Comparing the efficacy and pregnancy outcome of intrauterine balloon and intrauterine contraceptive device in the prevention of adhesion reformation after hysteroscopic adhesiolysis in infertile women: a prospective, randomized, controlled trial study.

STUDY OBJECTIVE: To evaluate the efficacy and pregnancy outcomes of intrauterine balloon and intrauterine contraceptive devices in the prevention of adhesion reformation following hysteroscopic adhesiolysis in infertile women with moderate to severe intrauterine adhesion. DESIGN: A prospective, randomized, controlled trial study. SETTING: A tertiary university hospital. PATIENTS: A total of 130 patients with moderate (American Fertility Society [AFS] score of 5-8) and severe (AFS score of 9-12) intrauterine adhesions were recruited. INTERVENTIONS: 86 patients were evenly allocated to group treated with an IUD for 1 month and group treated with an IUD for 2 months. 44 patients were allocated to group treated with a Foley catheter balloon.(IUD: Yuangong IUD). MEASUREMENTS AND MAIN RESULTS: The primary outcome measures were the AFS score, endometrial thickness, and pregnancy outcome. After hysteroscopy, the AFS score was significantly decreased(P<0.05), whereas endometrial thickness was significantly increased across the three groups(P<0.001). Notably, the decline in the AFS score in the balloon group was greater than that in the IUD-1-month group and IUD-2-month group(P<0.01), with no significant difference between the IUD groups(P = 0.298). Lastly, In addition, the extent of the increase in endometrial thickness(P = 0.502) and the pregnancy outcomes(P = 0.803) in the three groups were not significantly different. CONCLUSION: Inserting a balloon or placing an IUD for one or two months can effectively lower the risk of adhesion recurrence and restore the shape of the uterine cavity. While the therapeutic effect of the balloon was superior to that of the IUD, no significant differences were observed in the one-month and two-month IUD groups. TRIAL REGISTRATION: This research was registered in the Chinese Clinical Trial Registry ( http://www.chictr.org.cn/enIndex.aspx ); Clinical trial registry identification number: ChiCTR-IOR-17,011,943 ( http://www.chictr.org.cn/showprojen.aspx?proj=17979 ). Date of trial registration: July 11, 2017.

Safranal exerts a neuroprotective effect on Parkinson's disease with suppression of NLRP3 inflammation activation.

BACKGROUND: Parkinson's disease (PD) is a common central nervous system neurodegenerative disease. Neuroinflammation is one of the significant neuropathological hallmarks. As a traditional Chinese medicine, Safranal exerts anti-inflammatory effects in various diseases, however, whether it plays a similar effect on PD is still unclear. The study was to investigate the effects and mechanism of Safranal on PD. METHODS: The PD mouse model was established by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP firstly. Next, the degree of muscle stiffness, neuromuscular function, motor retardation and motor coordination ability were examined by observing and testing mouse movement behavior. Immunofluorescence staining was used to observe the expression of tyrosine hydroxylase (TH). The dopamine (DA) content of the striatum was detected by High-performance liquid chromatography (HPLC). The expression of TH and NLRP3 inflammasome-related markers NLRP3, IL-1ß, and Capase-1 were detected by Real-time Polymerase Chain Reaction (qRT-PCR) and western blotting (WB) respectively. RESULTS: Through behavioral testing, Parkinson's mouse showed a higher muscle stiffness and neuromuscular tension, a more motor retardation and activity disorders, together with a worse motor coordination compared with sham group. Simultaneously, DA content and TH expression in the striatum were decreased. However, after using Safranal treatment, the above pathological symptoms of Parkinson's mouse all improved compared with Safranal untreated group, the DA content and TH expression were also increased to varying degrees. Surprisingly, it observed a suppression of NLRP3 inflammation in the striatum of Parkinson's mouse. CONCLUSIONS: Safranal played a neuroprotective effect on the Parkinson's disease and its mechanism was related to the inhibition of NLRP3 inflammasome activation.

Discovery of Pesticide Candidates from Natural Plant Products: Semisynthesis and Characterization of Andrographolide-Based Esters and Study of Their Pesticidal Properties and Toxicology.

To explore the use of nonfood plant-derived secondary metabolites for plant protection, a series of ester derivatives for controlling the major migratory agricultural pests were obtained by structural modification of andrographolide, a labdane diterpenoid isolated from Andrographis paniculata. Compound Id showed good insecticidal activity against the fall armyworm Spodoptera frugiperda Smith. Compounds IIa (LC50: 0.382 mg/mL) and IIIc (LC50: 0.563 mg/mL), the acaricidal activities of which were, respectively, 13.1 and 8.9 times that of andrographolide (LC50: 4.996 mg/mL), exhibited strong acaricidal and control effects against Tetranychus cinnabarinus Boisduval. Against Aphis citricola Van der Goot, compounds IIIc and IVb displayed 3.9- and 3.7-fold pronounced aphicidal activity of andrographolide. Effects of compound Id on three protective enzymes (superoxide dismutase, peroxidase, and catalase) of S. frugiperda were also observed. The obvious differences of epidermal cuticle structures of mites treated with compound IIa were determined by scanning electron microscopy. Structure-activity relationships indicated that 14-ester derivatives of andrographolide showed potential insecticidal/acaricidal activities and can be further utilized as lead compounds.

Construction and Single-Crystal Structures of N-Isoxazolin-5-ylcarbonylindole Derivatives, and Their Pesticidal Activities and Toxicology Study.

To explore natural product-based pesticide candidates, a series of indole derivatives containing the isoxazoline skeleton at the N-1 position were synthesized by 1,3-dipolar [2 + 3] cycloaddition reaction. Their structures were characterized by melting points (mp), infrared (IR) spectra, proton nuclear magnetic resonance spectra (1H NMR), carbon-13 nuclear magnetic resonance spectra (13C NMR), and high resolution mass spectrometry (HRMS). The single-crystal structures of five compounds were presented. Against Tetranychus cinnabarinus Boisduval, compound 3b showed greater than 3.8-fold acaricidal activity of indole and good control effects under glasshouse conditions. Against Aphis citricola Van der Goot, compounds 3b and 3q exhibited 48.3- and 36.8-fold aphicidal activity of indole and 6-methylindole, respectively. Particularly, compound 3b showed good bioactivities against T. cinnabarinus and A. citricola. Against Eriosoma lanigerum Hausmann, compound 3h and 3i showed 2.1 and 1.9 times higher aphicidal activity compared to indole. Furthermore, the construction of the epidermal cuticle layer of 3b-treated carmine spider mites was distinctly damaged, which ultimately led to their death.

First Report of Nigrospora sphaerica causing Leaf Spot on Rhododendron simsii in China.

Rhododendron simsii (indoor azalea) is widely cultivated for its high ornamental value (Xu et al. 2021). In April to May 2023, a leaf spot disease occurred in a field study at the Baili Azalea Forest Area (27°12'N, 105°48'E), Guizhou Province, China. About 500 plants were investigated, and the results showed that the incidence of leaf spot was 20 ~ 30%. To study this disease, 10 plants showing severe symptoms were collected. Initially, the symptoms were round or irregularly shaped brown spots (1 to 10 mm). With time, the spots enlarged and merged. Symptomatic leaves were washed with sterile distilled water, and 5 × 5 mm pieces of the infected tissues were removed. After surface sterilization (30 s with 75% ethanol, 2 min with 3% NaOCl, then washed three times with sterilized distilled water), the leaf pieces were dried and placed on potato dextrose agar (PDA) and incubated at 25℃ for 5 days. Fungal colonies developed from leaf tissues, and the germinated spores were transferred onto PDA for further purification and morphological observation. Three isolates (GUBJ23, GUBJ24, and GUBJ12) with similar morphology were obtained from five affected leaves. The representative strain GUBJ23 was selected for further study. On PDA the mycelium was initially white but with sporulation turned gray and then black. Black, single-celled conidia, spherical to sub-spherical, from 11.80 to 21.39 × 13.38 to 21.83 µm (n = 50) in diameter were borne singly on hyaline vesicles at the tips of conidiophores. These morphological characteristics were similar to those of Nigrospora sphaerica (Wang et al. 2017). To confirm the identification, primer pairs for the internal transcribed spacer (ITS) region (ITS5/ITS4), ß-tubulin (TUB2) (Bt-2a/Bt-2b), and the translation elongation factor 1-alpha (TEF1-α) (EF1-728F/EF1-986R), were used for PCR amplification of DNA from strain GUBJ23 (Carbone and Kohn 1999; Glass et al. 1995; White et al. 1990). The resulting sequences were deposited in GenBank with accession numbers OR818025 (ITS), OR835150 (TUB2), and OR835147 (TEF1-α). BLAST searches of the sequences revealed 99.80% identity (503/504 bp) of the ITS sequence, 100.00% identity (395/395 bp) of the TUB2 sequence, and 100.00% identity of the TEF1-α sequence (241/241 bp) with N. sphaerica LC7294 (accessions KX985932, KY019602, and KY019397, respectively.) Based on a combined dataset of ITS, TEF1-α, and TUB2 sequences, a phylogenetic tree was constructed using the maximum likelihood method and confirmed that isolates GUBJ23, GUBJ24, and GUBJ12 were N. sphaerica (Wang et al. 2017). Leaves of three healthy R. simsii plants were spray-inoculated with a spore suspension (105 conidia/mL), and an additional three plants were sprayed with sterile water. These plants were incubated at 25℃ in 75% relative humidity. After 5 to 7 days of inoculation, 0.5 to 1.8 mm spots appeared on the leaves. At 10 to 14 days after inoculation, grayish brown, semicircular or irregular lesions appeared on the leaves, usually with a diameter of 0.8 to 3 mm. The symptoms were like symptoms seen on naturally infected leaves, while the control leaves remained asymptomatic. The pathogen was re-isolated from diseased leaves and identified by morphological characterization and molecular analyses (ITS, TUB and TEF1-α), and the reisolated pathogen was identical to N. sphaerica. Thus completing Koch's postulates. According to previous research, N. sphaerica is a widely distributed phytopathogenic fungus that has a wide host range (Wang et al. 2017). This study is the first to identify N. sphaerica as the cause of leaf spot disease in R. simsii. Given the popularity of R. simsii as a pot plant and landscape shrub in Asia and othr regions, the occurrence of leaf spot disease seriously affects its ornamental and economic value. Therefore, it is crucial to establish and implement effective disease management practices to reduce impact of the disease.

Perception of the Biocontrol Potential and Palmitic Acid Biosynthesis Pathway of Bacillus subtilis H2 through Merging Genome Mining with Chemical Analysis.

Bacillus has been widely studied for its potential to protect plants from pathogens. Here, we report the whole genome sequence of Bacillus subtilis H2, which was isolated from the tea garden soil of Guiyang Forest Park. Strain H2 showed a broad spectrum of antagonistic activities against many plant fungal pathogens and bacteria pathogens, including the rice blast fungus Magnaporthe oryzae, and showed a good field control effect against rice blast. The complete genome of B. subtilis H2 contained a 4,160,635-bp circular chromosome, with an average G + C content of 43.78%. Through the genome mining of strain H2, we identified 7 known antimicrobial compound biosynthetic gene clusters (BGCs) including sporulation killing factor, surfactin, bacillaene, fengycin, bacillibactin, subtilosin A, and bacilysin. Palmitic acid (PA), a secondary metabolite, was detected and identified in the H2 strain through genome mining analysis and gas chromatography-mass spectrometry (GC-MS). Additionally, we propose, for the first time, that the type II fatty acid synthesis (FAS) pathway in Bacillus is responsible for PA biosynthesis. This finding was confirmed by studying the antimicrobial activity of PA and conducting reverse transcription-quantitative polymerase chain reaction (RT-qPCR) experiments. We also identified numerous genes associated with plant-bacteria interactions in the H2 genome, including more than 94 colonization-related genes, more than 34 antimicrobial genes, and more than 13 plant growth-promoting genes. These findings contribute to our understanding of the biocontrol mechanisms of B. subtilis H2 and have potential applications in crop disease control.

Biocontrol potential of endophytic bacterium Bacillus altitudinis GS-16 against tea anthracnose caused by Colletotrichum gloeosporioides.

Background: As one of the main pathogens causing tea anthracnose disease, Colletotrichum gloeosporioides has brought immeasurable impact on the sustainable development of agriculture. Given the adverse effects of chemical pesticides to the environment and human health, biological control has been a focus of the research on this pathogen. Bacillus altitudinis GS-16, which was isolated from healthy tea leaves, had exhibited strong antagonistic activity against tea anthracnose disease. Methods: The antifungal mechanism of the endophytic bacterium GS-16 against C. gloeosporioides 1-F was determined by dual-culture assays, pot experiments, cell membrane permeability, cellular contents, cell metabolism, and the activities of the key defense enzymes. Results: We investigated the possible mechanism of strain GS-16 inhibiting 1-F. In vitro, the dual-culture assays revealed that strain GS-16 had significant antagonistic activity (92.03%) against 1-F and broad-spectrum antifungal activity in all tested plant pathogens. In pot experiments, the disease index decreased to 6.12 after treatment with GS-16, indicating that strain GS-16 had a good biocontrol effect against tea anthracnose disease (89.06%). When the PE extract of GS-16 treated mycelial of 1-F, the mycelial appeared deformities, distortions, and swelling by SEM observations. Besides that, compared with the negative control, the contents of nucleic acids, protein, and total soluble sugar of GS-16 group were increased significantly, indicating that the PE extract of GS-16 could cause damage to integrity of 1-F. We also found that GS-16 obviously destroyed cellular metabolism and the normal synthesis of cellular contents. Additionally, treatment with GS-16 induced plant resistance by increasing the activities of the key defense enzymes PPO, SOD, CAT, PAL, and POD. Conclusions: We concluded that GS-16 could damage cell permeability and integrity, destroy the normal synthesis of cellular contents, and induce plant resistance, which contributed to its antagonistic activity. These findings indicated that strain GS-16 could be used as an efficient microorganism for tea anthracnose disease caused by C. gloeosporioides.

A randomized, controlled clinical study of low-molecular-weight heparin improving pregnancy outcomes in PCOS women undergoing IVF: study protocol.

BACKGROUND: Polycystic ovary syndrome (PCOS), an incidence of 10-15% in women of reproductive age, shows sex hormone disorders, luteal insufficiency, and the tendency of placental villus space thrombus. The incidence of early pregnancy loss in women with PCOS is three to eight times higher than that in non-PCOS women. PCOS women were reported in a pre-thrombotic state, which was manifested by accelerated thrombin production, increased PAI-1 activity, and fibrinogen. Other research also found an over-activated state of women with PCOS in immune system. Therefore, changing the prethrombotic state of PCOS through anticoagulation may be a new way to improve the adverse pregnancy outcome of PCOS. Low-molecular-weight heparin (LMWH) is the most common used anticoagulant drug in pregnancy, and it also was proposed for the prevention of recurrent abortion, although the application of LMWH in PCOS population during early pregnancy has not been reported. The objective of this study is to investigate the effect of LMWH on pregnancy outcomes after invitro fertilization-frozen embryo transfer (IVF-FET) in patients with polycystic ovary syndrome. METHODS: A total of 356 PCOS women aged between 20 and 38 years which prepared for IVF followed with FET will be enrolled in the study. The patients, from four different hospitals stratified by age and body mass index (BMI), will be randomly divided into the study group who will be treated with LMWH started on the day of progesterone transformation (hormone therapy) during FET cycle and the control group without additional medicine. Serum or urine hCG test will be given 14 days after embryo transfer to confirm biochemical pregnancy. If pregnancy is positive, LMWH+ hormone therapy/hormone therapy will be continued for another 2 weeks. Transvaginal ultrasonography will be performed 14 days later to confirm intrauterine pregnancy. The primary outcome is the ongoing pregnancy, which is defined as intrauterine live fetus with ultrasound after 12 weeks of gestation. DISCUSSION: This is the first study protocol to investigate the efficacy of LMWH as an adjuvant drug for IVF-FET outcomes in PCOS women, by comparing differences in ongoing pregnancy rate, clinical pregnancy rate, live birth rate, and early pregnancy loss rate between LMWH group and the control group. TRIAL REGISTRATION: ClinicalTrials.gov ChiCTR2000036527. Registered on August 24, 2020.

First report of Diaporthe eres causing leaf spot on Rhododendron latoucheae Franch. in China.

Rhododendron latoucheae Franch. is an evergreen shrub with charming fragrance and large and abundant flowers that make it highly attractive as an ornamental species. The species is distribution in southwest China covers several different habitats and environments (Zhang, et al. 2022). From May to July in 2023, symptoms of leaf spot were observed on R. latoucheae over a wide portion of the Baili Azalea Forest Area (27°10' to 27°20'N, 105°04' to 106°04'E), Guizhou Province, China. About 500 plants were surveyed, and the incidence of leaf spot on R. latoucheae leaves was 12%, significantly reducing their ornamental and economic value. The affected leaves had irregular, grey white lesions with a clear blackish brown boundary and faint black conidiomata in a brown center. To isolate the pathogen, 15 symptomatic leaves were collected from 10 plants. A few black dots were picked from the lesions with a sterilized needle, plated on water agar, and incubated at 25°C for 24 h to observe spore germination (Choi et al. 1999). Then the germinated spores were transferred onto PDA for further purification and morphological observation. Three single-spore isolates (GULJ1-L7, GULJ1-L8, and GULJ1-L9) identical in morphology were obtained. The isolate GULJ 1-L7 was used for further study. Colonies on PDA irregular grew white felty aerial mycelium, becoming white felted aerial mycelium in the centre and grey-brown mycelium at the marginal area on the upper surface, while the lower surface presents alternating white, tan and taupe. Colony with conidiomata irregularly distributed over agar surface. In the representative isolate, darkly pigmented pycnidia (flask-shaped) were produced over the colony surface on PDA after about 30 days, and oozed milky or yellowish mucilaginous drops. The fungus produced two types of conidia, α and ß. Regular α conidia were 5.15-10.29 × 1.54-3.33 µm (n = 50), hyaline, elongated, biguttulate and non-septate. Beta conidia were 20.34-31.91 × 1.01-1.90 µm (n = 50), aseptate, hyaline, smooth, spindle shaped, slightly curved to bent. The morphological features were consistent with the description of Diaporthe eres (Pereira, et al. 2022). The pathogen was confirmed to be D. eres by amplification and sequencing of the internal transcribed spacer region (ITS), the partial ß-tubulin (TUB), the partial translation elongation factor 1-alpha (TEF) genes and the calmodulin (CAL) using primers ITS1/ITS4, Bt-2a/Bt-2b, EF1-728F/EF1-986R, and CAL-228F/CAL-737R, respectively (Tao et al. 2020). Sequences from PCR amplification were deposited in GenBank with accession numbers OR740563 (ITS), OR754301 (TUB), OR754298 (TEF), and OR754295 (CAL) respectively. BLAST searches of the sequences revealed 99.07% (533/538 nt), 100% (490/490 nt), 99.69% (317/318 nt) and 98.95% (376/380 nt) homology with those of D. eres AR5193T from GenBank (KJ210529.1, KJ420799.1, KJ210550.1 and KJ434999.1), respectively. Phylogenetic analysis (MEGA 7.0) using the maximum-likelihood method placed the isolate GULJ1-L7 in a well-supported cluster with D. eres CBS 138694T. The pathogen was thus identified as D. eres based on the morphological characterization and molecular analyses (Feng, et al. 2013; Tao, et al. 2020). The pathogenicity of GULJ1-L7 was tested through a pot assay. Due to the difficulty of artificial planting wild R. latoucheae, we conducted a pot essay to detect the pathogenicity of GULJ1-L7 using a closely related Rhododendron delavayi Franch. Ten healthy R. delavayi plants were scratched with a sterilized needle (0.45 mm in diameter) on three leaves per plant. Plants were inoculated by spraying α and ß spore mixture suspension (106 spores ml-1) of GULJ1-L7 onto leaves until runoff, and the control leaves were sprayed with sterile water. The plants were maintained at 25°C and 75% relative humidity in a growth chamber. The pathogenicity test was repeated three times. After 14 days, the treated leaves developed brown lesions similar to those in the field, whereas the control had no symptoms. The same fungus was reisolated from the infected leaves and identified based on a morphological characterization and molecular analyses. These results fulfilled Koch's postulates. To our knowledge, this is the first report of leaf spot on R. latoucheae caused by D. eres in China. The fungal pathogen identification will provide valuable information for prevention and management of leaf spot disease associated with R. latoucheae.

Quantifying stakeholders' preference for implantable medical devices in China: a discrete choice experiment.

OBJECTIVES: This study aims to gain insight into each attribute as presented in the value of implantable medical devices, quantify attributes' strength and their relative importance, and identify the determinants of stakeholders' preferences. METHODS: A mixed-methods design was used to identify attributes and levels reflecting stakeholders' preference toward the value of implantable medical devices. This design combined literature reviewing, expert's consultation, one-on-one interactions with stakeholders, and a pilot testing. Based on the design, six attributes and their levels were settled. Among 144 hypothetical profiles, 30 optimal choice sets were developed, and healthcare professionals (decision-makers, health technology assessment experts, hospital administrators, medical doctors) and patients as stakeholders in China were surveyed. A total of 134 respondents participated in the survey. Results were analyzed by mixed logit model and conditional logit model. RESULTS: The results of the mixed logit model showed that all the six attributes had a significant impact on respondents' choices on implantable medical devices. Respondents were willing to pay the highest for medical devices that provided improvements in clinical safety, followed by increased clinical effectiveness, technology for treating severe diseases, improved implement capacity, and innovative technology (without substitutes). CONCLUSIONS: The findings of DCE will improve the current evaluation on the value of implantable medical devices in China and provide decision-makers with the relative importance of the criteria in pricing and reimbursement decision-making of implantable medical devices.

Sleep disturbance exacerbates atherosclerosis in type 2 diabetes mellitus.

Background: Short sleep duration and poor sleep quality are important risk factors for atherosclerosis. The use of smart bracelets that measure sleep parameters, such as sleep stage, can help determine the effect of sleep quality on lower-extremity atherosclerosis in patients with type 2 diabetes. Objective: To investigate the correlation between sleep disorders and lower-extremity atherosclerosis in patients with type 2 diabetes. Methods: After admission, all patients were treated with lower-extremity arterial ultrasound and graded as having diabetic lower-extremity vascular lesions according to the results. A smart bracelet was used to obtain the patient sleep data. The correlation between sleep patterns and diabetic lower-extremity atherosclerosis, diabetic foot, and various metabolic indices was verified. Results: Between August 2021 and April 2022, we screened 100 patients with type 2 diabetes, with 80 completing sleep monitoring. Univariate ordered logistic regression analysis indicated that patients with a sleep score below 76 (OR = 2.707, 95%CI: 1.127-6.488), shallow sleep duration of 5.3 h or more (OR=3.040, 95 CI: 1.005-9.202), wakefulness at night of 2.6 times or more (OR = 4.112, 95%CI: 1.513-11.174), and a deep sleep continuity score below 70 (OR = 4.141, 95%CI: 2.460-615.674) had greater risk of high-grade lower limb atherosclerosis. Multivariate ordinal logistic regression analysis revealed that the risk of high-grade lower limb atherosclerosis was higher in patients with 2.6 or more instances of nighttime wakefulness (OR = 3.975, 95%CI: 1.297-12.182) compared with those with fewer occurrences. The sleep duration curve of patients with different grades of diabetic lower-extremity atherosclerosis was U-shaped. According to the results of the one-way analysis of variance, the higher the deep sleep continuity score, the lower the Wagner scale score for diabetic foot (P < 0.05). Conclusions: Sleep disorders (long, shallow sleep duration, frequent wakefulness at night, and poor continuity of deep sleep) can worsen lower limb atherosclerosis in patients with type 2 diabetes. This finding can provide a new method for medical professionals to prevent and treat diabetic lower-extremity vascular lesions.

Severe thyrotoxicosis induced by tislelizumab: a case report and literature review.

Immune checkpoint inhibitors (ICIs) have made significant breakthroughs in the treatment of a variety of malignancies. As its use increases, the unique immune-mediated toxicity profile of ICls are becoming apparent. We report a case of immune-related endocrine adverse events (irAE) in a patient with hepatocellular carcinoma treated with anti-programmed cell death protein 1 (PD-1) (tislelizumab). Although many irAEs have been reported, few cases of severe thyrotoxicosis have been described after immunotherapy in the literature. We present the case of a 49-year-old male who experienced a Grade 3 tislelizumab-related adverse reaction according to Common Terminology Criteria for Adverse Events (CTCAE5.0) and received methylprednisolone, thiamazole, and levothyroxine sodium tablets. Early identification of irAEs, risk factors, regular monitoring, use of steroids and/or immunoglobulins, and adjuvant supportive care are critical to the clinical prognosis of patients. It should be underlined that the tumor benefits of ICI therapy outweigh the risks associated with ICI-induced endocrine disorders, and ICI treatment should not be stopped or delayed except in rare cases (adrenal crisis, severe thyrotoxicosis). The familiarity of healthcare professionals with irAEs of the thyroid when thyrotoxicosis occurs is important to facilitate an effective diagnosis and appropriate treatment of this increasingly common thyroid disorder.

Cost-effectiveness of open pancreaticoduodenectomy with or without Heidelberg TRIANGLE operation for pancreatic cancer in China.

OBJECTIVE: Pancreatic cancer is a digestive malignancy with dismal prognosis. The advent of Heidelberg TRIANGLE dissection technique brings a turning point to improve the chance of survival. Our study aimed to evaluated the cost-effectiveness of open pancreaticoduodenectomy (OPD) versus OPD combined with TRIANGLE operation (OPD-TRIANGLE) for patients with pancreatic cancer from the perspective of healthcare system in China. METHODS: Two hundred forty-six patients with pancreatic cancer who underwent OPD or OPD-TRIANGLE from January to September 2022 were enrolled in this study. We performed a decision tree model to assess clinical and economic implications of different surgical strategies. Estimation of health utilities was based on published literature, while costs were acquired from the hospitals, clinical expert consultations, and other local charge. The incremental cost-effectiveness ratio (ICER) was regarded as the primary outcome. Uncertainty of the findings was addressed via sensitivity analyses and scenario analyses. RESULTS: The results indicated that OPD-TRIANGLE group yielded additional 0.0402 QALYs at an incremental cost of US$1501.83 compared with OPD group, and the corresponding ICER was US$37,358.96 per QALY. The probabilities of OPD-TRIANGLE as the prior option were 52.8% at the WTP threshold of 60,000 US$/QALY. The main factors lined with costs incorporating total medical costs and operation-related costs. With 5-20% price reduction of OPD-TRIANGLE, the outcomes were also economically attractive. CONCLUSION: The findings of this population-based study suggested that OPD-TRIANGLE was likely to be cost-effective for patients with pancreatic cancer when compared against OPD. Further in-depth studies should be conducted to provide more comprehensive evidence.

Effects of Bacillus velezensis GUAL210 control on edible rose black spot disease and soil fungal community structure.

Introduction: Rose black spot is an economically important disease that significantly decreases flower yield. Fungicide and biological control are effective approaches for controlling rose black spot. The objective of this study was to evaluate the effect of application of biological and chemical control agents, including Bacillus velezensis (GUAL210), Bacillus sp. (LKW) and fungicide (CP) on the black spot disease and rhizosphere fungal community structure of edible rose. Methods: In this study, the R. chinensis 'Crimson Glory' was taken as the research object, and the field experiment was designed by randomized block design. The experiment contained 3 treatments (CP, GUAL210, LKW) and 1 control. The control effect and growth promoting effect of fungicide and biological control on rose black spot were compared. The composition and diversity of rhizosphere soil fungal community of different treatments of rose were studied by high-throughput sequencing method. The fungal community composition, correlation of environmental factors and differences in metabolic pathways related to rose disease were analyzed, and the correlation between rhizosphere soil fungal community of rose and biological control of disease was explored. Results and discussion: Both disease incidence and disease index differed significantly among groups (LKW < GUAL210 < CP < CK), and disease control effect exhibited no significant difference between GUAL210 and LKW (60.96% and 63.86%, respectively). Biological control was superior to chemical control in terms of disease prevention effects and duration, and it significantly increased the number of branches and flowers of rose plants. Ascomycota and Basidiomycota accounted for more than 74% of the total fungal abundance, and the abundance of Ascomycota was highest in CK, followed by GUAL210, CP and LKW, which was consistent with the disease occurrence in each group. The analysis of metabolic pathways showed that the HSERMETANA-PWY in each experimental group was significantly lower than that in control group. The Shannon index in each experimental group was significantly lower than that in control group. PCoA analysis showed that the rhizosphere fungal community structure in each experimental group was significantly different from that in control group. Trichoderma, Paraphaeosphaeria, Suillus, Umbelopsis in GUAL210, and Galerina in LKW replaced Mortierella, Pestalotiopsis, Ustilaginoidea, Paraconiothyrium, Fusarium, and Alternaria as dominant flora, and played a nonneglectable role in reducing disease occurrence. The difference in rhizosphere fungal community structure had an important impact on the incidence of rose black spot disease. Biological control is crucial for establishing environment-friendly ecological agriculture. GUAL210 has promising prospects for application and development, and may be a good substitute for chemical control agents.

First report of Pseudopithomyces chartarum causing leaf spot on Tetrapanax papyrifer in Guizhou, China.

Tetrapanax papyrifer (Hook.) K. Koch, widely utilized in clinical practices in traditional Chinese medicine, is a medicinal plant whose dried stem pich exhibits activities such as lactation induction, diuresis, and anti-inflammatory effects. The species is native to the southwest of China, such as Guizhou and Yunnan provinces. It thrives in sunlight and warmth and is planted in fertile valleys in the region (Zhang et al. 2023). In July 2021, a leaf spot-like disease was observed on approximately 15% of T. papyrifer (Big T. papyrifer) in a field in Shibing County (127.2°E, 25.2°N), Guizhou Province, China. The symptomatic leaves displayed irregular, watery dark brown lesions with black conidiomata in gray centers and surrounded by yellow halos. To identify the causal agent leading to the disease, 15 symptomatic leaves from five trees in one field were collected. These leaves underwent surface sterilization, which included 30s in 75% ethanol, 2 min in 3% NaOCl, and three times of washing with sterilized distilled water. Thereafter, small pieces of the symptomatic leaf tissues (0.2 × 0.2 cm) were plated on PDA and incubated at 25°C for seven days (Fang 2007). Three isolates were obtained based on the improved single spore isolation method proposed by Gong et al. (2010), and named as GUTC 321, GUTC 523 and GUTC 873. The fungal colonies on PDA were villiform, creamy-white, whorled, and sparse aerial mycelium on the surface with black, gregarious conidiomata. The conidia were ellipsoid, mid brown to dark brown, mainly with 3-4 transverse septa, usually divided by longitudinal septum, often constricted at the septa, 21.8 (12.6-34.5) × 13.9 (8.8-19.8) µm (n=50). The morphological features were consistent with the descriptions of Pseudopithomyces chartarum (Ariyawansa et al. 2015). All three isolates exhibited identical morphological properties. The potential pathogen was confirmed as P. chartarum by amplification and sequencing of the internal transcribed spacer regions (ITS), large subunit ribosomal (LSU) and translation elongation factor 1 alpha (TEF1) genes with primers ITS4/ITS5, LROR/LR7 and EF-983F/EF-2218R, respectively (Ariyawansa et al. 2015; Jayasiriet al. 2019). BLASTn analyses of the sequences showed 100% identity among the three isolates and a high homology (ITS, 99.8%: 598/599; LSU, 100%: 853/853; and TEF1, 100%: 871/871) with those of P. chartarum sequences in GenBank (MT123059, OK655822, and MK360080, respectively). The sequences of the genes from isolate GUTC321 were deposited in GenBank under accession numbers OP269599 (ITS), OP237015 (LSU), and OR069689 (TEF1). Phylogenetic analyses of the concatenated ITS-LSU-TEF1 sequence (2,685 bp) of GUTC 321 using PhyloSuite 1.2.2 with PartitionFinder model revealed that the isolate clustered closely with P. chartarum isolate CBS 329.86T (Cecilia 1986). The pathogenicity of GUTC 321 was tested thereafter on ten healthy T. papyrifer plants grown in pots in growth chamber. The plants were inoculated by spraying with spore suspension (106 spores mL-1) of GUTC 321 or sterile water (control) onto leaves that had been slightly injured with sterilized SiO2 (0.1-0.25 mm) until runoff. The plants were maintained at 25°C in the growth chamber, and monitored for symptom development. Local lesions began to appear on all GUTC 321-inoculated leaves, but not on those of the control plants, 48 hours after inoculation. Seven days after the inoculation, lesions similar to those observed on field plants occurred on GUTC321-inoculated plants but not on the control plants, the lesions observed only in inoculated leaves. The same fungus was reisolated and identified based on the morphological characterization and molecular analyses (ITS, LSU and TEF1) from the infected leaves thus fulfilling Koch's postulates. To our knowledge, this is the first report of leaf spot on T. papyrifer caused by P. chartarum in China. Considering the significance of T. papyrifer in Chinese medicine, approximate management measures need to be developed and applied to control the disease in the crop.

Characteristics and management of tumor treating fields-related dermatological complications in patients with glioblastoma.

Tumor treating fields (TTFields) is a novel approved modality for the treatment of glioblastoma (GBM) exhibiting a satisfactory effect. Although TTFields has shown considerable safety for the normal brain, dermatological adverse events (DAEs) often occur during therapy. However, studies focused on the identification and management of DAEs are rare. The clinical data and photos of skin lesions from 9 patients with GBM were retrospectively analyzed, and the types and grades of individual scalp dermatitis were evaluated based on the Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v 5.0). Adherence and safety were also evaluated on the basis of the device monitoring data. Eight patients (88.9%) exhibited grade 1 or grade 2 CTCAE DAEs, all of whom were cured after interventions. The adherence was >90%, with no relevant safety events reported. Finally, a guideline for preventing DAEs in patients with GBM was proposed. The identification and management of TTFields-related DAEs is necessary and urgent in patients with GBM. Timely interventions of DAEs will help to improve the adherence and quality of life of patients, which ultimately improves prognosis. The proposed guideline for preventing DAEs in patients with GBM assists in the management of healthcare providers and may avoid dermatologic complications.

First Report of Leaf Spot Caused by Clonostachys rosea on Tea (Camellia sinensis) in China.

Tea (Camellia sinensis), which originated in southwest of China 60 - 70 million years ago, is widely consumed as a beverage for its potential enhancing effect on human health with rich polyphenol content (Pan et al. 2022). From October to December in 2021, a disease with symptoms similar to leaf spot affected the quality and yield of tea Puer (102°73 'E, 25°07' N), Yunnan province, China. Based on the survey, leaf spot symptoms were observed on approximately 60% of tea plants in a 5,700 m2 field. The symptoms initially appeared as shrinking, yellowing, and later became circular or irregular brown spots. To isolate the pathogen, 10 symptomatic leaves were collected from 10 trees, and portions of the diseased tissue (0.5×0.5 cm) were cut at the junction of infected and healthy tissues. After surface sterilization (0.5 min with 75% ethanol and 2 min with 3% NaOCl, washed three times with sterilized distilled water), the disinfected pieces were dried and plated onto potato dextrose agar (PDA) and incubated at 25°C in the dark for 5 days. Four single-spore isolates, FH-1, FH-5, FH-6 and FH-7, were obtained, these isolates were identical in morphology and in the sequences of internal transcribed spacer region [ITS] and translation elongation factor 1-alpha [TEF] genes. Therefore, the representative isolate FH-5 was used for further study. Fungal colonies were white or light yellow on PDA after 7 days incubated at 28ºC. Conidia were hyaline, round or oval, aseptate, occur singly or in clusters on hyphae or conidia stalks, and measured as 2.94 ± 1.79 × 1.82 ± 0.2 µm (n = 50). Primary conidiophores is Verticillium-like (Fig1.K,L), which generally formed first, 1-3-level verticillate, mostly with divergent branches and phialides, and measured as 16.67 ± 4.39 µm (n = 50). Secondary conidiophores is penicillate (Fig1.I,J), which generally appearing after one week, sometimes even more often branched, and with a length of 16.02 ± 3.83 µm (n = 50). The morphological features were consistent with the descriptions of Clonostachys rosea Schroers H.J. (Schroers et al. 1999). The pathogen was confirmed to be C. rosea by amplification and sequencing of the internal transcribed spacer region (ITS) and translation elongation factor 1-alpha (TEF) genes using primers ITS1/ITS4 and EF1-728F/EF1-986R, respectively (Fu Rongtao 2019). The sequences of PCR products were deposited in GenBank with accession numbers ON332533 (ITS) and OP080234 (TEF). BLAST searches of the obtained sequences revealed 99.22% (510/514 nucleotides) and 98.37% (241/245 nucleotides) homology with those of C. rosea HQ-9-1 form GenBank (MZ433177 and MZ451399, respectively). Phylogenetic analysis (MEGA 7.0) using the maximum likelihood method placed the isolate FH-5 in a well-supported cluster with C. rosea. The pathogenicity of FH-5 was tested through a pot assay. Ten healthy tea plants were scratched with a sterilized needle on the leaves. Plants were inoculated by spraying a spore suspension (105 spores·mL-1) of FH-5 onto leaves until runoff, and the control leaves sprayed with sterile water. Inoculated plants were put in an artificial climate box at 25℃, 70% relative humidity. The pathogenicity test was replicated three times. Symptoms developed on all inoculated leaves but not on the control leaves. Lesions around the wound edge became pale yellow, and brown spots were first observed at 72 h after inoculation, and typical lesions similar to those observed on field plants appeared after two weeks. The same fungus was reisolated and identified based on the morphological characterization and molecular analyses (ITS and TEF) from the infected leaves but not from the noninoculated leaves. In addition, C. rosea has also been reported to cause diseases to broad bean (N. Afshari et al. 2017 ), garlic (Diaz et al. 2022), beet (Haque M.E et al. 2020) and other plants. To our knowledge, this is the first report of leaf spot on tea caused by C. rosea in China. This study provides valuable information for the identification and control of the leaf spot on tea.

Cost-effectiveness of preimplantation genetic testing for aneuploidy for women with subfertility in China: an economic evaluation using evidence from the CESE-PGS trial.

BACKGROUND: There are a large number of infertile couples in China, but its treatment is notoriously expensive and not currently covered by insurance. The utility of preimplantation genetic testing for aneuploidy as an adjunct to in vitro fertilization has been debated. OBJECTIVE: To investigate the cost-effectiveness of preimplantation genetic testing for aneuploidy (PGT-A) versus conventional technology in in vitro fertilization (IVF) from the perspective of the healthcare system in China. METHODS: Following the exact steps in the IVF protocol, a decision tree model was developed, based on the data from the CESE-PGS trial and using cost scenarios for IVF in China. The scenarios were compared for costs per patient and cost-effectiveness. One-way sensitivity analysis and probabilistic sensitivity analysis were performed to confirm the robustness of the findings. MAIN OUTCOME MEASURES: Costs per live birth, Costs per patient, Incremental cost-effectiveness for miscarriage prevention. RESULTS: The average costs per live birth of PGT-A were estimated as ¥39230.71, which is about 16.8% higher than that of the conventional treatment. Threshold analysis revealed that PGT-A would need to increase the pregnancy rate of 26.24-98.24% or a cost reduction of ¥4649.29 to ¥1350.71 to achieve the same cost-effectiveness. The incremental costs per prevented miscarriage was approximately ¥45600.23. The incremental cost-effectiveness for miscarriage prevention showed that the willingness to pay would be ¥43422.60 for PGT-A to be cost-effective. CONCLUSION: The present cost-effectiveness analysis demonstrates that embryo selection with PGT­A is not suitable for routine applications from the perspective of healthcare providers in China, given the cumulative live birth rate and the high costs of PGT­A.

Phospholipase C: Diverse functions in plant biotic stress resistance and fungal pathogenicity.

Phospholipase C (PLC) generates various second messenger molecules and mediates phospholipid hydrolysis. In recent years, the important roles of plant and fungal PLC in disease resistance and pathogenicity, respectively, have been determined. However, the roles of PLC in plants and fungi are unintegrated and relevant literature is disorganized. This makes it difficult for researchers to implement PLC-based strategies to improve disease resistance in plants. In this comprehensive review, we summarize the structure, classification, and phylogeny of the PLCs involved in plant biotic stress resistance and fungal pathogenicity. PLCs can be divided into two groups, nonspecific PLC (NPC) and phosphatidylinositol-specific PLC (PI-PLC), which present marked differences in phylogenetic evolution. The products of PLC genes in fungi play significant roles in physiological activity and pathogenesis, whereas those encoded by plant PLC genes mediate the immune response to fungi. This review provides a perspective for the future control of plant fungal diseases.

First Report of Grey Spot on Tobacco caused by Alternaria alstroemeriae in China.

Tobacco (Nicotiana tabacum L.) is an important economic crop belonging to family Solanaceae and is widely cultivated in China (Basit 2021). From April to July in 2022, a foliar disease with symptoms similar to grey spot was extensively observed on tobacco in Guangxi Province (24°52' N, 111°23' E), China. Field surveys were conducted in 18 towns and the disease incidence was 0.89% to 6.95%. Symptomatic leaves displayed irregular, dark brown lesions surrounded by yellow halos and accompanied with black conidiomata in gray centers (Fig 1A-E). Symptomatic leaves were collected from 54 different tobacco plants. After surface sterilization (0.5 min in 75% ethanol and 1 min in 3% NaOCl, washed three times with sterilized distilled water), small pieces of symptomatic leaf tissue (0.2 × 0.2 cm) were plated on PDA and incubated at 25°C for 5 days (Fang 2007). Three single-spore isolates, GUCC BZ6-3, GUCC LJ3-4, and GUCC XH1-13 were obtained, which were identical in morphology and molecular analysis. Therefore, the representative isolate GUCC BZ6-3 was used for further study. The colonies on PDA were villiform, greyish (Fig 1F-G). Conidia were abundant, ovoid, with 2-6 transverse septa and 1-2 longitudinal septa 12.60 (9.43 to 14.76) × 4.30 (3.57 to 5.14) µm (n=50) (Fig 1H-S). The morphological features were consistent with Alternaria alstroemeriae E.G. Simmons & C.F. Hill (Simmons 2007; Nishikawa & Nakashima, 2013). The pathogen was confirmed to be A. alstroemeriae by amplification and sequencing of the ITS, GAPDH, LSU, TEF1, and RBP2 genes using primers ITS1/ITS4, gpd1/gpd2, LSU1Fd/LR5, EF1-728F/EF1-986R, and RPB2-5F2/fRPB2-7cR, respectively (Woudenberg 2013). The sequences of the PCR products were deposited in GenBank with accession numbers ON693856 (RBP2), ON714497 (ITS), ON694345 (GAPDH), ON931420 (TEF1) and ON714499 (LSU). BLAST searches of the obtained sequences revealed 99% (565/567 nucleotides), 99% (577/579 nucleotides), 99% (908/911 nucleotides), 99% (238/239 nucleotides), and 99% (751/753 nucleotides) homology with those of A. alstroemeriae in GenBank (MH863036, KP124154, MH874589, KP125072, and KP124765, respectively). Phylogenetic analyses of the sequence data consisted of Bayesian and Maximum likelihood analyses of the combined aligned dataset (MEGA 7.0 and PhyloSuite 1.2.2). The GUCC BZ6-3 in a well-supported cluster with A. alstroemeriae (Fig 2). The pathogen was thus identified as A. alstroemeriae based on morphological characterization and molecular analyses. The pathogenicity of GUCC BZ6-3 was tested through pot assay and carried out three times (Fang 2007). Ten healthy 30-day-old tobacco plants were inoculated by spraying a spore suspension (106 spores·ml-1) of strain GUCC BZ6-3 onto leaves until runoff, and the control leaves were sprayed with sterile water. The plants were maintained at 28°C with high relative humidity (95%) in a growth chamber. The symptoms developed on all inoculated leaves but not on the control. The lesions were first visible 48 h after inoculation, and typical lesions similar to those observed on field plants appeared after 7 days. The same fungus was reisolated and identified based on the morphological characterization and molecular analyses from the infected leaves but not from the noninoculated leaves. Results of pathogenicity experiments fulfilled Koch's postulates. To our knowledge, this is the first report of grey spot disease on tobacco caused by A. alstroemeriae in China. Our findings would be of great importance for the diagnosis and control of the emerging grey spot on tobacco.