse events (six vertebral compression fracture [VCF], five of them had VCF before SBRT; and two hemiparesis). No grade 5 adverse events were observed. Therefore, risk-adapted SBRT for cervical spine metastases achieved high pain control and LC rates with acceptable adverse events.

Length of Alcohol Abstinence Predicts Posttransplant Delirium in Living Donor Liver Transplant Recipients with Alcoholic Cirrhosis.

OBJECTIVES: History of alcohol abuse is a predictive factor for posttransplant delirium. We aimed to investigate whether preoperative abstinence was associated with posttransplant delirium in liver transplant recipients with alcohol-related cirrhosis. MATERIALS AND METHODS: From January 2014 to December 2019, 84 patients with alcohol-related cirrhosis who received living donor liver transplant were retrospectively reviewed and divided into a delirium group (n = 46, 54.8%) and a nondelirium group (n = 38, 45.2%) using the Richmond Agitation- Sedation Scale and the Confusion Assessment Method for the Intensive Care Unit. RESULTS: In the delirium group versus the nondelirium group, patients were more likely to have preoperative hepatic encephalopathy (58.7% vs 31.6%; P = .013), more likely to have higher Model for End-Stage Liver Disease scores (27.05 ± 10.56 vs 18.85 ± 7.96; P < .001), less likely to have preoperative alcohol abstinence (43.5% vs 68.4%%; P = .022), had longer duration of mechanical ventilation (7.57 ± 7.82 vs 2.50 ± 5.96 days; P = .001), and had longer stays in the intensive care unit (14.85 ± 15.01 vs 8.84 ± 7.84 days; P = .021) and in the hospital (37.89 ± 18.85 vs 27.15 ± 10.43 days; P = .002). Multivariate analysis revealed that preoperative alcohol abstinence (odds ratio 4.953; 95% CI, 1.519-16.152; P = .008) was a significant predictor and that more patients had abstinence durations <3 months (60.9% vs 34.2%; P = .048) in the delirium group. CONCLUSIONS: A high incidence of posttransplant delirium in liver transplant recipients with alcohol- related cirrhosis was associated with preoperative abstinence. Abstinence >6 months before living donor liver transplant is suggested to reduce the risk of posttransplant delirium.

Artery Reconstruction in Right Lobe Living Donor Liver Transplantation: Donor-Recipient Vessel Ratio Is Key to Choosing Recipient Artery.

BACKGROUND: The aims of this study were to investigate if recipient artery choice in right lobe living donor liver transplant affects postoperative complications and discuss solutions accordingly. METHODS: Three hundred fourteen right lobe living donor liver transplantation patients were divided into 2 groups: 163 patients using right hepatic artery as the recipient vessel and 151 patients using left hepatic artery as the recipient vessel. Cases involving 2 recipient blood vessels or the use of other blood vessels as recipient vessels were excluded. RESULTS: Overall vascular embolism rate in both groups was 1.3%, and our complication rate was lower than those in previous studies. There was no significant difference in complication rate between the groups, but a significant difference in recipient/donor artery size ratio was noted. CONCLUSIONS: Although left hepatic artery's anatomical position makes it less affected by bile duct anastomosis and thus fewer postoperative complications, we believe that the ratio of the donor-recipient blood vessel size and the length of the anastomosis vessel stumps are the key factors that affect the outcome of the vascular anastomosis.

Elucidation of the Mechanisms and Effective Substances of Paeoniae Radix Rubra Against Toxic Heat and Blood Stasis Syndrome With a Stage-Oriented Strategy.

In the clinical practice of traditional Chinese medicine, toxic heat and blood stasis syndrome (THBSS) is a common syndrome observed in various critical diseases. Paeoniae Radix Rubra (PRR) has known therapeutic effects on THBSS. However, its pharmacodynamic mechanisms and effective substances in the treatment of THBSS still need further elucidation. Our previous study indicated that THBSS had three stages of progression, and the abnormal biochemical indices of each stage were different. Therefore, this study aimed to elucidate the pharmacodynamic mechanisms and effective substances of PRR for the treatment of THBSS with a stage-oriented strategy. Specifically, research was performed separately in two stable stages of THBSS: the excessive heat and little blood stasis (EHLBS) and blood stasis (BS) stages. THBSS model rats, at different time periods after syndrome initiation (first 5 h for EHLBS and 24 h later for BS), were used to conduct the two-stage investigation. Targeted metabonomics analysis was performed to elucidate the pharmacodynamic mechanisms of PRR in the treatment of EHLBS or BS. Based on the relationship between the individual differences in blood drug concentrations and pharmacodynamic effects, partial least squares regression analysis was employed to screen for the effective substances from the original constituents and metabolites of PRR. We found that PRR could upregulate primary bile acid biosynthesis, glycerophospholipid metabolism, ether lipid metabolism, and five amino acid metabolic pathways (e.g., arginine and proline metabolism) to treat EHLBS. Meanwhile, PRR alleviated BS by upregulating primary bile acid biosynthesis and downregulating glycerophospholipid metabolism. But PRR had no obvious effects on ether lipid metabolism and amino acid metabolism in this stage. In total, 17 and 9 potential effective substances were found in the EHLBS and BS stages, respectively, among which there were only five common compounds between the two stages. To our knowledge, sixteen compounds were regarded as potential effective substances of PRR for the first time. Therefore, the pharmacodynamic mechanisms and effective substances of PRR in the treatment of EHLBS and BS were partly different. Overall, this stage-oriented strategy provides a new way to study the pharmacodynamic mechanisms and effective substances of traditional Chinese drugs.

Ion-based high-order harmonic generation from water window to keV region with a transverse disruptive pulse for quasi-phase-matching.

A scheme for ion-based high-harmonic generation from water window to keV x-ray is investigated. He1+ ions with 54.42-eV ionization potential extend the harmonic cutoff energy to 1 keV. The transverse selective-zoning method of quasi-phase-matching is utilized to overcome the severe plasma dispersion in a highly ionized medium. The calculated conversion efficiency reaches about 15% of the perfect phase-matching condition. Wavelength tunability is achieved by incorporating a programmable spatial-light modulator to control the quasi-phase-matching pattern.

Using the Cystic Duct for Biliary Reconstruction in Dual-Graft Living Donor Liver Transplantation: A Case Report.

In Taiwan, living donor liver transplant (LDLT) has accounted for the majority of liver transplantation due to organ shortage. Dual-graft LDLT is a feasible way to resolve the insufficient graft size and remnant liver in donors. We presented a heavy-weight patient underwent dual-graft LDLT, and cystic duct was used to resolve the inadequate bile duct length and limited appropriate position in dual-graft LDLT. We harvested a right lobe graft (segment 5, 6, 7, and 8 without middle hepatic vein) and a left lobe graft (segment 1, 2, 3, and 4 without middle hepatic vein) stepwise, and placed the grafts orthotopically. For proper tension and length of biliary reconstruction, we anastomosed the right intrahepatic duct of the right lobe graft to cystic duct of the recipient. Before the biliary reconstruction, the metal probe was inserted in the lumen of cystic duct in recipient to ensure the patency and destroy the Heister valve of cystic duct, then the internal biliary stent (5 Fr pediatric feeding tube) was placed in the donor's right intrahepatic duct to recipient's cystic duct and common bile duct, which allows the endoscopic removal of the internal stent. The patient has survived more than 16 months with normal liver function.

[Clinical effect of cortical incision with rapid maxillary expansion to assist orthodontic-orthognathic treatment of skeletal Class â ¢ malocclusion].

PURPOSE: To investigate the clinical effect of rapid maxillary expansion with cortical osteotomy combined with orthodontic- orthognathic treatment for skeletal Class Ⅲ malocclusion. METHODS: A total of 84 patients with skeletal Class Ⅲ malocclusion admitted to Jining Dental Hospital from March 2018 to May 2020 were randomly divided into experimental group and control group, with 42 cases in each group. The control group was treated with orthodontic-orthognathic treatment, while the experimental group was treated with orthodontic-orthognathic treatment with rapid maxillary arch expansion by cortical incision. The time of closing gap, alignment time, maxillary first molar and maxillary central incisor tooth movement distance in the sagittal direction were compared between the two groups. Before treatment and 4 weeks after treatment, the vertical distance from the end of the upper central incisor edge to the horizontal plane(U1I-HP), the distance from the apex of the upper central incisor to the coronal plane(U1I-CP), the vertical distance from the edge of the upper pressure groove to the coronal plane(Sd-CP), the vertical distance from the upper alveolar seat point to the horizontal plane(A-HP), the vertical distance from the point of the upper lip to the coronal plane(Ls-CP), and the vertical distance from the inferior point of nose to coronal plane(Sn-CP) were measured, and the relevant changes were calculated. During the treatment period, the complications of the two groups were compared. SPSS 20.0 software package was used for statistical analysis of the data. RESULTS: There was no significant difference in alignment time, A-HP change, Sn-CP change, maxillary first molar movement distance and maxillary central incisor movement distance between the two groups (P＞0.05). The closing interval in the experimental group was significantly shorter than that of the control group (P＜0.05). The changes of U1I-HP, U1I-CP, Sd-CP, and Ls-CP in the experimental group were significantly higher than those in the control group (P＜0.05). There was no significant difference in the incidence of complications between the two groups during treatment (P＞0.05). CONCLUSIONS: Rapid maxillary expansion of cortical incision assisted orthodontic-orthognathic treatment of skeletal Class Ⅲ malocclusion patients can shorten the closing gap time and improve the treatment effect, which has no obvious influence on the sagittal direction of the teeth.