Application of endoscopic retrograde cholangiopancreatography for treatment of obstructive jaundice after hepatoblastoma surgery: A case report.

BACKGROUND: We aimed to investigate the effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) for treating obstructive jaundice (OJ) post hepatoblastoma (HB) surgery (post-HB OJ) by analyzing the data of a case and performing a literature review. CASE SUMMARY: Clinical data of one patient with post-HB OJ treated by ERCP were retrospectively analyzed. Furthermore, clinical characteristics and insights into the diagnosis and treatment of post-HB OJ in children were summarized via searching various databases and platforms, such as China National Knowledge Infrastructure, Wanfang database, CQVIP database, PubMed, Ringer Link, and Google Scholar. The patient reported herein underwent five chemotherapy sessions after the diagnosis of HB and right hemihepatectomy after tumor size reduction; these were followed by two postoperative chemotherapy sessions. Three months postoperatively, the patient developed icteric sclera, strong tea-colored urine, and clay-like stools, and showed signs of skin itchiness; blood analysis showed significantly an increased conjugated bilirubin (CB) level (200.3 µmol/L). Following the poor efficacy of anti-jaundice and hepatoprotective treatments, the patient underwent ERCP. Intraoperative imaging showed a dilated bile duct in the porta hepatis with significant distal stenosis. A 5 Fr nasopancreatic tube was placed in the dilated area through the stricture for external drainage, and the patient was extubated on postoperative day 6. Postoperatively, the patient's stool turned yellow, and the CB level decreased to 78.2 µmol/L. Fifteen days later, ERCP was repeated due to unrelieved jaundice symptoms, wherein a 7 Fr nasobiliary drainage tube was successfully placed. Three months post-ERCP, the jaundice symptoms resolved, and the CB level was reduced to 33.2 µmol/L. A follow-up examination one year postoperatively revealed no jaundice symptoms and normal CB level. CONCLUSION: Post-HB OJ is rare. Compared to biliary tract reconstruction, ERCP is less invasive and has a better therapeutic effect.

Pediatric Classic Prescription Xiaoruwan Based on Ancient Literature / 中国实验方剂学杂志

Xiaoruwan is one of the classic prescriptions included in the Catalogue of Ancient Classic Prescriptions （the Second Batch of Pediatrics） published by the National Administration of Traditional Chinese Medicine（TCM） in 2022 with definite clinical efficacy， but it has not been converted into Chinese patent medicine preparations. The authors collected 173 pieces of data based on ancient literature on Xiaoruwan by the method of bibliometrics and selected 99 pieces of effective data， involving 46 ancient books of TCM. The study analyzed the historical development origin， prescription names， formulation rules， dosage， drug origin， preparation method and usage， indications and functions， and other aspects of Xiaoruwan. The results showed that Xiaoruwan was presumably derived from Ying Hai Miao Jue Lun（《婴孩妙诀论》） written by TANG Minwang， a doctor in the Song Dynasty. In the records of ancient medical books， there are names such as Xiaoshiwan，Yangshi Xiaoruwan， and Kuaige Xiaoshiwan， but they are mainly recorded in the name of Xiaoruwan. The prescription was composed of Cyperi Rhizoma， Amomi Fructus， Citri Reticulatae Pericarpium， Massa Medicata Fermentata， Hordei Fructus Germinatus， and Glycyrrhizae Radix et Rhizoma. In terms of processing method， Cyperi Rhizoma， Massa Medicata Fermentata， and Hordei Fructus Germinatus are fried， Glycyrrhizae Radix et Rhizoma is processed， and raw materials of Amomi Fructus and Citri Reticulatae Pericarpium are used directly. In terms of function， it is effective in warming the middle， improving digestion， stopping vomiting， and digesting milk and food. The main indications include vomiting， diarrhea， night crying， and other diseases caused by milk and food stagnation. The dosage of the most used prescription in the records of ancient books is Cyperi Rhizoma 41.30 g， Amomi Fructus 20.65 g， Citri Reticulatae Pericarpium 20.65 g， Massa Medicata Fermentata 20.65 g， Hordei Fructus Germinatus 20.65 g， and Glycyrrhizae Radix et Rhizoma 20.65 g， which are prepared into pills. In the taking method， it is recommended to take it with warm boiled water or ginger soup after meals. The study summarized the historical evolution of Xiaoruwan and identified the key information， with a view to providing a reference for the modern development and research of Xiaoruwan.

Effectiveness and Safety of Chinese Medicine at Shenque (CV 8) for Primary Dysmenorrhea: A Systematic Review and Meta-Analysis of Randomized Controlled Trials / 中国结合医学杂志

BACKGROUND@#Primary dysmenorrhea (PD) is the most common complaint associated with menstruation and affects up to three-quarters of women at some stage of their reproductive life. In Chinese medicine, navel therapy, treatment provided at Shenque (CV 8), is used as a treatment option for PD.@*OBJECTIVE@#To evaluate the effect of navel therapy on pain relief and quality of life in women with PD, compared with Western medicine (WM).@*METHODS@#China National Knowledge Infrastructure (CNKI), Chinese Scientific Journal Database (VIP), SinoMed and Wanfang Database, MEDLINE, the Cochrane Library, Embase, Web of Science, and the International Clinical Trial Registry of the U.S. National Institutes of Health were searched from their inceptions to April 1, 2021. Randomized controlled trials (RCTs) assessing therapeutic effects of navel therapy on PD were eligible for inclusion. RevMan 5.4 software was used for data analyses. The certainty of the evidence was assessed using the online GRADEpro tool.@*RESULTS@#Totally 24 RCTs involving 2,614 participants were identified. Interventions applied to acupuncture point CV 8 included: herbal patching, moxibustion or combined navel therapy (using at least 2 types of stimulation). Compared to placebo, there was a significant effect in favor of navel therapy on reducing overall menstrual symptom scores at the end of treatment [mean difference: -0.82, 95% confidence interval (CI): -1.00 to -0.64, n=90; 1 RCT]. As compared with Western medicine, navel therapy had a superior effect on pain intensity as assessed by Visual Analogue Scale at the end of treatment [standardized mean difference (SMD): -0.64, 95% CI: -1.22 to -0.06, I2=80%, n=262; 3 RCTs]; on symptom resolution rate at 3-month follow-up (risk ratio: 1.94, 95% CI: 1.47 to 2.56, n=1527, I2=38%; 13 RCTs); and on global menstrual symptoms score at the end of treatment (SMD: -0.67, 95% CI: -0.90 to -0.45, I2=63%, n=990; 12 RCTs). Subgroup analyses showed either a better or an equivalent effect comparing navel therapy with Western medicine. No major adverse events were reported. The methodological quality of included trials was poor overall.@*CONCLUSIONS@#Navel therapy appears to be more effective than Western medicine in decreasing menstrual pain and improving overall symptoms of PD. However, these findings need to be confirmed by well-designed clinical trials with adequate sample size (Systematic review registration at PROSPERO, No. CRD42021240350).

Mechanism of hyperproteinemia-induced blood cell homeostasis imbalance in an animal model.

Hyperproteinemia is a metabolic disorder associated with increased plasma protein concentration (PPC) and is often clinically complicated by malignant diseases or severe infections. At present, however, research on the molecular mechanism underlying high PPC (HPPC) is scant. Here, an animal model of primary hyperproteinemia was constructed in an invertebrate ( Bombyx mori) to investigate the effects of HPPC on circulating blood cells. Results showed that HPPC affected blood cell homeostasis, leading to increased reactive oxygen species levels, and induced programmed cell death dependent on the endoplasmic reticulum-calcium ion signaling pathway. HPPC induced the proliferation of blood cells, mainly granulocytes, by activating the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway. Supplementation with the endocrine hormone active substance 20E significantly reduced the impact of HPPC on blood cell homeostasis. Thus, we identified a novel signaling pathway by which HPPC affects blood cell homeostasis, which differs from hyperglycemia, hyperlipidemia, and hypercholesterolemia. In addition, we showed that down-regulation of gene expression of the hematopoietic factor Gcm could be used as a potential early detection indicator for hyperproteinemia.

DNA Methylation and Transcription of HLA-F and Serum Cytokines Relate to Chinese Medicine Syndrome Classification in Patients with Chronic Hepatitis B / 中国结合医学杂志

OBJECTIVE@#To explore the molecular bases of Chinese medicine (CM) syndrome classification in chronic hepatitis B (CHB) patients in terms of DNA methylation, transcription and cytokines.@*METHODS@#Genome-wide DNA methylation and 48 serum cytokines were detected in CHB patients (DNA methylation: 15 cases; serum cytokines: 62 cases) with different CM syndromes, including dampness and heat of Gan (Liver) and gallbladder (CHB1, DNA methylation: 5 cases, serum cytokines: 15 cases), Gan stagnation and Pi (Spleen) deficiency (CHB2, DNA methylation: 5 cases, serum cytokines: 15 cases), Gan and Shen (Kidney) yin deficiency (CHB3, DNA methylation: 5 cases, serum cytokines: 16 cases), CHB with hidden symptoms (HS, serum cytokines:16 cases) and healthy controls (DNA methylation: 6 cases). DNA methylation of a critical gene was further validated and its mRNA expression was detected on enlarged samples. Genome-wide DNA methylation was detected using Human Methylation 450K Assay and furthered verified using pyrosequencing. Cytokines and mRNA expression of gene were evaluated using multiplex biometric enzyme-linked immunosorbent assay (ELISA)-based immunoassay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively.@*RESULTS@#Totally 28,667 loci, covering 18,403 genes were differently methylated among CHB1, CHB2 and CHB3 (P<0.05 and |Δβ value| > 0.17). Further validation showed that compared with HS, the hg19 CHR6: 29691140 and its closely surrounded 2 CpG loci were demethylated and its mRNA expressions were significantly up-regulated in CHB1 (P<0.05). However, they remained unaltered in CHB2 (P>0.05). Levels of Interleukin (IL)-12 were higher in CHB3 and HS than that in CHB1 and CHB2 groups (P<0.05). Levels of macrophage inflammatory protein (MIP)-1α and MIP-1β were higher in CHB3 than other groups and leukemia inhibitory factor level was higher in CHB1 and HS than CHB2 and CHB3 groups (P<0.05). IL-12, MIP-1α and MIP-1β concentrations were positively correlated with human leukocyte antigen F (HLA-F) mRNA expression (R2=0.238, P<0.05; R2=0.224, P<0.05; R=0.447, P<0.01; respectively). Furthermore, combination of HLA-F mRNA and differential cytokines greatly improved the differentiating accuracy among CHB1, CHB2 and HS.@*CONCLUSIONS@#Demethylation of CpG loci in 5' UTR of HLA-F may up-regulate its mRNA expression and HLA-F expression was associated with IL-12, MIP-1α and MIP-1β levels, indicating that HLA-F and the differential cytokines might jointly involve in the classification of CM syndromes in CHB.@*REGISTRATION NO@#ChiCTR-RCS-13004001.

Comparison of two starch-based flocculants with polyacrylamide for the simultaneous removal of phosphorus and turbidity from simulated and actual wastewater samples in combination with FeCl3.

Two laboratory-made cationic starch-based flocculants (St-CTA and St-AD) with different chain architectures were used to simultaneously remove phosphorus and turbidity from two simulated wastewaters and one actual wastewater with laboratory and pilot scales, respectively, in conjunction with FeCl3. A commercial polyacrylamide (PAM) has been also tried and compared with aforementioned starch-based flocculants. The removal extents of phosphorus and turbidity increased, the required dosages of FeCl3 decreased, and floc properties improved after dosing each polymeric flocculant after FeCl3 in all tested wastewaters due to their synergistic effects. However, the three flocculants exhibited different improvement efficiencies on the treated wastewaters containing different forms of phosphorus and showed various synergistic mechanisms owing to their distinct structural features. In inorganic-phosphorus-simulated wastewater, the linear nonionic PAM with a high molecular weight had a more notable contribution than the two starch-based flocculants due to its efficient bridging flocculation effect. Given the branched-chain structure and high positive charge density of St-AD, it had a higher efficiency in treating real wastewater and organic-phosphorus-simulated wastewater than PAM and linear cationic St-CTA. These results may serve as references for the design and selection of a suitable flocculant in treating target wastewaters.

New terpenoids and triketides from culture of the fungus Botrysphaeria laricina.

Three new isopimarane-type diterpenoids, botrysphins G-I (1-3), a new muurolane-type sesquiterpenoid, 11,12-dihydroxylentideusether (4), and two new triketides, 4-dechlorobotrysphone C (5) and 4,5-dihydroxy-3-methoxy-6-undecanoyloxy-2-cyclohexen-1-one (6), together with one known diterpenoid, sphaeropsidin A (7), one sesquiterpenoid, lentideusether (8), and one triketide sphaeropsidone (9), were isolated from culture of the fungus Botrysphaeria laricina associated with the moss Rhodobryum umgiganteum. The structures of the new compounds were established on the basis of extensive spectroscopic techniques including HRMS and 1D and 2D NMR data. Compounds 1 and 2 exhibited NO inhibitory activity with IC50 values of 13.9 µM and 41.9 µM, respectively. At the same time, these two compounds showed quinone reductase inducing activity with 2.7-fold of induction for 1 at 12.5 µM and 1.6-fold for 2 at 25.0 µM.

PEAMOtecan, a novel chronotherapeutic polymeric drug for brain cancer.

Glioblastoma multiforme (GBM) is an aggressive and difficult to treat form of brain cancer. In this work, we report on a novel chronotherapeutic polymeric drug, PEAMOtecan, for GBM therapy. PEAMOtecan was synthesized by conjugating camptothecin, a topoisomerase I inhibitor, to our proprietary, 'clickable' and modular polyoxetane polymer platform consisting of acetylene-functionalized 3-ethyl-3-(hydroxymethyl)oxetane (EAMO) repeat units (Patent No.: US 9,421,276) via the linker 3,3'-dithiodipropionic acid (DDPA) with a disulfide bond (SS) extended by short-chain polyethylene glycol (PEG). We show that PEAMOtecan is a highly modular polymer nanoformulation that protects covalently bound CPT until slowly being released over extended periods of time dependent on the cleavage of the disulfide and ester linkages. PEAMOtecan kills glioma cells by mitotic catastrophe with p53 mutant/knockdown cells being more sensitive than matched wild type cells potentially providing cancer-specific targeting. To establish proof-of-principle therapeutic effects, we tested PEAMOtecan as monotherapy for efficacy in a mouse orthotopic glioma model. PEAMOtecan was administered by one-time, convection-enhanced delivery (CED) intra-tumorally to achieve superior distribution and extended drug release over time. In addition, the near-infrared (NIR) dye Cy5.5 was coupled to the polymer providing live-animal imaging capability to track tissue distribution and clearance of the injected polymer over time. We show that PEAMOtecan significantly improves the survival of mice harboring intra-cranial tumors (p = .0074 compared to untreated group). Altogether, these results support further development and testing of our nanoconjugate platform.

Efficient removal of phosphorus from turbid water using chemical sedimentation by FeCl3 in conjunction with a starch-based flocculant.

Phosphorus removal is an important issue in the field of water and wastewater treatment. In this study, a starch-based flocculant (St-CTA), as an assisting agent, was fed after the application of traditional inorganic precipitant of ferric chloride (FeCl3) to remove inorganic and organic phosphorus from their respective simulated turbid wastewaters. The effects of various influencing factors, including CTA content of St-CTA, dosage, initial pH, initial turbidity, and initial total phosphorus (TP), were investigated systematically. This modified chemical sedimentation process assisted by St-CTA not only showed high efficient in removing TP and turbidity but also evidently reduced the required dosage of FeCl3. This combination exhibited better efficiency in removing organic TP than in removing inorganic TP from water. The synergistic mechanisms of FeCl3 and St-CTA were discussed in detail by combination of apparent removal effects and floc properties. St-CTA exhibits strong charge neutralization and bridging flocculation effects and can thus efficiently aggregate and precipitate various phosphorus and iron complexes previously formed through chemical sedimentation, adsorption, and chelation. Besides, the validation of this combination usage was further confirmed by treating a real wastewater, and half of the required FeCl3 dosage and one third of the total cost were saved after addition of only 0.4 mg/L St-CTA when 90% TP and 95% turbidity were reduced. This study thus provided a novel technique for the diminution of TP and turbidity in turbid wastewater, considerable reduction of FeCl3 dosage and final cost, and lowering of secondary pollution risk.

Advances in Research on Different Compatibility Ratios of Coptidis Rhizoma-Evodia Fructus / 中国实验方剂学杂志

Coptidis Rhizoma-Evodia Fructus is a classic herb pair in traditional Chinese medicine prescriptions, the famous prescription is called Zuojinwan, which comes from Danxi Xinfa, is composed of Coptidis Rhizoma-Evodia Fructus (6∶1). In this formula, Coptidis Rhizoma has the effect of clearing heat and drying diuresis, purging fire to remove toxin and clearing heart. Evodia Fructus has the effects of expelling cold and alleviating pain, checking upward adverse flow of Qi tostop vomiting, and assisting yang to stop diarrhea. Coptidis Rhizoma has the properties of bitter and cold, and Evodia Fructus has the properties of pungent and calidus. Pungent drugs have divergent effects, and bitter drugs have sedimentation effect, when used in combination, they can clear the liver and purge fire, calm the adverse-rising energy and stop vomiting. On the basis of Zuojinwan, Coptidis Rhizoma-Evodia Fructus medicine has derived different compatibility ratios. Different ratios are different in terms of efficacy, usage, clinical application. Although with the application of modern analytical instruments and the development of molecular pharmacology theory, the chemical constituents and Pharmacological effects of Coptidis Rhizoma and Evodia Fructus have been fully studied, as to the principle of compatibility, and the study of pharmacological effects and chemical constituents after the compatibility of the two drugs in different proportions, there is still no comprehensive system summary. This article makes a systematic and comprehensive explanation of Coptidis Rhizoma-Evodia Fructus from the aspects of famous literature, chemical composition, pharmacological effects and clinical applicationthrough querying literature and ancient books. In order to make this herb pair more standardized, and provide reference materials for further research and development for this herb pair.

The role of ferroptosis in digestive system cancer.

Ferroptosis is a type of regulated cell death dependent on iron and reactive oxygen species. Ferroptosis is distinct from other cell death modalities, including apoptosis, autophagy and necrosis. Dysregulated ferroptosis has been implicated in a number of diseases, including neuropathy, ischemia reperfusion injury, acute kidney failure and cancer. The digestive system consists of several organs. The morbidity and mortality rates of digestive system cancer are high. The current review summarizes the role of ferroptosis in digestive system cancer. A large number of molecules, including tumor protein p53, retinoblastoma protein, nuclear factor E2-related factor 2, KH RNA binding domain containing signal transduction associated 1, cysteine dioxygenase type 1, metallothionein-1G, nuclear receptor coactivator 4, CDGSH iron sulfur domain 1, heat shock protein family A (Hsp70) member 5 and acyl-CoA synthetase long chain family member 4, regulate ferroptosis in digestive system cancer. Drugs such as cisplatin, baicalein, haloperidol, artesunate, piperlongumine, saponin and bromelain may cause cancer cell death by inducing ferroptosis. An improved understanding of ferroptosis in digestive system cancer may give rise to novel diagnostic and making therapeutic strategies.

Highly efficient inhibition of spring viraemia of carp virus replication in vitro mediated by bavachin, a major constituent of psoralea corlifonia Lynn.

As one of nine piscine viruses recognized by the International Office of Epizootics, spring viraemia of carp virus (SVCV) is an important pathogen bringing high mortality to cyprinids. Up to now, there is no approved therapy on SVCV, making them strong public health threat in aquaculture. In this study, the anti-SVCV activities of 12 plant crude extracts were investigated by using epithelioma papulosum cyprini (EPC) cells. Among these plants, Psoralea corylifolia Linn. showed the highest inhibition on SVCV replication, with an inhibitory percentage of 67.98%. Further studies demonstrated that bavachin (BVN), one of the major constituents of Psoralea corylifolia Linn., was also highly effective to SVCV infection. The half maximal inhibitory concentrations (IC50) of BVN on SVCV glycoprotein and nucleoprotein expression were 0.46 (0.29-0.73) and 0.31 (0.13-0.55) mg/L, respectively. In addition, SVCV-induced apoptosis which may be negative to SVCV replication was inhibited by BVN. The apoptotic cells were decreased 21.42% for BVN compared with SVCV group. These results indicated that the inhibition of BVN on SVCV replication was, in some extent, via blocking SVCV induced apoptosis. Furthermore, cellular morphological damage induced by SVCV was also blocked by BVN treatment. Mechanistically, BVN did not affect SVCV infectivity and cannot be used for prevention of SVCV infection. Time-of-addition and viral binding assays revealed that BVN mainly inhibited the early events of SVCV replication but did not interfere with SVCV adsorption. In conclusion, BVN was considered to develop as a promising agent to treat SVCV infection.

Bubble-generating polymersomes loaded with both indocyanine green and doxorubicin for effective chemotherapy combined with photothermal therapy.

The combination of chemotherapy and photothermaltherapy (PTT) via stimuli-responsive nanovesicles has great potential in tumor treatment. In the present study, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug and photosensitizing agent for the synergistic chemo-photothermal tumor therapy. Photosensitizer indocyanine green (ICG) was encapsulated into the bilayer of polymersomes formed by amphiphilic triblock copolymer PCL8000-PEG8000-PCL8000 through thin film re-hydration method, while chemotherapeutic doxorubicin (DOX) was loaded into the hydrophilic lumen using a transmembrane ammonium bicarbonate gradient loading procedure. Under acidic condition or laser irradiation, the ammonium bicarbonate (NH4HCO3) encapsulated in the bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would decompose to produce CO2 bubbles, resulting in destruction of vesicle structure and rapid drug release. In vitro drug release study confirmed that acidic environment and NIR laser irradiation could accelerate DOX release from the BG-DIPS. Cellular uptake study indicated that laser-induced hyperthermia highly enhanced endocytosis of BG-DIPS into 4T1-Luc cancer cells. In vitro cytotoxicity study demonstrated that BG-DIPS exhibited much higher cytotoxicity than free drugs under laser irradiation. In vivo biodistribution study indicated that BG-DIPS could accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. Furthermore, in vivo antitumor study showed that BG-DIPS with laser irradiation efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli-response controlled drug delivery and combination chemo-photothermal tumor therapy. STATEMENT OF SIGNIFICANCE: The combination of chemotherapy and photothermaltherapy via stimuli-responsive nanovesicles has great potential in tumor treatment. Herein, bubble-generating polymersomes, which can generate bubbles in response to low pH or hyperthermia, were fabricated to simultaneously encapsulate chemotherapeutic drug (DOX) and photosensitizing agent (ICG) for the synergistic chemo-photothermal tumor therapy. The results in vitro and in vivo demonstrated that bubble-generating DOX-ICG-co-delivery polymersomes (BG-DIPS) would accelerate DOX release from the BG-DIPS and accumulate in the tumor region, prolong drug retention, and increase photothermal conversion efficiency. BG-DIPS with laser irradiation could efficiently inhibited 4T1-Luc tumor growth with reduced systemic toxicity. Hence, the formulated bubble-generating polymersomes system was a superior multifunctional nanocarrier for stimuli-response controlled drug delivery and combination chemo-photothermal tumor therapy.

DenTimol as A Dendrimeric Timolol Analogue for Glaucoma Therapy: Synthesis and Preliminary Efficacy and Safety Assessment.

In this work, we report the synthesis and characterization of DenTimol, a dendrimer-based polymeric timolol analog, as a glaucoma medication. A timolol precursor ( S)-4-[4-(oxiranylmethoxy)-1,2,5-thiadiazol-3-yl]morpholine (OTM) was reacted with the heterobifunctional amine polyethylene glycol acetic acid (amine-PEG-acetic acid, Mn = 2000 g/mol) via a ring opening reaction of an epoxide by an amine to form the OTM-PEG conjugate. OTM-PEG was then coupled to an ethylenediamine (EDA) core polyamidoamine (PAMAM) dendrimer G3 to generate DenTimol using the N-(3-(dimethylamino)propyl)- N'-ethylcarbodiimide hydrochloride (EDC)/ N-hydroxysuccinimide (NHS) coupling reaction. MALDI mass spectrometry, 1H NMR spectroscopy, and HPLC were applied to characterize the intermediate and final products. Ex vivo corneal permeation of DenTimol was assessed using the Franz diffusion cell system mounted with freshly extracted rabbit cornea. The cytotoxicity of DenTimol was assessed using the WST-1 assay. Our results show that DenTimol is nontoxic up to an OTM equivalent concentration of 100 µM. DenTimol is efficient at crossing the cornea. About 8% of the dendrimeric drug permeated through the cornea in 4 h. Its IOP-lowering effect was observed in normotensive adult Brown Norway male rats. Compared to the undosed eye, an IOP reduction by an average of 7.3 mmHg (∼30% reduction from baseline) was observed in the eye topically treated with DenTimol (2 × 5 µL, 0.5% w/v timolol equivalent) in less than 30 min. Daily dosing of DenTimol for a week did not cause any irritation or toxicity as confirmed by the histological examination of ocular tissues, including the cornea, ciliary body, and retina.

Advances in the antitumor activities and mechanisms of action of steroidal saponins / 中国天然药物

The steroidal saponins are one of the saponin types that exist in an unbound state and have various pharmacological activities, such as anticancer, anti-inflammatory, antiviral, antibacterial and nerves-calming properties. Cancer is a growing health problem worldwide. Significant progress has been made to understand the antitumor effects of steroidal saponins in recent years. According to reported findings, steroidal saponins exert various antitumor activities, such as inhibiting proliferation, inducing apoptosis and autophagy, and regulating the tumor microenvironment, through multiple related signaling pathways. This article focuses on the advances in domestic and foreign studies on the antitumor activity and mechanism of actions of steroidal saponins in the last five years to provide a scientific basis and research ideas for further development and clinical application of steroidal saponins.

Advances in the antitumor activities and mechanisms of action of steroidal saponins / 中国天然药物

The steroidal saponins are one of the saponin types that exist in an unbound state and have various pharmacological activities, such as anticancer, anti-inflammatory, antiviral, antibacterial and nerves-calming properties. Cancer is a growing health problem worldwide. Significant progress has been made to understand the antitumor effects of steroidal saponins in recent years. According to reported findings, steroidal saponins exert various antitumor activities, such as inhibiting proliferation, inducing apoptosis and autophagy, and regulating the tumor microenvironment, through multiple related signaling pathways. This article focuses on the advances in domestic and foreign studies on the antitumor activity and mechanism of actions of steroidal saponins in the last five years to provide a scientific basis and research ideas for further development and clinical application of steroidal saponins.

Key symptoms selection for two major syndromes diagnosis of Chinese medicine in chronic hepatitis B / 中国结合医学杂志

<p><b>OBJECTIVE</b>To identify key symptoms of two major syndromes in chronic hepatitis B (CHB), which can be the clinical evidence for Chinese medicine (CM) doctors to make decisions.</p><p><b>METHODS</b>Standardization scales on diagnosis for CHB in CM were designed including physical symptoms, tongue and pulse appearance. The total of 695 CHB cases with dampness-heat (DH) syndrome or Pi (Spleen) deficiency (SD) syndrome were collected for feature selection and modeling, another 275 CHB patients were collected in different locations for validation. Key symptoms were selected based on modified information gain (IG), and 5 classifiers were applied to assist with models training and validation. Classification accuracy and area under receiver operating characteristic curves (AUC) were evaluated.</p><p><b>RESULTS</b>(1) Thirteen DH syndrome key symptoms and 13 SD syndrome key symptoms were selected from original 125 symptoms; (2) The key symptoms could achieve similar or better diagnostic accuracy than the original total symptoms; (3) In the validation phase, the key symptoms could identify syndromes effectively, especially in DH syndrome, which average prediction accuracy on 5 classifiers could achieve 0.864 with the average AUC 0.772.</p><p><b>CONCLUSION</b>The selected key symptoms could be simple DH and SD syndromes diagnostic elements applied in clinical directly. (Registration N0.: ChiCTR-DCC-10000759).</p>

Impact of fluorescent silicon nanoparticles on circulating hemolymph and hematopoiesis in an invertebrate model organism.

Silicon nanoparticles (SiNPs) have attractive potential applications in biological and medical fields, and yet their impact on animals is still controversial, and there have been no reports of their effects on hematopoiesis. In this study, the effects of SiNPs on hemocytes and hematopoiesis were investigated by administering SiNPs via a vascular injection into an invertebrate model, the silkworm. Our results show that the ability of SiNPs to enter different types of circulating hemocytes and their impact on those hemocytes differed significantly. Rapid accumulation of SiNPs was observed in granulocytes, oenocytoids, and spherulocytes, which have immune functions in the circulating hemolymph, whereas SiNPs did not easily enter prohemocytes, which can differentiate into granulocytes, oenocytoids, and spherulocytes and replenish them. The SiNPs that entered the hemocytes initiated autophagy and apoptosis via the lysosomal/mitochondrial pathway. High-dose SiNPs weakly stimulated lysosomal activity in hematopoietic organs, but did not lead to a significant increase in reactive oxygen species or severe autophagy or apoptosis in the organ tissues. We suggest that the damage caused by high-dose SiNPs to hematopoiesis is self-healing, because few SiNPs entered the hematopoietic stem cells in the circulating hemolymph, so the damage to the hematopoietic tissues was limited.

Improvement Strategies for Chinese Herbal Medicine Packaging / 中国中医药信息杂志

There are several disadvantages on the packaging of Chinese herbal medicine, such as unified packaging specification, misused packaging material and uncompleted or no packaging label information. These problems usually result in low quality of medicine, and will bring negative effects on the industry in the long term. Moreover, packaging design is usually too ordinary, without any regional features. Improving the packaging quality and changing the packaging style do not only make Chinese herbal medicine become “safe medicine” or “environmental-friendly medicine”, but also an important measure to raise the competitive power of Chinese herbal medicine in markets at home and abroad.

A pragmatic observational feasibility study on integrated treatment for musculoskeletal disorders: Design and protocol / 中国结合医学杂志

<p><b>BACKGROUND</b>Musculoskeletal disorders (MSD) comprise a wide range of conditions, associated with an enormous pain and impaired mobility, and are affecting people's lives and work. Management of musculoskeletal disorders typically involves a multidisciplinary team approach. Positive findings have been found in previous studies evaluating the effectiveness of complementary therapies, though little attention has been paid to evaluating of the effectiveness of integrated packages of care combining conventional and complementary approaches for musculoskeletal conditions in a National Health Service (NHS) setting.</p><p><b>OBJECTIVE</b>To determine the feasibility of all aspects of a pragmatic observational study designed: (1) to evaluate the effectiveness and cost effectiveness of integrated treatments for MSDs in an integrated NHS hospital in the UK; (2) to determine the acceptability of the study design and research process to patients; (3) to explore patients' expectation and experience of receiving integrated treatments.</p><p><b>METHODS</b>This is an observational feasibility study, with 1-year recruitment and 1-year follow-up, conducted in Royal London Hospital for Integrated Medicine, University College London Hospital Trust, UK. All eligible patients with MSDs newly referred to the hospital were included in the study. Interventions are integrated packages of care (conventional and complementary) as currently provided in the hospital. SF-36™ Health Survey, short form Brief Pain Inventory, Visual Analogue Scale, and modified Client Service Receipt Inventory will be assessed at 4/5 time points. Semi-structured interview/focus group will be carried out before treatment, and 1 year after commence of treatment.</p><p><b>DISCUSSION</b>We intend to conduct a pragmatic observational study of integrated medical treatment of MSDs at a public sector hospital. It will inform the design of a future trial including recruitment, retention, suitability of the outcome measures and patients experiences.</p>