Discussion on the Underlying Disease of Wei （卫）-Qi-Ying （营）-Blood Syndrome Differentiation System： Taking Epidemic Cerebrospinal Meningitis as an Example / 中医杂志

Epidemic cerebrospinal meningitis shows a high degree of consistency with the law of transmission among wei （卫）-qi-ying （营）-blood， in terms of the onset of the season， contagiousness， symptoms， pathogenesis， as well as characteristics of the transmission. It is proposed to use epidemic cerebrospinal meningitis as an example to explore the underlying disease of wei-qi-ying-blood syndrome differentiation system. Epidemic meningitis invades the brain from the upper respiratory tract along the nervous system， and its overall pathogenesis follows from entering the lung system （prodromal period） to entering the blood （bacteremia period， sepsis period） and then entering the brain （shock period）. According to the four-dimensional qualitative principle of epidemic pathogen tropism， it corresponds to disease of both wei and qi syndrome， then blazing of both qi and ying syndrome， and then heat blocking pericardium， exuberant heat stirring wind， and internal block and external collapse syndrome. This article explored the laws of transmission among wei-qi-ying-blood and its underlying diseases described in On Warm Heat （《温热论》）， and revealed the original appearance of the disease model under the laws of transmission among wei-qi-ying-blood to guide the clinical practice.

Integrated Traditional Chinese and Western Medicine Treatment for Acute Lymphoblastic Leukemia Complicated with Severe COVID-19 in Recovery Stage： A Case Report / 中医杂志

This paper reported a case of severe COVID-19 in the recovery stage with acute lymphoblastic leukemia treated by integrated traditional Chinese and western medicine， with the intention of shedding light on the clinical diagnosis and treatment of similar conditions. The patient， who had acute lymphoblastic leukemia， developed COVID-19 infection during the bone marrow suppression period after chemotherapy. Treatment with western medicine was mainly anti-infection， symptomatic management， and supportive care. During the recovery stage， considering the patient's chemotherapy history and disease progression， the overall syndrome was identified as deficiency of both qi and yin and binding of phlegm and blood. Based on the “state-target” combined treatment strategy， herbal prescriptions were selected and modified to address the “deficiency state”， “disease target”， and “symptom target”. In addition to western medicine， the patient was administered with Shengmai Powder （生脉散） and Compound Zhebei Granules （复方浙贝颗粒） in its modifications to boost qi， nourish yin， and reinforce healthy qi， nourish and cool the blood， ultimately achieving satisfactory therapeutic effects.

Academician TONG Xiaolin's Understanding and Experience in Treating Severe Cases of COVID-19 / 中医杂志

This article highlighted the invaluable expertise of Academician TONG Xiaolin in managing severe cases of COVID-19， thereby providing ideas for the treatment of severe and critically ill patients with SARS-CoV-2 infection by integrating traditional Chinese and western medicine. It is believed that COVID-19 belongs to the “cold dampness epidemic” in traditional Chinese medicine， which is caused by pathogenic qi of cold and dampness. The course of the disease can be divided into four stages： constraint， block， collapse， and deficiency， and the severe cases are mainly in the block and collapse stages. The pathogenesis at the block stage is described as epidemic toxins blocking the lung， which should be treated by diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals. The primary formula used is Zilong Xuanbai Chengqi Decoction （子龙宣白承气汤） with modifications based on individual condition. The pathogenesis at the collapse stage is described as internal block and external collapse， which should be treated by restoring yang to save from collapse， boosting qi to relieve collapse， diffusing the lung and unblocking the bowels， resolving phlegm and unblocking collaterals， usually with the formula Poge Zilong Xuanbai Chengqi Decoction （破格子龙宣白承气汤） with modifications.

Genetic diversity analysis and fingerprints of Chrysanthemum×morifolium based on SSR molecular markers / 生物工程学报

The present study aims to explore the genetic diversity of germplasm resources of Chrysanthemum×morifolium (hereinafter, C.×morifolium) at the molecular level and to establish a fingerprint database of C.×morifolium varieties. We employed 12 pairs of primers with high levels of polymorphism, clear bands, and high degrees of reproducibility to analyze the SSR molecular markers and genetic diversity of 91 C.×morifolium materials and 14 chrysanthemum- related materials. With regard to constructing the fingerprints of the tested materials, we chose 9 pairs of core primers. The findings revealed that 12 primer pairs detected 104 alleles in 105 samples, ranging from 2 to 26. The average number of observed alleles (Na) per site was 9.25. The average number of effective alleles (Ne) per site was 2.745 6, with its range being 1.276 0 to 4.742 5. Shannon genetic diversity index (I) values ranged between 0.513 3 and 2.239 9 (M=1.209 0). Nei's gene diversity index (H) ranged between 0.216 3 and 0.789 1 (M=0.578 0). The observed heterozygosity (Ho) ranged between 0.223 3 and 0.895 2 (M=0.557 5). The expected heterozygosity (He) ranged between 0.217 4 and 0.793 3 (M=0.580 8). The polymorphism information content (PIC) ranged between 0.211 5 and 0.774 0 (M=0.532 9). The genetic similarity (GS) ranged between 0.228 5 and 1.000 0 (M=0.608 3). Cluster analysis revealed that when the genetic distance (GD) equals to 0.30, the tested materials can be classified into 2 groups. When the GD equals to 0.27, the first group can be divided into 6 subgroups; accordingly, 105 tested materials can be divided into 7 subgroups. The cophenetic correlation test was carried out based on the cluster analysis, and the corresponding results showed that the cluster map correlated with the genetic similarity coefficient (r=0.952 73). According to the results of Structure population analysis, we obtained the optimal population number, with the true number of populations (K) being 3 and the population being divided concerning Q≥0.5. Three subgroups, i.e., Q1, Q2 and Q3, included 34, 33 and 28 germplasms, respectively, and the remaining 10 germplasms were identified as the mixed population. During the experiment, 9 pairs of core primers were screened among the total of 12 for a complete differentiation regarding 105 tested materials, and the fingerprints of 91 C.×morifolium materials and 14 chrysanthemum-related materials were further constructed. Overall, there were significant genetic differences and rich genetic diversity among C.×morifolium materials, which would shed light on the garden application and variety selection fields of C.×morifolium. The fingerprint database of 105 C.×morifolium varieties and chrysanthemum-related species may provide technical support for future research regarding the identification and screening system of C.×morifolium varieties.

Comparative transcriptome analysis linked to key volatiles reveals molecular mechanisms of aroma compound biosynthesis in Prunus mume.

BACKGROUND: Mei (Prunus mume) is the only woody plant in the genus Prunus with a floral fragrance, but the underlying mechanisms of aroma compound biosynthesis are unclear despite being a matter of considerable interest. RESULTS: The volatile contents of the petals of two cultivars with significantly different aromas, Prunus mume 'Xiao Lve' and Prunus mume 'Xiangxue Gongfen', were characterised by GC-MS at different flowering periods, and a total of 44 volatile compounds were detected. Among these, the main substances forming the typical aroma of P. mume were identified as eugenol, cinnamyl acetate, hexyl acetate and benzyl acetate, with variations in their relative concentrations leading to sensory differences in the aroma of the two cultivars. We compiled a transcriptome database at key stages of floral fragrance formation in the two cultivars and used it in combination with differential analysis of floral volatiles to construct a regulatory network for the biosynthesis of key aroma compounds. The results indicated that PmPAL enzymes and PmMYB4 transcription factors play important roles in regulating the accumulation of key biosynthetic precursors to these compounds. Cytochrome P450s and short-chain dehydrogenases/reductases might also influence the biosynthesis of benzyl acetate by regulating production of key precursors such as benzaldehyde and benzyl alcohol. Furthermore, by analogy to genes with verified functions in Arabidopsis, we predicted that three PmCAD genes, two 4CL genes, three CCR genes and two IGS genes all make important contributions to the synthesis of cinnamyl acetate and eugenol in P. mume. This analysis also suggested that the downstream genes PmBGLU18-like, PmUGT71A16 and PmUGT73C6 participate in regulation of the matrix-bound and volatile states of P. mume aroma compounds. CONCLUSIONS: These findings present potential new anchor points for further exploration of floral aroma compound biosynthesis pathways in P. mume, and provide new insights into aroma induction and regulation mechanisms in woody plants.

Progress on the origin, function and evolutionary mechanism of RHR transcription factor family.

Transcription factors are a class of proteins that regulate gene transcription and expression by binding to gene-specific sequences and play an essential role in regulating the biological activities of cells. The RHR (Rel-homology region) transcription factor family is the primary member of the IF (immunoglobulin fold) transcription factor superfamily, whose members contain the conserved Rel domain and IPT (immunoglobulin-like fold) domain. As an ancient transcription factor family, the RHR family continues differentiation on gene gain and loss through gene duplication, mutation, and silencing, accompanied with the evolution of diverse species. Natural selection has led to different rates of evolution among members of the family, and some domains of the protein family have shown unique mechanisms of evolution. However, the current reviews about the origin and differentiation of RHR family are rare. In this review, we summarize the research results on the distribution, classification, function, and evolution of the members of the RHR family in order to provide a reference and new idea for studying the evolution mechanism of the whole transcription factor family and the evolutionary relationship among species.

Protection and mechanism of neoeriocitrin on Aβ 25-35 injured PC12 cells / 国际中医中药杂志

Objective:To study the protective effect of neoeriocitrin on PC12 cell injury induced by amyloid β protein fragment 25-35 (Aβ 25-35), and explore its role in preventing and treating AD. Methods:The MTT method was used to detect the effect of Neoeriocitrin on the proliferation of normal PC12 cells and Aβ 25-35 damaged PC12 cells, and the intervention concentration of neoeriocitrin solution was screened. The PC12 cells were divided into the normal control group, model group, estradiol group and neoeriocitrin group according to the random number table method. The normal control group and model group were cultured with DMEM for 24 h; DMEM and 1×10 -3 μmol/L estradiol solution were added to the estradiol group; DMEM and 6×10 4 μmol/L neoeriocitrin solution were added to the neoeriocitrin group. After 2 hours of culture, except for the normal control group, the remaining groups were added with 20 μmol/L Aβ 25-35 stock solution, and the culture was continued for 22 h. AnnexinV-FITC/PI double labeling was used to detect apoptosis rate, Western blot method was used to detect estrogen receptor β (estrogen receptor β, ERβ) and p-P38/P38 protein expression. The content of acetylcholine (ACh) was detected, and the activity of Choline acetyl transferase (ChAT) and Acetylcholin esterase (AChE) in the supernatant of PC12 cells were detected. Results:Compared with the model group, the cell apoptosis rate [(8.080 ± 0.578)% vs. (18.500 ± 0.870)%] significantly decreased ( P<0.01), the expression of ERβ protein (0.348 ± 0.042 vs. 0.273 ± 0.006) significantly increased ( P<0.01), p-P38/P38 protein expression (0.372 ± 0.058 vs. 0.571 ± 0.063) significantly decreased ( P<0.01), the content of ACh [(14.319 ± 1.039) μg/mg vs. (9.157 ± 1.605) μg/mg], ChAT activity [(0.715 ± 0.053) U/mg vs. (0.280 ± 0.093) U/mg] significantly increased ( P<0.01), AChE activity [(2.607 ± 2.048) U/mg vs. (6.038 ± 1.867) U/mg] significantly reduced ( P<0.01). Conclusions:Neoeriocitrin can promote the proliferation of PC12 cells damaged by Aβ25-35, inhibit cell apoptosis, and has a certain cytoprotective effect. Its mechanism may be related to the regulation of ERβ expression and inhibition of P38 protein phosphorylation, thereby improving the function of the cholinergic system related.

Comparison of methods for enriching urine proteins / 生物工程学报

The abundance of proteins in human urine is low and easily to be masked by high-abundance proteins during mass spectrometry analysis. Development of efficient and highly selective enrichment methods is therefore a prerequisite for achieving deep coverage of urine protein markers. Notably, different experimental methods would affect the urine protein enrichment efficacy and the coverage of urine proteome. In this study, ultrafiltration, nitrocellulose membrane enrichment and saturated ammonium sulfate precipitation were used to process 10 mL urine samples from five healthy volunteers and five bladder cancer patients. The urine proteins were enriched and separate by SDS-PAGE to compare the purification efficiency of different methods. Moreover, the peptide identification effects of different purification methods were analyzed by mass spectrometry to determine the best method for enriching urine protein histones. Saturated ammonium sulfate precipitation method outperformed the ultrafiltration and the nitrocellulose membrane enrichment methods in terms of the protein enrichment efficacy and quality. The interference of highly abundant albumin was reduced, whereas the amount of low-abundance protein was increased, and the sensitivity of mass spectrometry identification was increased. The saturated ammonium sulfate precipitation method may be applied for large-scale urine processing for screening clinical diagnostic markers through proteomics.

Influence of Target-controlled Infusion of Remifentanil Combined with Propofol on Hemodynamics in Middle-aged and Elderly Patients with Intracranial Aneurysm Clipping / 中国药师

Objective:To observe the effect of intravenous anesthesia with target-controlled infusion (TCI) of remifentanil combined with propofol on hemodynamics in middle-aged and elderly patients with intracranial aneurysm clipping. Methods:Totally 40 cases of middle-aged and elderly patients undergoing intracranial aneurysm clipping were divided into combined anesthesia group and propofol group according to the random number table. The combined anesthesia group was treated with remifentanil combined with propofol target intravenous anesthesia, and propofol group was treated with propofol intravenous hypotension. The changes of mean arterial pressure(MAP),heart rate(HR),cardiac output(CO) and heart index(CI) before the induction of anesthesia (T1), tracheal intubation (T2), before aneurysm clipping(T3), after aneurysm clipping(T4) and extubation (T5) were observed. The anesthesia maintenance time, extubation time, postoperative wake-up time and adverse reactions were compared. Results:There were no significant differences in MAP and HR between the groups(P > 0.05), the levels of MAP,HR,CO and CI at T2,T3and T4were significantly lower than those at T1,and CO and CI were significantly lower in combined group than those in propofol group(P < 0.05). Conclusion:TCI remifentanil combined with propofol can maintain hemodynamic stability, shorten extubation time and wake-up time, and reduce the incidence of adverse reactions in the patients with intracranial aneurysm clipping.

Research progress of hyperprolactinemia induced by antipsychotic drugs / 中华全科医师杂志

During the treatment of psychotic disorders it should be aware that many commonly used antipsychotic drugs have the risk of inducing hyperprolactinemia.This review focuses on the pathogenesis,clinical symptoms and treatment strategy of the antipsychotic drug-induced hyperprolactinemia.

The pathway regulation and targeted therapy of tumor stem cells regulatory and targeting therapy of tumor stem cell related signal pathway / 中国生化药物杂志

Cancer stem cells are thought to be the seed of tumor formation, through complex signalings and cytokines in the surrounding microenvironment regulate the development and metastasis of tumor.Tumor stem cells have the characteristics of self-renewal and differentiation, the intracellular signaling pathways regulating self-renewal and differentiation of cancer stem cell include Wnt, Hedgehog signaling pathway.The tumor microenvironment is the dimensional environment surrounding the tumor,including the extracellular matrix, surrounding blood capillary,stromal cells ( fibroblasts, mesenchymal stem cells, tumor-associated endothelial cells, inflammatory cells) and cytokines secreted by stromal cells.Cancer stem cells maintain a close communication with the cells in the tumor microenvironment.In this paper, the cell surface maker of cancer stem cell,cancer stem cells and regulation of cytokine in the microenvironment,intracellular signaling pathways of cancer stem cells are reviewed to show complex regulatory networks in the tumor microenvironment.This review should help providing a new direction on specific cancer therapy for cancer stem cells in cacer treatment.

Clinical study of internal fixator remove time in different age patients after non-fusion cross injured vertebral screw of thoracolumbar vertebral fracture / 中国医师进修杂志

Objective To analyze the internal fixator remove time in different age patients after non-fusion cross injured vertebral screw of thoracolumbar vertebral fracture. Methods Sixty-eight patients who had underwent non-fusion cross injured vertebral screw were divided into 2 group according to the age:young group (20-44 years, 36 cases) and middle aged group (45-59 years, 32 cases). The numeric rating score (NRS), Oswestry disablility index (ODI), discoideum index (DI) and kyphotic Cobb angle 6, 9, 12 and 15 months after surgery were compared between 2 groups. Results The kyphotic Cobb angle, ODI and NRS 9, 12 and 15 months after surgery in 2 groups were significantly lower than those 6 months after surgery, which was in young group: (37.34 ± 6.86)° , (36.81 ± 6.78)° and (36.90 ± 6.97)° vs. (56.31 ± 3.56)° , (2.45 ± 0.55)%, (2.24 ± 0.53)% and (2.09 ± 0.41)% vs. (3.02 ± 0.89)%, (18.46 ± 2.73), (18.44 ± 3.05) and (18.28 ± 2.98) scores vs. (19.79 ± 2.85) scores, and in middle aged group: (37.11 ± 6.80)° , (35.58 ± 5.48)° and (35.40 ± 5.44)° vs. (56.03 ± 3.68)° , (2.21 ± 0.41)%, (2.08 ± 0.43)%and (1.97 ± 0.39)%vs. (3.04 ± 0.93)%, (19.17 ± 2.99), (18.57 ± 2.98) and (18. 43 ± 2.92) scores vs. (20.95 ± 2.49) scores. There were statistical differences (P<0.05). The DI 12 and 15 months after surgery in young group were significantly lower than that 6 and 9 months after surgery:(50.59 ± 4.60)%and (47.57 ± 4.30)%vs. (56.60 ± 3.98)%and (56.32 ± 3.87)%, and there were statistical differences (P<0.05). The DI 15 months after surgery in middle aged group was significantly lower than that 6, 9 and 12 months after surgery:(47.95 ± 4.87)%vs. (56.34 ± 3.97)%, (56.13 ± 3.88)%and (55.63 ± 3.94)%, and there were statistical differences (P<0.05). Conclusions The internal fixator remove time in the young patients after non-fusion of cross injured vertebral screw of thoracolumbar vertebral fracture is 9 months after surgery, and in the middle aged patients is 12 months after surgery. Intervertebral disc degeneration is one of the risk factors for delayed removal.

Research progress on integrated molecular pathological classification of diffuse lower-grade gliomas / 中国肿瘤临床

Diffuse lower-grade glioma is a diversified group of infiltrative brain tumors comprising WHO grades II and III astrocytomas, oligodendrogliomas, and mixed oligoastrocytomas. These tumors exhibit a wide range of clinical heterogeneity;thus, histopathological classification does not adequately predict clinical outcomes. In recent years, a number of molecular markers closely related to the clini-cal features and prognosis of gliomas have been discovered. These molecular markers include isocitrate dehydrogenase (IDH) muta-tion, chromosome 1p/19q codeletion, ATRX mutation, TERT promoter mutation, and MGMT promoter methylation. Furthermore, nu-merous studies focusing on the integrated molecular classification of diffuse lower-grade gliomas combined with these molecular markers have been conducted. Results indicate that integrated molecular pathological classification can improve the diagnostic and prognostic accuracy and facilitate therapeutic formulation. This paper reviews the research progress on integrated molecular classifica-tion of diffuse lower-grade gliomas.

Efficacy and safety of double doses of SHUGANJIEYU capsules in treating moderate depressive disor-der:a multicenter, random, double-blind, and parallel-controlled trial / 中国神经精神疾病杂志

Objective To explore the efficacy and safety of double dosage of SHUGANJIEYU capsule on mod?erate depression. Methods The study was conducted by a multicenter, random, double-blind and parallel-controlled trial. Trial group received SHUGANJIEYU capsules 4# twice a day. Control group got two SHUGANJIEYU capsules and two simulated ones twice a day. The study lasted 56 days (8 weeks) for both groups. Primary efficacies were evalu? ated by the total score and score changed rate of Hamilton depression scale-17 (HAMD-17)and Hamilton anxiety scale (HAMA) as well safety by reported adverse events and laboratory tests for patients. Results One hundred twenty patients were recruited in trial group and 120 patients in control group. After a 8-week treatment, the remission ratio was 84.2% and 63.3% for the trial group and the control group, respectively according to the HAMD-17. The differ?ence in the remission ratio was significant (P0.05). Conclusion SHUGANJIEYU capsule ex?hibits a good therapeutic effect on the depressive symptoms and anxiety symptoms in patients with moderate depres?sion. Double doses of SHUGANJIEYU capsule can increase the effect of SHUGANJIEYU and accelerates SHUGAN?JIEYU-induced improvement of depression symptoms with an acceptable safety.

Repair of rabbit radius defect by using recombinant of hBMP2/hVEGF165 modified BMSCs with porous nano-hydroxyapatite/polyamide 66 composite / 中华创伤杂志

Objective To assess the effect of bone defect repair using the recombinant of adenovirus-mediated hBMP2 and hVEGF165 genes transfer of BMSCs with porous nano-hydroxyapatite/polyamide 66 (n-HA/PA66).Methods Sixty male adult New Zealand rabbits were assigned to groups A,B and C according the completely random design,with 20 rabbits per group.Bone defect of 15 mm in length was made in the middle segment of bilateral radii in rabbits.In Group A,the defects were filled with nothing on the left side in blank controls (Group A1) and with n-HA/PA66 material alone on the right side (Group A2).In Group B,the defects were filled with hVEGF165/BMSCs/n-HA/PA66 on the left side (Group B1) and hBMP2/BMSCs/n-HA/PA66 on the right side (Group B2).In Group C,the defects were filled with BMSCs/n-HA/PA66 on the left side (Group C1) and hBMP2/hVEGF165/BMSCs/n-HA/PA66 on the right side (Group C2).Radiological analysis,HE staining,and Masson coloration were performed 2,4,8 and 12 weeks after operation.Results Radiographs,HE staining and Masson staining taken 8 weeks after cell transplantation showed large amount of new cartilage grown into the defect area and massive bony tissue formation around the margin in Group C2.At postoperative 12 weeks,Group C2 showed transplants were surrounded by outer bone tissues with superior bone repair effect to other groups (P ＜ 0.05).Number of vessels in Group C2 increased compared with that in other groups (P ＜ 0.05).Number of vessels was greater in Group B1 than in Group B2 (P ＜ 0.05),and both were greater than those in Groups A2 and C1 (P ＜ 0.05).Moreover there was no significant difference between Groups A2 and C1 (P ＞0.05).Conclusion hBMP2/hVEGF165 genes transferred BMSCs seeded on porous n-HA/PA66 can contribute to osteogenesis during the repair of rabbit radius defect.

[The molecular mechanism of necroptosis].

Programmed necrosis called necroptosis, is different from traditional necrosis and apoptosis, it has attracted considerable attention over the last few years. Necroptosis can be initiated through many factors such as tumor necrosis factor receptor (TNFR) or pattern recognition receptor (PRR), and receptor-interacting protein (RIP) 1 and 3 are two key proteins during the process. A lot of molecules have been characterized as modulators and effectors of necroptosis, including poly(ADP-ribose) polymerase (PARP-1), reactive oxygen species (ROS), Ca(2+), which can destruct mitochondria or other organelles and induce cell dead through caspase-independent pathway. Then, damage-associated molecular pattern (DAMP) molecules were released from necroptosis cells, recognized and internalized by phagocytes. Here, we briefly discuss the initiation and execution of necroptosis and the clearance of death cells.

Progress in sodium channelopathies and biological functions of voltage-gated sodium channel blockers / 生物工程学报

Voltage-gated sodium channels (VGSCs), which are widely distributed in the excitable cells, are the primary mediators of electrical signal amplification and propagation. They play important roles in the excitative conduction of the neurons and cardiac muscle cells. The abnormalities of the structures and functions of VGSCs can change the excitability of the cells, resulting in a variety of diseases such as neuropathic pain, epilepsy and arrhythmia. At present, some voltage-gated sodium channel blockers are used for treating those diseases. In the recent years, several neurotoxins have been purified from the venom of the animals, which could inhibit the current of the voltage-gated sodium channels. Usually, these neurotoxins are compounds or small peptides that have been further designed and modified for targeted drugs of sodium channelopathies in the clinical treatment. In addition, a novel cysteine-rich secretory protein (CRBGP) has been isolated and purified from the buccal gland of the lampreys (Lampetra japonica), and it could inhibit the Na+ current of the hippocampus and dorsal root neurons for the first time. In the present study, the progress of the sodium channelopathies and the biological functions of voltage-gated sodium channel blockers are analyzed and summarized.