Recurrent spontaneous pneumothorax secondary to lung cystic lesions in a case of convalescent COVID-19: a case report and literature review.

BACKGROUND: While spontaneous pneumothorax has been documented in COVID-19 patients, reports on recurrent spontaneous pneumothorax due to cystic lesions in convalescent COVID-19 patients are scarce. The progression of these lung cystic lesions remains inadequately explored. CASE PRESENTATION AND LITERATURE REVIEW: An 81-year-old male, a non-smoker with a history of rheumatoid arthritis, presented with fever, cough, and expectoration for 14 days. Initially diagnosed with moderate COVID-19, he deteriorated to severe COVID-19 despite adherence to local treatment guidelines. Successive identification of three cystic lesions termed "bulla" or "pneumatocele", and one cystic lesion with air-fluid level, referred to as "pneumo-hamatocele" (PHC), occurred in his lungs. Gradual improvement followed anti-inflammatory therapy and optimal supportive care. However, on day 42, sudden worsening dyspnea prompted a computed tomography (CT) scan, confirming a right spontaneous pneumothorax and subcutaneous emphysema, likely due to PHC rupture. Discharge followed chest tube implementation for pneumothorax resolution. On day 116, he returned to the hospital with mild exertional dyspnea. Chest CT revealed recurrent right pneumothorax from a remaining cyst in the right lung. Apart from our patient, literature retrieval identified 22 COVID-19 patients with spontaneous pneumothorax due to cystic lesions, with a male predominance (95.6%; 22/23). Diagnosis of pneumothorax and lung cystic lesions occurred around day 29.5 (range: 18-35) and day 26.4 (± 9.8) since symptom onset, respectively. Except for one patient whose pneumothorax occurred on day seven of illness, all patients eventually recovered. CONCLUSIONS: Recurrent spontaneous pneumothorax secondary to lung cystic lesions may manifest in convalescent COVID-19 patients, particularly males with COVID-19 pneumonia. Chest CT around 2 to 3 weeks post-symptom onset may be prudent to detect cystic lesion development and anticipate spontaneous pneumothorax.

Clinical features, diagnosis, and management of pembrolizumab-induced myasthenia gravis.

Myasthenia gravis (MG) is a rare but life-threatening adverse event with pembrolizumab. What is known about pembrolizumab-induced MG is largely based on case reports. This analysis collected pembrolizumab-induced MG cases from Chinese and English databases published from September 1, 2014, to June 30, 2022. Demographic and clinical information of the patients, management, and outcome data were collected and analyzed. Sixty-five patients with a median age of 73 years (range 30-86), including 43 male patients (66.2%), were included. Eight patients (12.3%) with prior MG experienced worsening symptoms after receiving pembrolizumab. The median time to the onset of MG was four weeks (range 0.7-27). The most common symptoms were ptosis (81.5%, 53 patients), diplopia (50.8%, 33 patients), dyspnea (44.6%, 29 patients), trunk or peripheral weakness (43.1%, 28 patients), and dysphagia (30.8%, 20 patients). Concurrent myositis and myocarditis occurred in 13 (20.0%) and 17 patients (26.2%). Pembrolizumab was discontinued in 63 patients (96.9%). Forty-four patients (67.7%) received combination therapies based on steroids (intravenous immune globulin, plasmapheresis, or immunosuppressants). Twenty-seven patients (41.5%) had symptoms completely recovered. Fourteen patients (21.5%) died from immunotoxicity or primary cancers. Clinicians should consider the possibility of pembrolizumab-induced MG, especially during the first eight weeks of therapy. Patients should be treated as early as possible, regardless of the severity of the initial symptoms.

Clinical characteristics, treatment, and management of pembrolizumab induced hemophagocytic lymphohistiocytosis.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal adverse reaction to pembrolizumab. The clinical characteristics of pembrolizumab induced HLH are unknown. Exploring the clinical features of pembrolizumab induced HLH is crucial for the treatment and prevention of immune checkpoint inhibitor-induced HLH. METHODS: The literature related to pembrolizumab induced HLH was collected for retrospective analysis by searching the Chinese and English databases from inception until August 31, 2023. RESULTS: A total of 24 patients were included, including 17 men (70.8%) with a median age of 61 years (41,80). The time between the last infusion and the start of HLH ranged from 2 to 46 days, with a median time of 14 days. Fever (100%) was the most common symptom, accompanied by splenomegaly (14 cases, 58.3%) and hepatomegaly (6 cases, 25.0%). Laboratory examination revealed revealed anemia (18 cases, 75.0%), leukopenia (12 cases, 50.0%), thrombocytopenia (20 cases, 83.3%), hypertriglyceridemia (11 cases, 45.8%), hypofibrinogenemia (11 cases, 45.8%). decreased natural killer cell function (7 cases, 29.2%), and elevated soluble CD25(15 cases, 62.5%). All patients developed hyperferriinemia, with a median of 30,808 ng/mL (range 1303 ~ 100,000). Bone marrow biopsy showed hemophagocytosis (15 cases, 62.5%). After discontinuation of pembrolizumab and treatment with steroids, etoposide, intravenous immunoglobulin, cytokine blocking, and immunosuppression, 17 patients recovered or improved, and 5 patients eventually died. CONCLUSION: HLH should be suspected when unexplained fever, cytopenia, splenomegaly, and elevated aminotransferase occur in patients using pembrolizumab. Screening for risk factors before treatment with pembrolizumab may be necessary to prevent HLH.

Clinical characterization, treatment, and outcome of nivolumab-induced bullous pemphigoid.

BACKGROUND: Bullous pemphigoid (BP) is a serious and rare complication of nivolumab. This study aimed to explore the clinical characteristics of nivolumab-induced BP and provide a reference for prevention and treatment of BP. METHODS: Literature on nivolumab-induced BP was collected for retrospective analysis by searching both Chinese and English databases as of July 31, 2023. RESULTS: Sixty patients were included, with a median age of 71 years (range 30 to 85 years), and they were predominantly male (78.3%). The median time to onset of BP was 31 weeks (range 2.4, 216) after nivolumab administration. Tense bullae (93.3%), pruritus (55.0%), and urticarial plaques (31.7%) were the most common manifestations. Lesions were found on the limbs (50.0%), trunk (38.3%), palms and soles (15.0%). Skin biopsies mainly showed subepidermal bullous/blister (50.0%) and eosinophilic infiltration (46.7%). Direct immunofluorescence showed mainly linear deposition of C3 and IgG (46.7%) at the dermal-epidermal junction. The patients stopped taking nivolumab and received systemic steroids (73.3%), topical steroids (63.3%), monoclonal antibodies (21.7%), doxycycline/minocycline (30.0%) and other treatments. Symptoms improved or were relieved in 88.4% of patients but did not improve in 8.3% of patients. CONCLUSION: Clinicians should closely monitor symptoms of BP in those receiving and discontinuing nivolumab, especially in older men. Early diagnosis and timely initiation of treatment may improve patient outcomes.

Clinical features, diagnosis, and management of dasatinib-induced nephrotic syndrome.

Knowledge of dasatinib-induced nephrotic syndrome is largely based on case reports. The clinical features of dasatinib-induced nephrotic syndrome are unknown. We collected case reports of 25 patients with nephrotic syndrome and analyzed their clinical characteristics. Overall, the onset of nephrotic syndrome ranged from 10 days to 5 years after dasatinib administration. Nine patients (36.0%) had clinical symptoms, mainly periorbital edema and lower-extremity edema. Serum albumin ranged from 1.2 g/dL to 3.7 g/dL in 10 patients (38.5%). The 24-h urine protein values ranged from 3.54 g/day to 118 g/day. Kidney biopsy of 13 patients (52.0%) mainly showed focal foot process effacement, mesangial hyperplasia, endothelial cell damage and focal segmental glomerulosclerosis. Proteinuria resolved or recovered after dasatinib discontinuation or dose reduction or switching to other tyrosine kinase inhibitors (TKIs).

Spectrum of voriconazole-associated periostitis in clinical characteristics, diagnosis and management.

PURPOSE: Previous knowledge about the relationship between voriconazole exposure and periostitis was mainly based on limited case reports and few retrospective studies. The purpose of this study was to assess the clinical characteristics, diagnosis and management of voriconazole-associated periostitis. METHODS: Case reports and case series from 1998 to November 30, 2021 on periostitis induced by voriconazole were collected for retrospective analysis. RESULTS: Forty four patients (18 male and 26 female) from 34 studies were included in total. The median age was 58 years (29-74). The majority of patients had undergone organ transplantation (50.0%) or suffered from hematologic malignancy (31.81%). The median onset time of symptoms was 6 months after the start of voriconazole. The most common initial symptom was diffuse skeletal pain (68.28%) which can be severe and even disabling (66.7%). Ribs (37.21%), femurs (32.56%), scapulae (25.58%), humerus (23.26%), and clavicle (23.26%) were the common involved locations. Most cases were accompanied by different degrees of elevated serum alkaline phosphatase and fluoride level, while some presented with elevated bone-specific alkaline phosphatase. The main radiological features included periosteal reaction and multifocal high radiotracer uptake on bone scintigraphy. The formation of new bone was characterized with bilateral, irregular, nodular, as well as high density. The resolution of symptoms was observed with discontinuation of voriconazole in all patients, of whom 18 patients (52.94%) were relieved within a week. Itraconazole, posaconazole or isavuconazole were safe alternatives to voriconazole in voriconazole-induced periostitis. CONCLUSION: Voriconazole-induced periostitis is an infrequent complication characterized by bone inflammation involving one or multiple skeletal areas. Bony pain, elevated serum alkaline phosphatase as well as fluoride level are suspicious signs during voriconazole treatment.

Analysis of clinical characteristics of Kounis syndrome induced by contrast media.

BACKGROUND: Understanding the relationship between contrast agents and Kounis syndrome (KS) is mainly based on case reports. The purpose of this research is to explore the clinical characteristics of contrast media induced KS. METHODS: We searched for contrast-induced KS case reports through Chinese and English databases from 1991 to October 31, 2021. RESULTS: A total of 26 patients (19 men and 7 women,) were included, with a median age of 60 years (range 30-83). The contrast agents that cause KS mainly included gadolinium-based contrast agent (7 cases), iodine-containing contrast media (12 cases). KS mainly occurred within 30 min after administration and mainly manifests as chest pain and allergic reactions. Electrocardiogram (ECG) mainly showed ST elevation. Echocardiography mainly revealed normal. Coronary angiography showed normal, coronary vasospasm, stent thrombosis, occlusion and stenosis. After treatment with steroids, antihistamines and anti-ischemic therapy, 24 patients recovered completely and 2 patients died. CONCLUSIONS: KS is a rare adverse reaction of contrast media. Radiologists should recognize this rare but serious disease to ensure rapid diagnosis and proper management.

Analysis of the Clinical Characteristics of Hyponatremia Induced by Trimethoprim/Sulfamethoxazole.

BACKGROUND: Trimethoprim-sulfamethoxazole (TMP/SMX) causes hyperkalemia, and hyponatremia caused by TMP/SMX is a challenge for clinicians. We described the clinical features of hyponatremia induced by TMP/SMX after collecting cases. SUMMARY: The median age of the 24 patients (10 males and 14 females) was 67 years (range: 28-90 years). Hyponatremia induced by TMP/SMX manifested as nausea (41.7%) and vomiting (29.2%) or asymptomatic hyponatremia (20.8%). The median duration of hyponatremia was 5 days (range: 3-10 days). The median serum sodium concentration was 118 mmol/L (range: 101-128.1 mmol/L). The serum sodium levels gradually returned to the normal range at 4 days (median; range: 2-14 days) after withdrawing TMP/SMX. KEY MESSAGES: TMP/SMX-induced hyponatremia is a rare and serious adverse reaction. Clinicians should be aware of electrolyte disturbances caused by TMP/SMX and should always consider electrolyte monitoring.

Analysis of the clinical characteristics of lamotrigine-induced haemophagocytic lymphohistiocytosis.

WHAT IS KNOWN AND OBJECTIVE: Lamotrigine is currently known to be related to haemophagocytic lymphohistiocytosis (HLH). Knowledge regarding the association between HLH and lamotrigine is mainly based on case reports. The purpose of this study was to evaluate the clinical characteristics of lamotrigine-induced HLH. METHODS: We collected literature from 1994 to 31 August 2020 in Chinese and English on HLH induced by lamotrigine for retrospective analysis. RESULTS AND DISCUSSION: A total of 17 patients (12 men and 5 women) from 15 studies were included, with a median age of 29 years old (range 4-47). Symptoms of lamotrigine-induced HLH were reported to have occurred within 6-24 days following treatment initiation. Six cases reported doses that ranged from 25 mg every other day to 800 mg once daily. The major clinical features of lamotrigine-induced HLH are fever, cytopenia, rash and hyperferritinaemia. Bone marrow showed haemophagocytosis. Fifteen patients improved with drug discontinuation, and 2 patients eventually died. WHAT IS NEW AND CONCLUSION: Hemophagocytic lymphohistiocytosis is a potentially serious adverse reaction to lamotrigine (LTG). Patients should be informed that if they experience any symptoms of HLH while taking lamotrigine, they should immediately seek medical attention.

Analysis of clinical features of tacrolimus-induced optic neuropathy.

WHAT IS KNOWN AND OBJECTIVE: Tacrolimus is associated with optic neuropathy. The clinical features of tacrolimus-induced optic neuropathy (TION) are unclear. The purpose of this article is to explore the clinical features of TION. METHODS: TION-related case reports were collected and analysed by searching Chinese and English databases from 1989 to 31 December 2021. RESULTS AND DISCUSSION: Twelve males and 7 females were included, with a median age of 54 years (range 23-66). TION onset time ranged from 2 months to 16 years after administration, and the main clinical features were blurred vision (4 cases), decreased visual acuity (7 cases), decreased visual acuity (5 cases), grey films (3 cases), visual field damage (3 cases) and headache (2 cases). Fifteen patients developed bilateral optic neuropathy. Ophthalmological examination showed visual acuity ranging from 20/25 to blindness, pupillary examination revealed relative afferent pupillary defect in 9 patients and marked decrease in colour vision in 15 eyes. The optic disc showed pallor (10 cases), oedema (8 cases), atrophy (4 cases) and haemorrhage (2 cases). After discontinuation or dose reduction of tacrolimus, symptoms improved in 10 patients, 1 patient recovered completely, and 4 patients did not recover. WHAT IS NEW AND CONCLUSION: TION presents diverse clinical manifestations. TION should be promptly identified and treated to prevent severe and permanent vision loss.

Retrospective analysis of skin photosensitivity induced by pirfenidone.

WHAT IS KNOWN AND OBJECTIVE: Knowledge regarding the association between photosensitivity and pirfenidone is based mainly on case reports. The purpose of this article was to evaluate the clinical characteristics of photosensitivity associated with pirfenidone. METHODS: We collected studies on photosensitivity induced by pirfenidone published from 2008 to 31 August 2021 in Chinese and English for a retrospective analysis. RESULTS AND DISCUSSION: The median age was 70 years (range 57-80) in 22 patients with pirfenidone-induced photosensitivity. The dose at the onset of symptoms ranged from 600 to 2403 mg for the treatment of idiopathic pulmonary fibrosis. Pirfenidone-induced photosensitivity occurred within 1 week in some patients and up to 8 months in others. The most common clinical manifestation of photosensitivity caused by pirfenidone was itching on body parts exposed to sunlight (back of hands, face, neck, and limbs) in 15 patients followed by erythema in 13 patients. Histopathological examination revealed necrotic keratinocytes, lymphocytic inflammatory cell infiltrate, hyperkeratosis and liquefaction degeneration in 5 patients. The photosensitivity test showed a markedly decreased minimum erythema dose (MED) of 7-228 mJ/cm2 UV-B in 4 patients and 4.86-12 J/cm2 UV-A in 5 patients. The clinical symptoms were significantly improved or completely relieved with a median time of 4 weeks (range 1-8) after drug withdrawal, dose reduction or systemic and topical glucocorticoid therapy. WHAT IS NEW AND CONCLUSION: Clinicians should be aware of the potential phototoxic effects of pirfenidone and should inform patients to take pirfenidone during (or after) a meal, avoid sun exposure, wear protective clothing, and apply broad-spectrum sunscreen with high ultraviolet UVA and UVB protection.

Clinical features, diagnosis and management of cephalosporin-induced acute generalized exanthematous pustulosis.

WHAT IS KNOWN AND OBJECTIVE: Acute generalized exanthematous pustulosis (AGEP) is a serious and rare adverse reaction of cephalosporins. We aimed to describe the clinical features of cephalosporin-induced AGEP and provide a reference for rational clinical use of cephalosporins. METHODS: We systematically searched Chinese and English databases for cephalosporin-induced TGEP-related case reports, retrospective studies, clinical studies, and review articles published before May 2022. RESULTS AND DISCUSSION: A total of 43 patients from 35 articles were eligible, of which 28 (65.1%) were female, with a median age of 69 years. A total of 11 cephalosporins were suspected, the most commonly involved were ceftriaxone (41.9%), cephalexin (16.3%), and cefepime (9.3%). AEGP erupted primarily within 14 days after administration, manifested as nonfollicular pustules on an erythematous base, distributed favourably to the extremities (44.2%), trunk (23.3%), face (23.3%), and could involve the oral mucosa (11.6%). During AGEP resolution, the affected area had desquamation (39.5%). The acute phase of the disease may be accompanied by fever (>38.0°C) and elevated neutrophil count (>7500/mm3 ). Histology of AGEP showed subcorneal pustules (56.3%), intraepidermal cavernous pustules (37.5%), with papillary dermal edema (37.5%), containing neutrophils and eosinophilic infiltration (71.9%). After drug discontinuation, the median time to resolution of AGEP symptoms was 10 days (range 2, 90). WHAT IS NEW AND CONCLUSION: Cephalosporin-induced AGEP is rare and should be properly diagnosed. This serious cutaneous adverse reaction is self-limiting and has a favourable prognosis, usually resolves with drug interruption, and may require additional interventions, such as topical steroids.

Effect of miRNA-200b on the proliferation of liver cancer cells via targeting SMYD2/p53 signaling pathway. / MiR-200b通过靶向调控SMYD2/p53信号通路抑制肝癌细胞增殖（英文）.

OBJECTIVES: Our previous study has verified that high level of SET and MYND domain-containing protein 2 (SMYD2) plays an important role in acquiring aggressive ability for liver cancer cells in hepatocellular carcinoma. MiR-200b as a tumor suppressor gene involves in a variety of cancers. This study aims to investigate the correlation between miR-200b and SMYD2 in hepatocellular carcinoma and the underlying mechanism. METHODS: Firstly, the levels of SMYD2 and miR-200b in hepatocellular carcinoma tissues and matched adjacent non-tumor liver tissues were tested with real-time reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Secondly, we evaluated the interaction between miR-200b and SMYD2 using dual-luciferase reporter assay. Thirdly, we elucidated the effect of miR-200b on SMYD2 and its downstream targets p53/CyclinE1. Finally, we silenced SMYD2 in hepatocellular carcinoma cell lines to investigate its effect on tumor proliferation and cell cycle progression, and further confirmed the correlation among SMYD2 and p53/CyclinE1. RESULTS: Compared with the matched adjacent non-tumor liver tissues, miR-200b was obviously decreased, and SMYD2 was significantly increased in hepatocellular carcinoma (both P<0.05). Spearman's rank correlation revealed that miR-200b expression was negatively correlated with SMYD2 (P<0.01). Computer algorithm and dual-luciferase reporter assay revealed that miR-200b directly targeted and suppressed SMYD2 in HEK 293T cells. The down-regulated miR-200b expression promoted hepatoma cell proliferation (P<0.05) and increased SMYD2 expression(P<0.01), while the up-regulated expression of miR-200b had an opposite effect. The knockdown of SMYD2 suppressed the proliferation of MHCC-97L cells (P<0.01), down-regulated CyclinE1, and up-regulated p53 expression (both P<0.05). CONCLUSIONS: MiR-200b is involved in hepatocellular carcinoma progression via targeting SMYD2 and regulating SMYD2/p53/CyclinE1 signaling pathway and may be used as a potential target for hepatocellular carcinoma treatment.

Analysis of the clinical characteristics of insulin autoimmune syndrome induced by alpha-lipoic acid.

WHAT IS KNOWN AND OBJECTIVE: Alpha-lipoic acid (ALA) is widely used as a dietary supplement and antiageing agent. Insulin autoimmune syndrome (IAS) is the most serious adverse reaction reported with the use of ALA. The purpose of this study was to explore the clinical characteristics of ALA-induced IAS and provide a scientific reference for clinical diagnosis, treatment and prevention. METHODS: We collected literature on IAS cases induced by ALA for retrospective analysis in Chinese and English. RESULTS AND DISCUSSION: The median age of 37 patients (28 females and 9 males) was 61 years (range 32-82). The symptoms occurred at night and in the early morning (60.7%), in the late postprandial period (50.0%) or after fasting (35.7%), within hours in some patients and up to 2 months in others after stopping ALA or during medication treatment. Autonomic nervous system symptoms (81.1%) and neurological hypoglycaemia (64.9%) are the main clinical manifestations of hypoglycaemia. The blood glucose concentration at the onset of hypoglycaemia was 2.19 mmol/L (median, range 1.09-3.52), the insulin concentration was ≥100 µIU/ml (94.6%), and the C-peptide concentration was ≤20 ng/ml (83.3%). Testing for IgG insulin autoantibodies (IAAs) was positive in 37 patients. Pancreatic imaging was unremarkable on computed tomography (CT), magnetic resonance imaging (MRI) and abdominal sonography. Hypoglycaemia disappeared within 5 days to 8 months after withdrawing ALA alone or using corticosteroid treatment. IAA turned negative in 7 months (median; range 2-36). Follow-up showed no recurrent hypoglycaemic episodes at 7.25 months (median; range 1-36). WHAT IS NEW AND CONCLUSION: ALA-induced IAS is a clinically rare autoimmune disease with hypoglycaemia that occurs during medication treatment or after drug withdrawal that should be treated promptly.

Analysis of the clinical characteristics of acute arthritis induced by clopidogrel.

WHAT IS KNOWN AND OBJECTIVE: Knowledge regarding the association between clopidogrel exposure and acute arthritis is based mainly on case reports. The purpose of this article was to assess the clinical characteristics of clopidogrel-induced acute arthritis. METHODS: We collected literature from 1998 to 2020 in Chinese and English on acute arthritis induced by clopidogrel for retrospective analysis. RESULTS AND DISCUSSION: The median age of 21 patients (6 females and 15 males) was 63 years (range 34-77). The median time of symptom onset was 10 days (range 0.21-21) overall. The median onset time of symptoms of clopidogrel-induced arthritis was 14 days (range 3-21) and 3 days (range 0.21-7) in patients with and without a loading dose of clopidogrel, respectively. Arthralgias (100%), joint swelling (61.9%), fever (57.1%), rash (33.3%) and pruritus (28.6%) were the most common accompanying symptoms. Most cases were accompanied by different degrees of acute inflammation markers: the median ESR was 68 mm/h (range 10-120), and the median CRP was 142.4 mg/L (range 2.3-408). X-ray films were unremarkable. Symptoms disappeared completely in all patients at a median time of 4 days (range 0.17-30) after the discontinuation of clopidogrel. Prasugrel, ticagrelor and ticlopidine can be used as safe alternatives to clopidogrel in patients with clopidogrel-induced acute arthritis with no recurrence of arthritis. WHAT IS NEW AND CONCLUSION: Clopidogrel-induced arthritis is a rare adverse reaction and should be suspected in patients with arthralgia and fever during clopidogrel use.

[Study on tanshinones regulating root-associated microbiomes of Salvia miltiorrhiza].

The plant root-associated microbiomes include root microbiome and rhizosphere microbiome, which are closely related to plant life activities. Nearly 30% of photosynthesis products of plants are used to synthesize root compounds, there is evidence that root compounds regulate and significantly affect the root microbiome Tanshinones are the main hydrophobic components in Salvia miltiorrhiza. In order to study whether these compounds can regulate the root-associated microbiomes of S. miltiorrhiza, our study first identified a white root S. miltiorrhiza(BG) which contains little tanshinones. Retain of the fifth intron of tanshinones synthesis key enzyme gene SmCPS1 leading to the early termination of the SmCPS1 gene, and a stable white root phenotype. Further, wild type(WT) and BG were planted in greenhouse with nutrient soil(Pindstrup, Denmark) and Shandong soil(collected from the S. miltiorrhiza base in Weifang, Shandong), then high-throughput sequencing was used to analyze the root-associated microbiomes. The results showed that the tanshinones significantly affected the root-associated microbiomes of S. miltiorrhiza, and the impact on root microbiomes was more significant. There are significant differences between WT and BG root microbiomes in species richness, dominant strains and co-occurrence network. Tanshinones have a certain repelling effect on Bacilli which belongs to Gram-positive, while specifically attract some Gram-negative bacteria such as Betaproteobacteria and some specific genus of Alphaproteobacteria. This study determined the important role of tanshinones in regulating the structure of root-associated microbiomes from multiple angles, and shed a light for further improving the quality and yield of S. miltiorrhiza through microenvironment regulation.

[Effect of lamivudine and silymarin on liver fibrosis-relevant factors in HBV transgenic mice with alcohol drinking].

OBJECTIVE: To observe the role of lamividine and silymarin preventing and curing liver fibrosis-relevant factors induced by alcohol drinking in hepatitis B virus (HBV) transgenic mice (Tg mice).
 Methods: Forty HBV-Tg BALB/C mice with 1.3 copy were randomly divided into 4 groups: a control group, a model group, a lamivudine group and a silymarin group. Tg mice in control group were treated with normal saline via intragastric administration; Tg-mice in the model group were treated with 50% alcohol (5 mL/kg) once a day via intragastric administration; while Tg-mice in lamivudine group and silymarin group were treated with alcohol (5 mL/kg) plus laminvudine (100 mg/kg) and silymarin (200 mg/kg) once a day via intragastric administration respectively. All groups were raised for 10 weeks. The levels of HBV-DNA copy number, ALT, AST in serum, the degree of inflammation, the degree of fibrosis, the mRNA expression levels of TGF-ß1, Smad3, Smad7 and connective tissue growth factor (CTGF), and the protein expression levels of TGF-ß1, CTGF and α-SMA in liver tissue were detected. All the images were scanned with electronic computer and the data were analyzed with SPSS13.0 software.
 Results: Compared with the control group, liver injury were significantly aggravated, while HBV-DNA copies, mRNA levels of TGF-ß1, Smad3, Smad7 and CTGF as well as the protein levels of TGF-ß1, CTGF and α-SMA were significantly increased (P<0.05). Compared with the model group, liver injury were significantly attenuated in silymarine group and lamivudine group, while mRNA levels of TGF-ß1, Smad3 and CTGF as well as the protein levels of TGF-ß1, CTGF and α-SMA were significantly decreased; mRNA level of Smad7 was further increased (P<0.05); the levels of ALT and AST in serum were decreased in the silymarine group (P<0.05).
 Conclusion: Lamivudine and silymarin relieve the histological damage in the liver of alcohol-fed Tg mice. The mechanisms for the beneficial effects of lamivudine or silymarin might be related to inhibiting the expression of TGF-ß1, Smad3 and CTGF, modulating the expression of Smads and suppressing the activation of HSC.

Transforming growth factor-ß1 regulates the telomerase reverse transcriptase in rat hepatic stellate cells.

OBJECTIVE: To determine the effect of transforming growth factor-ß1 (TGF-ß1) on the expression of telomerase in hepatic stellate cells (HSCs) in rats and the role of TGF-ß1 in the development of liver fibrosis. METHODS: Primary HSCs were isolated from normal rats by density gradient separation and divided into 2 groups for culturing. The morphology of HSCs was identified by the inverted fluorescence microscope. The purity of HSCs was identified by immunohistological expression and fluorescence analysis. One group of HSCs was treated with different concentrations (0, 0.1, 1, and 10 ng/mL) of TGF-ß1 for 24 h, while the other group was treated with 1 ng/mL TGF-ß1 and cultured for 3, 6, and 9 days. The mRNA expression of telomerase reverse transcriptase (TERT) was assessed and compared by polymerase chain reaction. RESULTS: Cell morphology showed that TGF-ß1 triggered the differentiation of HSCs from a quiescent phenotype into highly activated myofibroblasts. TERT mRNA expression in the primary HSCs showed slight increase with the culture time, though with no statistical difference between the results at various time points (P>0.05). TGF-ß1 at 0.1 ng/mL did not significantly affect the TERT mRNA level compared with the 0 ng/mL group, while 1 ng/mL and 10 ng/mL TGF-ß1 significantly decreased the level of TERT mRNA (P<0.05). TGF-ß1 at 1 ng/mL had only weak effect on TERT mRNA expression after the 3 day treatment compared with the 0 ng/mL group (P>0.05). TGF-ß1 at 1 ng/mL significantly inhibited TERT mRNA expression 6 days after the treatment (P<0.05). TGF-ß1 inhibited the expression of TERT mRNA level in the HSCs in both dose- and time-dependent manner. CONCLUSION: TGF-ß1 may contribute to the transdifferentiation of HSCs by reducing TERT levels to develop hepatic fibrosis.

[Effect of notoginseng radix on expression quantity of TGF-beta1/ Smads and CTGF mRNA in rats with alcoholic liver disease].

OBJECTIVE: To evaluate the effect of Notoginseng Radix on hepatic expression of transforming growth factor beta1 (TGF-beta1) and connective tissue growth factor (CTGF) in rats with alcoholic liver disease (ALD), in order to discuss its protective effect on alcoholic cirrhosis. METHOD: Fifty SD male rats were divided into the normal control group, the model group, the high-dose and low-dose Notoginseng Radix groups (3.0, 12.0 g x kg(-1)) and the magnesium isoglycyrrhizinate group (24 mg x kg(-1)), with 10 rats in each group. Apart from the control group, other groups were administered with ethanol-cornoil-pyrazole for 14 weeks to establish the alcoholic liver disease model. During the establishment of the model, the high-dose and low-dose Notoginseng Radix groups were administered with 12 g x kg(-1) x d(-1) Notoginseng Radix for 14 weeks, once everyday. Efforts were made to detect liver function, pathology with Masson staining, and the expressions of TGF-beta1, Smad3, Smad7 and CTGF mRNA. RESULT: Compared with the rats in model group, rats in Notoginseng Radix groups showed significant reduction in liver ALT, AST, collagen fiber deposition, and TGF-beta1, Smad3 and CTGF mRNA expressions in liver tissues, with the increase in the expression quantity of Smad7 mRNA. There were differences between the Notoginseng Radix groups. No significant difference was observed between the high-dose Notoginseng Radix group and the magnesium isoglycyrrhizinate group. CONCLUSION: Notoginseng Radix can affect TGF-beta1/Smads signaling pathway and reduce the expression of CTGF.

Peginterferon alpha versus other antiviral regimes for Chinese HBeAg-positive chronic hepatitis B patients.

OBJECTIVE: To conduct a meta-analysis to determine the efficacy of peginterferon alpha (PEG-IFN α) therapy versus IFN α, adefovir dipivoxil (ADV) and entecavir (ETV) for HBeAg-positive chronic hepatitis B patients in China. METHODS: MEDLINE database and 3 main Chinese biomedical databases between 1966 and 2012 was retrieved. Two reviewers independently screened all reports to identify randomized controlled trials that evaluated PEG-IFN α therapy for the treatment of chronic hepatitis B in China. RESULTS: Fourteen trials met the eligibility criteria for this Meta analysis. PEG-IFN α therapy was more effective than IFN α therapy in achieving ALT normalization, serum HBV DNA clearance, HBeAg seroconversion, serum HBeAg clearance and fibrosis improvement in Chinese hepatitis B patients (P<0.05). PEG-IFN α was obviously superior to ETV in HBeAg seroconversion and serum HBeAg clearance (P<0.05), but the seroconversion rate was low. The combination therapy of PEG-IFN α and ADV was more effective than ADV monotherapy in ALT normalization, serum HBV DNA clearance and HBeAg seroconversion (P<0.05). PEG-IFN α showed no priority to other treatment regimes in HBsAg clearance. CONCLUSION: Treatment with PEG-IFN α is safe and effective, and can be prescribed as firstline treatment options for chronic hepatitis B patients in China. Data are too limited to exclude a substantial benefit or harm of PEG-IFN α combination therapy for CHB patients in China.