Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

Background/Aims: Treatment indications for patients with chronic hepatitis B (CHB) remain contentious, particularly for patients with mild alanine aminotransferase (ALT) elevation. We aimed to evaluate treatment effects in this patient population. Methods: This rollover study extended a placebo-controlled trial that enrolled non-cirrhotic patients with CHB and ALT levels below two times the upper limit of normal. Following 3 years of randomized intervention with either tenofovir disoproxil fumarate (TDF) or placebo, participants were rolled over to open-label TDF for 3 years. Liver biopsies were performed before and after the treatment to evaluate histopathological changes. Virological, biochemical, and serological outcomes were also assessed (NCT02463019). Results: Of 146 enrolled patients (median age 47 years, 80.8% male), 123 completed the study with paired biopsies. Overall, the Ishak fibrosis score decreased in 74 (60.2%), remained unchanged in 32 (26.0%), and increased in 17 (13.8%) patients (p<0.0001). The Knodell necroinflammation score decreased in 58 (47.2%), remained unchanged in 29 (23.6%), and increased in 36 (29.3%) patients (p=0.0038). The proportion of patients with an Ishak score ≥ 3 significantly decreased from 26.8% (n=33) to 9.8% (n=12) (p=0.0002). Histological improvements were more pronounced in patients switching from placebo. Virological and biochemical outcomes also improved in placebo switchers and remained stable in patients who continued TDF. However, serum HBsAg levels did not change and no patient cleared HBsAg. Conclusions In CHB patients with minimally raised ALT, favorable histopathological, biochemical, and virological outcomes were observed following 3-year TDF treatment, for both treatment-naïve patients and those already on therapy.

ObjectiveTo explore the radiosensitization and underlying mechanism of Xuefu Zhuyutang on subcutaneous transplanted esophageal carcinoma. MethodThe subcutaneous xenograft model of human esophageal carcinoma ECA-109 in nude mice was induced and the model mice were divided into a model group， an irradiation group， a Xuefu Zhuyutang group， and a combination group， with six nude mice in each group. After the intervention， the transplanted tumors were removed and weighed， and the tumor inhibition rate of each group was calculated according to the formula. The protein expression of hypoxia-inducible factor-1α （HIF-1α） and vascular endothelial growth factor A （VEGFA） was detected by immunohistochemistry （IHC）. The protein expression of mammalian target of rapamycin （mTOR）， HIF-1α， VEGFA， and vascular endothelial growth factor receptor 2 （VEGFR2） in transplanted tumors was detected by Western blot. The mRNA expression of mTOR， HIF-1α， and VEGFA in transplanted tumors was detected by real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the conditions in the model group， the tumor weight decreased in the irradiation group and the Xuefu Zhuyutang group （P<0.05）， as well as the combination group （P<0.01）. Compared with the irradiation group， the combination group showed decreased tumor weight （P<0.05）， with tumor inhibition rate of 57.37%. Compared with the model group， the irradiation group， the Xuefu Zhuyutang group， and the combination group showed decreased protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. Compared with the irradiation group， the combination group showed down-regulated protein expression of VEGFR2， p-mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01） and reduced mRNA expression of mTOR， HIF-1α， and VEGFA （P<0.05， P<0.01）. ConclusionXuefu Zhuyutang can inhibit the growth of transplanted esophageal carcinoma ECA-109 in nude mice and shows an obvious radiosensitization effect in combination with radiotherapy. The mechanism may be related to the inhibition of the mTOR/HIF-1α/VEGFA signaling pathway to improve the hypoxic state of tumors.

Xiebaisan is one of the 100 classical prescriptions published by the state， and the research and development of its compound preparation has gradually become an upsurge. The research and development of classical prescriptions should start from the theory of traditional Chinese medicine and clinical practice， laying a solid foundation for research and development. Based on the above thinking， this study adopts the methods of traceability and bibliometrics to analyze the source， pathogenesis， efficacy， Fangyi and clinical application of Xiebaisan in order to further promote its literature research work. The results show that the origin of Xiebaisan can be traced back to the prescription of Xiefeitang in Yinhai Jingwei（Volume 1）. Although there are more than 20 prescriptions with the same name of Xiebaisan developed in later generations， they either reflect the inheritance and development of Qian Yi's thought of composing prescriptions， or only the meaning of "Xiebai" in the name of the prescription. The main pathogenesis of Xiebaisan is adverse lung Qi of heat. Mori Cortex and Lycii Cortex are sweet and cold， which can clear away lung heat and reduce adverse Qi， and then cough and asthma can stop. Supplemented with Glycyrrhizae Radix et Rhizoma and japonica rice， which are endowed with the meaning of nourishing earth and generating gold， to invigorate spleen and replenish Qi. The compatibility of Xiebaisan can clear away lung heat， relieve cough and asthma， and norish erath and generate gold to treat lung heat， asthma and cough. Although the main treatment of Xiebaisan recorded in ancient books involves various diseases and syndromes of internal， external， gynecology and pediatrics， the pathogenesis of Xiebaisan is "adverse lung Qi of heat". Modern clinical application of Xiebaisan focuses on the respiratory system， skin and subcutaneous tissue system， ear， nose and throat system， digestive system， ophthalmic system， etc.， and it has more advantages in the treatment of pneumonia， cough， bronchitis， epistaxis， acne， bronchiectasis， postinfectious cough， constipation and other diseases. The syndrome differentiation of the above diseases is in accordance with the relevant syndrome types with lung heat as the main pathological factor， so we can modify and apply the prescription appropriately.

Kaixinsan recorded in an ancient medical book named Beiji Qianjin Yaofang is one of the famous classical formula，which is one of the common prescriptions used by ancient physicians to treat amnesia. In the process of using this prescription，later generations of physicians derived many kinds of associated prescriptions. The effect and indications of these prescription have been inherited and expanded from those in the Beiji Qianjin Yaofang because of the changes in dosages. Therefore，it is necessary to verify the effect and indications of the formulas and the rules of dosage changes. The research results showed that its basic effects included to nourish the mind，induce resuscitation，strengthen the spleen and calm the mind，and keep balance between heart-Yang and kidney-Yin. The main indications included amnesia，sorrow and sadness，fright and fear，and so on，which may differ slightly in different dynasties. In Song，Jin and Yuan dynasties，it also demonstrated the effect of warming the heart and Yang，clearing away heat and relieving wind besides the basic effects， with basically the same indications （slightly different from those in previous dynasties）. In Ming dynasty，it demonstrated the effect of nourishing Yin，clearing away heat and nourishing blood besides the basic effects，and the indications expanded to farsightedness，nearsightedness，spermatorrhea and blurred urine. In the Qing dynasty，its effect also included to nourish the heart and kidney on the basis of the Ming dynasty，and the indications were basically the same with those in the previous dynasties. The compatibility ratio of ancient physicians in the application of this prescription and its associated prescriptions showed some remarkable features，for example，Ginseng Radix et Rhizoma and Poria should be increased and their ratio was≈1∶1 in the treatment of amnesia，sorrow，sadness，fright，fear，farsightedness，spermatorrhea and blurred urine，with ratio of Polygalae Radix to Acori Tatarinowii Rhizoma≈1∶1； the dosage of Polygalae Radix and Acori Tatarinowii Rhizoma should be increased in the treatment of nearsightedness，and their ratio was≈1∶1. The compatibility ratio of Polygalae Radix-Ginseng Radix et Rhizoma-Poria-Acori Tatarinowii Rhizoma=2∶3∶3∶2 was the most frequent，which basically included the indications of this prescription and its associated prescriptions. According to statistics，the average dosages that ancient physicians used were significantly higher than those in the modern times，Polygalae Radix 57 g，Ginseng Radix et Rhizoma 62 g，Poria 70 g，and Acori Tatarinowii Rhizoma 54 g，respectively in ancient times，while Polygalae Radix 11 g，Ginseng Radix et Rhizoma 15 g，Poria 17 g，and Acori Tatarinowii Rhizoma 9.5 g，respectively in modern times. The above textual research results can provide some reference for preparation of tradition Chinese medicine products of Kaixinsan.

Textual research on Chinese herbs is the preliminary work for the preparation of famous classical prescriptions. Through literature review，it was found that the researches of Persicae Semen focused on chemical compositions，pharmacological mechanism and medical record analysis in the recent years，and few researches based on the ancient literature were about the origin，concocting methods，flavor，meridian tropism，effects and indications. Textual research shows that the most commonly used names are Taoren and Taoheren，with a wide range of producing areas. The plant origin of Persicae Semen has not changed much since ancient times. Before the Qing dynasty，the plant origin of Persicae Semen was from the seeds of a kind of fruit named Shantao or Maotao，and in modern times，the seeds of Amygdalus persica or A. davidiana have become the major source. While different books have different views on Latin names for the origin of the Persicae Semen. We suggest that the Latin names of A. persica and A. davidiana should be more reasonable for Tao and Shantao respectively .In the concocting methods of Persicae Semen for activating vital energy and blood circulation，raw Persicae Semen should be used with peel and tip，while for moisturizing dryness，it should be fried into yellow without peel. Therefore，in the concocting methods of Persicae Semen for Taohe Chengqitang and Taohong Siwutang，the raw materials should be fried into yellow without peel or tip，while for Shentong Zhuyutang，raw Persicae Semen materials should be used with peel and tip. The indications of Persicae Semen include amenorrhea，lump，parasite，obstruction of chest，cough and asthma，constipation，etc.，and the people with blood deficiency，blood dryness and the pregnant women should use it with caution or should not use it. The modern clinical application of Persicae Semen is only a partial inheritance of ancient literature，which means that the Persicae Semen still has many effects to be verified and studied，and it is worthwhile for further exploration in order to expand its clinical application. The records of ancient literature on flavor，meridian tropism，and quality evaluation of Persicae Semen were consistent with those in Chinese Pharmacopoeia. Because of the similar appearance，it is especially difficult to distinguish Persicae Semen and Armeniacae Semenis Amarum after crushing ，requiring much time and money for identification. It is recommended that medical institutions should purchase Persicae Semen without crushing as far as possible，then decide the best concocting methods according to the clinical requirement.

The Shentong Zhuyutang is recorded in an ancient medical book named Yilin Gaicuo， and it is one of the classical prescriptions. Based on the literature reviewed，it is generally found that the Shentong Zhuyutang is evolved from the prescription named Chentongsan that recorded by Danxi Xinfa. Statistics on the dosage of clinical research on this prescription in recent years， reference to the textbook and pharmacopoeia dose， at the same time to respect the original dosage， verify historical changes， and ensure the safety of prescriptions， at the same time consider the pharmacy's dispenses， the author recommends that the clinical dosage of Shentong Zhuyutang could be 3 gram of Gentianae Macrophyllae Radix， 6 gram of Chuanxiong Rhizoma， 10 gram of Persicae Semen， 10 gram of Carthami Flos， 6 gram of Glycyrrhizae Radix Et Rhizoma， 3 gram of Notopterygii Rhizoma Et Radix， 5 gram of Myrrha， 12 gram of Angelicae Sinensis Radix， 5 gram of Cyperi Rhizoma，12 gram of Cyathulae Radix， and 6 gram of Pheretima used as a reference. The efficacy of the compound preparation can be marked as promoting blood circulation， removing blood stasis， removing wind and dampness， and relieving pain. At present， most of its research is focused on clinical research and experimental research， and there are few literature on the research of Shentong Zhuyutang from the level of key information verification. The diseases it treats include more than 10， such as Gubi， Pibi， Xuebi， shechuanchuan， headache， postpartum pain and dysmenorrhea， especially in the study of Gubi， which means that it has a huge market demand and broad development prospects in orthopedic diseases， the core point of "blood stasis and cold dampness evil" should be closely held in the course of treatment. Some scholars deem that Shentong Zhuyutang should not be used the method of Force Sweat in the treatment of Bizheng，while others believe that this prescription should be used with caution in menstruation， pregnancy and blood deficiency. Modern pharmacological studies have shown that Shentong Zhuyutang has obvious anti-inflammatory， relieve pain， anticoagulan， nerve and bone protection. In view of the fact that there are less researches on Shentong Zhuyutang except for Gubi， this suggests that the mechanism of this prescription treat other diseases has a relatively broad research space.

The classical prescription Kaixinsan，which is recorded in an ancient medical book named Beiji Qianjin Yaofang，is one of the famous prescriptions used by ancient physicians to treat amnesia. Research on classical prescriptions has attracted more and more attention from scientific research institutions and related enterprises. Based on ancient books，textual research on origins and development of prescriptions，combing the evolution of prescriptions，preparations，oral ways，taboos and others are the important contents of the study on classical prescriptions. The research results show that the creation of Kaixinsan in Beiji Qianjin Yaofang can be traced back to Kaixinsan recorded in Jiyanfang and Dingzhiwan recorded in Gujinluyanfang. Later generations of physicians created many associated prescriptions in the process of applying Kaixinsan，and the efficacy of these prescriptions was constantly expanded with the development of the times. In the Tang and Song dynasties，Kaixinsan and its associated prescriptions were mainly used to treat amnesia，sorrow，fear，and other diseases. In the Jin and Yuan dynasties，these prescriptions were also used to treat convulsions and yawning. In the Ming dynasty， they were mainly for the treatment of hyperopia， myopia， sprematorrhea，and constipation. In the Qing dynasty，these herbs could be used to treat auricular deafness， aging and sweating. The dosage of Ginseng Radix et Rhizoma and Poria should be increased in the treatment of farsightedness，spermatorrhea and blurred urine，and in the treatment of nearsightedness，the dosage of Polygalae Radix and Haliotidis Concha should be increased. The main pathogenesis of the disease that Kaixinsan and its associated prescriptions treated could be summarized as the deficiency of heart and spleen，imbalance between heart-Yang and kidney-Yin，and the internal resistance of phlegm stagnation. By summarizing the contents of the preparation of tradition Chinese medicine products for Kaixinsan and its associated prescriptions，it is suggested that the dosage form of Kaixinsan can be pills，with the specification size confroming to the most record of ancient generations of physicians，as big as Firmiana platanifolia's fruit.The volume of a single pill is about 0.25 mL and the weight is about 0.3 g. The initial dosage is fifteen pills，which can be modified according to the severity of the illness，with no more than forty pills for each time，three times a day. Also，some excitant food like the sour food，sweet food and mutton should be avoided during the medication. The above research results can provide literature basis for the development of compound tradition Chinese Medicine preparation of Kaixinsan.

OBJECTIVE: To investigate the molecular mechanisms underlying the effects of arsenic trioxide (As METHODS: Transplantation of LVG hamster hearts to Lewis rats was performed by anastomosis of vessels in the neck using end-to-end anastomosis with a non-suture cuff technique. Four groups of recipient rats (n=6 in each) were treated with normal saline (control), As RESULTS: Expression of Nrf2-ARE-HO-1 signaling pathway was upregulated in heart xenografts in rats treated with As CONCLUSION Combination treatment with As
Animals ; Arsenic Trioxide ; Cricetinae ; Heart Transplantation ; Heme Oxygenase-1/metabolism* ; Heterografts ; Leflunomide ; NF-E2-Related Factor 2/metabolism* ; Rats ; Rats, Inbred Lew ; Signal Transduction