Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Cerebral fat embolism (CFE) combined with pulmonary fat embolism (PFE) is an extremely rare and serious complication after fat injection. In order to improve the understanding of the mechanism of this complication, this article reported the diagnosis, treatment and pathological results of a patient with CFE and PFE after facial autologous fat injection. A 34-year-old female underwent an injection of autologous fat in her right cheek at another institution in March 2021 and developed into a coma. 1.5 hours later, she was taken to the Emergency Department of the Second Affiliated Hospital of Hainan Medical University. CT revealed a massive infarction in the right cerebral hemisphere and bilateral acute pneumonia. The patient was treated with dehydration, anti-infection, anticoagulation and microcirculation improvement in the intensive care unit. But the patient died due to the critical condition. Postmortem autopsy and histopathological examination, revealed ischemic stroke with hemorrhagic transformation, and pulmonary embolism with acute pneumonia. It was speculated that the fat embolus passed through the damaged main trunk or branch of the right facial artery, and then retrograde to the right external carotid artery, common carotid artery and internal carotid artery to cause middle cerebral artery occlusion. At the same time, the embolus returned to the right atrium along with the accompanying vein of the above artery, and reached the pulmonary vascular bed through the pulmonary circulation, resulting in pulmonary embolism. Plastic surgeons should have extensive knowledge with the anatomical structure of facial blood vessels, master the injection techniques, and improve the awareness of fat embolism when performing facial fat transplantation.

Cerebral fat embolism (CFE) combined with pulmonary fat embolism (PFE) is an extremely rare and serious complication after fat injection. In order to improve the understanding of the mechanism of this complication, this article reported the diagnosis, treatment and pathological results of a patient with CFE and PFE after facial autologous fat injection. A 34-year-old female underwent an injection of autologous fat in her right cheek at another institution in March 2021 and developed into a coma. 1.5 hours later, she was taken to the Emergency Department of the Second Affiliated Hospital of Hainan Medical University. CT revealed a massive infarction in the right cerebral hemisphere and bilateral acute pneumonia. The patient was treated with dehydration, anti-infection, anticoagulation and microcirculation improvement in the intensive care unit. But the patient died due to the critical condition. Postmortem autopsy and histopathological examination, revealed ischemic stroke with hemorrhagic transformation, and pulmonary embolism with acute pneumonia. It was speculated that the fat embolus passed through the damaged main trunk or branch of the right facial artery, and then retrograde to the right external carotid artery, common carotid artery and internal carotid artery to cause middle cerebral artery occlusion. At the same time, the embolus returned to the right atrium along with the accompanying vein of the above artery, and reached the pulmonary vascular bed through the pulmonary circulation, resulting in pulmonary embolism. Plastic surgeons should have extensive knowledge with the anatomical structure of facial blood vessels, master the injection techniques, and improve the awareness of fat embolism when performing facial fat transplantation.

Atrial Fibrillation/complications* ; Humans ; Pulmonary Disease, Chronic Obstructive/complications* ; Pulmonary Veins

Alzheimer's disease （AD） is a deleterious neurodegenerative disorder， which has become a significant public health concern and economic burden. The pathogenesis of AD is complex and involves several hypotheses such as amyloid β-protein （Aβ） deposition， Tau protein hyperphosphorylation， oxidative stress， and inflammation. There is an urgent need for a holism-based comprehensive intervention with multi-pathway， multi-level， and multi-target characteristics， which demonstrates the unique advantage of traditional Chinese medicine （TCM）. Therefore， it is of great significance to conduct and promote research on TCM treatment of AD. Danggui Shaoyaosan （DSS） from the Synopsis of Golden Chamber （《金匮要略》） by ZHANG Zhongjing （150 AD-219 AD） was originally designed for reliving gynecological ailments. It is a classic TCM formula that modulates liver and spleen and dispels blood stasis and water retention. Since the late 1980s when Japanese researchers reported its therapeutic effect on AD， it has been widely used in the clinic with clear effects. The elucidation of the mechanism of this formula helps exert its effects. Hereby， this paper reviewed relative research progress and made an analysis in terms of attenuating aberrant accumulation of Aβ and hyperphosphorylated Tau protein， anti-inflammatory and antioxidant activities， mediating neurotransmitters， ameliorating lipid metabolism， modulating gut microbiota， reduced neuron apoptosis， decreasing intracellular Ca²⁺ overloading， and increasing the expression of estradiol. This paper is expected to provide references for understanding the scientific connotation of DDS in the treatment of AD and lay a solid foundation for further investigation.

ObjectiveTo investigate the mechanism of Danggui Shaoyaosan （DSS） in the improvement of the cognitive ability of SAMP8 mice with Alzheimer's disease （AD） via regulating the ubiquitin-proteasome pathway （UPP）. MethodFifteen SAMR1 mice were used as a normal group， and 60 SAMP8 mice were randomly divided into a model group and DSS high， medium， and low-dose groups （57.6， 28.8， and 14.4 g·kg^-1·d^-1）， with 15 mice in each group. Intragastric administration was conducted for eight continuous weeks. Place navigation and spatial capacity were evaluated by Morris water maze. Pathological structure changes in neurons in the hippocampal CA1 area was detected by hematoxylin-eosin （HE） staining. The protein expression levels of hippocampal β-amyloid protein（Aβ） and phosphorylation（p）-Tau were determined by immunohistochemical staining （IHC） and enzyme-linked immunosorbent assay （ELISA）， and the mRNA and protein expression levels of hippocampal ubiquitin （Ub）， ubiquitin ligase E3 （E3）， 26S proteasome， ubiquitin carboxyl terminal hydrolase-1 （UCHL1）， and UCHL3 were determined by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultAs compared with the normal group， the escape latency was prolonged in the model group （P<0.05） with the reduced number of crossing platform quadrants and time ratio in the platform quadrant （P<0.05）. The model group decreased neurons and condensed cell bodies in the CA1 area， and increased β-amyloid precursor protein （β-APP） and p-Tau positive cells （P<0.05）. In the model group， the protein expression levels of Aβ and p-Tau were increased （P<0.05）， the mRNA and protein expression levels of Ub were increased （P<0.05）， and the mRNA and protein expression levels of E3， 26S proteasome， UCHL1， and UCHL3 were decreased （P<0.05）. As compared with the model group， the escape latency was shortened in the DSS high and medium-dose groups （P<0.05） with an increased number of crossing platform quadrants and residence time ratio （P<0.05）. The pathological changes in CA1 of each DSS group were significantly improved， and the number of β-APP positive staining cells decreased （P<0.05）. The number of p-Tau positive staining cells decreased in the DDS medium and low-dose groups （P<0.05）. The protein expression levels of Aβ and p-Tau in each DDS group decreased （P<0.05）， and the mRNA expression level of Ub in each group decreased （P <0.05）. The mRNA expression levels of 26S， E3， and UCHL3 in the DDS high and medium-dose groups increased （P<0.05）， and the mRNA expression level of UCHL1 in the DDS medium-dose group increased （P<0.05）. The protein expression level of Ub in each DDS group decreased， and the protein expression levels of 26S， E3， UCHL1+3 in the DDS high and medium-dose groups increased （P<0.05）. ConclusionDSS can improve the cognitive ability of SAMP8 mice， and its mechanism may be related to the reduction of the abnormal deposition of Aβ and p-Tau via decreasing the expression of Ub and increasing that of E3， 26S， UCHL1， and UCHL3 in the UPP.

ObjectiveTo investigate the protective effect of Danggui Shaoyaosan （DSS）-contained serum on β-amyloid （Aβ）_1-40-injured rat adrenal pheochromocytoma PC12 cells and its mechanism in regulating ubiquitin-proteasome pathway （UPP）. MethodAβ_1-40 was used to intervene PC12 cells to prepare the cell models of Alzheimer's disease （AD）， and the experiment was divided into the blank， model， and DSS-contained serum high， medium， and low-dose groups （10%， 5%， and 2.5%）. Cell viability and apoptosis were detected using cell counting kit-8 （CCK-8） method and flow cytometry， respectively. The content of Aβ and p-Tau protein was determined by enzyme-linked immunosorbent assay （ELISA）. The ubiquitin （Ub）， ubiquitin ligase E3 （E3）， 26S proteasome， ubiquitin carboxyl terminal hydrolase1 （UCHL1）， and UCHL3 protein expressions of UPP were displayed using immunofluorescence cytochemistry （ICC）， and the mRNA and protein expression levels of Ub， E3-parkin， 26S， UCHL1， and UCHL3 were determined by real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultThe data of the CCK8 experiment verified that 5 μmol·L^-1 and 48 hours were the optimal conditions for modeling Aβ_1-40-injured PC12 cells. As compared with the blank group， the cell viability rate in the model group decreased （P<0.05） with an increased apoptosis rate （P<0.05）， the content of Aβ and p-Tau contents was elevated （P<0.05）， the mRNA and protein expression levels of Ub increased， and the mRNA and protein expression levels of 26S， E3， and UCHL1+3 decreased （P<0.05）. As compared with the model group， the cell viability rate in the DSS-contained medium-dose group increased （P<0.05）， whereas the apoptosis rate in each DSS-contained group decreased （P<0.05）. The content of Aβ in each DDS-contained group decreased （P<0.05）， and the content of p-Tau in the DDS-contained high and medium-dose groups decreased （P<0.05）. The mRNA expression level of Ub decreased， and that of 26S increased in each DDS-contained group （P<0.05）. The mRNA expression level of UCHL1 in the DDS-contained medium-dose group increased （P<0.05）， and the mRNA expression levels of E3 and UCHL 3 in the DDS-contained high and medium-dose groups increased （P<0.05）. The protein expression level of Ub in each DDS-contained group decreased， and the protein expression levels of 26S， E3， and UCHL1+3 in the DDS high and medium-dose groups increased. The DSS-contained serum medium-dose group exerted the optimal effect. ConclusionDSS-contained serum can increase cell viability rate， reduce cell apoptosis rate， eliminate Aβ and p-Tau protein deposits， and exert protective effects on Aβ_1-40-injured PC12 cells. Its mechanism may involve UPP via decreasing the expression of Ub and increasing that of 26S， E3， UCHL1， and UCHL3.

Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ²=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ²=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.
China/epidemiology* ; Cities ; Drug Resistance ; Drug Resistance, Viral/genetics* ; Female ; Genotype ; HIV Infections/epidemiology* ; HIV Seropositivity/drug therapy* ; HIV-1/genetics* ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Reverse Transcriptase Inhibitors/therapeutic use* ; Sexual and Gender Minorities