Bacterial interactome disturbance in chronic obstructive pulmonary disease clinical stability and exacerbations.

RATIONALE: Our understanding of airway dysbiosis in chronic obstructive pulmonary disease (COPD) remains incomplete, which may be improved by unraveling the complexity in microbial interactome. OBJECTIVES: To characterize reproducible features of airway bacterial interactome in COPD at clinical stability and during exacerbation, and evaluate their associations with disease phenotypes. METHODS: We performed weighted ensemble-based co-occurrence network analysis of 1742 sputum microbiomes from published and new microbiome datasets, comprising two case-control studies of stable COPD versus healthy control, two studies of COPD stability versus exacerbation, and one study with exacerbation-recovery time series data. RESULTS: Patients with COPD had reproducibly lower degree of negative bacterial interactions, i.e. total number of negative interactions as a proportion of total interactions, in their airway microbiome compared with healthy controls. Evaluation of the Haemophilus interactome showed that the antagonistic interaction networks of this established pathogen rather than its abundance consistently changed in COPD. Interactome dynamic analysis revealed reproducibly reduced antagonistic interactions but not diversity loss during COPD exacerbation, which recovered after treatment. In phenotypic analysis, unsupervised network clustering showed that loss of antagonistic interactions was associated with worse clinical symptoms (dyspnea), poorer lung function, exaggerated neutrophilic inflammation, and higher exacerbation risk. Furthermore, the frequent exacerbators (≥ 2 exacerbations per year) had significantly reduced antagonistic bacterial interactions while exhibiting subtle compositional changes in their airway microbiota. CONCLUSIONS: Bacterial interactome disturbance characterized by reduced antagonistic interactions, rather than change in pathogen abundance or diversity, is a reproducible feature of airway dysbiosis in COPD clinical stability and exacerbations, which suggests that we may target interactome rather than pathogen alone for disease treatment.

A versatile multi-tone laser system for manipulating atomic qubits based on a fiber Mach-Zehnder modulator and second harmonic generation.

Stimulated Raman transition is a fundamental method to coherently manipulate quantum states in different physical systems. Phase-coherent dichromatic radiation fields matching the energy level splitting are the key to realizing stimulated Raman transition. Here we demonstrate a flexible-tuning, spectrum-clean and fiber-compatible method to generate a highly phase-coherent and high-power multi-tone laser. This method features the utilization of a broadband fiber Mach-Zehnder modulator working at carrier suppression condition and second harmonic generation. We generate a multi-tone continuous-wave 532 nm laser with a power of 1.5 Watts and utilize it to manipulate the spin and motional states of a trapped 171Yb+ ion via stimulated Raman transition. For spin state manipulation, we acquire an effective Rabi frequency of 2π × 662.3 kHz. Due to the broad bandwidth of the fiber modulator and nonlinear crystal, the frequency gap between tones can be flexibly tuned. Benefiting from the features above, this method can manipulate 171Yb+ and 137Ba+ simultaneously in the multi-species ion trap and has potential to be widely applied in atomic, molecular and optical physics.

Prompt successful response to a COVID-19 outbreak: Performance of community-based rapid screening station.

An outbreak occurred in Wanhua District of Taipei City. It was traced to a cluster infection originating from a teahouse. To prevent further large-scaled community spread, the Taipei City Government established the first community rapid test screening station. This report describes the station's strategy and performance and key factors that contributed to its operation. The project involves collaboration among various departments of Taipei City Government, including the health, environmental, police, transportation, and fire departments. The station provides rapid screening, polymerase chain reaction (PCR) testing, and immediate isolation and follow-up medical services upon the detection of a positive case. These services are accessible to local residents and are intended to ease hospitals' burdens. In 36 days, a total of 8532 people were tested, and 419 confirmed cases were identified. Over the same period, the weekly number of positive cases in Wanhua District decreased from 356 to 40, and the PCR positive rate decreased from 21.7% to 1.2%. The policy of establishing rapid screening station, contact tracing and mask wearing policy are key strategies for interrupting chains of transmission of COVID-19. This intervention has become a model for preventing the spread of the epidemic and establishing community rapid screening stations in Taiwan.

Management and outcomes of surgical patients with intestinal Behçet's disease and Crohn's disease in southwest China.

BACKGROUND: Gastrointestinal involvement in Behçet's disease (GIBD) and Crohn's disease (CD) are inflammatory diseases sharing a considerable number of similarities. However, different from CD, the operative and postoperative management of GIBD remains largely empirical because of the lack of comprehensive treatment guidelines. AIM: To compare surgical patients with GIBD and those with CD in a medical center and identify notable clinical features and effective postoperative treatment for surgical patients with GIBD. METHODS: We searched patients diagnosed with CD and GIBD who underwent operations for gastrointestinal complications from 2009 to 2015 at West China Hospital of Sichuan University. A total of 10 surgical patients with GIBD and 106 surgical patients with CD were recruited. Information including demographic data, medication, and operative and postoperative parameters were collected and analyzed. As the incidence of surgical GIBD is low, their detailed medical records were reviewed and compared to previous studies. Moreover, the prognoses of CD and GIBD were evaluated respectively between groups treated with biological and non-biological agents. RESULTS: Indication for first surgery was often acute intestinal perforation for GIBD patients (7/10 vs 0/106, P < 0.001), whereas intestinal fistulae (0/10 vs 44/106, P = 0.013) and ileus (0/10 vs 40/106, P = 0.015) were the indications for surgical CD patients. Approximately 40% of patients with GIBD and 23.6% of patients with CD developed postoperative complications, 50% of patients with GIBD and 38.7% of patients with CD had recurrence postoperatively, and 40% (4/10) of patients with GIBD and 26.4% (28/106) of patients with CD underwent reoperations. The average period of postoperative recurrence was 7.87 mo in patients with Behçet's disease (BD) and 10.43 mo in patients with CD, whereas the mean duration from first surgery to reoperation was 5.75 mo in BD patients and 18.04 mo in CD patients. Surgical patients with GIBD more often used corticosteroids (6/10 vs 7/106, P < 0.001) and thalidomide (7/10 vs 9/106, P < 0.001) postoperatively, whereas surgical patients with CD often used infliximab (27/106), azathioprine, or 6-mercaptopurine (74/106) for maintenance therapy. CONCLUSION: Patients suffering GIBD require surgery mostly under emergency situations, which may be more susceptible to recurrence and reoperation and need more aggressive postoperative treatment than patients with CD.

Risk factors for overt hepatic encephalopathy after transjugular intrahepatic portosystemic shunt creation in patients with liver cirrhosis.

OBJECTIVE: This study aimed to determine the risk factors and establish a risk score for post-transjugular intrahepatic portosystemic shunt (TIPS) overt hepatic encephalopathy (OHE). METHODS: Altogether 299 and 62 cirrhotic patients receiving TIPS from January 2015 to March 2018 were divided into the derivation and validation cohorts, respectively. The data of the derivation cohort were analyzed for risk factors of post-TIPS OHE. A risk score was established from the derivation cohort and verified by the validation cohort. RESULTS: During a median follow-up of 112.6 weeks, 52 (17.4%) patients in the derivation cohort experienced post-TIPS OHE. Logistic regression showed that alcoholic cirrhosis (odds ratio [OR] 3.068, 95% confidence interval [CI] 1.423-6.613, P = 0.004), stent diameter of 10 mm (OR 12.046 [95% CI 2.308-62.862], P = 0.003), portal pressure gradient (PPG) decrement ≥60% (OR 3.548 [95% CI 1.741-7.230], P < 0.001), model for end-stage liver disease (MELD) score ≥10 (OR 2.695 [95% CI 1.203-6.035], P = 0.016), blood ammonia (OR 1.009 [95% CI 1.000-1.018], P = 0.043) and notable hydrothorax (OR 4.393 [95% CI 1.554-12.415], P = 0.005) were associated with an increased risk of post-TIPS OHE. The risk score reached a promising risk evaluation of post-TIPS OHE when verified by the validation cohort (sensitivity 71.4%, specificity 70.7%, accuracy 71.0%). CONCLUSIONS: Alcoholic cirrhosis and notable hydrothorax are independent risk factors for post-TIPS OHE in liver cirrhosis, together with the stent diameter of 10 mm, PPG decrement ≥60%, MELD score ≥10 and blood ammonia. The established risk score is reliable to identify high-risk individuals of developing post-TIPS OHE.

Traceability of Geographical Origin in Gentiana straminea by UPLC-Q Exactive Mass and Multivariate Analyses.

The root of Gentiana straminea Maxim. (Gentianaceae), is officially listed as "Qin-Jiao" in the Chinese Pharmacopoeia for the treatment of rheumatic arthritis, icteric hepatitis, constipation, pain, and hypertension. To establish the geographical origin traceability in G. straminea, its chemical profiles were determined by a UPLC-Q exactive mass spectrometer, from which 43 compounds were identified by comparing retention times and mass spectrometry. Meanwhile, a pair of isomers (loganin and secologanol) was identified by mass spectrometry based on their fragmentation pathway. A total of 42 samples from difference habitats were determined by an UPLC-Q exactive mass spectrometer and the data were assayed with multivariate statistical analysis. Eight characteristic compounds were identified to determine the geographical origin of the herb. To estimate the key characteristic markers associated with pharmacological function, the inhibiting activities of nitric oxide (NO) production in lipopolysaccharide (LPS)-induced macrophages were examined. This finding is crucial in realizing the determination of botanical origin and evaluating the quality of G. straminea.

[Assessing abundance and specificity of different types of sgRNA targeting miRNA precursors].

CRISPR/Cas technology enables efficient and specific editing the genome. Since different bacterial sources or artificially modified Cas9, as well as Cpf1 and other nucleases, recognize different PAMs (protospacer adjacent motifs), different gene editing nucleases may use different types of sgRNAs (small guide RNA). MicroRNAs (miRNAs) are a class of regulatory small non-coding RNAs. To determine whether specific targets for sgRNAs in miRNA precursor exit, the abundance and specificity of 11 different types of sgRNA targeting 28 645 miRNA precursors were analyzed in the present study using the CRISPR-offinder, a bioinformatics software developed in our own laboratory. The CRISPR/Cas9 lentivirus technology was used to target the miR-302/367 cluster in a porcine cell line, and its knockout efficiency for the miRNA target was evaluated. The results show that there are about 8 different types of sgRNAs that can target individual miRNA precursors. By assessing the off-target effect, only 18.2% of the sgRNAs showed high specificity for targeting the porcine miRNA precursors. Lastly, using the miR-302/367 cluster target as an example, we showed that the CRISPR/Cas9 lentivirus technology was 40% efficient in successfully establishing correct knockout of the target miRNA in the porcine cell line. This present study provides an important resource for the use of CRISPR/Cas technology to target miRNAs for knockout studies.

[Studies on difference of chemical compositions in plant species of Tripterygium genus].

We studied the content of chemical compositions and correlation among species of Tripterygium genus by principal component analysis(PCA) and variance analysis(ANOVA), and we also studied the difference among the 3 species.Using [BMIm]PF6 ionic liquid-based ultrasonic-assisted extraction, we determined the contents of 11 compounds including wilforgine, wilforzine, triptophenolide, wilforine, triptoquinone A, triptolide, tripterin, egallocatechin, epigallocatechin, catechin, and epicatechin in 28 batches of the Tripterygium species by HPLC and PCA. Partial least squares analysis (PLS) and ANOVA were also performed to verify the results.The analysis results of PCA and PLS showed that three species of Tripterygium genus were clustered into three regions respectively, and triptoquinone A was the important factor which affected the aggregation of these three species.There was a significant difference among the contents of 11 chemical components in the three species(P<0.000 1).These results indicated that there was a certain correlation between the chemical compositions and the classification of the species, and the difference of the chemical compositions among the three species was obvious. In this work, the content determination method is rapid and accurate, and the analysis method is simple and convenient, which provides a reference for the classification, the efficacy and the toxicity of the species.

[Evaluation of genetic diversity and population structure of genus Tripterygium based on SSR markers].

The genus Tripterygium is an immune suppressor in the Chinese traditional medicines. Due to the habitat destruction and anthropogenic over-exploitation, the wild genus Tripterygium plants have decreased dramatically in recent years or even been endangered. It is critical to evaluate and protect genus Tripterygium wild resource. In this research, simple sequence repeat (SSR) molecular markers were applied to the investigation of the genetic diversity and genetic structure of 28 populations for genus Tripterygium (396 samples from 9 provinces in China). We found a high level of genetic diversity (percentage of polymorphic loci PPL = 77.29%, Shannon's information index I = 0.639 4; Nei's expected heterozygosity H = 0.359 9) and high genetic differentiation among the populations (gene flow N_m = 0.228 7). Based on Nei's genetic distance, the phylogenic tree of populations was constructed and 28 populations were divided into 6 clusters according to STRUCTURE clustering analysis. T. hypoglaucumwas was mainly divided into 3 clusters, including Sichuan, Yunnan and Guizhou- Chongqing. T. regelii was separated to cluster 4, while T. wilfordii was divided into two clusters: the transition type LQ and NY were divided into cluster 5, and the others were in cluster 6. These results provide a theory basis for the conservation of wild resource, research of genetic polymorphism and molecular marker for assisted breeding of genus Tripterygium.

[Identification of Tibetan medicine "Dida" of Gentianaceae using DNA barcoding].

The ITS2 barcode was used toidentify Tibetan medicine "Dida", and tosecure its quality and safety in medication. A total of 13 species, 151 experimental samples for the study from the Tibetan Plateau, including Gentianaceae Swertia, Halenia, Gentianopsis, Comastoma, Lomatogonium ITS2 sequences were amplified, and purified PCR products were sequenced. Sequence assembly and consensus sequence generation were performed using the CodonCode Aligner V3.7.1. The Kimura 2-Parameter (K2P) distances were calculated using MEGA 6.0. The neighbor-joining (NJ) phylogenetic trees were constructed. There are 31 haplotypes among 231 bp after alignment of all ITS2 sequence haplotypes, and the average G±C content of 61.40%. The NJ tree strongly supported that every species clustered into their own clade and high identification success rate, except that Swertia bifolia and Swertia wolfangiana could not be distinguished from each other based on the sequence divergences. DNA barcoding could be used as a fast and accurate identification method to distinguish Tibetan medicine "Dida" to ensure its safe use.

[Studies on dosage-efficacy/toxicity relationship of anti-hypoxia effects and quality standard of Tibetan medicine Brassicea Radix extract].

To evaluate the efficacy and safety associated with anti-hypoxia effect and establish the quality standard for Brassicea Radix extract, the investigations of acute toxicity and subacute toxicity were carried out to preliminarily appraise the toxicity, and the models of normal pressure hypoxia, acute cerebral ischemia and sodium nitrite poisoning in mice were used to evaluate the effect of enhancing anoxia endurance. Then according to the methods described in the Appendix of Chinese Pharmacopoeia (2010 edition), the sulfuric acid-phenol method was applied to determine the content of polysaccharide, and the water, ash and insoluble matter in water inspections were carried out and the control medicinal herb was identified with the samples by qualitative TLC. The results indicated that ① the toxic effects (LD50) of mice was 56.73 g•kg⁻¹ by oral administration of Brassicea Radix extract, while Dm and Dn were respective 86.80 g•kg•d⁻¹ and 35.55 g•kg•d⁻¹;②the determined effective dosage of Brassicea Radix extract which could enhance anoxia endurance was 0.388 g•kg⁻¹â€¢d⁻¹; ③ the methods of TLC and the content of polysaccharide were established. The method of quality control has been recorded in Sichuan Province Standard for Tibetan Medicine, which is reliable, accurate and simple, with good reproducibility. Meanwhile, given the prominent effect on anti-hypoxia and good safety, it provided important basis for clinic safe and effective usage and the development of health products.

[Simultaneous determination of 5 compounds in Tripterygium hypoglaucum based on ultrasound-assisted ionic liquid coupled with HPLC].

Using six kinds of ionic liquids as extractants, ultrasonic-assisted extraction coupled with HPLC method was developed for the simultaneous determination of wilforgine, wiforizine, triptophenolide, wilforine and triptoquinone A in Tripterygium hypoglaucum. The separation was performed on an Inertsil ODS-4 column with the mobile phase of acetonitrile-0.1% phosphoric acid in gradient elution at a flow rate of 0.75 mL•min⁻¹. Detection wavelength was 220 nm and the column temperature was 30℃. Under the optimal extractions, the results showed that triptophenolide and triptoquinone A had the highest extraction yield by using 0.6 mol•L⁻¹ [BMIm]PF6 methanol solution as extraction solvent with the solid-liquid ratio of 1∶10. The calibration curves of triptophenolide and triptoquinone A showed a good linearity in the range of 0.000 65-0.026, 0.066 55-2.662 µg (r=0.999 9)respectively. The average recovery was 102.4% and 97.90% with RSD of 2.5% and 1.5%, respectively. Wilforgine, wiforizine and wilforine had the highest extraction yield when using 0.6 mol• L⁻¹ [BMIm]PF6absolute ethanol solution as extraction solvent with the solid-liquid ratio of 1∶10. The content of wilforgine, wiforizine and wilforine from 0.023 9-0.956, 0.002 7-0.108, 0.006 4-0.256 µg showed a good linearity (r=0.999 9), and the average recovery was 100.6%,99.50% and 98.70% with RSD of 2.1%,1.9% and 2.7%, respectively. The results indicated that this method is convenient, reliable and green, and can be used as a reliableanalytical method for the quality control of T.hypoglaucum.

Effect of different radial hole designs on pullout and structural strength of cannulated pedicle screws.

Cannulated pedicle screws are designed for bone cement injection to enhance fixation strength in severely osteoporotic spines. However, the screws commonly fracture during insertion. This study aims to evaluate how different positions/designs of radial holes may affect the pullout and structural strength of cannulated pedicle screws using finite element analysis. Three different screw hole designs were evaluated under torsion and bending conditions. The pullout strength for each screw was determined by axial pullout failure testing. The results showed that when the Von Mises stress reached the yield stress of titanium alloy the screw with four radial holes required a greater torque or bending moment than the nine and twelve hole screws. In the pullout test, the strength and stiffness of each screw with cement augmentation showed no significant differences, but the screw with four radial holes had a greater average pullout strength, which probably resulted from the significantly greater mean maximum lengths of cement augmentation. Superior biomechanical responses, with lower stress around the radial holes and greater pullout strength, represented by cannulated pedicle screw with four radial holes may worth recommending for clinical application.

Transcalvarial brain herniation volume after decompressive craniectomy is the difference between two spherical caps.

Decompressive craniectomy (DC) is a surgical procedure used to relieve severely increased intracranial pressure (ICP) by removing a portion of the skull. Following DC, the brain expands through the skull defect created by DC, resulting in transcalvarial herniation (TCH). Traditionally, people measure only changes in the ICP but not in the intracranial volume (ICV), which is equivalent to the volume of TCH (V(TCH)), in patients undergoing DC. We constructed a simple model of the cerebral hemispheres, assuming the shape of the upper half of a sphere with a radius of 8 cm. We hypothesized that the herniated brain following DC also conforms to the shape of a spherical cap. Considering that a circular piece of the skull with a radius of a was removed, V(TCH) is the volume difference between 2 spherical caps at the operated side and the corresponding non-operated side, which represents the pre-DC volume underneath the removed skull due to the bilateral symmetry of the skull and the brain. Subsequently, we hypothesized that the maximal extent of TCH depends on a because of the biomechanical limitations imposed by the inelastic scalp. The maximum value of V(TCH) is 365.0 mL when a is 7.05 cm and the height difference between the spherical caps (Δh) at its maximum is 2.83 cm. To facilitate rapid calculation of V(TCH), we proposed a simplified estimation formula, Vˆ(TCH)=1/2A(2)Δh, where A=2a. With the a value ranging between 0 and 7 cm, the ratio between Vˆ(TCH) and V(TCH) ranges between 0.77 and 1.27, with different Δh values. For elliptical skull defects with base diameters of A and C, the formula changes to Vˆ(TCH)=1/2ACΔh. If our hypothesis is correct, surgeons can accurately calculate V(TCH) after DC. Furthermore, this can facilitate volumetric comparisons between the effects of DCs in skulls of varying sizes, allowing quantitative comparisons between ICVs in addition to ICPs.

[The species traceability of the ultrafine powder and the cell wall-broken powder of herbal medicine based on DNA barcoding].

Ultrafine powder and cell wall-broken powder of herbal medicine lack of the morphological characters and microscopic identification features. This makes it hard to identify herb's authenticity with traditional methods. We tested ITS2 sequence as DNA barcode in identification of herbal medicine in ultrafine powder and cell wall-broken powder in this study. We extracted genomic DNAs of 93 samples of 31 representative herbal medicines (28 species), which include whole plant, roots and bulbs, stems, leaves, flowers, fruits and seeds. The ITS2 sequences were amplified and sequenced bidirectionally. The ITS2 sequences were identified using Basic Local Alignment Search Tool (BLAST) method in the GenBank database and DNA barcoding system to identify the herbal medicine. The genetic distance was analyzed using the Kimura 2-parameter (K2P) model and the Neighbor-joining (NJ) phylogenetic tree was constructed using MEGA 6.0. The results showed that DNA can be extracted successfully from 93 samples and high quality ITS2 sequences can be amplified. All 31 herbal medicines can get correct identification via BLAST method. The ITS2 sequences of raw material medicines, ultrafine powder and cell wall-broken powder have same sequence in 26 herbal medicines, while the ITS2 sequences in other 5 herbal medicines exhibited variation. The maximum intraspecific genetic-distances of each species were all less than the minimum interspecific genetic distances. ITS2 sequences of each species are all converged to their standard DNA barcodes using NJ method. Therefore, using ITS2 barcode can accurately and effectively distinguish ultrafine powder and cell wall-broken powder of herbal medicine. It provides a new molecular method to identify ultrafine powder and cell wall-broken powder of herbal medicine in the quality control and market supervision.

Biomechanical study of expandable pedicle screw fixation in severe osteoporotic bone comparing with conventional and cement-augmented pedicle screws.

Pedicle screws are widely utilized to treat the unstable thoracolumbar spine. The superior biomechanical strength of pedicle screws could increase fusion rates and provide accurate corrections of complex deformities. However, osteoporosis and revision cases of pedicle screw substantially reduce screw holding strength and cause loosening. Pedicle screw fixation becomes a challenge for spine surgeons in those scenarios. The purpose of this study was to determine if an expandable pedicle screw design could be used to improve biomechanical fixation in osteoporotic bone. Axial mechanical pull-out test was performed on the expandable, conventional and augmented pedicle screws placed in a commercial synthetic bone block which mimicked a human bone with severe osteoporosis. Results revealed that the pull-out strength and failure energy of expandable pedicle screws were similar with conventional pedicle screws augmented with bone cement by 2 ml. The pull-out strength was 5-fold greater than conventional pedicle screws and the failure energy was about 2-fold greater. Besides, the pull-out strength of expandable screw was reinforced by the expandable mechanism without cement augmentation, indicated that the risks of cement leakage from vertebral body would potentially be avoided. Comparing with the biomechanical performances of conventional screw with or without cement augmentation, the expandable screws are recommended to be applied for the osteoporotic vertebrae.

The effect of different humeral prosthesis fin designs on shoulder stability: a computational model.

Humeral prostheses commonly use a fin structure as an attachment point for the supraspinatus muscle in total shoulder arthroplasty (TSA), but these fins may cause injury to the muscle during implantation, inadvertently influencing stability. In order to prevent supraspinatus injury, the effect of different humeral prostheses on shoulder joint stability needs to be investigated. A commercially available prosthesis and two modified humeral prostheses that substituted the fin structure for 2 (2H) or 3 holes (3H) were evaluated using computational models. Glenohumeral abduction was simulated and the superioinferior/anterioposterior stability of the shoulder joint after TSA was calculated. The results revealed that the 2H design had better superioinferior stability than the other prostheses, but was still less stable than the intact shoulder. There were no obvious differences in anterioposterior stability, but the motion patterns were clearly distinguishable from the intact shoulder model. In conclusion, the 2H design showed better superioinferior stability than the 3H design and the commercial product during glenohumeral joint abduction; the three prostheses show similar results in anterioposterior stability. However, the stability of each tested prosthesis was not comparable to the intact shoulder. Therefore, as a compromise, the 2H design should be considered for TSA because of its superior stability.

Intracranial metastasis of hepatocellular carcinoma: review of 45 cases.

BACKGROUND: Although extrahepatic metastasis of hepatocellular carcinoma (HCC) is not uncommon, intracranial metastasis is relatively rare. METHODS: We reviewed HCC cases admitted in our hospital in the past 16 years, and there were only 45 cases with clinically diagnosed intracranial metastasis. Their age ranged from 14 to 82 years with the peak in the 3rd and 4th decades, which is much younger than the average age of the HCC patients. RESULTS: Of the 45 patients, 39 (39/45, 86.7%) had hepatitis B related and 20 (20/45, 44.4%) had cirrhosis of the liver. Intracranial hemorrhage as the initial manifestation was common in our series (18/45, 40%). Hemiparesis was found in 14 cases, scalp mass in 9 cases, headache in 13 cases, diplopia in 3 cases (1 ultimately became totally blind), homonymous hemianopsia in 2 cases, dysarthria in 3 cases, gait disturbance in 1 case, seizure in 3 cases, and aphasia in 1 case. The modes of therapy for patients with intracranial metastasis included conservative medical treatment only or surgical excision and/or radiotherapy. In this series, elevated AFP was noted in 32 patients, and alpha fetoprotein higher than several thousands was even noted in 30 patients; extraordinary high level (>70000) was also seen in more than one-half of the patients. CONCLUSIONS: HCC patients with intracranial metastasis presented a very poor prognosis. In general, they deteriorated rapidly and expired without active treatment. Surgical excision of the intracranial metastatic mass, followed by radiotherapy, can improve the life quality and prolong survival time.