The role of CBL-CIPK signaling in plant responses to biotic and abiotic stresses.

Plants have a variety of regulatory mechanisms to perceive, transduce, and respond to biotic and abiotic stress. One such mechanism is the calcium-sensing CBL-CIPK system responsible for the sensing of specific stressors, such as drought or pathogens. CBLs perceive and bind Calcium (Ca2+) in response to stress and then interact with CIPKs to form an activated complex. This leads to the phosphorylation of downstream targets, including transporters and ion channels, and modulates transcription factor levels and the consequent levels of stress-associated genes. This review describes the mechanisms underlying the response of the CBL-CIPK pathway to biotic and abiotic stresses, including regulating ion transport channels, coordinating plant hormone signal transduction, and pathways related to ROS signaling. Investigation of the function of the CBL-CIPK pathway is important for understanding plant stress tolerance and provides a promising avenue for molecular breeding.

[Expression of SOX10 and GATA3 in breast cancer and their significance].

Objective: To investigate the expression characteristics of SOX10 and GATA3 in breast cancer and the value of their combination. Methods: A total of 360 breast cancer specimens with SOX10 immunohistochemical staining were collected from the Department of Pathology in Shenzhen People's Hospital from 2018 to 2021, including 268 cases with simultaneous SOX10 and GATA3 staining. The expression of SOX10 and GATA3 in primary and metastatic breast cancer was detected, and the correlations between SOX10 and GATA3 and the molecular types and clinicopathological features of breast cancer were compared, and the distribution differences among each group were statistically analyzed. Results: The overall expression of SOX10 and GATA3 in breast cancer were 25.8%(93/360) and 81.7%(219/268), and that in triple negative breast cancer (TNBC) were 83.3%(80/96) and 42.7%(32/75), respectively. SOX10 was strongly associated with TNBC (P<0.001), whereas GATA3 was highly expressed in luminal A, luminal B and HER2 over expression breast cancers (P<0.001). The expression of SOX10 and GATA3 was negatively correlated in TNBC, and the combined expression rates of SOX10 and GATA3 in breast cancer and TNBC could reach 97.8% (262/268) and 94.7%(71/75), respectively. In addition, the expression of SOX10 was closely correlated with high histological grade, high Ki-67 proliferation index and lymph node metastasis, and negatively correlated with AR. The expression of GATA3 was correlated with low histological grade and lymph node metastasis, and positively correlated with AR, and the difference was statistically significant. Conclusions: SOX10 is a sensitive marker of TNBC, while GATA3 is highly expressed in non-triple negative breast cancer. The two complementary, combined application of SOX10-GATA3 can improve the detection rate of breast cancer, especially TNBC. SOX10 is associated with malignant characteristics of the tumor, suggesting that SOX10 can be used as a prognostic marker and potential therapeutic target for breast cancer.

[Rib cartilage framework supporting combined with local flap grafting for correction of cryptotia].

Objective: To investigate the curative effect of rib cartilage framework supporting combined with local flap grafting for correction of cryptotia. Methods: Fourteen cases (nineteen ears) were corrected by rib cartilage framework supporting combined with local flap grafting method from January 2017 to March 2019. Part of the 7th rib cartilage was carved into a scalloped cartilage piece, which was implanted on the retroauricular cartilage to release and expand the deformed cartilage. A "M" incision was designed on the retroauricular skin to make the local flap grafting. Results: All corrected auricles were followed up for four months to three year and abtained satisfactory and stable appearance. In one case, the edge of the helix was broken two weeks after the operation, and well healed after repairing. Conclusions: The rib cartilage framework supporting combined with local flap grafting method can fully correct the deformity of cryptotia, and the long-term effect is satisfied. It can be an important complement to the classic methods.

Anesthetic management of a patient with limb-girdle muscular dystrophy 2B:CARE-compliant case report and literature review.

BACKGROUND: Limb-girdle muscular dystrophies (LGMDs) belong to few neuromuscular disorders mainly involving pelvic and shoulder girdle muscles. Also, cardiac or pulmonary complications, increased rhabdomyolysis risk when exposed to volatile anesthetics and succinylcholine may increase anesthesia related risks. However, current reports about the anesthesia management of these patients are limited. CASE PRESENTATION: We described our anesthetic management of a 36 years old woman with LGMD 2B receiving arthroscopic knee surgery. In consideration of the high risk of rhabdomyolysis, total intravenous anesthesia (TIVA) was selected for her surgery. Considering the unpredictable respiratory depression, opioid based patient-controlled intravenous analgesia was replaced with an intra-articular cocktail therapy consisting of 20 ml of 0.2% ropivacaine. Also, we reviewed the literatures on anesthetic management of LGMD through searching PubMed, in order to provide a comprehensive and safe guidance for the surgery. CONCLUSIONS: Carefully conducted general anesthesia with TIVA technique is a good choice for LGMD patients. Neuraxial anesthesia may be used if general anesthesia needs to be avoided. To warrant safe anesthesia for surgery, any decision must be well thought out during perioperative period.

[Experts consensus on the management of delirium in critically ill patients].

To establish the experts consensus on the management of delirium in critically ill patients. A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group. Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 36 experts to reassess all the statements. (1) Delirium is not only a mental change, but also a clinical syndrome with multiple pathophysiological changes. (2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function. (3) Pain is a common cause of delirium in critically ill patients. Analgesia can reduce the occurrence and development of delirium. (4) Anxiety or depression are important factors for delirium in critically ill patients. (5) The correlation between sedative and analgesic drugs and delirium is uncertain. (6) Pay attention to the relationship between delirium and withdrawal reactions. (7) Pay attention to the relationship between delirium and drug dependence/withdrawal reactions. (8) Sleep disruption can induce delirium. (9) We should be vigilant against potential risk factors for persistent or recurrent delirium. (10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases, and can also be alleviated with the improvement of primary diseases. (11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis. (12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium, especially subclinical delirium. (13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium. (14) Daily assessment is helpful for early detection of delirium. (15) Hopoactive delirium and mixed delirium are common and should be emphasized. (16) Delirium may be accompanied by changes in electroencephalogram. Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant. (17) Pay attention to differential diagnosis of delirium and dementia/depression. (18) Pay attention to the role of rapid delirium screening method in delirium management. (19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium. (20) The key to the management of delirium is etiological treatment. (21) Improving environmental factors and making patient comfort can help reduce delirium. (22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium. (23) Communication with patients should be emphasized and strengthened. Family members participation can help reduce the incidence of delirium and promote the recovery of delirium. (24) Pay attention to the role of sleep management in the prevention and treatment of delirium. (25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium. (26) When using antipsychotics to treat delirium, we should be alert to its effect on the heart rhythm. (27) Delirium management should pay attention to brain functional exercise. (28) Compared with non-critically illness related delirium, the relief of critically illness related delirium will not accomplished at one stroke. (29) Multiple management strategies such as ABCDEF, eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients. (30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment. (31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management. Consensus can promote delirium management in critically ill patients, optimize analgesia and sedation therapy, and even affect prognosis.

Increased risk of hepatocellular carcinoma in chronic hepatitis C patients with new onset diabetes: a nation-wide cohort study.

BACKGROUND: The impact of diabetes for hepatocellular carcinoma (HCC) development in chronic hepatitis C (CHC) patients remains controversial. AIM: To investigate the risk of HCC in CHC patients who develop new onset diabetes. METHODS: We conducted a nation-wide cohort study by using Taiwanese National Health Insurance Research Database, which comprised of data from >99% of entire population. Among randomly sampled one million enrollees, 6251 adult CHC patients were identified from 1997 to 2009. Diabetes was defined as new onset in the patient who was given the diagnosis in the years 1999-2009 but not in 1997-1998. The cohorts of CHC with new onset diabetes (n = 1100) and 1:1 ratio age-, gender-, and inception point (onset date of diabetes) matched nondiabetes (n = 1087) were followed up from the inception point until the development of HCC, withdrawal from insurance, or December 2009. RESULTS: After adjustment for competing mortality, patients with new onset diabetes had a significantly higher cumulative incidence of HCC (Relative Risk = 1.544, 95% CI = 1.000-2.387, modified log-rank test, P = 0.047) as compared to those without. After adjustment for age, gender, cirrhosis, hyperlipidaemia, CHC treatment, diabetes treatment, comorbidity index, obesity and statins therapy by Cox proportional hazard model, diabetes was still an independent predictor for HCC (hazard ratio (HR) = 1.906, 95% CI = 1.102-3.295, P = 0.021). The risk for HCC was increased in those who were 40-59 years old, independent of other variables (HR = 3.086, 95% CI = 1.045-9.112, P = 0.041), and after adjustment for competing mortality (modified log-rank test, P = 0.009). CONCLUSION: Chronic hepatitis C patients who develop diabetes are at an increased risk of hepatocellular carcinoma over time.

Increased risk of hepatocellular carcinoma in chronic hepatitis B patients with new onset diabetes: a nationwide cohort study.

BACKGROUND: Diabetes increases the risk of hepatocellular carcinoma (HCC), however, the time-relationship between hepatitis B virus and diabetes for the development of HCC remains unclear. AIM: To explore the risk of HCC in chronic hepatitis B patients with newly diagnosed diabetes. METHODS: We conducted a nationwide cohort study by using Taiwanese National Health Insurance Research Database, which covers over 99% of entire population. Among randomly sampled one million enrollees, 14 523 chronic hepatitis B patients were diagnosed in years 1997-2009. We defined new onset diabetes as patients who were given the diagnosis in the years 1999-2009, but not in 1997-1998. The cohorts of chronic hepatitis B with new onset diabetes (n = 2099) and 1:1 ratio age-, gender- and inception point (onset date of diabetes)- matched nondiabetes (n = 2080) were followed up from the inception point until development of HCC, withdrawal from insurance or December 2009. RESULTS: After adjustment for competing mortality, patients with new onset diabetes had a significantly higher cumulative incidence of HCC [relative risk = 1.628, 95% confidence interval (CI) = 1.114-2.378, modified log-rank test, P = 0.012] as compared to nondiabetes patients. After adjustment for age, gender, hyperlipidaemia, chronic hepatitis B treatment, statins therapy, cirrhosis, comorbidity index and obesity, diabetes was still an independent predictor for HCC (hazard ratio = 1.798, 95% CI = 1.194-2.707, P = 0.005). CONCLUSION: Chronic hepatitis B patients with newly diagnosed diabetes have an increased risk of hepatocellular carcinoma over time.

A modified method of labia minora reduction: the de-epithelialised reduction of the central and posterior labia minora.

OBJECTIVE: The aim of this study was to introduce a new method of labiaplasty. Here we describe the surgical procedure, outcomes and the advantages and disadvantages of this method. METHOD: The medical records of 167 patients aged between 20 and 43 years who underwent reduction of the labia minora from May 2006 to March 2011 were reviewed. The procedures performed in these studies used de-epithelialised reduction of the middle and posterior sections of the labia minora. RESULTS: All the surgeries were performed successfully, and 164 patients experienced an uneventful postoperative period. A minor dehiscence occurred in one patient, who recovered with no requirement for additional treatment. Another two women felt that the reduction was not fully achieved. All of the patients were satisfied with the eventual aesthetic appearance. CONCLUSIONS: The de-epithelialised reduction of the middle and posterior portion of the labia minora is a simple and safe method that is associated with satisfactory outcomes.

Vitamin D receptor gene polymorphisms and distinct clinical phenotypes of hepatitis B carriers in Taiwan.

Vitamin D exhibits immunomodulatory and antiproliferative effects through vitamin D receptor (VDR) in chronic infections and cancers. We genotyped the BsmI (rs1544410), ApaI (rs7975232) and TaqI (rs731236) polymorphisms of VDR gene in 250 Taiwanese chronic hepatitis B virus (HBV) carriers who were categorized into six phenotypes. After adjustment for age and sex, the frequencies of the VDR B/b, B/a, B/T, B/a/T in patients with hepatitis flare(s) were lower than those without (7 vs 20%, P=0.009; 1 vs 9%, P=0.004; 3 vs 10%, P=0.007; 1 vs 9%, P=0.005, respectively); in contrast, T/t, A/T, A/t, b/A/t were higher in flare(s) (8 vs 3%, P=0.003; 49 vs 34%, P=0.027; 2 vs 1%, P=0.004; 0.5 vs 0%, P=0.001, respectively). In addition, B/b, B/B, T/t, b/A, B/a, B/A, B/T, B/t, A/t, b/A/T, B/a/T, B/A/T, B/A/t, b/A/t were higher in patients positive for HBeAg. The distribution of VDR genotypes was comparable between patients with and without hepatocellular carcinoma (HCC). VDR gene polymorphisms are associated with distinct clinical phenotypes in Taiwanese HBV carriers but not with HCC development.

Cytotoxic T-lymphocyte epitopes for HLA-B53 and other HLA types in the malaria vaccine candidate liver-stage antigen 3.

The development of an effective preerythrocytic vaccine against Plasmodium falciparum malaria is likely to require inclusion of components from several preerythrocytic antigens. The association of HLA-B53 with resistance to severe malaria in West Africa provided evidence that HLA class I-restricted CD8(+) T-cell responses play a role in protective immunity in African children, supporting data from rodent models of malaria. Previously, a single epitope from liver-stage-specific antigen 1 (LSA-1) has been shown to be recognized by HLA-B53-specific cytotoxic T lymphocytes (CTL), but HLA-B53 epitopes were not found in four other antigens. In this study we measured CTL responses to peptides from the recently sequenced antigen liver-stage antigen 3 (LSA-3) and identified in it a new epitope restricted by HLA-B53. Several CTL epitopes restricted by other class I types were also identified within LSA-3 in studies in The Gambia and Tanzania. CTL were also identified to an additional P. falciparum antigen, exported protein 1 (Exp-1), the homologue of which is a protective antigen in a rodent model of malaria. These findings emphasize the diversity of P. falciparum antigens recognized by CD8(+) T cells in humans and support the inclusion of components from several antigens in new CTL-inducing vaccines against malaria.

Improved method for distinguishing the human source of mosquito blood meals between close family members.

We have developed a simple and relatively cheap method to distinguish the origin of mosquito blood meals between close family members, effective for both laboratory and field samples. Each blood meal was squashed on to filter paper and eluted overnight with 0.5 mL phosphate-buffered saline. Deoxyribonucleic acid (DNA) was extracted using a chemical matrix (Insta-gene) which bound to everything from the blood meal except DNA, which remained in the supernatant. Following extractions, reference DNA samples taken directly from finger-prick blood of human subjects and those from blood meals of unknown origin were amplified with human microsatellite markers using a thermal cycler. Polymerase chain reaction products were then run on an ABI gel (Automated Biosystems) to obtain a genotype for each sample. The DNA from each mosquito blood meal was then matched to an individual host. With laboratory samples, human DNA which had been extracted from mosquito blood meals up to 12 h after feeding could be used. One important application of this method will be to identify which members of a community are most at risk from vector-borne diseases. It also has numerous potential applications in studies of insect biting behaviour in both human and veterinary science.

DNA-based vaccines for malaria: a heterologous prime-boost immunisation strategy.

A generic approach to inducing high level CD8+ T cell responses would be of value for prophylactic and therapeutic immunisation against several infectious diseases. However, it has been very difficult to achieve such immune responses using available vaccination strategies. Malaria is one of several diseases against which a new generation of better CD8+ T cell-inducing vaccines might be useful and is unusual in that it allows assessment of vaccine efficacy in small numbers of volunteers in carefully controlled challenge studies. Here we review the identification of a heterologous prime-boost regime using DNA priming and recombinant modified vaccinia Ankara (MVA) boosting that induces high level T cell responses in both mice and non-human primates. Clinical trials to determine whether this prime-boost approach is immunogenic in humans are in progress.

Biological problems with the replacement of a vector population by Plasmodium-refractory mosquitoes.

Attempts are being made to backcross into Anopheles gambiae s.s. the gene(s) which cause zoophily in Anopheles quadriannulatus. Such a backcrossed strain might be preferable to a Plasmodium-refractory strain as a basis for genetic control because a refractory strain could select for evasion of refractoriness in the wild Plasmodium population. The species composition of the malaria vector population in several Tanzanian villages was overwhelmingly An. gambiae s.s. in a normal rainy season, but consisted of four species, all proved by ELISA and/or PCR to carry P. falciparum sporozoites, at the time of the heavy rains associated with El Niño. Thus any scheme, for malaria transmission control by replacement of vectors by genetically-manipulated non-vectors, would have to be able to replace more than one species.