Investigation of rock genesis and geodynamic significance based on Sr-Yb granite classification and geochemical characteristics: A case study from Guangxi, China.

The intrusive bodies in the study area are categorized into two intrusive units, γπK2 and ηoπK2, based on rock structure characteristics and intrusive contact relationships. The primary lithologies are granite porphyry and quartz monzonite porphyry. Through LA-ICP-MS zircon U-Pb dating, the weighted mean ages of zircon ^206Pb/^238U for these two units were determined to be 84.09 ± 0.86 Ma and 86.10 ± 0.76 Ma, respectively. According to geochemical characteristics and Sr-Yb granite classification, the quartz monzonite porphyry is classified as Zhejiang-Fujian type granite, and the granite porphyry as Nanling type granite. The study explores the geodynamic significance of granites in the area based on Sr-Yb granite classification, identifying the lower crust metamorphic facies as amphibolite facies. The source rocks are primarily basic granulites and felsic granulites, reflecting a thermally active lower crust with poorly developed fluids. Additionally, Sr-Yb granite classification aids in determining the crustal thickness of the lower crust, which is crucial for understanding continental geological evolution. This paper discusses the optimal locations and conditions for mineralizing fluid precipitation, noting that tungsten-tin mineralization is associated with Nanling type granites and that the mineralization process generally occurs later than the diagenetic process under conditions of low pressure and low oxygen fugacity. Tungsten-tin prospecting should focus on areas where the surrounding rock temperature ranges from 300 to 500 °C, with particular attention to the contact zones of sedimentary rocks or near structural fault zones.

Cross-species analysis and comparison of the inner ear between chickens and mice.

The inner ear of mammals includes the cochlea and vestibule, which house specialized hair cells that are responsible for hearing and balance, respectively. While cochlear hair cells fail to regenerate following damage, those of the utricle, which is part of the vestibular apparatus, show partial regeneration. In birds, the macula lagena, a unique ear structure in this clade, has the ability to regenerate hair cells similarly to the utricle. Many studies have sought to explain regeneration in terms of evolution and species differences. However, it remains unclear what the cellular and molecular basis is behind the differences in inner ear structures and between avians and mammals. In the present study, we first investigated the anatomical structures of the inner ear of both chickens and rodents. We then performed RNA sequencing (RNA-Seq) and made cross-species analyses of the expression of homologous genes obtained from the inner ear tissue from both chickens and mice. Finally, we focused on the lagena, the basilar papilla, and the utricle in chickens and identified differentially expressed genes between tissues and determined the expression patterns of genes involved in inner ear structure formation by single-cell RNA sequencing and bulk RNA-Seq. We concluded that the cellular and molecular composition of the lagena is more similar to that of the utricle than the cochlea. Taken together, our study provides a valuable resource for the study of inner ear evolution and development.

Glutamate-aspartate transporter dysfunction enhances aminoglycoside-induced cochlear hair cell death via NMDA receptor activation.

Glutamate is a crucial neurotransmitter for hearing transduction in the cochlea, but excess glutamate is detrimental to the survival of cochlear sensory cells. Glutamate-aspartate transporter (GLAST) is the major transporter for glutamate removal; however, its role in aminoglycoside-induced hair cell loss is not well studied. In the present study, we first investigated the localization and expression of GLAST over the course of development of the mouse cochlea, and we found that inhibition of GLAST increased hair cell death. However, when the glutamate receptor NMDAR was inhibited by D-AP5, hair cell death was no longer increased by the GLAST inhibitor. Our results indicate that GLAST inhibition aggravates damage to cochlear hair cells, which may occur via NMDAR, and this suggests new clinical strategies for ameliorating the ototoxicity associated with the dysfunction of glutamate metabolism.

CLCA2 overexpression suppresses epithelial-to-mesenchymal transition in cervical cancer cells through inactivation of ERK/JNK/p38-MAPK signaling pathways.

Cervical cancer is an important malignant tumor threatening the physical and mental health of women in the world. As a new calcium activated chloride channel protein, calcium activated chloride channel (CLCA2) plays an important role in tumorigenesis and development. But its role and exact regulatory mechanism in cervical cancer are still unclear. In our study, we found CLCA2 was significantly decreased in cervical cancer cells, and overexpression of CLCA2 inhibited the proliferation, migration and invasion, and promotes apoptosis of cervical cancer cells, and CLCA2 inhibited EMT (Epithelial-mesenchymal transition) through an p38 / JNK / ERK pathway. The results in vivo were consistent with those in vitro. In conclusion, overexpression of CLCA2 inhibited the progression of cervical cancer in vivo and in vitro. This may provide a theoretical basis for CLCA2 as a new indicator of clinical diagnosis and prognosis of cervical cancer or as a potential target of drug therapy.

The heterogeneity of mammalian utricular cells over the course of development.

BACKGROUND: The inner ear organ is a delicate tissue consisting of hair cells (HCs) and supporting cells (SCs).The mammalian inner ear HCs are terminally differentiated cells that cannot spontaneously regenerate in adults. Epithelial non-hair cells (ENHCs) in the utricle include HC progenitors and SCs, and the progenitors share similar characteristics with SCs in the neonatal inner ear. METHODS: We applied single-cell sequencing to whole mouse utricles from the neonatal period to adulthood, including samples from postnatal day (P)2, P7 and P30 mice. Furthermore, using transgenic mice and immunostaining, we traced the source of new HC generation. RESULTS: We identified several sensory epithelial cell clusters and further found that new HCs arose mainly through differentiation from Sox9+ progenitor cells and that only a few cells were produced by mitotic proliferation in both neonatal and adult mouse utricles. In addition, we identified the proliferative cells using the marker UbcH10 and demonstrated that in adulthood the mitotically generated HCs were primarily found in the extrastriola. Moreover, we observed that not only Type II, but also Type I HCs could be regenerated by either mitotic cell proliferation or progenitor cell differentiation. CONCLUSIONS: Overall, our findings expand our understanding of ENHC cell fate and the characteristics of the vestibular organs in mammals over the course of development.

[Clinical effect of fluid resuscitation guided by intra-abdominal pressure and oxygenation index for severe acute pancreatitis patients].

OBJECTIVE: To investigate the effect of the liquid resuscitation therapy strategy using intra-abdominal pressure (IAP) and oxygenation index (PaO2/FiO2) as the end point in patients with severe acute pancreatitis (SAP). METHODS: A retrospective study was performed, including 84 patients with SAP in emergency intensive care unit of Qingzhou Hospital Affiliated to Shandong First Medical University from January 2018 to August 2021. According to the status of fluid balance at admission, all patients were divided into the positive fluid balance group (43 cases) and the negative fluid balance group (41 cases). The clinical data including gender, age, etiology, underlying disease, acute physiology and chronic health evaluation II (APACHE II) and sequential organ failure assessment (SOFA) of all patients were collected. Fluid balance, PaO2/FiO2, IAP, compliance rate, new mechanical ventilation rate and overall hospital stay of 1 week after admission were recorded and compared between the two groups. RESULTS: After 72 hours of treatment, the cumulative fluid balance was (5 219.5±1 038.4) mL in the positive fluid balance group; IAP was higher than that before treatment [mmHg (1 mmHg ≈ 0.133 kPa): 11.9±2.0 vs. 11.7±2.1], but no significant difference was found (P > 0.05); PaO2/FiO2 was significantly higher than that before treatment (mmHg: 299.8±51.4 vs. 220.5±50.4, P < 0.05). After 72 hours of treatment, the cumulative fluid balance in negative fluid balance group was (-3 542.4±1 310.6) mL; IAP was significantly lower than before treatment (mmHg: 11.4±1.8 vs. 15.2±1.9, P < 0.05); PaO2/FiO2 was significantly higher than that before treatment (mmHg: 309.9±50.9 vs. 215.4±49.7, P < 0.05). In the fluid resuscitation goals, after 72 hours of treatment, the compliance rate in the negative fluid balance group was significantly higher than that in the positive fluid balance group [82.93% (34/41) vs. 62.79% (27/43), P < 0.05]; 1 week after admission, the new mechanical ventilation rate in the negative fluid balance group was significantly lower than that in the positive fluid balance group [21.95% (9/41) vs. 41.86% (18/43), P < 0.05]; however, there was no significant difference in overall hospital stay between the two groups (days: 41.2±10.9 vs. 39.1±11.5, P > 0.05). After treatment, 70 patients survived and 14 patients died (including 9 cases in the positive fluid balance group and 5 cases in the negative fluid balance group). CONCLUSIONS: Using IAP and PaO2/FiO2 to guide liquid therapy could result in effective fluid resuscitation in SAP. The treatment strategy effectively improved prognosis of patients with SAP.

FGF21 impedes peripheral myelin development by stimulating p38 MAPK/c-Jun axis.

Fibroblast growth factor 21 (FGF21) as a metabolic stress hormone, is mainly secreted by the liver. In addition to its well-defined roles in energy homeostasis, FGF21 has been shown to promote remyelination after injury in the central nervous system. In the current study, we sought to examine the potential roles of FGF21 in the peripheral nervous system (PNS) myelination. In the PNS myelin development, Fgf21 expression was reversely correlated with myelin gene expression. In cultured primary Schwann cells (SCs), the application of recombinant FGF21 greatly attenuates myelination-associated gene expression, including Oct6, Krox20, Mbp, Mpz, and Pmp22. Accordingly, the injection of FGF21 into neonatal rats markedly mitigates the myelination in sciatic nerves. On the contrary, the infusion of the anti-FGF21 antibody accelerates the myelination. Mechanistically, both extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (MAPK) were stimulated by FGF21 in SCs and sciatic nerves. Following experiments including pharmaceutical intervention and gene manipulation revealed that the p38 MAPK/c-Jun axis, rather than ERK, is targeted by FGF21 for mediating its repression on myelination in SCs. Taken together, our data provide a new aspect of FGF21 by acting as a negative regulator for the myelin development process in the PNS via activation of p38 MAPK/c-Jun.

[Experience on single-lung mechanical ventilation combined with damage control in treatment of patients with severe multiple trauma].

On April 6, 2020, a case of severe crush injuries in head, neck, chest and right upper extremity was admitted to Qingzhou Hospital Affiliated to the First Medical University of Shandong Province. In addition to the crush injuries, the case also suffered from shock, crush syndrome, trauma-induced coagulopathy (TIC), and acute respiratory distress syndrome (ARDS). The female patient was 44 years old, and was admitted to the hospital at 07:00 on April 6, 2020 due to traffic accident with head, neck, chest, right upper limb injuries with disturbance of consciousness for 1 hour. Admission physical examination: body temperature was 35.6 centigrade. The patient was drowsy, with swelling and cyanosis around the right orbit and right cheek. The skin was severely abraded with blood seepage. The conjunctiva was pale. The lips were slightly cyanotic. The right chest collapsed and deformed with abnormal breathing. The skin of chest wall was blue and purple with extensive feeling of holding snow under the skin. The breath sound of right lung was low and dry and wet rales could be heard. Laboratory examination: routine blood test showed that white blood cell count (WBC) was normal, red blood cell count (RBC), hemoglobin (Hb) and platelet count (PLT) decreased, blood glucose increased; urine routine examination showed glucose +++, urine occult blood +++, urinary protein +++, visible transparent and granular tube type; coagulation indicators and blood biochemical examination were abnormal. Arterial blood gas analysis showed that pH and arterial partial pressure of oxygen (PaO2) decreased. X-ray showed comminuted fracture of distal humerus and proximal end of right ulna and radius with dislocation of right elbow joint. CT showed swelling of soft tissue around the right orbit and depressed fracture of inner wall. After admission, single-lung ventilation, tracheotomy and prone ventilation were applied to increase oxygenation level and relieving ARDS. Fluid of damage control for resuscitation was applied to reverse shock and blood transfusion was used to control hemorrhage and TIC. According to the patient's conditions and theory of damage control surgery, right chest drainage and amputation of the right upper extremity amputation were performed in time. Then, the resection in the middle and lower part of right lung, lung repairment, and internal rib fixation were performed. Finally, selective operation was performed to cover the open wound with healing dressing, using negative pressure for suction and carrying out "stamp" skin grafting on the right chest. After treatment, the patient was out of danger, and satisfactory clinical results were achieved in the end.

High expression of survivin predicts poor prognosis in cervical squamous cell carcinoma treated with paclitaxel and carboplatin.

Lack of effective biomarkers is one of the challenges in current neoadjuvant chemotherapy to predict drug response and sensitivity of cervical squamous cell carcinoma (CSCC). The present study was designed to investigate the correlation of the expression of survivin, an inhibitor of apoptosis with the prognosis of CSCC patients undergoing neoadjuvant chemotherapy.A total of 117 CSCC patients treated with paclitaxel and carboplatin between May 2015 and April 2017 in the Second Hospital of Lanzhou University were retrospectively analyzed. The pathologic diagnosis and classification of CSCC were based on the Guidelines of the International Federation of Gynaecology and Obstetrics (FIGO). The efficacy was defined as complete remission (CR), partial remission (PR), and stability disease (SD). The expressions of survivin, vascular endothelial growth factor (VEGF), and Ki67 were determined with immunohistochemistry. Data were analyzed with SPSS software.Univariate analysis showed that survivin expression had no correlation with ages, FIGO stage, macroscopic type, lymphovascular invasion, depth of lymphovascular invasion, lymph node metastasis, and tumor size among 117 CSCC patients. However, survivin expression was positively correlated with pathological grade (R = 0.691, P < .001). Multivariate analysis revealed that survivin expression was independently correlated with grades (P < .001). In addition, the analysis of correlation indicated that survivin expression is positively correlated with VEGF expression (R = 0.820, P < .001) and Ki67 expression (R = 0.673, P < .001). The numbers (percentages) of complete remission (CR), partial remission (PR), and stability disease (SD) were 11 (9.4%), 91 (77.8%), and 15 (12.8%) respectively after the treatment of paclitaxel and carboplatin. Univariate analysis showed that efficacy of treatment was negatively correlated with pathological grade (R = 0.513, P < .001), Ki67 expression (R = 0.586, P < .001), VEGF expression (R = 0.476, P < .001) and survivin expression (R = 0.519, P < .001). Multivariate analysis revealed that efficacy of treatment was independently correlated with grades (P = .028), Ki67 (P < .001), and survivin expression (P = .015).The results suggested that survivin expression is negatively correlated with the prognosis of CSCC patients treated with paclitaxel and carboplatin. Therefore, survivin expression might be a marker for prognosis in CSCC following neoadjuvant chemotherapy.

Salidroside ameliorates Adriamycin nephropathy in mice by inhibiting ß-catenin activity.

Salidroside is a major phenylethanoid glycoside in Rhodiola rosea L., a traditional Chinese medicine, with multiple biological activities. It has been shown that salidroside possesses protective effects for alleviating diabetic renal dysfunction, contrast-induced-nephropathy and other kidney diseases. However, the involved molecular mechanism was still not understood well. Herein, we examined the protective effects of salidroside in mice with Adriamycin (ADR)-induced nephropathy and the underlying molecular mechanism. The results showed that salidroside treatment ameliorates proteinuria; improves expressions of nephrin and podocin; and reduces kidney fibrosis and glomerulosclerosis induced by ADR. Mechanistically, ADR induces a robust accumulation of ß-catenin in the nucleus and stimulates its downstream target gene expression. The application of salidroside largely abolishes the nuclear translocation of ß-catenin and thus inhibits its activity. Furthermore, the activation of ß-catenin almost completely counteracts the protective roles of salidroside in ADR-injured podocytes. Taken together, our data indicate that salidroside ameliorates proteinuria, renal fibrosis and podocyte injury in ADR nephropathy, which may rely on inhibition of ß-catenin signalling pathway.

Pre-B cell leukemia transcription factor 3 induces inflammatory responses in human umbilical vein endothelial cells and murine sepsis via acting a competing endogenous RNA for high mobility group box 1 protein.

The present study investigated the roles of pre-B cell leukemia transcription factor 3 (PBX3) in sepsis. Reverse transcription-quantitative polymerase chain reaction and western blot analysis indicated that overexpression of the PBX 3'­untranslated region (UTR) promoted high mobility group box 1 (HMGB1) protein expression in human umbilical vein endothelial cells (HUVECs) (P<0.01). Furthermore, post­treatment of PBX3 small interfering (si)RNA suppressed lipopolysaccharide (LPS)­mediated HMGB1 release and attenuated HMGB1­mediated hyperpermeability and leukocyte migration in HUVECs and septic mice (P<0.01). Additionally, post­injection of PBX3 siRNA also induced the downregulation of cecal ligation and puncture­induced HMGB1 release, production of IL­6 and mortality (P<0.01). Mechanistically, the 3'UTRs of PBX3 and HMGB1 were identified to harbor six common micro (mi)RNA binding sites, and PBX 3'UTR increased HMGB1 expression in a 3'UTR­ and miRNA­dependent manner. Notably, the coding sequence of PBX3 did not increase HMGB1 expression in HUVECs. Collectively, the present study indicates that PBX 3'UTR may induce inflammatory responses and sepsis via acting as a competing endogenous RNA for HMGB1.

The incidence of inflammatory bowel disease in Northern China: a prospective population-based study.

AIMS & BACKGROUNDS: Although inflammatory bowel diseases (IBD) are emerging and increasing in China, epidemiologic data are rarely available. This study was to investigate the epidemiological and clinical characteristics of IBD in Northern China. METHODS: This is a prospective, population-based study of incidence of IBD in Daqing, Heilongjiang province of Northern China from March 1, 2012 to February 28, 2013. All incident patients with IBD were clinically identified by IBD specialist group from five main General Hospitals covering the healthcare service for 1,343,364 residents in the urban areas of Daqing. IBD cases included in this study were followed-up for three months for diagnosis confirmation. RESULTS: A total of 27 new IBD cases including 25 cases of ulcerative colitis (UC) and 2 cases of Crohn's disease (CD) were identified. The population at risk was 1,343,364 person years. Age-adjusted incidence for total IBD, CD and UC were 1.77, 0.13, and 1.64 per 100,000 population, respectively. A male predominance was found in CD patients (male to female ratio was 2 ∶ 0). In contrast, no obvious gender predominance was found in UC patients (male to female ratio was 1 ∶ 1.1). CD patients were diagnosed at an average age of 39.5 years. The main disease phenotypes of UC were distal colitis with a 24% of proctitis and 56% of left-sided colitis. The mean diagnostic age of UC patients was 48.9 years. CONCLUSIONS: This is the first report on the incidence of IBD in the Northern Chinese population. A lower incidence of IBD, similar male predominance for CD, similar disease phenotype of UC, and lower disease activity was observed in Daqing compared to that in Southern China.

Treat ankylosing spondylitis with methazolamide.

BACKGROUND: Increased bone resorption and new bone information are two characteristics of ankylosing spondylitis (AS). Much evidence has shown that carbonic anhydrase inhibitors can restrain bone resorption. We had detected increased expression of carbonic anhydrase I (CA1) in synovium of patients with AS. This study aimed to evaluate the effectiveness and safety of methazolamide, an anti-carbonic anhydrase drug, for treating patients with AS. METHODS: Two patients, called as S and L, were diagnosed with active AS based on BASDAI and BASFI assessments, radiographic data and other clinical indices. They took methazolamide tablets at a dose of 25 mg twice every day. RESULTS: Patient S's BASDAI score fell from 5.4 to 4.4, while patient L's BASDAI fell from 2.4 to 2. Patient S's BASFI score change from 2.7 to 2.9, while patient L's BASFI score fell from 1.2 to 0.2. The ESR values of patient S were considerably reduced, while the ESR value of patient L remained unchanged and in the normal range. The calcium concentration of patient S decreased from 3.05 mmol/L to 2.39 mmol/L. The CT evidence indicates that the articular surfaces of the erosive sacroiliac joints became clearer and the area of the calcium deposits began decreased. No significant systemic side effects were observed in either patient. CONCLUSIONS: The above results indicate that methazolamide was effective for active AS. Methazolamide may improve AS symptoms by inhibiting carbonic anhydrase activity during the processes of bone reporption and new bone formation.

The expression of PADI4 in synovium of rheumatoid arthritis.

PADI4 that catalyzes the conversion of peptidylarginine to citrulline is associated with rheumatoid arthritis in some populations. The current study investigated the expressions of PADI4 in synovial fluid of RA (n = 73), osteoarthritis (OA, n = 96) and ankylosing spondylitis (AS, n = 32) using ELISA and western blotting following immuno-precipitation (n = 6 for each diseases). The study also compared the mRNA level of PADI4 in the synovial membrane of RA with the levels in the samples of OA and AS (n = 6 for each diseases) using real time PCR. ELISA detected a higher level of PADI4 in SF of RA than in samples of OA and AS (P = 0.0001). The level of PADI4 was significantly correlated with the level of rheumatic factor (P = 0.015), but not with anti cyclic citrullinated peptide antibody (anti-CCP) in the RA fluids. Western blotting confirmed the expression of PADI4 in SF of RA. Quantitative PCR measured higher transcription of PADI4 in the synovial membrane of RA than in the samples of OA and AS. The results confirmed increased expression of PADI4 in synovium of RA.

Detection of HPV types and neutralizing antibodies in Gansu province, China.

A total of 82 samples from patients with cervical cancer (Group 1) and 50 samples from patients with other genital diseases (Group 2) were collected in Gansu, China. All 132 samples were tested for HPV DNA with a typing kit that can detect 21 types of HPV, and also tested for neutralizing antibodies against HPV-16, -18, -58, -45, -6, and -11 using pseudovirus-based neutralization assays. The results revealed that 28% (23/82) of sera in Group 1 were positive for type-specific neutralizing antibodies with a titer range of 160-640, of which 23.2% (19/82), 2.4% (2/82), 2.4% (2/82), 1.2% (1/82), and 1.2% (1/82) were against HPV-16, -58, -6, -18, and -45, respectively. Only one serum (2%) in Group 2 was positive for neutralizing antibodies, which were against HPV-6 with a titer of 2,560. Overall, 85.4% (70/82) of samples in Group 1 were HPV DNA-positive, compared with 28% (14/50) of samples in Group 2. The seven most common types detected in Group 1 were HPV-16 (80%), HPV-52 (7.1%), HPV-66 and HPV-11 (5.7% each), and HPV-58, HPV-18, and HPV-33 (4.3% each), while the four most common types in Group 2 were HPV-16 (12%), HPV-52 and HPV-11 (6% each), and HPV-68 (4%). The concordance between HPV DNA and corresponding neutralizing antibodies was 32.9% (27/82) with a significant difference (P < 0.005). More specifically, the concordance was 42.7% (35/82) for HPV-16 in Group 1. The full-length sequences of six HPV types (HPV-16, -58, -33, -59, -11, and -68) were determined and showed 99% identities with their reported genomes.