How Chinese Herbal Medicine Prevents Epidemics: From Ancient Pestilences to COVID-19 Pandemic.

The ongoing coronavirus disease 2019 (COVID-19) pandemic calls for effective control and prevention. Chinese medicine (CM) has developed systematic theories and approaches for infectious disease prevention over 2000 years. Here, we review and analyze Chinese herbal medicines (CHM) used in infectious disease prevention from ancient pestilences to modern epidemics and pandemics to share cumulative preventive medical experience. A total of 829 formulas, including 329 herbs from 189 ancient books, 131 formulas with 152 herbs, and 13 Chinese patent medicines (CPM) from 30 official Chinese prevention programs used in ancient epidemics, SARS, influenza and COVID-19 prevention, were reviewed and analyzed. Preventive CHM mainly has four functions and can be taken orally or applied externally. CHM that kill pathogens (Realgar [Xionghuang], Cyrtomium Fortunei J. Sm[Guanzhong]) were commonly used externally for disinfection in ancient prevention while CHM tonifying Qi (Astragali Radix [Huangq], Glycyrrhizae Radix et Rhizoma [Gancao]) are used for modern prevention. Taking CHM that expel pathogens (Realgar [Xionghuang], Lonicerae Japonicae Flos[Jinyinhua]) and CHM eliminating dampness (Atractylodis Rhizoma [Cangzhu], Pogostemonis Herba[Guanghuoxiang]) have been commonly used from ancient times to COVID-19. Damp toxins are a common characteristic of infectious diseases such as SARS and COVID-19. Thus, taking CHM expelling damp toxins and tonifying Qi are the main methods for SARS and COVID-19 prevention. CHM with different approaches have been widely used in infectious disease prevention from ancient times to the present. Multiple CM prevention methods may provide new perspectives for future pandemics.

Intervention effect of pinelliae decoction for purging stomach-fire on malignant transformation of bone marrow mesenchymal stem cells in the gastric cancer microenvironment.

OBJECTIVE: The study aimed to simulate the microenvironment of gastric cancer to promote the malignant transformation of bone marrow mesenchymal stem cells (BMSCs) and further evaluate the effect of Pinelliae Decoction for Purging Stomach-Fire and its disassembled prescriptions on BMSCs. METHODS: Transwell co-culture was performed on the human gastric cancer cell strains BGC-823 and BMSCs to simulate the microenvironment of gastric cancer. The drug-containing serum prepared by Pinelliae Decoction for Purging Stomach-Fire and its disassembled prescriptions was used, and its influence on BMSCs with malignant transformation was observed. RESULTS: BMSCs were harvested successfully from the rat bone marrow, and flow cytometer identification indicated that CD44+/CD34- cells accounted for 70.64%. The co-culture of BGC-823 cells can induce malignant transformation of BMSCs. And the drug-containing serum can induce G2 phase arrest, inhibit cell proliferation, simultaneously inhibit TERT and c-myc expression, lower the cellular ability of chemotactic migration, inhibit the tumor-forming ability of BGC-823 in nude rats and promote the tumor apoptosis. CONCLUSION: The effective components of Pinelliae Decoction for Purging Stomach-Fire in gastric cancer treatment are pinelliae and dried ginger, and the main acting mechanism is to inhibit tumor cell proliferation and chemotactic migration and promote apoptosis.

[Effects of Banxia Xiexin Decoction Containing Serum on Proliferation, Invasion and Metastasis of Gastric Cancer Peritoneal Metastasis Cell Line GC9811-P].

Objective To observe the effects of Banxia Xiexin Decoction (BXD) containing ser- um on proliferation, invasion and metastasis of in vitro human gastric cancer peritoneum cell strain GC9811-P (which has high metastatic potential). Methods BXD containing serum was prepared. GC9811-P cells were inoculated in the E-Plate 96 and CIM Plate 16, and then 0, 25, 50, 100 µL/mL BXD containing serums were added respectively. Meanwhile, GC9811-P cells were stained by Diff-Quik stai- ning method. Inhibition of BXD containing serum on cell index (CI) for proliferation of GC9811-P cells, invasion and metastasis were observed by real time cellular analysis (RTCA) and Diff-Quik staining method. Results BXD containing serum could obviously inhibit the proliferation of GC9811-P cells. The Cl approximated to 0 after 70 h. Most stained Diff-Quik cells died. Cell migration curve showed that 25, 50, 100 µL/mL BXD containing serums could obviously inhibit the capacities for cell migration of GC9811-P cells in concentration dependent manner. The number of migration cells was reduced more obviously, as com- pared with 0 µL/mL BXD containing serum (P <0. 05). Conclusion BXD containing serums could inhibit the proliferation, invasion and metastasis of GC9811-P cells, which might be associated with blocking peritoneal metastasis of gastric cancer.

Flexibility of theory of mind in a matrix game when the opponent's level changes.

This study used a matrix game to explore adolescents' and young adults' flexibility of theory of mind (ToM) and to examine whether prediction could promote a person's ToM reasoning when the opponent's level of ToM changed during the course of the game. A total of 202 participants of different ages (13, 16, 19, and 24 years) were presented with the task. Results showed that the ToM flexibility in prediction and decision making was not significantly different across the age groups. A person's flexibility of ToM was better when the opponent's level was stable than when the level changed. It was even more difficult for a person to adapt when the opponent changed from a higher-order to lower-order level. The results showed prediction to be a kind of information clue that would prompt people to think further. It is both feasible and discriminative to explore even higher levels of ToM with matrix games.

[Responses of stomata and Kranz anatomy of maize leaves to soil water shortages].

Seedlings of the popular maize cultivar "Zhengdan-958" growing in pots individually were exposed to suitable soil water conditions as control, light water shortage, moderate water shortage, and severe water shortage, corresponding to soil water contents between 75%-85%, 65%-75%, 55%-65%, and 45%-55% of field water capacity, respectively. Responses of stomatal aperture, Kranz anatomy, and vascular bundle structure to different water contents of maize leaves were investigated. Results showed that under increased water shortages, the levels of H2O2 in both guard cells and subsidiary cells were enhanced, also the fluorescence intensity of H2O2 labeled with fluorescent dye increased, while stomatal aperture and conductance decreased gradually. Moreover, Kranz cells were messily arranged and the cell size became smaller and smaller, and the structure of bundle sheath cells went irregular; and the sectional area of the big bundle and xylem, the cell number of phloem, and the thickness of whole leaf and of upper and lower epidermis reduced. In addition, the number of chloroplasts in mesophyll cells and vascular bundle sheath cells decreased, particularly under the moderate water deficit, chloroplasts in Kranz cells which located in the inside of cytoplasmic membrane and cling on the cell wall spread to the direction of cell center. It demonstrated that stomatal closing of maize could be regulated by H2O2 in guard cells and subsidiary cells together, and H2O2 in subsidiary cells maybe played a cooperative role. In conclusion, under increased soil water shortages, drought-induced H2O2 accumulations in both guard cells and subsidiary cells of maize leaves participated in the regulation of stomatal closing. And, the size of Kranz cells and bundle sheath cells, the cell number of phloem, and the area of the xylem and phloem re- duced, thereby, reducing water shortage-induced damage.

Up-regulation of pVHL along with down-regulation of HIF-1α by NDRG2 expression attenuates proliferation and invasion in renal cancer cells.

The majority of renal cell carcinomas (RCCs) are characterized by loss of function of the tumor suppressor gene von Hippel Lindau (VHL), which acts as ubiquitin ligase for hypoxia-inducible factor-1α (HIF-1α). In the absence of VHL, HIF-1α protein becomes stabilized and contributes to tumorigenesis. Recent data demonstrate the antitumor efficacy of VHL promoter in RCC cells. This study demonstrates that N-Myc downstream-regulated gene 2 (NDRG2) is a potential regulator of VHL. NDRG2 is involved in proliferation and invasion of cancer cell, furthermore it is frequently down-regulated in renal cell carcinoma. Herein we evaluated the effect of NDRG2 overexpression on proliferation and invasion in human renal cancer cells. The human renal cancer cell line 786-O and A498 were infected with Ad-NDRG2 or Ad-LacZ. Overexpression of NDRG2 not only inhibited the growth of the cells, but also suppressed the invasion. Further study showed that the tumor suppressor gene VHL were up-regulated, whereas transcription factor HIF-1a and vascular endothelial growth factor (VEGF) were down-regulated in 786-O cells infected by Ad-NDRG2. Finally, in a nude mouse model, intratumoral injections of Ad-NDRG2 every 3 days for a total of seven times significantly inhibited the growth and angiogenesis of xenografted 786-O tumors. In conclusion, these data indicate that NDRG2 may be involved in proliferation and invasion by impacting the expression of VHL and HIF-1α. NDRG2 may be an attractive therapeutic target for renal cell carcinoma.

Correlation study of 3T-MR-DTI measurements and clinical symptoms of cervical spondylotic myelopathy.

OBJECTIVE: To discuss the correlation between diffusion tensor imaging (DTI) measurements, diffusion tensor tractography and the clinical symptoms of cervical spondylotic myelopathy. METHODS: Based on the Japanese Orthopedics Association (JOA) score, 104 cervical spondylotic myelopathy cases were first divided into four groups: mild, moderate, severe and serious groups. According to lesion signal characteristics, all cases were again divided into three groups: A(N/N): normal signal in both T1WI and T2WI; B (N/H): normal signal in T1WI but high signal in T2WI; and C (L/H): low signal in T1WI and high signal in T2WI. The apparent diffusion coefficient (ADC), fractional anisotropy (FA), λ1, λ2, and λ3 were measured and diffusion tensor tractography was performed in the seriously compressed section of the spinal cord. RESULTS: The FA values were positively correlated with JOA scores (r=0.883, P<0.05), and significantly different among four JOA groups (P<0.05). The ADC, λ2, and λ3 were significantly different among the moderate, severe and serious groups as well as among the A, B, and C groups (P<0.05). Declining FA values were found associated with increasing fiber bundle damage. CONCLUSIONS: The FA values and the change patterns of fiber bundle were more sensitive than T2WI for spinal cord lesion, and were positively correlated with clinical symptoms.

Age-related schema reliance of judgments of learning in predicting source memory.

Source memory refers to mental processes of encoding and making attributions to the origin of information. We investigated schematic effects on source attributions of younger and older adults for different schema-based types of items, and their schema-utilization of judgments of learning (JOLs) in estimating source memory. Participants studied statements presented by two speakers either as a doctor or a lawyer: those in the schema-after-encoding condition were informed their occupation only before retrieving, while those of schema-before-encoding were presented the schematic information prior to study. Immediately after learning every item, they made judgments of the likelihood for it to be correctly attributed to the original source later. In the test, they fulfilled a task of source attributing. The results showed a two-edged effect of schemas: schema reliance improved source memory for schema-consistent items while impaired that for schema-inconsistent items, even with schematic information presented prior to encoding. Compared with younger adults, older adults benefited more from schema-based compensatory mechanisms. Both younger and older adults could make JOLs based on before-encoding schematic information, and the schema-based JOLs were more accurate in predicting source memory than JOLs made without schema support. However, even in the schema-after-encoding condition, older adults were able to make metacognitive judgments as accurately as younger adults did, though they did have great impairments in source memory itself.

Flexibility of theory of mind in a matrix game when partner's level is different.

The development of theory of mind (ToM) was investigated as flexibility of prediction and decision-making in matrix games with 202 13-, 16-, 19-, and 24-year-old participants. The ToM flexibility of prediction and decision-making showed no significant differences among any age group. The ToM flexibility of prediction and decision-making of the 0th-order partner was better than that of the 1st-order partner. The ToM flexibility of prediction was better than the ToM flexibility of decision making. Matrix games are a feasible, effective, and discriminative way to explore higher levels of theory of mind.

Homologous recombination as an evolutionary force in the avian influenza A virus.

Avian influenza A viruses (AIVs), including the H5N1, H9N2, and H7N7 subtypes, have been directly transmitted to humans, raising concerns over the possibility of a new influenza pandemic. To prevent a future avian influenza pandemic, it is very important to fully understand the molecular basis driving the change in AIV virulence and host tropism. Although virulent variants of other viruses have been generated by homologous recombination, the occurrence of homologous recombination within AIV segments is controversial and far from proven. This study reports three circulating H9N2 AIVs with similar mosaic PA genes descended from H9N2 and H5N1. Additionally, many homologous recombinants are also found deposited in GenBank. Recombination events can occur in PB2, PB1, PA, HA, and NP segments and between lineages of the same/different serotype. These results collectively demonstrate that intragenic recombination plays a role in driving the evolution of AIVs, potentially resulting in effects on AIV virulence and host tropism changes.

Homologous recombination evidence in human and swine influenza A viruses.

Dynamic gene mutation and the reassortment of genes have been considered as the key factors responsible for influenza A virus virulence and host tropism change. This study reports several significant evidence demonstrating that homologous recombination also takes place between influenza A viruses in human and swine lineages. Moreover, in a mosaic descended from swine H1N1 subtype and human H2N2, we found that its minor putative parent might be a derivative from the human cold-adapted vaccine lineage, which suggests that live vaccine is capable of playing a role in genetic change of influenza A virus via recombination with circulating viruses. These results would be important for knowing the molecular mechanism of mammal influenza A virus heredity and evolution.

Cross-species recombination in the haemagglutinin gene of canine distemper virus.

Canine distemper virus (CDV) has high prevalence in the world dog population and poses an important conservation threat to many carnivore species. In this study, extensive phylogenetic and recombination analyses were performed on all available complete haemagglutinin gene sequences and a strain (AF178038) isolated from giant panda was identified as putative recombinant. Interestingly, the mosaic was produced by recombination between genotypes European wildlife and Asia-1 and the recombination event involves viruses infecting different host species. This finding may have important implications for the evolution of CDV.

Homologous recombination is unlikely to play a major role in influenza B virus evolution.

Influenza B viruses cause a significant amount of morbidity and mortality. The occurrence of homologous recombination in influenza viruses is controversial. To determine the extent of homologous recombination in influenza B viruses, recombination analyses of 2,650 sequences representing all eight segments of the influenza B viruses were carried out. Only four sequences were indentified as putative recombinants, which were verified using phylogenetic methods. However, the mosaics detected here were much likely to represent cases of laboratory-generated artificial recombinants. As in other myxoviruses, it is unlikely that homologous recombination plays a major role in influenza B virus evolution.

[Observation on the long-term complications after esophageal replacement with colon].

OBJECTIVE: To study the etiology and preventive measures of the long-term postoperative complication after esophageal replacement with colon for esophageal benign disease. METHODS: To review the clinical data of 577 patients with esophageal replacement with colon our department, including 123 cases of esophageal benign disease. Of all, there were 25 cases-time for 11 cases following with severe complication: redundancy and dilated colon 12 cases-time, severe stricture of stoma 4, macrocyst esophagus 2, colon-stomach stoma expansion 4, mechanical obstruction of colon 3. The etiology included iatrogenic and functionality. The therapy included stricture form or resection, redundancy segment resection, obstructed segment solution and stoma resection and form. RESULTS: Eight cases underwent once operation, 2 case twice, 1 case three times. After operation, 9 cases took food normally, 2 improved symptoms obviously. CONCLUSIONS: The iatrogenic and functionality factor contributed to severe complication after esophageal replacement with colon for esophageal benign disease. The preventive measure is followed during operation: cervical esophageal-colon anastomosis exceed 2.5 centimeter, abdominal colon-stomach anastomosis reflux, channel width of colon passage, intestinal canal lay up straight. Re-operation is best choice to for local stricture, colon expansion, redundancy and dilated colon.

Effects of elevated pO3 on carbon cycle between above and belowground organs of trees.

Translocation of carbohydrate from leaves to roots via phloem and reallocation from roots to leaves via xylem regulate the allocation of carbon (C) between above and belowground organs of trees. To quantitatively analyze effects of elevated ozone concentrations pO3 on the internal cycle of C, juvenile beech and spruce were grown in phytotrons and exposed to ambient and elevated pO3 (i.e. twice-ambient O3 levels, restricted to < 150 ppb) for two growing seasons. The translocation of C in the phloem and xylem was quantitatively studied by investigating the phloem/xylem-loading of sugars, the differentiation of stem conductive tissue and the hourly water flow through the stem. Results in the present study shown, elevated pO3 significantly decreased C translocation from shoot to roots in beech by reducing both sugar concentration in the phloem and conductive phloem area. Elevated pO3 also significantly decreased C reallocation from the roots to the shoot in beech by reducing both of sugar concentration in the xylem and transpiration rate. The adverse effects of elevated pO3 on C translocation in the phloem and xylem, however, were small in spruce. Contrasting to beech, spruce is less sensitive to elevated pO3, regarding to phloem differentiation and sugar concentrations in the phloem and xylem.

[Effects of residues of organochlorine pesticides on reproductive endocrine in human].

OBJECTIVE: To explore effects of residues of organochlorine pesticides on reproductive endocrine in human. METHODS: The accumulative levels of the pesticides in the pregnant women's venous blood were determined and were grouped to understand the associations among the pesticides, hormones, and genes. RESULTS: (1) With the increase of blood burden of organochlorine pesticides, levels of the hormones such as follicle stimulating hormone (FSH), estradiol (E2) and progesterone (P) in the maternal blood and FSH, luteinizing hormone (LH) and E2 in the umbilical cord blood increased in dose-effect manner, respectively. However, the hormones, for example, LH in the women blood and P in the cords blood decreased respectively with the rising pesticides' levels and an obvious dose-effect relationship was found. (2) The expressional abundances of alpha-estrogen receptor (alpha-ER), beta-endorphin (beta-EP) and gonadotropin releasing hormone (GnRH) in the placentae and alpha-ER and beta-EP in the cord tissues went up respectively in dose-effect manner following the rising pesticides' burdens. (3) The times of the previous adverse pregnancy outcomes increased with the increase of the residues' burdens and there were significant differences between the control and various residue groups, but the times in the high-residue was smaller than that in the mid-residue group (P < 0.01). The average weights of the newborn in various residue groups were heavier comparing to the control. There was no significant difference between the high residue group and the control. However, significances existed among the low, intermediate, and control group (P < 0.05). Moreover, the rank from high to low was the low-residue, mid-residue and high residue group. CONCLUSION: The residues of organochlorine pesticides (DDT and BHC and their metabolites) possess reproductive and developmental toxicities, and present mostly the estrogenic activity under the joint exposure in which the total BHC concentration was higher than that of the total DDT in maternal blood.

Nuclear factor-kappaB activation on the reactive oxygen species in acute necrotizing pancreatitic rats.

AIM: To investigate the potential role of nuclear factor kappa-B (NF-kappaB) activation on the reactive oxygen species in rat acute necrotizing pancreatitis (ANP) and to assess the effect of pyrrolidine dithiocarbamate (PDTC, an inhibitor of NF-kappaB). METHODS: Rat ANP model was established by retrograde injection of 5% sodium taurocholate into biliopancreatic duct. Rats were randomly assigned to three groups (10 rats each): Control group, ANP group and PDTC group. At the 6th h of the model, the changes of the serum amylase, nitric oxide (NO), malondialdehyde (MDA), superoxide dismutase (SOD) and pancreatic morphological damage were observed. The expressions of inducible nitric oxide (iNOS) were observed by SP immunohistochemistry. And the expressions of NF-kappaB p65 subunit mRNA were observed by hybridization in situ. RESULTS: Serum amylase and NO level decreased significantly in ANP group as compared with PDTC administrated group ((7 170.40+/-1 308.63) U/L vs (4 074.10+/-1 719.78) U/L, P<0.05), ((76.95+/-9.04) micromol/L vs (65.18+/-9.02) micromol/L, P<0.05) respectively. MDA in both ANP and PDTC group rose significantly over that in control group ((9.88+/-1.52) nmol/L, (8.60+/-1.41) nmol/L, vs (6.04+/-1.78) nmol/L, P<0.05), while there was no significant difference between them. SOD levels in both ANP and PDTC group underwent a significant decrease as compared with that in control ((3 214.59+/-297.74) NU/mL, (3 260.62+/-229.44) NU/mL, vs (3 977.80+/-309.09) NU/mL, P<0.05), but there was no significant difference between them. Though they were still higher than those in Control group, pancreas destruction was slighter in PDTC group, iNOS expression and NF-kappaB p65 subunit mRNA expression were lower in PDTC group as compared with ANP group. CONCLUSION: We conclude that correlation among NF-kappaB activation, serum amylase, reactive oxygen species level and tissue damage suggests a key role of NF-kappaB in the pathogenesis of ANP. Inhibition of NF-kappaB activation may reverse the pancreatic damage of rat ANP and the production of reactive oxygen species.

Effects of elevated pCO2 and/or pO3 on C-, N-, and S-metabolites in the leaves of juvenile beech and spruce differ between trees grown in monoculture and mixed culture.

Three and four-year-old saplings of beech (Fagus sylvatica L.) and spruce (Picea abies (L.) Karst.) grown in monoculture and mixed culture were exposed in phytotrons to (1) ambient air, (2) elevated pO(3), (3) elevated pCO(2), or (4) elevated pCO(2) plus elevated pO(3). After 5 months, the contents of soluble sugars, starch, soluble amino compounds, non-structural proteins (NSP), as well as reduced (GSH) and oxidized (GSSG) glutathione were determined in the leaves of both species in order to assess the effects of the gaseous regimes on primary metabolism. Elevated pO(3) did not affect sugar and starch levels in beech leaves in monoculture, but significantly increased sugar levels in beech leaves grown in mixed culture. In spruce needles, sugar levels tended to be enhanced in both culture types. Individual and combined exposure of elevated pCO(2) led to an increase in non-structural carbohydrate (soluble sugars plus starch) levels in beech and spruce leaves of both culture types. Differences in the responses of non-structural carbohydrate levels to elevated pCO(2) between beech and spruce were apparent from different contributions of sugars and starch to the increase in carbohydrate levels. Exposure to elevated pCO(2) and/or elevated pO(3) did not affect the levels of soluble amino compounds and NSP in beech leaves, but reduced amino compound levels in spruce needles of both culture types. Elevated pO(3) increased GSH levels in the leaves of both tree species in both culture types, while GSSG levels in monoculture were reduced in beech leaves, but significantly enhanced in spruce needles. Elevated pCO(2) reduced GSSG levels in beech and spruce leaves in monoculture, and GSH levels in spruce needles of both culture types. The combination of elevated pCO(2) and pO(3) increased GSSG levels in beech leaves of both culture types and in spruce needles in monoculture, but reduced GSH levels in spruce needles of both culture types. Apparently, under each gaseous regime, the culture type significantly altered primary metabolism of the leaves of beech and spruce.