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As an independent medical system, the scientific value behind traditional Chinese medicine (TCM) is gaining appreciation because of growing evidence about mechanisms and efficacy. The aim of this special issue is to introduce this ancient medicine to readers through the compiled research papers focusing on TCM. The papers in this issue cover many research fields such as TCM theory, traditional Chinese prescription, syndrome biomarkers, and acupuncture. In particular for acupuncture, the focus on the history of acupuncture, the importance of precise acupoint positioning, the effect of Fu's subcutaneous needling among patients with shoulder pain, and the effect of electroacupuncture on senile plaque and insulin signaling pathway in the olfactory bulb of transgenic mice. By combining, the papers in this issue and TCM papers published elsewhere provide scientific evidence to improve understanding this ancient Oriental form of medicine.

Multidrug‐resistant tuberculosis (MDR‐TB), defined as tuberculosis (TB) resistant to at least isoniazid and rifampicin, is a major concern of TB control worldwide. However, the diagnosis of MDR‐TB remains a huge challenge to its prevention and control. To identify new diagnostic methods for MDR‐TB, a mass spectrometry strategy of data‐independent acquisition and parallel reaction monitoring was used to detect and validate differential serum proteins. The bioinformatic analysis showed that the functions of differential serum proteins between the MDR‐TB group and the drug‐sensitive tuberculosis group were significantly correlated to the complement coagulation cascade, surface adhesion and extracellular matrix receptor interaction, suggesting a disorder of coagulation in TB. Here, we identified three potential candidate biomarkers such as sCD14, PGLYRP2 and FGA, and established a diagnostic model using these three candidate biomarkers with a sensitivity of 81.2%, a specificity of 90% and the area under the curve value of 0.934 in receiver operation characteristics curve to diagnose MDR‐TB. Our study has paved the way for a novel method to diagnose MDR‐TB and may contribute to elucidate the mechanisms underlying MDR‐TB.

Yin-deficiency-heat (YDH) syndrome is a common sub-health state of the human body in traditional Chinese medicine (TCM). However, due to the lack of objective quantitative diagnostic indicators, patients with early-stage YDH syndrome cannot be treated in time and can develop a pathological (disease) state. Therefore, it is necessary to apply modern diagnostic techniques in order to identify the biological markers for the diagnosis of early-stage YDH syndrome. In the present study, we performed Solexa sequencing and non-targeted metabolomics analysis using high-performance liquid chromatography coupled with mass spectrometry to screen differentially expressed mRNAs and differential metabolites in individuals with early-stage YDH syndrome and healthy controls. Bioinformatics methods were used to perform enrichment analysis of differentially expressed mRNAs and differential metabolites for biological functions and signaling pathways. Furthermore, we found that differentially expressed mRNAs and differential metabolites were related to energy metabolism. Real-time PCR was used to validate the mRNA expression in the serum of subjects with early-stage YDH syndrome. We found that the mitochondrially encoded NADH dehydrogenase 2 (MT-ND2) mRNA was differentially expressed in the serum of individuals with early-stage YDH syndrome. Receiver operating characteristic (ROC) curve and logistic regression analysis were used to evaluate the efficacy of the diagnostic model based on eight differential metabolites. We combined the three metabolites such as Glycine, Sphingomyelin, and Isocitrate to establish the diagnostic model with a sensitivity of 0.853 and a specificity of 0.800. The combination of the above three metabolites may serve as a potential biomarker for the diagnosis of early-stage YDH syndrome. Our study reveals potential biomarker for the diagnosis of early-stage YDH syndrome and also provides a new method for the quantification and objectification of TCM syndromes.

To illustrate the mechanism of lymphatic reabsorption in knee joint effusion. The current investigation employed transmission electron microscopy (TEM) and scanning electron microscopy (SEM) techniques to reveal the ultrastructure of the knee synovial membrane in New Zealand rabbits and human. Ultrastructural changes of the synovial lymphatic stomata were observed by using trypan blue absorption and sodium hydroxide (NaOH) digestion methods, and the animal models of synovitis. New Zealand rabbits and human synovial membranes were composed of two types of synovial cells: type A and type B. No lymphatic stomata were found among type A synovial cells, whereas lymphatic stomata with the diameters ranging 0.74-3.26 µm were found in type B synovial cells, and some stomata were closed. After the NaOH digestion, a number of sieve pores, similar to lymphatic stomata in size and shape, were observed in the dense fibrous connective tissue underneath the type B synovial cells. After injecting trypan blue into the rabbit knee joint cavity, absorption of trypan blue through the lymphatic stomata was observed, suggesting the absorption function of the synovial lymphatic stomata. In the rabbit knee joint synovitis models, the synovial lymphatic stomata diameter enlarged. Some macrophages migrated from the lymphatic stomata, indicating that the synovial lymphatic stomata were involved in the joint effusion absorption and inflammatory response. Our study is the first to report the existence of synovial lymphatic stomata in the New Zealand rabbits and human knee joints. Lymphatic stomata may have an important role in the reabsorption of joint effusion.

Although several studies detected the BRCA1 germ-line mutations in Chinese women with familial breast cancer, most of them did not employ conventional full gene sequencing, especially in eastern China. In addition, the clinicopathological features of BRCA1-associated breast cancer in Chinese women were not well investigated. In this study, we screened the complete coding regions and exon-intron boundaries of BRCA1 by polymerase chain reaction (PCR)-sequencing assay. Immunohistochemistry analyses were performed on tumor samples to detect the expression of estrogen receptor (ER), progesterone receptor (PR), P53, and human epidermal growth factor receptor-2 (HER-2). Breast cancer patients having one or more affected relatives referred from the Zhejiang Cancer Hospital, eastern China during 2008-2011 were selected for the study. A total of 62 familial breast cancer patients received the BRCA1 germ-line mutation screening. Five deleterious mutations were detected in this cohort. The mutation rate was 11.3% (7/62). We found two novel mutations (3414delC and 5,280 C > T) and two recurrent mutations (5,273 G > A and 5589del8). BRCA1 mutation tumors tended to be negative for ER, PR, and HER-2, and exhibited high histological grade compared with tumors without BRCA1 mutations. Our study suggests that recurrent mutations may exist in eastern Chinese women with familial breast cancer and PCR-sequencing assay is a useful tool to screen these mutations. It also suggests that BRCA1-associated breast cancers in Chinese women exhibit an aggressive phenotype.

The discovery of a nonphagocytotic process of cell-in-cell phenomena can be traced to over a century ago. However, its biological significance remains poorly understood. Three types of cell-in-cell phenomena have been described so far, termed "cannibalism," "emperipolesis," and "entosis." These three kinds of cell-in-cell phenomena, apart from a common feature of one cell internal to another, are distinct both cytologically and biologically. In this review, we discussed them in their morphology, cell recognition, penetration mechanisms, and physiological roles, respectively.

Trichosanthin (TCS) is a type I ribosome-inactivating protein that is isolated from the root tubers of the Chinese medicinal herb Trichosanthes kirilowii Maximowicz. TCS has been used as an abortifacient for 1,500 years in China because of its high toxicity on trophoblasts. Over the past 20 years, TCS has been the subject of much research because of its potential antitumor activities. Many reports have revealed that TCS is cytotoxic in a variety of tumor cell lines in vitro and in vivo. Monoclonal antibody-conjugated TCS could enhance its antitumor efficacy; thus, TCS is considered to be a potential biological agent for cancer treatment. TCS is able to inhibit protein synthesis and consequently induce necrosis. Recent studies have demonstrated that TCS does indeed induce apoptosis in several tumor cell lines. Although TCS-induced apoptosis of tumor cell lines is now well known, the underlying mechanisms remain to be elucidated. The purpose of this review was to investigate the effects of TCS and its possible mechanisms of action, based on published literature and the results of our own studies.

Bone grafting is crucial in the surgical treatment of bone defects and nonunion fractures. Autogenous bone, allogenous bone, and biomaterial scaffold are three main sources of bone grafts. The biomaterial scaffold, both natural and synthetic, is widely accessible but weak in osteogenic potential. One approach to solve this problem is cell-based bone tissue engineering (BTE), established by growing living osteogenic cells on scaffold in vitro to build up its osteoinducitive capability. Mesenchymal stem cell (MSC) is suitable for use in cell-based BTE, but it remains a considerable challenge to induce MSCs to form solely bone and while preventing MSCs from differentiating into fats, muscles, and possibly neural elements in vivo. Recently, there is a drastic rise in use of genetically engineered MSCs, which can secrete growth factors or alter the transcription level, leading to osteoblast lineage commitment, bone formation, fracture repair, and spinal fusion. In this article, we reviewed the literatures regarding applications of genetically engineered MSCs in BTE. We addressed the currently applicable genes and candidate genes for MSCs modification, transduction efficiency and safety issues of the transfect vectors, and administration routes, and we briefly described in vivo tracking and potential clinical application of the genetically modified MSCs in BTE.

The ovarian bursa is a key player in maintaining adaptive ovarian microenvironment for ovulation. The lymphatic stomata are believed to be a major contributor to execute the function of the ovarian bursa, whereas little is known about their ultrastructure and regulation. Here, we examined the ultrastructure of lymphatic stomata in mouse ovarian bursa by scanning electron microscopy and transmission electron microscopy and investigated its regulation by estrogen. We found that the mesothelium on the visceral layer of mouse ovarian bursa was composed of the cuboidal and flattened cells. The lymphatic stomata with round and oval shapes were mainly among the cuboidal cells. The particles, cells, and fluid passed through the stomata and entered into the lymphatic drainage unit composed of connective tissue and lymphatic endothelial cells beneath the stomata. We also used trypan blue as a tracer and found that the absorption of trypan blue through the lymphatic stomata was increased by estrogen that enlarged the average opening area of lymphatic stomata. Furthermore, we detected that there existed estrogen receptors in the nuclei of the mesothelial cells on the visceral ovarian bursa by using immunoelectron microscopy. Taken together, these data suggest that both the absorption and opening area of the lymphatic stomata in mouse ovarian bursa may be influenced by estrogen.

This study investigates the role of excitotoxicity in Alzheimer's disease and in multiinfarct dementia by examining, via immunohistochemical methods, the number of cells that are positive for N-methyl-D-aspartate (NMDA) receptor and the degree of colocalization between NMDA receptor and apoptosis markers such as TUNEL or activated caspase-3 in the frontal cortex of individuals with these two conditions, comparing the results with those from subjects who died of normal aging. We showed an increased number of NMDA receptor-positive cells and an increased number of TUNEL-labeled cells in the frontal cortex of subjects with Alzheimer's disease, especially in the deeper layers of the cortex. However, only about 10% of cells showed colocalization of NMDA receptor with the apoptosis markers studied, suggesting that NMDA-mediated excitotoxicity does not play a major role in neuronal apoptosis in Alzheimer's disease or in multiinfarct dementia.

The aim of this report was to investigate the ultrastructure and three-dimensional organization of the pleural lymphatic stomata in the adult rabbit costal pleura by electron microscopy. A computer image processing system attached to the scanning electron microscopy was used to get statistical evaluation of the dimensions of pleural lymphatic stomata. Mesothelial cells were digested by 2 mol/L NaOH solution in order to expose the submesothelial connective tissue with macula cribriformis. Two kinds of mesothelial cells were observed on the costal pleura: the flattened cells and the cuboidal ones. Both had microvilli on their surface. Pleural lymphatic stomata were located only in the regions of cuboidal mesothelial cells. The average area of a stoma was 7.20 ± 3.69 μm2 and their average density 121 ± 72/mm2. Pleural cavity is connected with the lympo-vascular system by lymphatic stomata and the interstitial layer with a dense network of lamina cribriformis. The macula cribriformis (7–60 μm in diameter) were found in subpleural connective tissue below the cuboidal mesothelial cells. Consequently on cross-section, the pathway represents a channel consisting of the stoma, the connective tissue space, and the gap between endothelial cells of the lymphatics. Closed lymphatic stomata and the milky spots composed of macrophages could be observed on the costal pleura. Our results suggest that the pleural cavity is connected with the lymphatic capillaries through the lymphatic stomata and the subpleural channel. This is the only “highway” from the pleural cavity to the vessels. This pathway may be importantly involved in the material exchange and the immunity of the pleura cavity. Microsc. Res. Tech. 62:240–246, 2003. © 2003 Wiley-Liss, Inc.

Nd-doped yttrium aluminum borate, Nd x Y 1-x Al 3 (BO 3 ) 4 (NYAB), with large sizes and good optical quality has been grown by the flux method. When the Judd-Ofelt (JO) theory of parity-forbidden electric-dipole transitions of rare earth ions on non-centrosymmetric sites was applied to NYAB, it resulted in a good fit on absorption of the crystal. According to the JO theory, the fitted intensity parameters Ω t (t = 2, 4, and 6) were calculated as 2.19 x 10 -20 , 1.97 x 10 -20 , and 3.10 × 10 -20 cm 2 , respectively, with a root mean square deviation of 1.22 x 10 -21 cm 2 . The emission properties of the excited 4 F 3/2 state have been studied, and the spectral parameters of NYAB crystal were compared with those of Nd x Gd 1-x Al 3 (BO 3 ) 4 (NGAB) crystal. A cw NYAB laser at 1.06 μm end-pumped by a high-power diode laser array has been demonstrated. A maximum output of 3.2 W at 1.06 μm has been achieved with an optical conversion efficiency of 29.1% and an average slope efficiency of 37.5%. It is found that these results approach those of Nd:YVO 4 crystal.