生物材料在多尺度力治疗学中应用的2022年度研究进展

随着对生物力学与力学生物学机制理解的深入,力学如何应用于疾病治疗受到越来越多的关注,由此产生了力治疗学这一新兴领域。生物材料与力治疗学的结合,为疾病的力学治疗提供了多样化的干预途径与丰富的技术手段。本文结合2022年度生物材料在力治疗学中应用的最新进展,着眼于多尺度的力治疗途径分析,从器官与组织、微组织、细胞与亚细胞和分子4个尺度,探讨生物材料如何服务于力治疗学应用,以期助力多学科交叉研究发展、推动力治疗研究的转化与应用。

软组织再生力医学

创伤、疾病和衰老造成的软组织、器官缺损或衰退对人类健康带来极大负担,软组织再生技术为解决上述问题带来了希望。近年来,随着生物力学、力学生物学与再生医学多学科交叉研究日益深入,力学逐渐成为调控软组织再生的关键因素之一。尽管如此,目前临床对于软组织的力学特性缺乏深入认识,也未完全掌握其在软组织疾病诊疗及软组织缺损修复中的潜在价值。本文通过总结国内外相关研究进展,提出“软组织再生力医学”这一概念。随后,从软组织多尺度生物力学、软组织再生力学生物学、软组织再生力医学技术及软组织再生力医学应用4个方面,系统描述力学因素对软组织发育和再生的影响机制。最后,对力医学应用于临床软组织疾病诊疗及软组织缺损修复的潜能进行展望,为软组织再生力医学的发展提供新方向。

Temperature-feedback two-photon-responsive metal-organic frameworks for efficient photothermal therapy

The realization of real-time thermal feedback for monitoring photothermal therapy(PTT)under near-infrared(NIR)light irradiation is of great interest and challenge for antitumor therapy.Herein,by assembling highly efficient photothermal conversion gold nanorods and a temperature-responsive probe((E)-4-(4-(diethylamino)styryl)-1-methylpyridin-1-ium,PyS)within MOF-199,an intelligent nanoplatform(AMPP)was fabricated for simultaneous chemodynamic therapy and NIR light-induced temperature-feedback PTT.The fluorescence intensity and temperature of the PyS probe are linearly related due to the restriction of the rotation of the characteristic monomethine bridge.Moreover,the copper ions resulting from the degradation of MOF-199 in an acidic microenvironment can convert H_(2)O_(2)into•OH,resulting in tumor ablation through a Fenton-like reaction,and this process can be accelerated by increasing the temperature.This study establishes a feasible platform for fabricating highly sensitive temperature sensors for efficient temperature-feedback PTT.

肿瘤力医学

恶性肿瘤对人类生命健康构成了巨大威胁。在全球范围内,恶性肿瘤已经成为世界人口的主要死因之一,据世界卫生组织统计,2020年全球近1/6的死亡是由恶性肿瘤导致的。中国的恶性肿瘤负担也在日益增加,随着人口老龄化和生活方式的改变,中国恶性肿瘤的发病率和死亡率逐渐增加,恶性肿瘤逐渐成为中国的主要死因之一。开发有效的诊疗手段对降低我国恶性肿瘤负担具有重要意义。多年来各种研究集中于利用肿瘤的生物化学特性诊断和治疗肿瘤,但这并不能完全解决肿瘤临床诊疗的诸多难题。随着生物力学和力学生物学与肿瘤学的交叉研究不断深入,力学因素逐渐成为备受关注的肿瘤新特征,调控肿瘤发生发展并有望成为肿瘤诊疗的新靶点。目前,许多临床医师对肿瘤的力学特征尚缺乏深入了解,也未完全掌握其在诊疗中的潜在价值。鉴于此,本文通过总结国内外相关研究,提出并系统性地介绍了肿瘤力医学这一概念,从肿瘤生物力学、肿瘤力生物学、肿瘤力诊断学和肿瘤力治疗学四个方面系统性地阐述肿瘤的多尺度力学特征及其对肿瘤生物学行为的影响,探讨力学特征在肿瘤诊疗中的潜在应用,旨在为肿瘤诊疗提供新的研究视角和解决方案。

Clinical Study of Photodynamic Therapy for Upper Gastrointestinal Tract Cancers

Objective： To evaluate the clinical effectiveness and adverse effects of photodynamic therapy （PDT） for the upper gastrointestinal tract cancers. Methods： 56 patients with upper gastrointestinal cancers in different clinical stages were treated with PDT. Diode laser （630 nm） was used as the light source and the parameters were as follows： power density 200 to 400 mW/cm, energy density 100 to 300 J/cm. PHOTOFRIN was used as photosensitizer, which was given in a dose of 2 mg/kg intravenously 12-24 h before irradiation. Results： Evaluation of the 56 patients＇ therapeutic effectiveness showed that 6 patients （10.7%） had a complete response （CR）, 33 patients （58.9%） partial response （PR）, 12 patients （21.4%） mild response （MR）, and 5 patients （8.9%） no response （NR）. The total response rate （CR＋PR） was 69.6%. No patients had severe adverse effects in this group. Conclusion： PDT is an effective and safe palliative modality for upper gastrointestinal tract cancers.

Key questions about the checkpoint blockade-are microRNAs an answer?

The introduction of immune-checkpoint blockade in the cancer therapy led to a paradigm change of the management of late stage cancers. There are already multiple FDA approved checkpoint inhibitors and many other agents are undergoing phase 2 and early phase 3 clinical trials. The therapeutic indication of immune checkpoint inhibitors expanded in the last years, but still remains unclear who can benefit. Micro RNAs are small RNAs with no coding potential. By complementary pairing to the 3' untranslated region of messenger RNA, microRNAs exert posttranscriptional control of protein expression. A network of microRNAs directly and indirectly controls the expression of checkpoint receptors and several microRNAs can target multiple checkpoint molecules,mimicking the therapeutic effect of a combined immune checkpoint blockade. In this review, we will describe the microRNAs that control the expression of immune checkpoints and we will present four specific issues of the immune checkpoint therapy in cancer:(1) imprecise therapeutic indication,(2) difficult response evaluation,(3) numerous immunologic adverse-events, and(4)the absence of response to immune therapy. Finally, we propose microRNAs as possible solutions for these pitfalls. We consider that in the near future microRNAs could become important therapeutic partners of the immune checkpoint therapy.

Synergetic anticancer effect of combined gemcitabine and photodynamic therapy on pancreatic cancer in vivo

AIM： To investigate the anti-tumor effects of combined cytotoxic drug （gemcitabine） and photodynamic therapy （PDT） on human pancreatic cancer xenograft in nude mice.METHODS： Human pancreatic cancer cell line SW1990 was used in the investigation of the in vivo effect of combined gemcitabine and PDT on human pancreatic cancer xenograft in mice. Sixty mice were randomly allocated into a control group （without treatment）, photosensitizer treatment group （2 mg/kg photosan, without illumination）, chemotherapy group （50 mg/kg gemcitabine i.p.）, PDT group （2 mg/kg photosan ＋ laser irradiation） and combined treatment group （photosan ＋ chemotherapy）, with 12 mice in each group. Tumor size was measured twice every week. Anti-tumor activity in different groups was evaluated by tumor growth inhibition （TGI）RESULTS： No significant anti-tumor effect was observed either in photosensitizer treatment group or in chemotherapy group. PDT led to necrosis in cancer lesions and significantly reduced tumor volume compared with photosensitizer on day 6 and at the following time points after initialization of therapy （0.24 ± 0.15-0.49 ± 0.08 vs 0.43 ± 0.18-1.25± 0.09, P 〈 0.05）. PDT significantly reduced tumor volume in combined treatment group compared with photosensitizer treatment group （0.12 ± 0.07-0.28 ± 0.22 vs 0.39 ± 0.15-2.20 ± 0.12, P 〈 0.05）, small dose chemotherapy group （0.12 ± 0.07-0.28 ± 0.12 vs 0.32 ± 0.14-1.16 ± 0.08, P 〈 0.05） and control group （0.12 ± 0.07-0.28 ± 0.12 vs 0.43 ± 0.18-1.25 ± 0.09, P 〈 0.05）. TGI was higher in the combined treatment group （82.42%） than in the PDT group （58.18%）.CONCLUSION： PDT has a significant anti-tumor effect, which is maintained for a short time and can be significantly enhanced by small doses of gemcitabine.

Success of photodynamic therapy in palliating patients with nonresectable cholangiocarcinoma: A systematic review and meta-analysis

To perform a systematic review and meta-analysis on clinical outcomes of photodynamic therapy (PDT) in non-resectable cholangiocarcinoma.METHODSIncluded studies compared outcomes with photodynamic therapy and biliary stenting (PDT group) vs biliary stenting only (BS group) in palliation of non-resectable cholangiocarcinoma. Articles were searched in MEDLINE, PubMed, and EMBASE. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic.RESULTSTen studies (n = 402) that met inclusion criteria were included in this analysis. The P for χ2 heterogeneity for all the pooled accuracy estimates was > 0.10. Pooled odds ratio for successful biliary drainage (decrease in bilirubin level > 50% within 7days after stenting) in PDT vs BS group was 4.39 (95%CI: 2.35-8.19). Survival period in PDT and BS groups were 413.04 d (95%CI: 349.54-476.54) and 183.41 (95%CI: 136.81-230.02) respectively. The change in Karnofsky performance scores after intervention in PDT and BS groups were +6.99 (95%CI: 4.15-9.82) and -3.93 (95%CI: -8.63-0.77) respectively. Odds ratio for post-intervention cholangitis in PDT vs BS group was 0.57 (95%CI: 0.35-0.94). In PDT group, 10.51% (95%CI: 6.94-14.72) had photosensitivity reactions that were self-limiting. Subgroup analysis of prospective studies showed similar results, except the incidence of cholangitis was comparable in both groups.CONCLUSIONIn palliation of unresectable cholangiocarcinoma, PDT seems to be significantly superior to BS alone. PDT should be used as an adjunct to biliary stenting in these patients.

Successful photodynamic therapy for biliary papillomatosis:A case report

Papillomatosis of the bile duct is a rare disease with a high risk of malignant transformation. Therapeutical options include partial hepatectomy and liver trans- plantation. A previously healthy 65-years old male developed jaundice and right upper abdominal quadrant pain in 1996. A villous adenoma of the distal bile duct was diagnosed. A Whipple procedure was performed. In 2002 the patient turned symptomatic again. An- other adenoma was found in the right hepatic duct resulting in a right hepatectomy. Two years later the patient again developed cholestasis. Alter drainage of the left hepatic duct with a percutaneous transhepatic cholangial drainage （PTCD） catheter, a recurrent biliary adenomatosis was diagnosed by cholangioscopy. As there was no surgical option left, the patient received photodynamic therapy （PDT） for the recurrent biliary papillomatosis. Three mo alter he received further photodynamic therapies, the bile duct epithelium appeared normal and the patient had no signs of adenomatosis, both macroscopically and histologically. The follow-up cholangioscopy in late 2005 revealed only a small papil-loma without the need for intervention. In early 2006, the patient died of multi organ failure without signs of extrahepatic cholestasis or cholangitis at the age of 75, 10 years after the diagnosis of biliary papillomatosis was established. The patient exceeded the average life expectancy of patients with biliary papillomatosis by far. Thus, PDT might be a sufficient therapeutic option for recurrent papillomatosis patients with no significant side effects.

In vitro and in vivo effects of ferulic acid on gastrointestinal motility:Inhibition of cisplatin-induced delay in gastric emptying in rats

AIM: To study the effects of ferulic acid on gastrointe-stinal motility both in vitro and in vivo.METHODS: Ferulic acid induced concentration-dependent stimulation of the basal tone of isolated guinea pig ileum (2-20 μmol/L) and isolated rat fundus (0.05-0.4 mmol/L). RESULTS: Ferulic acid significantly accelerated the gastrointestinal transit and gastric emptying in rats in a dose-dependent manner (50-200 mg/kg, po). Cisplatin (2.5-20 mg/kg, ip) induced a dose-dependent delay in gastric emptying in rats. Pretreatment with ferulic acid dose-dependently, significantly reversed the cisplatin-induced delay in gastric emptying. CONCLUSION: The endogenous prostaglandins (PGs) are involved in mediating the stimulant effects of ferulic acid. This effect of dietary ferulic acid may help improve other accompanying gastrointestinal symptoms such as abdominal discomfort and also may protect against emesis induced by cytotoxic drugs.

Dried-leaf Artemisia annua: A practical malaria therapeutic for developing countries?

Artemisinin from the plant Artemisia annua （A. annua） L., and used as artemisinin combination therapy （ACT）, is the current best therapeutic for treating malaria, a disease that hits children and adults especially in developing countries. Traditionally, A. annua was used by the Chinese as a tea to treat “fever”. More recently, investiga-tors have shown that tea infusions and oral consumption of the dried leaves of the plant have prophylactic and therapeutic effcacy. The presence of a complex matrix of chemicals within the leaves seems to enhance both the bioavailability and effcacy of artemisinin. Although about 1000-fold less potent than artemisinin in their antiplasmodial activity, these plant chemicals are mainly small molecules that include other artemisinic compounds, terpenes （mainly mono and sesqui）, favonoids, and polyphenolic acids. In addition, polysaccharide constituents of A. an-nua may enhance bioavailability of artemisinin. Rodent pharmacokinetics showed longer T？ and Tmax and greater Cmax and AUC in Plasmodium chabaudi -infected mice treated with A. annua dried leaves than in healthy mice. Pharmacokinetics of deoxyartemisinin, a liver metabolite of artemisinin, was more inhibited in infected than in healthy mice. In healthy mice, artemisinin serum levels were 〉 40-fold greater in dried leaf fed mice than those fed with pure artemisinin. Human trial data showed that when delivered as dried leaves, 40-fold less artemisinin was required to obtain a therapeutic response compared to pure artemisinin. ACTs are still unaffordable for many malaria patients, and cost estimates for A. annua dried leaf tablet production are orders of magnitude less than for ACT, despite improvements in the production capacity. Considering that for 〉 2000 years this plant was used in traditional Chinese medicine for treatment of fever with no apparent appearance of artemisinin drug resistance, the evidence argues for inclusion of affordable A. annua dried leaf tablets into the arsenal of drugs to combat malaria and other artemisinin-susceptible diseases.

Liver-targeted hydrodynamic gene therapy: Recent advances in the technique

One of the major research focuses in the field of gene therapy is the development of clinically applicable, safe, and effective gene-delivery methods. Since the first case of human gene therapy was performed in 1990, a number of gene-delivery methods have been developed, evaluated for efficacy and safety, and modified for human application. To date, viral-vectormediated deliveries have shown effective therapeutic results. However, the risk of lethal immune response and carcinogenesis have been reported, and it is still controversial to be applied as a standard therapeutic option. On the other hand, delivery methods for nonviral vector systems have been developed, extensively studied, and utilized in in vivo gene-transfer studies. Compared to viral-vector mediated gene transfer, nonviral systems have less risk of biological reactions. However, the lower gene-transfer efficiency was a critical hurdle for applying them to human gene therapy. Among a number of nonviral vector systems, our studies focus on hydrodynamic gene delivery to utilize physical force to deliver naked DNA into the cells in the living animals. This method achieves a high gene-transfer level by DNA solution injections into the tail vein of rodents, especially in the liver. With the development of genome editing methods, in vivo gene-transfer therapy using this method is currently the focus in this research field. This review explains the method principle, efficiency, safety, and procedural modifications to achieve a high level of reproducibility in large-animal models.

Multi-physics analysis of permanent magnet tubular linear motors under severe volumetric and thermal constraints

Permanent magnet tubular linear motors(TLMs) arranged in multiple rows and multiple columns used for a radiotherapy machine were studied. Due to severe volumetric and thermal constraints, the TLMs were at high risk of overheating. To predict the performance of the TLMs accurately, a multi-physics analysis approach was proposed. Specifically, it considered the coupling effects amongst the electromagnetic and the thermal models of the TLMs, as well as the fluid model of the surrounding air. To reduce computation cost, both the electromagnetic and the thermal models were based on lumped-parameter methods. Only a minimum set of numerical computation(computational fluid dynamics, CFD) was performed to model the complex fluid behavior. With the proposed approach, both steady state and transient state temperature distributions, thermal rating and permissible load can be predicted. The validity of this approach is verified through the experiment.

Treatment of Phenol Wastewater Using High Gravity Electrochemical Reactor with Multi-concentric Cylindrical Electrodes

A novel high gravity electrochemical reactor with multi-concentric cylindrical electrodes was used in the electrochemical treatment of 5 000 mg/L phenol-containing wastewater at a petrochemical plant, which can operate continuously and process in a large scale. The results show that the high gravity technology used in electrochemical treatment of phenol-containing wastewater can shorten the electrolysis time, decrease the electrolysis voltage, and reduce the energy consumption. The COD removal efficiency was high in the high-gravity field, and reached up to about 48%, which was about 2 times the value achieved in the normal gravity field at a processing capacity of 6 L, a high gravity factor of 80, a voltage of 12 V, an electrolysis time of 40 min, and a wastewater flowrate of 80 L/h.

Magnetic Nano-Amorphous-Iron-Oxide-Based Drug Delivery System with Dual Therapeutic Mechanisms

Smart nanoparticles that respond to pathophysiological parameters,such as p H,GSH,and H2O2,have been developed with the huge and urgent demand for the high-efficient drug delivery systems(DDS)for cancer therapy.Herein,cubic poly(ethylene glycol)(PEG)-modified mesoporous amorphous iron oxide(AFe)nanoparticles(AFe-PEG)have been successfully prepared as p H-stimulated drug carriers,which can combine doxorubicin(DOX)with a high loading capacity of 948 mg/g,forming a novel multifunctional AFe-PEG/DOX nanoparticulate DDS.In an acidic microenvironment,the AFe-PEG/DOX nanoparticles will not only release DOX efficiently,but also release Fe ions to catalyze the transformation of H2O2 to·OH,acting as fenton reagents.In vitro experimental results proved that the AFe-PEG/DOX nanoparticles can achieve combination of chemotherapeutic(CTT)and chemodynamic therapeutic(CDT)effects on Hela tumor cells.Furthermore,the intrinsic magnetism of AFePEG/DOX makes its cellular internalization efficiency be improved under an external magnetic field.Therefore,this work develops a new and promising magnetically targeted delivery and dual CTT/CDT therapeutic nano-medicine platform based on amorphous iron oxide.

Apoptosis Induced by Photodynamic Therapy with Benzoporphyrin Derivative Monoacid Ring A and Exploration of its Potential Mechanism in Bladder Cancer Cells

OBJECTIVE To investigate apoptosis induced by photodynamic therapy with benzoporphyrin derivative monoacid ring A （BPD-MA） and explore its potential mechanism in human bladder cancer cells. METHODS Photosensitization of BPD-MA was activated with a red light Laser （632.8nm） delivered at 10 mW/cm^2 to give a total dose of 2.4 J/cm^2. Cellular apoptosis was measured with flow cytometry analysis and an insitu terminal deoxyuridine nick end-labeling （TUNEL） assay. Changes in mitochondrial membrane potential （△φm） were monitored by a flow cy-tometric method with Rhodamine 123 staining and the expression of bcl- 2 in BIU-87 cells was detected with immunocytochemical staining. RESULTS At 8 h following photodynamic treatment, the degree of apoptosis was significantly increased when analyzed with flow cytometry and TUNEL assay. Treatment of the BIU-87 cells by PDT with BPD-MA resulted in the collapse of the △φm and a decrease of bcl-2 expression. CONCLUSION BPD-MA-mediated PDT can effectively induce apoptosis in BIU-87 cells. The mechanism probably is through a mitochondrial-initiated pathway.

Hemodynamic and antifibrotic effects of a selective liver nitric oxide donor V-PYRRO/NO in bile duct ligated rats

AIM: To assess whether a liver specific nitric oxide (NO) donor (V-PYRRO/NO) would prevent the development of portal hypertension and liver fibrosis in rats with bile duct ligation (BDL). METHODS: Treatment (placebo or V-PYRRO/NO 0.53 μmol/kg per hour) was administered i.v. to rats 2 d before BDL (D-2) and maintained until the day of hemodynamic measurement (D26). Intra-hepatic NO level was estimated by measuring liver cGMP level. Effects of V-PYRRO/NO on liver fibrosis and lipid peroxidation were also assessed. RESULTS: Compared to placebo treatment, V-PYRRO/ NO improved splanchnic hemodynamics in BDL rats: portal pressure was significantly reduced by 27% (P < 0.0001) and collateral circulation development was almost completely blocked (splenorenal shunt blood flow by 74%, P = 0.007). Moreover, V-PYRRO/NO significantly prevented liver fibrosis development in BDL rats (by 30% in hepatic hydroxyproline content and 31% in the area of fibrosis, P < 0.0001 respectively), this effect being probably due to a decrease in lipid peroxidation by 44% in the hepatic malondialdehyde level (P = 0.007). Interestingly, we observed a significant and expected increase in liver cGMP, without any systemic hemodynamic effects (mean arterial pressure, vascular systemic resistance and cardiac output) in both sham- operated and BDL rats treated with V-PYRRO/NO. This result is in accordance with studies on V-PYRRO/NO metabolism showing a specific release of NO in the liver.NO in BDL rats improved liver fibrosis and splanchnic hemodynamics without any noxious systemic hemo- dynamic effects.

Effect of Photodynamic Therapy with BPD-MA on the Proliferation and Apoptosis of Human Bladder Cancer Cells

OBJECTIVE To explore the effect of photodynamic therapy with benzoporphyrin derivative monoacid ring A （BPD-MA） on the proliferation and apoptosis of human bladder cancer cells. METHODS Photosensitization of BPD-MA was activated with a red light laser （632.8 nm） delivered at 10 mw/cm^2 to give a total dose of 2.4 J/cm^2. Cellular proliferative activity was measured using the 3-（4,5.- dimethylethiazil-2-yl）-2,5-Diph3-eyl tetrazolium bromide （MFi-） assay and 3H-thymidine incorporation. Cell apoptosis was determined with flow cytometry analysis and the terminal deoxyuridine nicked-labeling （TUNEL） assay. RESULTS At 24 h post photodynamic treatment, photodynamic therapy significantly decreased cellular proliferative activity. The rate of apoptosis in BIU-87 cells 8 h after photodynamic treatment significantly increased up to 26.11± 2.59% as analyzed with flow cytometry. In situ labeling of DNA cleavage products with the terminal deoxyuridine nicked-labeling （TUNEL） assay reinforced these observations, BPD-MA-mediated photosensitization increased the number of TUNEL-positive cells compared to the controls. However, laser irradiation alone, BPD-MA alone and sham radiation did not affect cellular proliferative activity or apoptosis of the human bladder cancer BIU-87 cells. CONCLUSION Photodynamic therapy with BPD-MA significantly decreases cellular proliferative activity and enhances apoptosis. Therapy using this method might be a promising approach to treat patients with bladder cancer.

Drug-induced liver injury in hospitalized patients with notably elevated alanine aminotransferase

AIM： To identify the proportion, causes and the nature of drug-induced liver injury （DILI） in patients with no- tably elevated alanine aminotransferase （ALT）. METHODS： All the inpatients with ALT levels above 10 times upper limit of normal range （ULN） were ret- rospectively identified from a computerized clinical laboratory database at our hospital covering a 12-mo period. Relevant clinical information was obtained from medical records. Alternative causes of ALT eleva- tions were examined for each patient, including bili- ary abnormality, viral hepatitis, hemodynamic injury, malignancy, DILI or undetermined and other causes. All suspected DILI cases were causality assessed usingthe Council for International Organizations of Medical Sciences scale, and only the cases classified as highly probable, probable, or possible were diagnosed as DILI. Comments related to the diagnosis of DILI in the medical record and in the discharge letter for each case were also examined to evaluate DILI detection by the treating doctors. RESULTS： A total of 129 cases with ALT 〉 i0 ULN were identified. Hemodynamic injury （n = 46, 35.7%）, DILl （n = 25, 19.4%） and malignancy （n = 21, 16.3%） were the top three causes of liver injury. Peak ALT val- ues were lower in DILI patients than in patients with hemodynamic injury （14.5 5.6 ULN vs 32.5 ：I： 30.7 ULN, P = 0.001）. Among DILI patients, one （4%） case was classified as definite, 19 （76%） cases were clas- sified as probable and 5 （20%） as possible according to the ClOMS scale. A hepatocellular pattern was ob- served in 23 （92%） cases and mixed in 2 （8%）. The extent of severity of liver injury was mild in 21 （84%） patients and moderate in 4 （16%）. Before discharge, 10 （40%） patients were recovered and the other 15 （60%） were improved. The improved patients tended to have a higher peak ALT （808 ＋ 348 U/L vs 623 ＋ 118 U/L, P = 0.016） and shorter treatment duration before discharge （8 ＋ 6 d vs 28 ~ 12 d, P = 0.008） compared with the recovered patients. Twenty-two drugs and 6 herbs were found associated with DILl. Antibacterials were the most common agents causing DILI in 8 （32%） cases, followed by glucocorticoids in 6 （24%） cases. Twenty-four （96%） cases received treatment of DILl with at least one adjunctive drug. Agents for treatment of DILI included anti-inflammatory drugs （e.g., glycyr- rhizinate）, antioxidants （e.g., glutathione, ademetionine 1,4-butanedisulfonate and tiopronin）, polyene phospha- tidyl choline and herbal extracts （e.g., protoporphyrin disodium and silymarin）. Diagnosis of DILl was not mentioned in the discharge letter in 60% of the cases. Relative to prevalent cases and cases from wards of internal medicine, incident cases and cases from surgi- cal wards had a higher risk of missed diagnosis in dis- charge letter [odds ratio （OR） 32.7, 95%CI （2.8-374.1）,CONCLUSION： DILI is mostly caused by use of anti- bacterials and glucocorticoids, and constitutes about one fifth of hospitalized patients with ALT 〉 10 ULN. DILI is underdiagnosed frequently.

In Vitro Study of Photodynamic Therapy for Treatment of Bacteremia in Whole Blood

Antibiotic resistance has been compromised hospitalized patients with serious infections. The main cases of bacteremia can be caused by antibiotic resistant pathogens. Photodynamic therapy （PDT） has been shown as an alternative for inactivation of microorganisms in blood. In this therapy photochemical mechanisms occur that may prevent the development of bacteria. This study aims optimization of PDT parameters for blood decontamination. Concentration ofphotosensitizer （PS）, light dose （LD） and incubation time （IT） were studied for hemolysis and cell toxic effects. It was observed that PDT can be used for microbial inactivation in total blood reducing 0.85 log10 CFU/mL ofS. aureus at 15 J/cm^2 and 50μg/mL of Photogem .