GPR56: A potential therapeutic target for neurological and psychiatric disorders.

GPR56, also known as GPR56/ADGRG1, is a member of the ADGRG subgroup belonging to adhesion G protein-coupled receptors (aGPCRs). aGPCRs are the second largest subfamily of the GPCR superfamily, which is the largest family of membrane protein receptors in the human genome. Studies in recent years have demonstrated that GPR56 is integral to the normal development of the brain and functions as an important player in cortical development, suggesting that GPR56 is involved in many physiological processes. Indeed, aberrant expression of GPR56 has been implicated in multiple neurological and psychiatric disorders, including bilateral frontoparietal polymicrogyria (BFPP), depression and epilepsy. In a recent study, it was found that upregulated expression of GPR56 reduced depressive-like behaviours in an animal model of depression, indicating that GPR56 plays an important role in the antidepressant response. Given the link of GPR56 with the antidepressant response, the function of GPR56 has become a focus of research. Although GPR56 may be a potential target for the development of antidepressants, the underlying molecular mechanisms remain largely unknown. Therefore, in this review, we will summarize the latest findings of GPR56 function in neurological and psychiatric disorders (depression, epilepsy, autism, and BFPP) and emphasize the mechanisms of GPR56 in activation and signalling in those conditions. After reviewing several studies, attributing to its significant biological functions and exceptionally long extracellular N-terminus that interacts with multiple ligands, we draw a conclusion that GPR56 may serve as an important drug target for neuropsychological diseases.

Telehealth Infrastructure, Accountable Care Organization, and Medicare Payment for Patients with Alzheimer's Disease and Related Dementia Living in Socially Vulnerable Areas.

Background: Structural social determinants of health have an accumulated negative impact on physical and mental health. Evidence is needed to understand whether emerging health information technology and innovative payment models can help address such structural social determinants for patients with complex health needs, such as Alzheimer's disease and related dementias (ADRD). Objective: This study aimed to test whether telehealth for care coordination and Accountable Care Organization (ACO) enrollment for residents in the most disadvantaged areas, particularly those with ADRD, was associated with reduced Medicare payment. Methods: The study used the merged data set of 2020 Centers for Medicare and Medicaid Services Medicare inpatient claims data, the Medicare Beneficiary Summary File, the Medicare Shared Savings Program ACO, the Center for Medicare and Medicaid Service's Social Vulnerability Index (SVI), and the American Hospital Annual Survey. Our study focused on community-dwelling Medicare fee-for-service beneficiaries aged 65 years and up. Cross-sectional analyses and generalized linear models (GLM) were implemented. Analyses were implemented from November 2023 to February 2024. Results: Medicare fee-for-service beneficiaries residing in SVI Q4 (i.e., the most vulnerable areas) reported significantly higher total Medicare costs and were least likely to be treated in hospitals that provided telehealth post-discharge services or have ACO affiliation. Meanwhile, the proportion of the population with ADRD was the highest in SVI Q4 compared with other SVI levels. The GLM regression results showed that hospital telehealth post-discharge infrastructure, patient ACO affiliation, SVI Q4, and ADRD were significantly associated with higher Medicare payments. However, coefficients of interaction terms among these factors were significantly negative. For example, the average interaction effect of telehealth post-discharge and ACO, SVI Q4, and ADRD on Medicare payment was -$1,766.2 (95% confidence interval: -$2,576.4 to -$976). Conclusions: Our results suggested that the combination of telehealth post-discharge and ACO financial incentives that promote care coordination is promising to reduce the Medicare cost burden among patients with ADRD living in socially vulnerable areas.

Preparing a Mice Model of Severe Acute Pancreatitis via a Combination of Caerulein and Lipopolysaccharide Intraperitoneal Injection.

The treatment of severe acute pancreatitis (SAP), with high mortality rates, poses a significant clinical challenge. Investigating the pathological changes associated with SAP using animal models can aid in identifying potential therapeutic targets and exploring novel treatment approaches. Previous studies primarily induced pancreatic injury through retrograde bile duct injection of sodium taviaurocholate, but the impact of surgical damage on the quality of the animal model remains unclear. In this study, we employed various frequencies of intraperitoneal Caerulein injections combined with different doses of LPS to induce pancreatic injury in C57BL/6J mice and compared the extent of injury across five intraperitoneal injection protocols. Regarding inducing acute pancreatitis in mice, an intraperitoneal injection protocol is proposed that results in a mortality rate as high as 80% within 5 days. Specifically, mice received ten daily intraperitoneal injections of Caerulein (50 µg/kg), followed by an injection of LPS (15 mg/kg) one hour after the last Caerulein administration. By adjusting the frequency and dosage of injected medications, one can manipulate the severity of pancreatic injury effectively. This model exhibits strong controllability and has a short replication cycle, making it feasible for completion by a single researcher without requiring expensive equipment. It conveniently and accurately simulates key disease characteristics observed in human SAP while demonstrating a high degree of reproducibility.

On-line monitoring of membrane fouling based on an improved electrical measurement method.

On-line monitoring of membrane fouling is essential in the water treatment process. Drawbacks such as low-sensitivity and off-line limitations limit the application of existing methods. An on-line monitoring method based on Electrical Resistance Tomography (ERT) sensors is put forward in this paper. The Particle Swarm Optimization with Simulated Annealing (PSO-SA) algorithm is used in optimizing the topologies of finite element models in order to decrease the ill-posedness of sensitivity matrices. The deep denoising extreme learning machine with an auto-encoder model and the K-singular value decomposition algorithm are used in ERT reconstruction to improve imaging quality. The lift-wavelet is adopted in measuring the permeate flux to improve measuring accuracy. The ERT pixel values of the membrane module and the result of flux are used to analyze the fouling status. The results of membrane fouling experiments demonstrate the following: (1) Based on the local ERT pixels, the "two stage" phenomenon of membrane fouling can be observed. (2) In the early stage, the fouling distribution of the localized membrane module is consistent with its ERT pixels. (3) The deposition process of foulants for the localized membrane module is synchronized with the variation of ERT pixels. (4) The integrity of the membrane module can be detected according to the ERT pixels. Therefore, the novel method can effectively reflect the membrane fouling process, especially in the early stages of membrane fouling.

Synthesis, optical properties, and application of novel chalcone skeleton as pH fluorescent probe: Based AIE + ESIPT strategy.

A series of "turn off" pH fluorescence probes with chalcone skeleton for basic system have been developed. The molecules emitted bright yellow fluorescence under acidic condition, resulting AIE coupled ESIPT characteristic and ICT process. What's more, the compounds exhibited excellent sensitivity and selectivity for detecting pH as a facile "On-Off" fluorescence probe, and the fluorescence of them were quenched with the ESIPT process interrupted under alkaline condition. Theoretical calculation for the related compounds also performed to verify the electron effect on photophysical properties and confirm the rational speculation on the mechanism.

Treatment and rehabilitation of post-traumatic elbow stiffness with heterotopic ossification.

AIM: To investigate surgical treatment, postoperative rehabilitation and prevention of heterotopic ossification (HO) in patients with post-traumatic elbow stiffness. METHODS: We performed a retrospective review of patients with post-traumatic elbow stiffness combined with HO between 2007 and 2021. This study was performed on a total of 15 patients (18 elbows) admitted to our hospital, consisting of 12 males and 3 females, with post-traumatic stiffness of the elbow combined with HO, where elbow function could not be recovered by rehabilitation and orthosis treatment. Fifteen patients were treated by surgical excision of heterotopic bones and release of elbow contracture combined with postoperative rehabilitation and orthosis-wearing. Comprehensive treatments, including radiation, oral ibuprofen medication, and manipulation techniques to improve range of motion, were used to prevent HO recurrence. The flexion-extension arc and functional score of the elbow were measured after treatment and compared with the preoperative measurements. Roentgenography was used to observe HO recurrence. RESULTS: After surgical treatment and postoperative rehabilitation, the patients' range of motion improved, and the functional score improved considerably. The postoperative flexion-extension arc and The Hospital for Special Surgery (HSS) functional score were statistically significantly higher than the preoperative values (p < 0.01). Roentgenographic examination showed no HO recurrence during the follow-up period. CONCLUSION: Surgical excision of heterotopic bones and elbow contracture release combined with postoperative rehabilitation and preventative HO measures can be an effective treatment for cases of post-traumatic elbow stiffness combined with HO, for which conservative treatment is ineffective.

Differences in vascular endothelial function and serum proteome between obese people with phlegm-dampness constitution and balanced constitution.

OBJECTIVE: To evaluate the extent of vascular endothelial dysfunction and preliminary identify serum protein biomarkers associated with obese individuals at risk for cardiovascular disease (CVD). METHODS: Fifteen obese volunteers with the phlegm-dampness constitution or balanced constitution were recruited for this study respectively. The clinical baseline data was collected, and the vascular endothelial function was evaluated using the EndoPATTM. Blood samples were collected for the serum proteome analysis. The differences in the serum protein expression levels between the two groups were detected and the protein interaction network analysis, correlation analysis, receiver operating characteristic (ROC) curve analysis, and random forest model investigation were conducted. RESULTS: There were no statistical differences found in the baseline data. For vascular endothelial function, the reactive hyperemia index (RHI) of the phlegm-dampness constitution obese group was significantly lower than that of the balanced constitution obese group (1.46 ± 0.30 vs 2.82 ± 0.78, P < 0.0001), indicating vascular endothelial dysfunction. There are 66 differentially expressed serum proteins between the two groups. apolipoprotein A2 (ApoA2), angiotensin-converting enzyme 2 (ACE-2), interleukin-33 (IL-33), and forkhead box P3 (FoxP3) showed significant differences and area under curve values of their ROC curves were greater than 0.7 and correlated significantly with RHI. CONCLUSION: Vascular endothelial dysfunction was present in the phlegm-dampness constitution obese group. Thus, alterations in the expression levels of key serum proteins, including ApoA2, ACE-2, IL-33, and FoxP3 could serve as potential biomarkers in the obese population at risk of CVD.

Purinergic P2X7 receptor as a potential therapeutic target in depression.

The elaborate mechanisms of depression have always been a research hotspot in recent years, and the pace of research has never ceased. The P2X7 receptor (P2X7R) belongs to one of the adenosine triphosphates (ATP)-gated cation channels that exist widely in brain tissues and play a prominent role in the regulation of depression-related pathology. To date, the role of purinergic P2X7R in the mechanisms underlying depression is not fully understood. In this review, we conclude that the purinergic receptor P2X7 is a potential therapeutic target for depression based on research results published over the past 5 years in Google Scholar and the National Library of Medicine (PubMed). Additionally, we introduced the functional characteristics of P2X7R and confirmed that excessive activation of P2X7R led to increased release of inflammatory cytokines, which eventually contributed to depression. Furthermore, the inhibition of P2X7R produced antidepressant-like effects in animal models of depression, further proving that P2X7R signalling mediates depression-like behaviours. Finally, we summarised related studies on drugs that exert antidepressant effects by regulating the expression of P2X7R. We hope that the conclusions of this review will provide information on the role of P2X7R in the neuropathophysiology of depression and novel therapeutic targets for the treatment of depression.

A Comprehensive Review on the Importance of MiRNA-206 in the Animal Model and Human Diseases.

MicroRNA-206 (miR-206) is a microRNA that is involved in many human diseases, such as myasthenia gravis, osteoarthritis, depression, cancers, etc. Both inhibition effects and progression roles of miR-206 have been reported for the past few years. High expression of miR-206 was observed in patients with osteoarthritis, gastric cancer and epithelial ovarian cancer compared to normal people. The study also showed that miR-206 promotes cancer progression in breast cancer patients and avascular necrosis of the femoral head. Meanwhile, several studies have shown that expression levels of miR-206 were down-regulated in laryngeal carcinoma cell multiplication, as well as in hepatocellular carcinoma, non-small lung cancer and infantile hemangioma. Moreover, miR-206 was up-regulated in the mild stage of amyotrophic lateral sclerosis patients and then down-regulated in the moderate and severe stages, indicating that miR-206 has the double effects of starting and aggravating the disease. In neuropsychiatric disorders, such as depression, miR-206 also plays an important role in the progression of the disease; the level of miR-206 is most highly expressed in the brains of patients with depression. In the current review, we summarize the role of miR-206 in various diseases, and miR-206 may be developed as a new biomarker for diagnosing diseases in the near future.

Functional analyses of Toxoplasma gondii dihydroorotase reveal a promising anti-parasitic target.

Toxoplasma gondii relies heavily on the de novo pyrimidine biosynthesis pathway for fueling the high uridine-5'-monophosphate (UMP) demand during parasite growth. The third step of de novo pyrimidine biosynthesis is catalyzed by dihydroorotase (DHO), a metalloenzyme that catalyzes the reversible condensation of carbamoyl aspartate to dihydroorotate. Here, functional analyses of TgDHO reveal that tachyzoites lacking DHO are impaired in overall growth due to decreased levels of UMP, and the noticeably growth restriction could be partially rescued after supplementation with uracil or high concentrations of L-dihydroorotate in vitro. When pyrimidine salvage pathway is disrupted, both DHOH35A and DHOD284E mutant strains proliferated much slower than DHO-expressing parasites, suggesting an essential role of both TgDHO His35 and Asp284 residues in parasite growth. Additionally, DHO deletion causes the limitation of bradyzoite growth under the condition of uracil supplementation or uracil deprivation. During the infection in mice, the DHO-deficient parasites are avirulent, despite the generation of smaller tissue cysts. The results reveal that TgDHO contributes to parasite growth both in vitro and in vivo. The significantly differences between TgDHO and mammalian DHO reflect that DHO can be exploited to produce specific inhibitors targeting apicomplexan parasites. Moreover, potential DHO inhibitors exert beneficial effects on enzymatic activity of TgDHO and T. gondii growth in vitro. In conclusion, these data highlight the important role of TgDHO in parasite growth and reveal that it is a promising anti-parasitic target for future control of toxoplasmosis.

ROP16 of Toxoplasma gondii Inhibits Innate Immunity by Triggering cGAS-STING Pathway Inactivity through the Polyubiquitination of STING.

cGAS-STING signaling is a major pathway in inducing type Ⅰ IFN, which plays a crucial role in the defense against T. gondii infection. In contrast, T. gondii develops multiple strategies to counteract the host defense, causing serious diseases in a wide range of hosts. Here, we demonstrate that T. gondii rhoptry protein 16 (ROP16) dampens type I interferon signaling via the inhibition of the cGAS (cyclic GMP-AMP synthase) pathway through the polyubiquitination of STING. Mechanistically, ROP16 interacts with STING through the SignalP domain and inhibits the K63-linked ubiquitination of STING in an NLS (nuclear localization signal)-domain-dependent manner. Consequently, knocking out the ROP16 in PRU tachyzoites promotes the STING-mediated production of type I IFNs and limits the replication of T. gondii. Together, these findings describe a distinct pathway where T. gondii exploits the ubiquitination of STING to evade host anti-parasite immunity, revealing new insights into the interaction between the host and parasites.

Ginsenoside Rh2: A shining and potential natural product in the treatment of human nonmalignant and malignant diseases in the near future.

BACKGROUND: Ginseng is well-known as one of the most valuable and commonly used Chinese medicines not only in ancient China but also worldwide including East, Russia, Southeast Asia, North America and some Western European countries. Ginsenosides, as one of the main high active components of Ginseng, have various pharmacological activities, such as anti-inflammatory, antianaphylaxis, anti-depression, and anticancer activities. Ginsenoside Rh2 (Rh2), one of the major bioactive ginsenosides in Panax ginseng, also exhibits versatile pharmacological activities, such as increasing non-specific resistance and specific immune response, improving cardiac function and fibrosis, anti-inflammatory effects and antitumor effects, which may serve as an excellent medicinal potential. PURPOSE: As one of hundreds of ginsenosides being identified from ginseng, Rh2 exerts a markedly pharmacological effect on various diseases without severe toxicity, it has attracted many researchers 'attention. Although Rh2 plays important roles in some animal models and cell lines to simulate human diseases, its underlying molecular mechanisms have yet to be determined. During the past ten years, nearly 450 studies on Rh2 in the treatment of complex disease have been reported, however, up to now, no comprehensive reviews about the roles of Rh2 in animal models and cellular lines of human nonmalignant and malignant diseases have been conducted. METHOD: We searched articles on ginsenoside-related diseases from December 2010 to February 2023 in peer-reviewed and nonclinical databases, which include Web of Science, Scopus, PubMed, China national knowledge internet and Medline, and using the following keywords: Ginsenoside Rh2, Human diseases, Cancer, Mechanisms, Chinese herbal medicine, Natural products and Signaling pathway. RESULTS: Therefore, in this review, we make a comprehensive summary on the roles of Rh2 and support the potential mechanisms of Rh2 according to the disease classification, including nonmalignant disease such as ulcerative colitis, neuropathic pain, Asthma, myocardial injury, depression and malignant disease such as breast cancer, colorectal cancer, hepatocellular carcinoma and gastric cancer. Finally, the combination therapy of Rh2 and other medications in human diseases are summarized, apart from that, there are other problems such as the bioavailability of oral administration Rh2 to be overcome in following research. CONCLUSION: These findings provide strong evidence that Ginsenoside Rh2 plays important roles in the treatment of nonmalignant and malignant diseases.

In Vitro Evaluation Reveals Effect and Mechanism of Artemether against Toxoplasma gondii.

Due to the limited effectiveness of existing drugs for the treatment of toxoplasmosis, there is a dire need for the discovery of new therapeutic options. Artemether is an important drug for malaria and several studies have indicated that it also exhibits anti-T. gondii activity. However, its specific effect and mechanisms are still not clear. To elucidate its specific role and potential mechanism, we first evaluated its cytotoxicity and anti-Toxoplasma effect on human foreskin fibroblast cells, and then analyzed its inhibitory activity during T. gondii invasion and intracellular proliferation. Finally, we examined its effect on mitochondrial membrane potential and reactive oxygen species (ROS) in T. gondii. The CC50 value of artemether was found to be 866.4 µM, and IC50 was 9.035 µM. It exhibited anti-T. gondii activity and inhibited the growth of T. gondii in a dose-dependent manner. We also found that the inhibition occurred primarily in intracellular proliferation, achieved by reducing the mitochondrial membrane integrity of T. gondii and stimulating ROS production. These findings suggest that the mechanism of artemether against T. gondii is related to a change in the mitochondrial membrane and the increase in ROS production, which may provide a theoretical basis for optimizing artemether derivatives and further improving their anti-Toxoplasma efficacy.

The efficacy and safety of dupilumab combined with methylprednisolone in the treatment of bullous pemphigoid in China.

We access the safety and efficacy of methylprednisolone combined with dupilumab in treating the bullous pemphigoid. 27 patients were enrolled, of which 9 received dupilumab in addition to methylprednisolone (dupilumab group, D group), while the other 18 patients were administered methylprednisolone alone (traditional group, T group). The median time to stop the formation of the new blister was 5.5 days (3.5-11.75 days) and 10 days (9-15 days) in the D group and the T group, respectively (p = 0.032). Additionally, the median time of complete healing reached was 21 days (16.25-31 days) and 29 days (25-50 days) in the D group and the T group, separately (p = 0.042). The median amount of cumulative methylprednisolone at the time of disease control was 240 mg (140-580 mg) and 460 mg (400-840 mg) in the D group and the T group, respectively (p = 0.031). The total amount of the methylprednisolone used at the time of complete healing reached was 792 mg (597-1,488.5 mg) in the D group while that was 1,370 mg (1,000-2,570 mg) in the T group (p = 0.028). No adverse event associated with dupilumab was recorded. Methylprednisolone in combination with dupilumab appeared superior to methylprednisolone alone in control of disease progression and the methylprednisolone-sparing effect.

[Treatment of stable degenerative lumbar spondylolisthesis with percutaneous endoscopic surgery through two different approaches].

OBJECTIVE: To assess the clinical effects of percutaneous endoscopic surgery through two different approaches for stable degenerative lumbar spondylolisthesis. METHODS: Sixty-four patients with stable degenerative lumbar spondylolisthesis who underwent percutaneous endoscopic procedures between January 2016 and December 2019 were divided into transforaminal approach group and interlaminar approach group according to surgical approaches, 32 patients in each group. There were 16 males and 16 females in transforaminal approach group, aged from 52 to 84 years old with an average of (66.03±9.60) years, L2 slippage in 4 cases, L3 slippage in 5, and L4 slippage in 23. There were 17 males and 15 females in interlaminar approach group, aged from 46 to 81 years old with an average of (61.38±9.88) years, L3 slippage in 3 cases, L4 slippage in 15, and L5 slippage in 14. Operative time, intraoperative fluoroscopy times, and postoperative bedtime were compared between two groups. Anteroposterior displacement values, interbody opening angles, and the percentage of slippage were measured on preoperative and postoperative 12-month dynamic radiographs. Visual analogue scale (VAS) of low back pain and lower extremity pain, and the Japanese Orthopaedic Association (JOA) score before and after surgery were observed, and clinical effects were evaluated according to the modified MACNAB criteria. RESULTS: All operations were successfully completed, and patients in both groups were followed up for more than 1 year, and without complications during follow-up period. ①There was no significant difference in operation time between two groups(P>0.05). Intraoperative fluoroscopy times were longer in transforaminal approach group than that in intervertebral approach group(P<0.05). Postoperative bedtime was shorter in transforaminal approach group than that in intervertebral approach group (P<0.05).② No lumbar instability was found on dynamic radiography at 12 months postoperatively in both groups. There were no significant differences in anteroposterior displacement values, interbody opening angles, and the percentage of slippage between two groups postoperative 12 months and preoperative 1 day(P>0.05). ③There was no significant difference between two groups in VAS of low back pain at 3 days and 1, 12 months after the operation compared with the preoperative(P>0.05), but the VAS of the lower extremity pain was significantly improved compared with the preoperative(P<0.05). Both of groups showed significant improvement in JOA score at 12 months compared with preoperatively(P<0.05). There was no significant difference in VAS of low back pain, lower extremity pain and JOA scores between two groups during the same period after surgery(P>0.05). According to modified Macnab criteria, excellent, good, fair and poor outcomes were 21, 7, 3 and 1 in transforaminal approach group respectively, and which in intervertebral approach group were 20, 7, 5 and 0, there was no significant difference in clinical effect between the groups(P>0.05). CONCLUSION: Intervertebral approach may reduce intraoperative fluoroscopy times and transforaminal approach can shorten postoperative bedtime, both approaches achieve satisfactory results in the treatment of stable degenerative lumbar spondylolisthesis with no progression of short-term slippage.

New compounds with hepatoprotective effects from the stems of Sabia parviflora.

Three new compounds, (8S)-2,2,7,7-tetramethyl-8-hydroxymethyl-6H-indanone-(2,3-b)-2H-pyran-9-O-ß-d-glucopyranoside (1), (7S,8S)-2,2,7-trimethyl-7-hydroxymethyl-8-hydroxy-2,7,8,9-tetrahydro-6H-naphtho-(2,3-b)-pyran-10-O-ß-d-glucopyranoside (2), 1-deoxy-1-(3,4-dihydro-7-methyl-2,3-dioxo-1(2H)-quinoxalinyl)pentitol-6-carboxylic acid (3), as well as six known compounds (4-9), were obtained. Their structures were determined by spectroscopy and comparison with NMR data of related compounds. Absolute configurations were determined by ECD spectroscopy. The hepatoprotective effects of these compounds were investigated on HepG2 and LO2 cells lines; compounds 1, 2, and 4 displayed moderate activity.

Mineralization Reduces the Toxicity and Improves Stability and Protective Immune Response Induced by Toxoplasma gondii.

Vaccination is an ideal strategy for the control and prevention of toxoplasmosis. However, the thermostability and effectiveness of vaccines limit their application. Here, calcium mineralization was used to fabricate Toxoplasma gondii tachyzoites as immunogenic core-shell particles with improved immune response and thermostability. In the current study, T. gondii RH particles coated with mineralized shells were fabricated by calcium mineralization. The mineralized shells could maintain the T. gondii tachyzoites structural integrity for at least 12 months and weaken the virulence. Immunization of mice with mineralized tachyzoites induced high levels of T. gondii-specific antibodies and cytokines. The immunized mice were protected with a 100% survival rate in acute and chronic infection, and brain cyst burdens were significantly reduced. This study reported for the first time the strategy of calcium mineralization on T. gondii and proved that mineralized tachyzoites could play an immune protective role, thus expanding the application of biomineralization in T. gondii vaccine delivery.

Complications of radical hysterectomy with pelvic lymph node dissection for cervical cancer: a 10-year single-centre clinical observational study.

BACKGROUND AND PURPOSE: The complications of radical surgery for cervical cancer can increase patient suffering and affect their quality of life. This retrospective study assessed the safety of radical hysterectomy (RH) with pelvic lymph node dissection (PLND) by observing the complications of patients with cervical cancer who underwent this procedure in a single centre over 10 years. Our findings may provide experience and evidence for preventing and reducing complications. METHODS: A total of 2226 cervical cancer patients who met the inclusion criteria were enrolled. All patients underwent RH + PLND. Intraoperative injury to adjacent tissues and short-term and long-term complications were recorded to analyze factors associated with the occurrence of complications. RESULTS: Postoperative complications occurred in 34.41% (766/2226) of patients, including 7.68% of patients with injury to adjacent tissues, 31.45% with short-term complications, and 2.96% with long-term complications. Age, tumor size, invasion depth, parametrial invasion, lymph vascular space invasion (LVSI), lymph node metastasis, International Federation of Gynaecology and Obstetrics (FIGO) stage, and surgical procedure were closely associated with the postoperative complications of RH + PLND (P < 0.05). CONCLUSIONS: The results of this study showed that RH + PLND for cervical cancer is safe and practical. Patients aged 40-60 years, with tumors ≥ 4 cm, invasion depth ≥ 2/3, parametrial invasion, LVSI, lymph node metastasis, FIGO stage > IB2, and who underwent open surgery were more prone to complications.

Diverse roles of the CIPK gene family in transcription regulation and various biotic and abiotic stresses: A literature review and bibliometric study.

CIPKs are a subclass of serine/threonine (Ser/Thr) protein kinases. CBLs are ubiquitous Ca2+ sensors that interact with CIPK with the aid of secondary Ca2+ messengers for regulation of growth and development and response to stresses faced by plants. The divergent roles of the CIPK-CBL interaction in plants include responding to environmental stresses (salt, cold, drought, pH, ABA signaling, and ion toxicity), ion homeostasis (K+, NH4 +, NO3 -, and microelement homeostasis), biotic stress, and plant development. Each member of this gene family produces distinct proteins that help plants adapt to diverse stresses or stimuli by interacting with calcium ion signals. CIPK consists of two structural domains-an N-terminal domain and a C-terminal domain-connected by a junction domain. The N-terminal domain, the site of phosphorylation, is also called the activation domain and kinase domain. The C-terminal, also known as the regulatory domain of CIPK, further comprises NAF/FISL and PPI. CBL comprises four EF domains and conserved PFPF motifs and is the site of binding with the NAF/FISL domain of CIPK to form a CBL-CIPK complex. In addition, we also performed a bibliometric analysis of the CIPK gene family of data extracted from the WoSCC. A total of 95 documents were retrieved, which had been published by 47 sources. The production over time was zigzagged. The top key terms were gene, CIPK, abiotic stress, and gene expression. Beijing Forestry University was the top affiliation, while The Plant Cell was the top source. The genomics and metabolomics of this gene family require more study.

A novel multi-epitope vaccine of HPV16 E5E6E7 oncoprotein delivered by HBc VLPs induced efficient prophylactic and therapeutic antitumor immunity in tumor mice model.

Human papilloma virus type 16 (HPV16) is the most prevalent etiologic agent associated with cervical cancer, and its early proteins E5, E6 and E7 play important roles in cervical epithelium transformation to cervical intraepithelial neoplasia and even cervical cancer. Hence, these oncoproteins are ideal target antigens for developing immunotherapeutic vaccines against HPV-associated infection and cervical cancer. Currently, multi-epitope vaccines have been a promising strategy for immunotherapy for viral infection or cancers. In this study, the E5aa28-46, E6aa37-57 and E7aa26-57 peptides were selected and linked to form a novel multi-epitopes vaccine (E765m), which was inserted into the major immune dominant region (MIR) of hepatitis B virus core antigen (HBc) to construct a HBc-E765m chimeric virus-like particles (cVLPs). The immunogenicity and immunotherapeutic effect of the cVLPs vaccine was evaluated in immunized mice and a tumor-bearing mouse model. The results showed that HBc-E765m cVLPs elicited high E5-, E6- and E7- specific CTL and serum IgG antibody responses, and also relatively high levels of the cytokines IFN-γ, IL-4 and IL-5. More importantly, the cVLPs vaccine significant suppressed tumor growth in mice bearing E5-TC-1 tumors. Our findings provide strong evidence that this novel HBc-E765m cVLPs vaccine could be a candidate vaccine for specific immunotherapy in HPV16-associated cervical intraepithelial neoplasia or cervical cancer.