[A brief discussion on the inspiration and thinking of the Metaverse concept to promote the innovative development of intelligent medicine in China].

Created by digital technology,the Metaverse is a digital platform where the digital virtual world and the actual real world can coexist to some extent. Based on the integration of Metaverse and medical science,this article describes the great development of intelligent medicine in the fields of medical practice,medical education and medical research,especially in the field of surgery. First,the technical source of the Metaverse concept in the field of intelligent medicine can be traced back to technology to generate actual digital data sets from human anatomy. Second,the successful industrial practice of Metaverse in the field of intelligent medicine conforms to the authentic and credible fundamental purpose of "taking people as the first priority and serving people"， that is， "virtual" must be based on "actual" for "actual".

[Construction and validation of a nomogram model of early related factors for hepatic insufficiency after hemihepatectomy].

Objectives: To investigate the early related factors for hepatic insufficiency after hemihepatectomy and to construct and validate a nomogram model. Methods: This was a retrospective cohort study.There were 207 patients with liver tumor who underwent hemihepatectomy in the Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from October 2016 to December 2022. Using the random number method,patients were randomly divided into a model group(n=166) and a validation group(n=41) according to an 4︰1 ratio. There were 118 males and 48 females in the modeling group,with an age (M(IQR)) of 59.0(13.3) years (range: 22.0 to 81.0 years),42 patients in the group with postoperative liver insufficiency and 124 patients in the group without postoperative liver insufficiency. There were 32 males and 9 females in the validation group, with an age of 54.0(19.0) years (rang: 25.0~81.0 years). The first results of the peripheral blood test of patients within 24 hours after surgery were collected,and the independent related factors for incomplete postoperative liver function were determined by multivariate Logistic regression analysis,and related factors of postoperative incomplete liver function were screened by best subset selection. A nomogram model of the risk of postoperative hepatic insufficiency after hemihepatectomy was constructed using R software,followed by internal and external validation of the model. Results: Multivariate logistic regression analysis showed that elevated D-dimer level and decreased antithrombin Ⅲ (AT-Ⅲ) activity within 24 hours after surgery were independent related factors for the development of postoperative hepatic insufficiency in hemihepatectomized patients. The results of the best subset selection showed that ALT,D-dimer, and AT-Ⅲ activity levels within 24 hours postoperatively were the most relevant factors for postoperative hepatic insufficiency. The R software was applied to build a nomogram prediction model based on the above three indicators in the model set,and the receiver operating characteristic(ROC) curve of the model showed an area under the curve of 0.803 and the calibration curve showed a U-index of -0.012 for the model(P=0.977). The results of the clinical decision analysis and the clinical impact curve indicated that the model had good clinical utility. The internal validation results of the Bootstrap method suggested that the model had reasonable consistency. The area under the ROC curve of the validation group model was 0.806,suggesting that the model had a good generalization prediction ability. Conclusions: The levels of ALT,D-dimer,and AT-Ⅲ activity within 24 hours after hemihepatectomy are valuable indicators for predicting liver insufficiency after hemihepatectomy. The nomogram model is reliable and can be used as an indicator for close postoperative monitoring.

Association of menopausal status and symptoms with depressive symptoms in middle-aged Chinese women.

OBJECTIVE: This study aims to examine the association of menopausal status and symptoms with depressive symptoms. METHODS: A community-based cross-sectional survey recruited 6745 women aged 40-55 years in the eastern, central and western regions of China in 2018. Menopausal status was categorized into reproductive stage, perimenopause or postmenopause according to the Stages of Reproductive Aging Workshop classification. Menopausal symptoms were determined by the modified Kupperman Menopausal Index and classified as none (total score < 15), mild (15 ≤ total score ≤ 24) or moderate to severe (total score ≥ 25). Logistic regression models were used to examine the associations of menopausal status and symptoms with depressive symptoms assessed by the Patient Health Questionnaire-9. RESULTS: The prevalence of depressive symptoms among women in the reproductive stage, perimenopause and postmenopause was 15.4%, 23.9% and 22.8%, respectively. After multivariable adjustment, perimenopause (odds ratio [OR] = 1.21, 95% confidence interval [CI]: 1.01-1.47) and postmenopause (OR = 1.28, 95% CI: 1.04-1.58) were associated with higher risk for depressive symptoms than during the reproductive stage. Mild (OR = 5.55, 95% CI: 4.68-6.59) and moderate-to-severe (OR = 14.77, 95% CI: 10.94-19.94) menopausal symptoms were associated with increased likelihood of depressive symptoms compared to the group reporting no menopausal symptoms. CONCLUSIONS: Menopausal status and symptoms were independently associated with the risk of depressive symptoms in middle-aged Chinese women.

[Comparison of follow-up treatment regimens for colorectal cancer liver metastases without objective response to neoadjuvant chemotherapy: direct surgery or surgery after second-line chemotherapy].

Objective: To compare the effect of direct surgery or surgery after second-line chemotherapy for colorectal cancer patients with liver metastases who did not achieve objective remission after neoadjuvant chemotherapy. Methods: A retrospective case cohort study was used. The clinical and pathological data of 107 patients with colorectal cancer liver metastases who did not achieve objective response to neoadjuvant chemotherapy at Department of Hepatobiliary Surgery,Cancer Hospital,Chinese Academy of Medical Sciences from December 2008 to December 2016 were retrospectively collected. There were 71 males and 36 females, median age was 57 years (range: 28 to 79 years). According to the different treatment regimens after neoadjuvant chemotherapy,107 cases were divided into a direct surgery group (direct group,n=65) and an operation after receiving second-line chemotherapy group (second-line group,n=42). The propensity score matching(PSM) of the Logistic regression model was used to match the bilobar distribution of liver metastases and the number of first-line chemotherapy cycles in the two groups of patients. The caliper value was set to 0.10 and the matching ratio was 1∶2. T test, Mann-Whitney U test, χ2 test or Fisher's exat test was used to analyzed the data between the tuo groups, respectively. Survival analysis design was used to investigate the difference in prognosis between the two groups of patients. Results: The follow-up time(M(IQR)) was 56.3(34.3) months (range: 2.1 to 95.0 months),and all patients were followed up. After PSM,there were 28 cases in the direct group and 42 cases in the second-line group, there were no significant differences in whether R0 resection was feasible,blood loss,blood transfusion,postoperative complications and postoperative hospital stay between the two groups (all P>0.05). The 1,3,and 5-year progression-free survival(PFS) rates of the direct group were 40.0%,16.5%,and 11.0%,and the 1,3,and 5-year overall survival(OS) rates were 98.5%,61.2%,and 41.4%,respectively, the second-line group 1,3,5 years PFS rates were 35.7%,14.3%,14.3%,1,3,5-year OS rate were 95.2%,55.1%,44.4%,respectively. The median PFS time of the direct group and the second-line group was 8.5 months and 7.5 months,respectively,and the difference was not statistically significant (P=0.826). The median OS time of the direct group and the second-line group were 33.8 months and 46.9 months,respectively. The difference was not statistically significant(P=0.646).The median PFS time of the direct group and second-line chemotherapy complete remission and partial remission group(CR/PR group) was 10.2 months and 9.1 months,respectively,and the difference was not statistically significant(P=0.669). The median OS time of the direct group and the second-line CR/PR group was 51.0 months and 46.9 months,respectively,and the difference was not statistically significant(P=0.427). The results of survival analysis suggested that major liver resection was an independent prognosis factor for PFS (HR=1.809,95%CI: 1.067 to 3.067,P=0.028) and OS(HR=2.751,95%CI: 1.317 to 5.747,P=0.007). Second-line chemotherapy was not an independent prognostic factor for PFS (HR=0.945, 95%CI:0.570 to 1.567,P=0.828) and OS (HR=0.866,95%CI: 0.468 to 1.602,P=0.646). Conclusions: There is no significant difference in the short-term outcome and long-term prognosis between direct surgery patients and second-line chemotherapy followed by surgery. Second-line chemotherapy is not an independent prognostic factor for colorectal cancer liver metastases patients who fail to achieve objective response after neoadjuvant chemotherapy.

Gender-specific SBNO2 and VPS13B as a potential driver of osteoporosis development in male ankylosing spondylitis.

To identify the critical genes and pathways that related to OP development in male AS patients, bioinformatic gene analysis and qRT-PCR validation were performed. SBNO2 and VPS13B were identified as the potential target for OP development, which may be valuable for the prevention of OP in male AS patients. INTRODUCTION: Osteoporosis (OP) is common in men with ankylosing spondylitis (AS). The specific pathogenesis of OP in AS, however, is still unclear. The present study attempted to identify potential genes associated with the development of OP in males with AS. METHODS: Gene expression profiles were downloaded from the GSE73754 and GSE35959 datasets from the Gene Expression Omnibus (GEO). Data from OsteoporosAtlas were downloaded as a supplement. Differentially expressed genes (DEGs) were determined with the limma package. The overlapping DEGs between male AS-related genes and OP-related genes were determined. The DEGs were validated by qRT-PCR in the blood samples of males with AS. Weighted gene co-expression network analysis (WGCNA) was utilized to establish a co-expression network to identify the hub genes. RESULTS: A total of 17 overlapping DEGs were identified; 6 genes in 17 overlapping DEGs were verified as the essential genes in the pathogenesis of OP in male AS by qRT-PCR analysis. After WGCNA, the modules of MEblue (> 0.6) and MEred (> 0.8) were screened out by the correlation analysis and were determined to function mainly in MAPK signaling pathway and osteoclast differentiation. Analysis of the two modules revealed VPS13B and SBNO2 as key genes due to the high degree of correlation. Both genes play an important role in bone metabolism regulation in male AS. Two hub genes MYD88 in MEblue and NCK1 in MEred with high degree of connectivity were selected. CONCLUSIONS: Gender-specific SBNO2 and VPS13B may be key genes involved in OP in male AS.

[Clinical observation of combined oral contraceptives drospirenone and ethinylestradiol tablets (â ¡) in the treatment of dysmenorrhea in Chinese women].

Objective: To evaluate the efficacy and safety of drospirenone and ethinylestradiol tablets (Ⅱ) in Chinese women with dysmenorrhea. Methods: This was a single-arm, open-label, interventional, multicenter, post-authorization safety/effectiveness study of drospirenone and ethinylestradiol tablets (Ⅱ) across 6 treatment cycles, a total of 526 patients were included in the dysmenorrhea subgroup. Visual analog scale (VAS) was used to assess the severity of menstrual pain. Secondary outcomes included unintended pregnancies, bleeding pattern, cycle control and safety. Results: After treated with drospirenone and ethinylestradiol tablets (Ⅱ), VAS of pain had decreased significantly compared with baselines [(49.5±23.7) vs (32.3±24.9) vs (20.7±19.4) vs (18.4±18.7) mm, P<0.01]. From the second cycle to the fifth cycle, the incidence of scheduled bleeding increased from 93.9% (450/479) to 96.4% (431/447). The duration of scheduled bleeding decreased from (5.7±2.7) to (5.4±1.8) days. The incidence of intermenstrual bleeding decreased from 9.0% (43/479) to 5.6% (25/447). 17.5% (92/526) patients reported adverse drug reactions, most frequently reported adverse events were breast pain, nausea, breast swelling, headache, and uterine bleeding. No death occurred during the study. Conclusion: Drospirenone and ethinylestradiol tablets (Ⅱ) is effective for the treatment of dysmenorrhea and has good safety.

Substrate Diversity of L-Threonic Acid Dehydrogenase Homologs.

Despite physiological importance of aldonic sugar acids for living organisms, little is known about metabolic pathways of these compounds. Here, we investigated the functional diversity of homologs of L-threonic acid dehydrogenase (ThrDH; UniProt ID: Q0KBC7), an enzyme composed of two NAD-binding domains (PF14833 and PF03446). Ten ThrDH homologs with different genomic context were studied; seven new enzymatic activities were identified, such as (R)-pantoate dehydrogenase, L-altronic acid dehydrogenase, 6-deoxy-L-talonate dehydrogenase, L-idonic acid dehydrogenase, D-xylonic acid dehydrogenase, D-gluconic acid dehydrogenase, and 2-hydroxy-3-oxopantoate reductase activities. Two associated metabolic pathways were identified: L-idonic acid dehydrogenase was found to be involved in the degradation of L-idonic acid through oxidation/decarboxylation in Agrobacterium radiobacter K84, while 2-hydroxy-3-oxopantoate reductase was found to participate in D-glucarate catabolism through dehydration/cleavage in Ralstonia metallidurans CH34.

[Efficacy analysis of the radiotherapy and chemotherapy in patients with stage â £ esophageal squamous carcinoma: a multicenter retrospective study of Jing-Jin-Ji Esophageal and Esophagogastric Cancer Radiotherapy Oncology Group (3JECROG R-01F)].

Objective: To evaluate the survival and prognostic factors of radiotherapy in patient with Ⅳ stage esophageal squamous carcinoma treated with radiation or chemoradiation. Methods: The medical records of 608 patients with stage Ⅳ esophageal squamous cell carcinoma who met the inclusion criteria in 10 medical centers in China from 2002 to 2016 were retrospectively analyzed. The overall survival and prognostic factors of all patients at 1, 3 and 5 years were analyzed. Results: The 1-, 3-, 5- year overall survival (OS) rates was 66.7%, 29.5% and 24.3% in stage ⅣA patients, and 58.8%, 29.0% and 23.5% in stage ⅣB patients. There was no statistical difference between the two groups (P=0.255). Univariate analysis demonstrated that the length of lesion, treatment plan, planned tumor target volume (PGTV) dose, subsequent chemotherapy, and degrees of anemia, radiation esophagitis, radiation pneumonia were related to the prognoses of patients with Ⅳ stage esophageal carcinomas after radiotherapy and chemotherapy (P<0.05). Multivariate analysis demonstrated that PGTV dose (OR=0.693, P=0.004), radiation esophagitis (OR=0.867, P=0.038), and radiation pneumonia (OR=1.181, P=0.004) were independent prognostic factors for OS. Conclusions: For patients with stage Ⅳ esophageal squamous cell carcinoma, chemoradiotherapy followed by sequential chemotherapy is recommended, which can extend the total survival and improve the prognosis of the patients. PGTV dose more than 60 Gy has better efficacy.

Bayesian modelling of a hepatitis A outbreak in men who have sex with men in Sydney, Australia, 1991/1992.

To control hepatitis A spread by vaccination, accurate estimation of transmissibility is vital. Regan et al. (2016) proposed a model of hepatitis A virus (HAV) transmission and used least squares to calibrate model to the 1991/1992 HAV outbreak in men who have sex with men (MSM) in Sydney, Australia. Based on the estimate of R0, they obtained the critical immunity of 70% and showed that when the proportion immune <70%, there is a definite chance for outbreaks to take place. The immunity level from previous surveys ranges from 32% to 64% after 1996 while no outbreaks in Australian MSMs have been reported since 1996. Further noticing the ill-distributed parameters, we argue that their estimate of R0 is not accurate. In this study, we revisited their model by Bayesian inference, which has privilege over least squares. We obtained the appropriate posterior distributions of parameters and the estimate of R0 ranges from 1.38 to 2.89, indicating a critical immunity of 65%. The reduction in critical immunity and outbreak probabilities predicts the absence of outbreaks in Australian MSMs since 1996. Our study shows the importance of using appropriate methods to provide reliable and accurate estimates of the model parameters especially the transmissibility.

The natural history and patterns of metastases from mucosal melanoma: an analysis of 706 prospectively-followed patients.

Background: We examined whether mucosal melanomas are different in their clinical course and patterns of metastases when arising from different anatomic sites. Our hypothesis was that metastatic behavior would differ from primary mucosal melanomas at different anatomical sites. Patients and methods: Clinical and pathological data from 706 patients were compared for their stage distribution, patterns of metastases, CKIT/BRAF mutation status, and overall survival for different anatomical sites. Results: The anatomic sites of the primary mucosal melanomas were from the lower GI tract (26.5%), nasal cavity and paranasal sinuses (23%), gynecological sites (22.5%), oral cavity (15%), urological sites (5%), upper GI tract (5%), and other sites (3.0%). At initial diagnosis, 14.5% were stage I disease, 41% Stage II, 21.5% Stage III, and 23.0% stage IV. Predominant metastatic sites were regional lymph nodes (21.5%), lung (21%), liver (18.5%), and distant nodes (9%). Oral cavity mucosal melanoma had a higher incidence of regional nodal metastases (31.7% versus 19.8%, P = 0.009), and a higher incidence of lung metastases (32.5% versus 18.5%, P = 0.007) compared to other primary mucosal melanomas. There was a 10% incidence of CKIT mutation and 12% BRAF mutation. Mucosal melanomas from nasal pharyngeal and oral, gastrointestinal, gynecological, and urological had a similar survival with a 1-year survival rate (88%, 83%, 86%), 2-year survival rate (66%, 57%, 61%), 5-year survival rate (27%, 16%, 20%), respectively. Conclusions: The largest sample size allows, for the first time, a comparison of primary melanoma stage and patterns of metastases across anatomical sites. With few exceptions, the presenting stages, incidence of nodal and distant metastases, the site of predilection of distant metastases, or overall survival were similar despite different primary anatomic sites. These findings suggest that clinical trials involving mucosal melanomas and the administration of systemic therapy can be applied equally to mucosal melanomas regardless of their primary anatomic site.

Predictor of massive bleeding following stent placement for malignant oesophageal stricture/fistulae: a multicentre study.

AIM: To evaluate retrospectively the incidence and predictors of massive bleeding after stent placement for malignant oesophageal stricture/fistulae. MATERIALS AND METHODS: This retrospective study comprised 519 patients with malignant oesophageal stricture/fistulae that were successfully treated with stent placement at three hospitals. The patients were divided into two groups based on the occurrence of massive bleeding. Univariate and multivariate analysis was performed to evaluate predictive factors of massive bleeding. RESULTS: Massive bleeding occurred in 54 of 519 patients 1-37 days following stent placement. All of the patients who developed massive bleeding died within 24 hours of the event. Univariate analysis showed massive bleeding was associated with the presence of a concomitant tracheal stent (p<0.001), the existence of concomitant oesophageal fistulae (p<0.001), and prior radiotherapy (p<0.001). Multivariate analysis exhibited that concomitant tracheal stent insertion (odds ratio [OR], 23.134; 95% confidence interval [CI], 9.523-56.199; p<0.001), the presence of oesophageal fistulae (OR, 3.724; 95% CI, 1.677-8.269; p=0.001), and prior radiotherapy (OR, 13.310; 95% CI, 5.464-32.421; p<0.001) were predictors of massive bleeding following stenting. CONCLUSIONS: The presence of oesophageal fistulae, prior radiotherapy, and concomitant tracheal stent are important factors contributing to bleeding after stenting.

Protective effect of ischemia preconditioning on ischemia-reperfusion injury in rat liver transplantation.

We explored the protective effect of ischemia preconditioning (IP) on ischemia-reperfusion injury in rat liver transplantation. An orthotopic liver transplantation model was utilized in the study. A total of 54 Sprague-Dawley rats were divided into a control group (group A, no liver transplantation), liver transplantation group (group B, heparin Ringer's lactate solution was perfused via the portal vein before donor liver collection), and liver transplantation with IP group (group C, IP was performed for different time periods before donor liver collection). Liver function, B-cell lymphoma 2 expression in hepatic cells, cell apoptosis, and cellular ultrastructure changes were detected after surgery. After surgery, serum alanine aminotransferase activity was significantly higher in group B than in group A, while it was not clearly enhanced in group C and decreased progressively with increasing cycles of IP as bile capacity gradually increased. Compared with group B, group C showed alleviated injury of hepatic cells, increased B-cell lymphoma 2 expression, and a lower apoptosis index. IP had a protective effect on ischemia-reperfusion injury in rat liver transplantation, and the mechanism correlated with increased B-cell lymphoma 2 expression in hepatic cells and inhibition of cell apoptosis.

Cloning and characterization of a farnesyl pyrophosphate synthase from Matricaria recutita L. and its upregulation by methyl jasmonate.

Matricaria recutita (L.), commonly known as chamomile, is one of the most valuable medicinal plants because it synthesizes a large number of pharmacologically active secondary metabolites known as α-bisabolol and chamazulene. Although the plant has been well characterized in terms of chemical constituents of essential oil as well as pharmacological properties, little is known about the genes responsible for biosynthesis of these compounds. In this study, we report a new full-length cDNA encoding farnesyl diphosphate synthase (FPS), a key enzyme in the pathway of biosynthesis of isoprenoids, from M. recutita. The cDNA of MrFPS comprises 1032 bp and encodes 343 amino acid residues with a calculated molecular mass of 39.4 kDa. The amino acid sequence homology and phylogenetic analysis indicated that MrFPS belongs to the plant FPS super-family and is closely related to FPS from the Asteraceae family. Expression of the MrFPS gene in Escherichia coli yielded FPS activity. Using real-time quantitative PCR, the expression pattern of the MrFPS gene was analyzed in different tissues of M. recutita as well as in response to methyl jasmonate. The expression analysis demonstrated that MrFPS expression varies in different tissues (with maximal expression in flowers and stems) and was significantly elevated in response to methyl jasmonate. This study will certainly enhance our understanding of the role of MrFPS in the biosynthesis and regulation of valuable secondary metabolites in M. recutita at a molecular level.

Effect of low temperatures on BAX and BCL2 proteins in rats with spinal cord ischemia reperfusion injury.

We evaluated changes in BAX and BCL2 expression levels after spinal cord ischemia/reperfusion injury (SCII) and hypothermia during operations in rats. Eighty rats were divided into four groups: Group A (N = 20, 18°C); Group B (N = 20, 28°C); Group C (N = 20, room temperature); and Group D (N = 20, sham operation control). Spinal cord ischemia was induced for 90 min. Hypothermia was induced 15 min before, and maintained during ischemia, followed by heating to normothermia for 30 min after reperfusion. Motor function of the lower limbs was evaluated according to the Tarlov score at 72 and 168 h. For each rat, spinal cord samples were taken at 6, 24, 72 h, and 1 week to evaluate the histopathological changes, neuronal apoptosis, and BAX and BCL2 expression levels. Compared with normothermia, hypothermia significantly improved hind limb function; Group B achieved a higher score than Group A. Group D showed no neurologic deficiency, while the other groups showed various degrees. Group C exhibited greater neuronal apoptosis, higher BAX expression, but lower BCL2 expression than the other groups. Compared with Group A, BAX was expressed less and BCL2 more in Group B, and there was less apoptosis in Group B. Hypothermia preserves hind limb motor function and reduces neuronal death, thereby protecting rats from SCII. The spinal cord may be protected from SCII by inhibition of BAX and activation of BCL2. However, deep hypothermia may inhibit the expression of BCL2, resulting in a worse outcome than mild hypothermia.

Long-term treadmill exercise improves spatial memory of male APPswe/PS1dE9 mice by regulation of BDNF expression and microglia activation.

Increasing evidence suggests that physical activity could delay or attenuate the symptoms of Alzheimer's disease (AD). But the underlying mechanisms are still not fully understood. To investigate the effect of long-term treadmill exercise on the spatial memory of AD mice and the possible role of ß-amyloid, brain-derived neurotrophic factor (BDNF) and microglia in the effect, male APPswe/PS1dE9 AD mice aged 4 months were subjected to treadmill exercise for 5 months with 6 sessions per week and gradually increased load. A Morris water maze was used to evaluate the spatial memory. Expression levels of ß-amyloid, BDNF and Iba-1 (a microglia marker) in brain tissue were detected by immunohistochemistry. Sedentary AD mice and wildtype C57BL/6J mice served as controls. The results showed that 5-month treadmill exercise significantly decreased the escape latencies (P < 0.01 on the 4th day) and improved the spatial memory of the AD mice in the water maze test. Meanwhile, treadmill exercise significantly increased the number of BDNF-positive cells and decreased the ratios of activated microglia in both the cerebral cortex and the hippocampus. However, treadmill exercise did not significantly alleviate the accumulation of ß-amyloid in either the cerebral cortex or the hippocampus of the AD mice (P > 0.05). The study suggested that long-term treadmill exercise could improve the spatial memory of the male APPswe/PS1dE9 AD mice. The increase in BDNF-positive cells and decrease in activated microglia might underpin the beneficial effect.

Molecular cloning and characterization of the full-length Hsp90 gene from Matricaria recutita.

Heat shock protein 90 (Hsp90) is one of the most abundant and conserved chaperone proteins and plays important roles in plant growth and responses to environmental stimuli. However, little is known regarding the sequence and function of Hsp90s in Matricaria recutita. In the present study, we cloned the full-length cDNA sequence of the hsp90 gene from this species. Using rapid amplification of cDNA ends technologies with 2 degenerate primers that were designed based on the hsp90 gene sequence from other members of Asteraceae, we isolated and characterized an Hsp90 homolog gene from M. recutita (Mr-Hsp90). The full-length Mr-hsp90 cDNA sequence, containing 2097 base pairs, encodes a protein of 698 amino acids. Based on amino acid sequence identity, Mr-Hsp90 showed high similarity to other cloned Hsp90 proteins. The Mr-Hsp90 protein was closely clustered with the Lactuca sativa in a phylogenetic tree. These results indicate that the cloned sequence of Mr-Hsp90 is a member of the Hsp90 family, which is reported for the first time in M. recutita. Next, we conducted a salt stress experiment to determine the protein's function under salt stress conditions. Survival of chamomile seedlings subjected to heat-shock pretreatment was significantly increased compared with groups that had not undergone heat-shock pretreatment in a salt stress environment. This indicates that Mr-Hsp90 plays an important role in the salt resistance of chamomile seedlings.

First Report of Rhexocercosporidium panacis Causing Rusty Root of Panax ginseng in Northeastern China.

In northeastern China, Asian ginseng (Panax ginseng) roots exhibited reddish brown lesions of various sizes, irregular shapes, and diffuse margins, typical of rusty root disease. The lesions remain superficial, smooth, and limited to the epidermal and peridermal tissues. In September 2013, 10 symptomatic roots were collected from each of three fields in Jilin and Heilongjiang provinces. One piece of symptomatic skin tissue from each root was excised, surface-disinfested in 1% NaClO for 3 min, rinsed three times with sterile water, and then placed on tetracycline-amended (50 µg/ml) potato dextrose agar. After incubation at 22 ± 1°C in the dark for a week, small olivaceous black colonies developed from the symptomatic tissue from five of the 30 samples. No spores were observed. A single hyphal tip of each colony was transferred to a fresh V8 agar plate to purify the culture. Two-week-old colonies on V8 agar were olivaceous gray, and 42 to 46 mm in diameter with an outer white margin (3 to 5 mm wide). Conidia produced in V8 broth after 3 weeks with a 12-h photoperiod were straight and hyaline, cylindrical or subcylindrical with no or one septum. Mature conidia were 12.8 to 21.8 × 2.2 to 4.5 µm (mean 18.2 × 3.0 µm, n = 100 conidia for each of three isolates). Three isolates selected randomly were further identified by analyzing the partial sequences of the ITS region of rDNA with primers ITS4 and ITS5 (5), and partial sequences of ß-tubulin with the primers tub2F and tub2R (1). Sequences of the three isolates (GenBank Accession Nos. KJ149287, KJ149288, and KJ149290 to 93) showed 99% to 100% homology with previously identified and deposited Rhexocercosporidium panacis isolates (DQ2499992 and DQ457119) for both loci (3). Therefore, the three isolates were identified as R. panacis and deposited in China General Microbiological Culture Collection Center (CGMCC3.17259 to 61). Pathogenicity of R. panacis in Asian ginseng was investigated using these three isolates as described previously with slight modifications (4). Bare roots of 3-year-old Asian ginseng were surface-disinfested as described above, and inoculated with mycelial plugs (4 mm diameter) cut from the margin of actively growing colonies of the isolates on V8 agar. Three mycelial plugs were placed on each root at 3-cm intervals and four roots (replicates) were inoculated for each isolate. Four additional roots were inoculated with non-colonized agar plugs as control. The treated roots were placed on moist filter paper in an enamel tray. The plates were sealed with plastic wrap to prevent desiccation and incubated in the dark at 18 ± 1°C. Four weeks post inoculation, all the inoculated ginseng roots showed red-brown lesions, which turned to dark red or black over time. R. panacis was recovered from symptomatic roots for all isolates and confirmed by ITS sequence analysis. The mock-inoculated control roots remained symptomless and no R. panacis was isolated. The inoculation experiment was repeated and showed the same results. R. panacis was reported in 2006 to infect roots of Panax quinquefolius (2,3,4). To our knowledge, this is the first report of R. panacis causing rusty root of P. ginseng. References: (1) P. R. Hirsch et al. Mycol. Res. 104:435, 2000. (2) Z. K. Punja et al. Can. J. Plant Pathol. 35:503, 2013. (3) R. D. Reeleder. Mycologia. 99:91, 2007. (4) R. D. Reeleder et al. Phytopathology 96:1243, 2006. (5) T. J. White et al. PCR Protocols: A Guide to Methods and Applications. Academic Press, San Diego, 1990.

[Analysis on the characteristics of natural foci of hemorrhagic fever with renal syndrome in Gansu Province, 2012-2022].

Objective: To explore the characteristics of natural foci of hemorrhagic fever with renal syndrome (HFRS) in Gansu Province. Methods: The information of HFRS case data and rodent density monitoring data from 2012 to 2022 in Gansu Province were collected and epidemiological methods were used to analyze and investigate the characteristics of the epidemic focus. Results: A total of 869 cases of HFRS were reported, and four patients died from 2012 to 2022. The annual incidence rate is between 0.05 per 100 000 and 1.21 per 100 000. The cases were mainly distributed in the eastern, southeast, southern, and south of the central region of Gansu Province. Most cases were distributed between age 20-60, and the sex ratio was 1.85∶1 (564∶305). Most cases were farmers (61.80%, 537/869), herdsmen (19.79%,172/869) and students (6.33%, 55/869). In a wild rat-type epidemic focus,the incidence peak was from November to January of the following year. The natural rodent hosts of HFRS were Rattus norvegicus, Apodemus agrarius, and Mus musculus. The hantaan virus carriage rates were 2.79% (21/754), 0.42% (5/1 179) and 0.31% (2/643),respectively. Three epidemic foci were defined: two derived from the Pingliang and Gannan prefecture new outbreaks epidemic foci, respectively, while the other was the residue of the Dingxi epidemic focus. Conclusions: The southern, south of the central region and eastern part of Gansu Province are current key HFRS epidemic foci dominated by Rattus norvegicus, Apodemus agrarius, and Mus musculus, respectively. The virus genotype is hantaan virus. Case reporting areas should strengthen epidemic monitoring; the key epidemic areas should strengthen and implement various prevention and control measures to reduce the harm caused by HFRS.

[Treatment status of tyrosine kinase inhibitor for newly-diagnosed chronic myeloid leukemia: a domestic multi-centre retrospective real-world study].

Objective: To retrospectively analyze the treatment status of tyrosine kinase inhibitors (TKI) in newly diagnosed patients with chronic myeloid leukemia (CML) in China. Methods: Data of chronic phase (CP) and accelerated phase (AP) CML patients diagnosed from January 2006 to December 2022 from 77 centers, ≥18 years old, and receiving initial imatinib, nilotinib, dasatinib or flumatinib-therapy within 6 months after diagnosis in China with complete data were retrospectively interrogated. The choice of initial TKI, current TKI medications, treatment switch and reasons, treatment responses and outcomes as well as the variables associated with them were analyzed. Results: 6 893 patients in CP (n=6 453, 93.6%) or AP (n=440, 6.4%) receiving initial imatinib (n=4 906, 71.2%), nilotinib (n=1 157, 16.8%), dasatinib (n=298, 4.3%) or flumatinib (n=532, 7.2%) -therapy. With the median follow-up of 43 (IQR 22-75) months, 1 581 (22.9%) patients switched TKI due to resistance (n=1 055, 15.3%), intolerance (n=248, 3.6%), pursuit of better efficacy (n=168, 2.4%), economic or other reasons (n=110, 1.6%). The frequency of switching TKI in AP patients was significantly-higher than that in CP patients (44.1% vs 21.5%, P<0.001), and more AP patients switched TKI due to resistance than CP patients (75.3% vs 66.1%, P=0.011). Multi-variable analyses showed that male, lower HGB concentration and ELTS intermediate/high-risk cohort were associated with lower cytogenetic and molecular responses rate and poor outcomes in CP patients; higher WBC count and initial the second-generation TKI treatment, the higher response rates; Ph(+) ACA at diagnosis, poor PFS. However, Sokal intermediate/high-risk cohort was only significantly-associated with lower CCyR and MMR rates and the poor PFS. Lower HGB concentration and larger spleen size were significantly-associated with the lower cytogenetic and molecular response rates in AP patients; initial the second-generation TKI treatment, the higher treatment response rates; lower PLT count, higher blasts and Ph(+) ACA, poorer TFS; Ph(+) ACA, poorer OS. Conclusion: At present, the vast majority of newly-diagnosed CML-CP or AP patients could benefit from TKI treatment in the long term with the good treatment responses and survival outcomes.

QSAR modeling of toxicity of acyclic quaternary ammonium compounds on Scenedesmus Quadricauda using 2D and 3D descriptors.

Optimized calculation of typical acyclic quaternary ammonium compounds (QACs) was performed at B3LYP/6-311G** level using density functional theory (DFT) method. A two- dimensional quantitative structure-activity relationship (2D-QSAR) model was established with the obtained structure parameters as theoretical descriptors. And then three-dimensional quantitative structure-activity relationship (3D-QSAR) models were built using comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) methods respectively. The 2D and 3D QSAR models exhibit optimum stability and predictive ability, revealing that steric and electronic effects influence the toxicity of acyclic QACs to Scenedesmus Quadricauda mostly.