1.Staged Efficacy of Qijia Rougan Prescription Combined with Entecavir for Chronic Hepatitis B-related Hepatic Fibrosis with Qi Deficiency and Collateral Stasis Syndrome Based on "Zhu Ke Jiao" Theory
Baixue LI ; Xin WANG ; Jibin LIU ; Li WEN ; Cen JIANG ; Wenjun WU ; Dong WANG ; Shuwan LIU ; Huabao LIU ; Yongli ZHENG ; Liang HUANG ; Yue SU ; Song ZHANG ; Yanan SHANG ; Hang ZHOU ; Quansheng FENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):180-188
ObjectiveThis paper aims to investigate and evaluate the staged efficacy and safety of the representative empirical prescription of the “Zhu Ke Jiao” theory, Qijia Rougan prescription, combined with entecavir in the treatment of hepatic fibrosis in chronic hepatitis B. MethodsA multicenter randomized controlled clinical study was conducted, and 101 patients diagnosed with chronic hepatitis B-related hepatic fibrosis (CHB-HF) who met the diagnosis and inclusion criteria were randomly assigned to an observation group (Qijia Rougan prescription + entecavir) and a control group (entecavir). The treatment duration was 24 weeks. Liver stiffness measurement (LSM), fibrosis-4 index (FIB-4), portal vein diameter, hepatitis B serology, biochemical indicators, hepatic fibrosis markers in serum [hyaluronic acid (HA), laminin (LN), procollagen Ⅲ peptide (PⅢP), and type Ⅳ collagen (Ⅳ-C)], and traditional Chinese medicine syndrome scores were used as efficacy evaluation indicators. Efficacy assessments and explorations of different staged subgroups of Qijia Rougan prescription were conducted according to LSM values based on the Metavir pathological staging standard. ResultsA total of 98 cases were included for statistical analysis, with 49 cases in the observation group and 49 in the control group. The general data of the patients in both groups were comparable. Compared with the same group before treatment, the observation group showed a significant reduction in LSM and FIB-4 (P<0.01), as well as notable improvements in LN, Ⅳ-C, and various TCM syndrome scores (P<0.05, P<0.01). When compared to the control group after treatment, the observation group demonstrated significant improvements in LSM, FIB-4, and various TCM syndrome score indicators (P<0.05, P<0.01), indicating that the observation group performed better than the control group. Subgroup analysis of the regression of hepatic fibrosis stages showed that compared to the same group before treatment, the observation group had better improvement in regression of stages F2 and F3 (P<0.05). When compared to the control group after treatment, the observation group exhibited superior improvement in regression of stage F3 (P<0.05). No adverse events occurred in either group during the treatment period. ConclusionCompared with entecavir alone, the combination of Qijia Rougan prescription and entecavir significantly improves the degree of hepatic fibrosis and clinical TCM symptoms in patients. The optimal intervention period is primarily during stage F3, which is a potential “interception” point of the “Zhu Ke Jiao” theory.
2.Prenatal diagnosis of 22q11.2 microduplication syndrome in a three-generation family: Clinical-genetic characteristics and literature review.
Yifan LIAO ; Yidong WEN ; Xiaoqin DENG ; Cimo WANG ; Zhirong SHANG ; Jinghong YANG ; Jiabing LI
Chinese Journal of Medical Genetics 2026;43(1):57-63
OBJECTIVE:
To explore the genetic etiology for a pregnant woman with a history of multiple adverse pregnancies and assess the phenotype-genotype correlation of 22q11.2 microduplication syndrome in her family.
METHODS:
Amniotic fluid sample was taken from a pregnant woman for whom non-invasive prenatal screening indicated chromosome 22 abnormalities in the fetus. Peripheral blood samples from the woman, her brother and parents were collected for high-throughput low-depth whole genome sequencing (CNV-seq). A pedigree traceability analysis of the results was conducted in conjunction with analysis of clinical manifestation. Relevant literature (from establishment to March 2025) was systematically searched. This study was approved by the Medical Ethics Committee of Mianyang Maternal and Child Health Care Hospital (Ethics No.: Lun Shen [2024]009).
RESULTS:
CNV-seq revealed that the fetus had harbored a 6.02 Mb duplication at 22q11.21q11.23. Karyotyping confirmed it as 46,X?dup(22)(q11.2). Pedigree verification demonstrated that the pregnant woman, her brother and mother had all carried the same duplication. Phenotypic analysis of the affected family members showed classic features of 22q11.2 microduplication syndrome, including hypernasal speech, low nasal bridge, congenital heart disease, and cognitive impairment. A total of 44 cases with full information (including three patients from this pedigree) were included in the analysis. The penetrance of 22q11.2 duplication was approximately 29.5% (13/44), and 52.3% (23/44) of the cases had inherited the variant from a phenotypically normal parent.
CONCLUSION
This study has identified the genetic basis for the woman's recurrent adverse pregnancies and phenotypic abnormalities in her family members. The scoliosis identified in her younger brother has not been previously reported, thereby may enrich the clinical phenotype of this syndrome. For fetuses identified with a 22q11.2 microduplication, detailed fetal imaging is recommended, and genetic counseling should be provided to the couples.
Humans
;
Female
;
Pregnancy
;
Prenatal Diagnosis/methods*
;
Chromosome Duplication/genetics*
;
Male
;
Pedigree
;
DiGeorge Syndrome/diagnosis*
;
Adult
;
Chromosomes, Human, Pair 22/genetics*
;
Abnormalities, Multiple
3.Stress distribution on the maxilla when wearing the Twin-block appliance for Class Ⅱ malocclusion
Shuai LI ; Hua LIU ; Yonghui SHANG ; Yicong LIU ; Qihang ZHAO ; Wen LIU
Chinese Journal of Tissue Engineering Research 2025;29(5):881-887
BACKGROUND:The Twin-block orthodontic appliance is commonly used for the correction of Class Ⅱ malocclusion.Its mechanism of action in stimulating mandibular growth has been confirmed in many studies,but its impact on maxillary growth is not very clear. OBJECTIVE:By establishing a finite element model to analyze the stress distribution of the maxillary complex,surrounding bone sutures,and maxillary dentition in patients with Class Ⅱ malocclusion wearing Twin-block orthodontic appliances. METHODS:One patient with Class Ⅱ malocclusion who underwent orthodontic treatment at Qingdao Hospital/Qingdao Municipal Hospital of Shandong Rehabilitation University was selected.The bite force data of the patient when wearing the Twin-block orthodontic appliance was measured,and CBCT data were collected.A finite element model was established,including the maxillary complex,peripheral sutures,Twin-block orthodontic appliance,and maxillary dentition.ABAQUS software was used to simulate the stress distribution in the maxilla and maxillary dentition when the patient was wearing the Twin-block appliance. RESULTS AND CONCLUSION:The equivalent stress on the maxillary anterior teeth was significantly smaller than that on the posterior teeth,and the maximum equivalent stress on both sides of the teeth were 4.797 5 Mpa and 8.716 1 Mpa,respectively,which were located at the first premolar.The maximum displacements were presented at the maxillary incisors on both sides of the teeth,which were 0.080 5 mm and 0.081 0 mm,respectively.The maximum equivalent stress on the bone suture was 1.284 Mpa,which was mainly concentrated in the pterygopalatine suture and the frontal-maxillary suture on both sides,and there was almost no difference in the force of the rest of bone sutures;the maximum displacement of the bone suture was 0.07 mm,with the pterygopalatine suture having the largest displacement,followed by the frontal-maxillary suture.The maximal equivalent stress on the maxillary complex was 27.18 Mpa,which was mainly concentrated on both sides of the anterior pyriform foramen of the maxilla,around the nasofrontal suture and around the pterygopalatine suture at the posterior part of the jaws.The maximal displacement of the maxilla was 0.07 mm,which was mainly concentrated on the maxillary alveolar bone.All these findings show that the occlusal force acts on the maxillary complex through the Twin-block appliance,resulting in clockwise rotation of the maxilla and steepening of the dentition plane.Measures should be taken to compensate for this tendency,for example,by considering maxillary molar elongation and intrusion in the process of occlusion,which are not only able to flatten the occlusal plane,but facilitate the mandibular protraction,thereby further improving Class Ⅱ malocclusion orthodontic treatment.
4.Mechanism of Ethoxysanguinarine in Regulating IRE1/RIDD Signaling Pathway to Inhibit Endoplasmic Reticulum Stress and Alleviate Cardiomyocyte Apoptosis
Zucheng SHANG ; Hongzheng LI ; Mengfan LI ; Wen SUN ; Guosheng LIN ; Aling SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):141-148
ObjectiveTo investigate the effects of ethoxysanguinarine (ETH) on angiotensin Ⅱ (Ang Ⅱ)-mediated cardiomyocyte apoptosis and its regulatory effects of inositol-requiring enzyme 1 (IRE1)/regulated IRE1-dependent decay (RIDD) signaling pathway and endoplasmic reticulum stress. MethodsWestern blot was used to detect the establishment of the H9c2 model via Ang Ⅱ stimulation, which was identified as a cardiomyocyte apoptosis model. Subsequently, the inhibitory effect of ETH on cell proliferation was assessed using the cell counting Kit-8 (CCK-8) to determine the optimal effective dose of ETH. H9c2 cardiomyocytes were divided into a blank group, a model group (Ang Ⅱ, 1 mmol·L-1), and low-, medium-, and high-dose ETH groups (1.25, 2.5, and 5 mmol·L-1). Morphological changes in cardiomyocytes induced by Ang Ⅱ were detected using phalloidin staining. Cardiomyocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) staining. The apoptosis cycle was detected by Annexin V/PI flow cytometry. Western blot was used to detect the expression levels of apoptosis-related proteins, endoplasmic reticulum stress, and IRE1/RIDD pathway-related proteins. ResultsWestern blot results showed that 1 mmol/mL Ang Ⅱ stimulation significantly increased the protein expression levels of Bip, p-IRE1, and Bid in H9c2 cells (P<0.05, P<0.01), indicating the induction of endoplasmic reticulum stress, activation of the IRE1/RIDD signaling pathway, and initiation of the apoptosis process. Compared with the blank group, the model group showed a significant increase in the surface area of H9c2 cells and the apoptosis rate of cardiomyocytes, as well as in both early and late apoptosis rates (P<0.01). The expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 proteins were significantly increased, while the expression level of Bcl-2 protein was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins were significantly increased (P<0.05, P<0.01). Compared with those in the model group, the surface area of cardiomyocytes and the apoptosis rate of cardiomyocytes in all ETH groups were significantly decreased after drug intervention. Both early and late apoptosis rates were significantly decreased. The expression level of cleaved-Caspase-8 was significantly decreased in the low-dose ETH group (P<0.05). The expression levels of Bid, Bax, and cleaved-Caspase-8 were significantly decreased in the medium-dose ETH group (P<0.05, P<0.01). The high-dose ETH group significantly reduced the expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 (P<0.05, P<0.01) and significantly increased the expression level of Bcl-2 (P<0.05). The level of p-IRE1 protein in the medium-dose ETH group was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins in the high-dose ETH group were significantly decreased (P<0.05, P<0.01). ConclusionETH can alleviate Ang Ⅱ-mediated cardiomyocyte apoptosis by inhibiting the IRE1/RIDD signaling pathway and further alleviate the cardiac injury caused by hypertension.
5.Mechanism of Naoxintong Capsules Against Ischemia-reperfusion Injury in Rats via Inhibiting Pericyte Contraction Based on RHOA/ROCK1 Pathway
Yinlian WEN ; Jinfeng SHANG ; Bohong WANG ; Wanting WEI ; Xiaolu ZHANG ; Guijinfeng HUANG ; Xin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):159-167
ObjectiveTo investigate the mechanism of Naoxintong capsules on ischemia-reperfusion (I/R) injury in rats based on the changes of pericytes mediated by Ras homolog family member A (RHOA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) pathway. MethodsNinety rats (15 rats for each group) were randomly divided into a sham operation group, a model group, a positive control group receiving Ginkgo biloba extract (21.6 mg·kg-1), and groups receiving Naoxintong capsules at low, medium, and high doses of 55, 110, and 220 mg·kg-1 (NXT-L, NXT-M, and NXT-H groups), respectively. Except for those in the sham operation group, all rats were subjected to transient middle cerebral artery occlusion (tMCAO) to establish the experiment model. Nerve function was assessed using a neurological function score. Cerebral blood flow was detected using a laser speckle contrast imager, and the cerebral infarction rate was calculated using 2,3,5-Triphenyl tetrazolium chloride (TTC) staining. Pathological changes were observed by hematoxylin-eosin (HE) staining and Nissl staining, while pericyte morphology was observed via transmission electron microscopy. Blood-brain barrier destruction was observed by Evans blue staining. Albumin and ischemia-modified albumin levels were measured using assay kits. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expression levels of RHOA, ROCK1, platelet-derived growth factor receptor β (PDGFRB), α-smooth muscle actin (α-SMA), tight junction protein (ZO-1), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). ResultsCompared with the sham operation group, the model group exhibited decreased neurological function scores, higher percentage reduction in blood flow, and increased cerebral infarction rates (P<0.01). Additionally, cortical neuronal nucleus shrinkage, edema, a decreased number of Nissl bodies, reduced pericyte area, elevated albumin content in the cortex (P<0.05), and increased ischemic modified albumin levels (P<0.01) were observed. The mRNA and protein expression levels of RHOA, ROCK1, PDGFRB, α-SMA, MMP-2, and MMP-9 were increased (P<0.01), while those of ZO-1 were decreased. Compared with the model group, all treatment groups showed improved neurological function scores, lower percentage reduction in blood flow, reduced cerebral infarction rates (P<0.01), alleviated cortical histological changes, increased number of Nissl bodies, expanded pericyte area, decreased albumin content in the cortex, and reduced ischemia-modified albumin levels (P<0.01). The mRNA and protein expression levels of RHOA, ROCK1, PDGFRB, α-SMA, MMP-2, and MMP-9 were decreased (P<0.01), while those of ZO-1 were increased. Among the treatment groups, the NXT-M group showed the most pronounced improvement in cerebral I/R injury. ConclusionNaoxintong capsules can restore cerebral blood supply, reduce microcirculation disturbance, and protect blood-brain barrier in rats with I/R injury. Its mechanism of action may be related to the inhibition of the RHOA/ROCK1 signaling pathway and reduced pericyte contraction.
6.Mechanism of Ethoxysanguinarine in Regulating IRE1/RIDD Signaling Pathway to Inhibit Endoplasmic Reticulum Stress and Alleviate Cardiomyocyte Apoptosis
Zucheng SHANG ; Hongzheng LI ; Mengfan LI ; Wen SUN ; Guosheng LIN ; Aling SHEN
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(13):141-148
ObjectiveTo investigate the effects of ethoxysanguinarine (ETH) on angiotensin Ⅱ (Ang Ⅱ)-mediated cardiomyocyte apoptosis and its regulatory effects of inositol-requiring enzyme 1 (IRE1)/regulated IRE1-dependent decay (RIDD) signaling pathway and endoplasmic reticulum stress. MethodsWestern blot was used to detect the establishment of the H9c2 model via Ang Ⅱ stimulation, which was identified as a cardiomyocyte apoptosis model. Subsequently, the inhibitory effect of ETH on cell proliferation was assessed using the cell counting Kit-8 (CCK-8) to determine the optimal effective dose of ETH. H9c2 cardiomyocytes were divided into a blank group, a model group (Ang Ⅱ, 1 mmol·L-1), and low-, medium-, and high-dose ETH groups (1.25, 2.5, and 5 mmol·L-1). Morphological changes in cardiomyocytes induced by Ang Ⅱ were detected using phalloidin staining. Cardiomyocyte apoptosis was assessed using terminal deoxynucleotidyl transferase dUTP nick and labeling (TUNEL) staining. The apoptosis cycle was detected by Annexin V/PI flow cytometry. Western blot was used to detect the expression levels of apoptosis-related proteins, endoplasmic reticulum stress, and IRE1/RIDD pathway-related proteins. ResultsWestern blot results showed that 1 mmol/mL Ang Ⅱ stimulation significantly increased the protein expression levels of Bip, p-IRE1, and Bid in H9c2 cells (P<0.05, P<0.01), indicating the induction of endoplasmic reticulum stress, activation of the IRE1/RIDD signaling pathway, and initiation of the apoptosis process. Compared with the blank group, the model group showed a significant increase in the surface area of H9c2 cells and the apoptosis rate of cardiomyocytes, as well as in both early and late apoptosis rates (P<0.01). The expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 proteins were significantly increased, while the expression level of Bcl-2 protein was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins were significantly increased (P<0.05, P<0.01). Compared with those in the model group, the surface area of cardiomyocytes and the apoptosis rate of cardiomyocytes in all ETH groups were significantly decreased after drug intervention. Both early and late apoptosis rates were significantly decreased. The expression level of cleaved-Caspase-8 was significantly decreased in the low-dose ETH group (P<0.05). The expression levels of Bid, Bax, and cleaved-Caspase-8 were significantly decreased in the medium-dose ETH group (P<0.05, P<0.01). The high-dose ETH group significantly reduced the expression levels of Bid, Bax, cleaved-Caspase-3, and cleaved-Caspase-8 (P<0.05, P<0.01) and significantly increased the expression level of Bcl-2 (P<0.05). The level of p-IRE1 protein in the medium-dose ETH group was significantly decreased (P<0.01). The expression levels of Bip, p-IRE1, and p-RIDD proteins in the high-dose ETH group were significantly decreased (P<0.05, P<0.01). ConclusionETH can alleviate Ang Ⅱ-mediated cardiomyocyte apoptosis by inhibiting the IRE1/RIDD signaling pathway and further alleviate the cardiac injury caused by hypertension.
7.Mechanism of Naoxintong Capsules Against Ischemia-reperfusion Injury in Rats via Inhibiting Pericyte Contraction Based on RHOA/ROCK1 Pathway
Yinlian WEN ; Jinfeng SHANG ; Bohong WANG ; Wanting WEI ; Xiaolu ZHANG ; Guijinfeng HUANG ; Xin LIU
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(12):159-167
ObjectiveTo investigate the mechanism of Naoxintong capsules on ischemia-reperfusion (I/R) injury in rats based on the changes of pericytes mediated by Ras homolog family member A (RHOA)/Rho-associated coiled-coil containing protein kinase 1 (ROCK1) pathway. MethodsNinety rats (15 rats for each group) were randomly divided into a sham operation group, a model group, a positive control group receiving Ginkgo biloba extract (21.6 mg·kg-1), and groups receiving Naoxintong capsules at low, medium, and high doses of 55, 110, and 220 mg·kg-1 (NXT-L, NXT-M, and NXT-H groups), respectively. Except for those in the sham operation group, all rats were subjected to transient middle cerebral artery occlusion (tMCAO) to establish the experiment model. Nerve function was assessed using a neurological function score. Cerebral blood flow was detected using a laser speckle contrast imager, and the cerebral infarction rate was calculated using 2,3,5-Triphenyl tetrazolium chloride (TTC) staining. Pathological changes were observed by hematoxylin-eosin (HE) staining and Nissl staining, while pericyte morphology was observed via transmission electron microscopy. Blood-brain barrier destruction was observed by Evans blue staining. Albumin and ischemia-modified albumin levels were measured using assay kits. Real-time fluorescence quantitative polymerase chain reaction (Real-time PCR) and Western blot were used to detect the mRNA and protein expression levels of RHOA, ROCK1, platelet-derived growth factor receptor β (PDGFRB), α-smooth muscle actin (α-SMA), tight junction protein (ZO-1), matrix metalloproteinase-2 (MMP-2), and matrix metalloproteinase-9 (MMP-9). ResultsCompared with the sham operation group, the model group exhibited decreased neurological function scores, higher percentage reduction in blood flow, and increased cerebral infarction rates (P<0.01). Additionally, cortical neuronal nucleus shrinkage, edema, a decreased number of Nissl bodies, reduced pericyte area, elevated albumin content in the cortex (P<0.05), and increased ischemic modified albumin levels (P<0.01) were observed. The mRNA and protein expression levels of RHOA, ROCK1, PDGFRB, α-SMA, MMP-2, and MMP-9 were increased (P<0.01), while those of ZO-1 were decreased. Compared with the model group, all treatment groups showed improved neurological function scores, lower percentage reduction in blood flow, reduced cerebral infarction rates (P<0.01), alleviated cortical histological changes, increased number of Nissl bodies, expanded pericyte area, decreased albumin content in the cortex, and reduced ischemia-modified albumin levels (P<0.01). The mRNA and protein expression levels of RHOA, ROCK1, PDGFRB, α-SMA, MMP-2, and MMP-9 were decreased (P<0.01), while those of ZO-1 were increased. Among the treatment groups, the NXT-M group showed the most pronounced improvement in cerebral I/R injury. ConclusionNaoxintong capsules can restore cerebral blood supply, reduce microcirculation disturbance, and protect blood-brain barrier in rats with I/R injury. Its mechanism of action may be related to the inhibition of the RHOA/ROCK1 signaling pathway and reduced pericyte contraction.
8.Trends in Metabolically Unhealthy Obesity by Age, Sex, Race/Ethnicity, and Income among United States Adults, 1999 to 2018
Wen ZENG ; Weijiao ZHOU ; Junlan PU ; Juan LI ; Xiao HU ; Yuanrong YAO ; Shaomei SHANG
Diabetes & Metabolism Journal 2025;49(3):475-484
Background:
This study aimed to estimate temporal trends in metabolically unhealthy obesity (MUO) among United States (US) adults by age, sex, race/ethnicity, and income from 1999 to 2018.
Methods:
We included 17,230 non-pregnant adults from a nationally representative cross-sectional study, the National Health and Nutrition Examination Survey (NHANES). MUO was defined as body mass index ≥30 kg/m2 with any metabolic disorders in blood pressure, blood glucose, and blood lipids. The age-adjusted percentage of MUO was calculated, and linear regression models estimated trends in MUO.
Results:
The weighted mean age of adults was 47.28 years; 51.02% were male, 74.64% were non-Hispanic White. The age-adjusted percentage of MUO continuously increased in adults across all subgroups during 1999–2018, although with different magnitudes (all P<0.05 for linear trend). Adults aged 45 to 64 years consistently had higher percentages of MUO from 1999–2000 (34.25%; 95% confidence interval [CI], 25.85% to 42.66%) to 2017–2018 (42.03%; 95% CI, 35.09% to 48.97%) than the other two age subgroups (P<0.05 for group differences). The age-adjusted percentage of MUO was the highest among non-Hispanic Blacks while the lowest among non-Hispanic Whites in most cycles. Adults with high-income levels generally had lower MUO percentages from 1999–2000 (22.63%; 95% CI, 17.00% to 28.26%) to 2017–2018 (32.36%; 95% CI, 23.87% to 40.85%) compared with the other two subgroups.
Conclusion
This study detected a continuous linear increasing trend in MUO among US adults from 1999 to 2018. The persistence of disparities by age, race/ethnicity, and income is a cause for concern. This calls for implementing evidence-based, structural, and effective MUO prevention programs.
9.Frequent association of malignant effusions in plasmablastic lymphoma:a single‑institutional experience of nine cases in Taiwan
Bo‑Jung CHEN ; Yu‑Ting KUO ; Sheng‑Tsung CHANG ; Khin‑Than WIN ; Shang‑Wen CHEN ; Sheng‑Yen HSIAO ; Yin‑Hsun FENG ; Yen‑Chuan HSIEH ; Shih‑Sung CHUANG
Blood Research 2025;60():22-
Purpose:
Plasmablastic lymphoma (PBL) is a rare, aggressive lymphoma that is characterized by terminal B-cell differ‑ entiation. In the West, PBL usually occurs in patients with immunodeficiencies, particularly those induced by human immunodeficiency virus (HIV) infection. We investigated the clinicopathological features of PBL at a single institute in Taiwan, where HIV infection is rare.
Methods:
This retrospective chart review identified PBL cases that were treated at a single institute in southern Tai‑ wan between 2008 and 2024.
Results:
We identified nine patients (four males and five females; median age 71 years). Of the eight patients tested for HIV, only one tested positive. Pathologically, the tumors showed plasmablastic morphology and immunopheno‑ type, and three (33%) cases tested positive for Epstein–Barr virus. Six (67%) patients presented with Stage IV disease, including five (56%) with malignant effusion. Six patients were treated with chemotherapy and the remaining three received only supportive care. During a median follow-up of 10 months, five patients died of progressive disease, two died of unrelated diseases, and two were alive with PBL relapse.
Conclusion
In Taiwan, PBL constitutes a rare and aggressive clinical condition and is frequently associated with malignant effusion. In contrast to Western patients, the PBL in most patients from Taiwan was unrelated to HIV infection.
10.Eccentric treadmill exercise promotes adaptive hypertrophy of gastrocnemius in rats.
Zhi-Qiang DAI ; Yu KE ; Yan ZHAO ; Ying YANG ; Hui-Wen WU ; Hua-Yu SHANG ; Zhi XIA
Acta Physiologica Sinica 2025;77(3):449-464
The present study aimed to investigate the effects of eccentric treadmill exercise on adaptive hypertrophy of skeletal muscle in rats. Thirty-two 3-month-old Sprague Dawley (SD) rats were selected and randomly assigned to one of the four groups based on their body weights: 2-week quiet control group (2C), 2-week downhill running exercise group (2E), 4-week quiet control group (4C), and 4-week downhill running exercise group (4E). The downhill running protocol for rats in the exercise groups involved slope of -16°, running speed of 16 m/min, training duration of 90 min, and 5 training sessions per week. Twenty-four hours after the final session of training, all the four groups of rats underwent an exhaustion treadmill exercise. After resting for 48 h, all the rats were euthanized and their gastrocnemius muscles were harvested for analysis. HE staining was used to measure the cross-sectional area (CSA) and diameter of muscle fibers. Transmission electron microscope was used to observe the ultrastructural changes in muscle fibers. Purithromycin surface labeling translation method was used to measure protein synthesis rate. Immunofluorescence double labeling was used to detect the colocalization levels of lysosomal-associated membrane protein 2 (Lamp2)-leucyl-tRNA synthetase (LARS) and Lamp2-mammalian target of rapamycin (mTOR). Western blot was used to measure the protein expression levels of myosin heavy chain (MHC) IIb and LARS, as well as the phosphorylation levels of mTOR, p70 ribosomal protein S6 kinase (p70S6K), and eukaryotic translation initiation factor 4E binding protein 1 (4E-BP1). The results showed that, compared with the 2C group rats, the 2E group rats showed significant increases in wet weight of gastrocnemius muscle, wet weight/body weight ratio, running distance, running time, pre- and post-exercise blood lactate levels, myofibrillar protein content, colocalization levels of Lamp2-LARS and Lamp2-mTOR, and LARS protein expression. Besides these above changes, compared with the 4C group, the 4E group further exhibited significantly increased fiber CSA, fiber diameter, protein synthesis rate, and phosphorylation levels of mTOR, p70S6K, and 4E-BP1. Compared with the quiet control groups, the exercise groups exhibited ultrastructural damage of rat gastrocnemius muscle, which was more pronounced in the 4E group. These findings suggest that eccentric treadmill exercise may promote mTOR translocation to lysosomal membrane, activating mTOR signaling via up-regulating LARS expression. This, in turn, increases protein synthesis rate through the mTOR-p70S6K-4E-BP1 signaling pathway, promoting protein deposition and inducing adaptive skeletal muscle hypertrophy. Although the ultrastructural changes of skeletal muscle are more pronounced, the relatively long training cycles during short-term exercise periods have a more significant effect on promoting gastrocnemius muscle protein synthesis and adaptive hypertrophy.
Animals
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Rats, Sprague-Dawley
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Physical Conditioning, Animal/physiology*
;
Rats
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Muscle, Skeletal/metabolism*
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TOR Serine-Threonine Kinases/metabolism*
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Male
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Hypertrophy
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Adaptation, Physiological/physiology*
;
Adaptor Proteins, Signal Transducing/metabolism*
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Ribosomal Protein S6 Kinases, 70-kDa/metabolism*
;
Intracellular Signaling Peptides and Proteins

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