Background::Whether functional gastrointestinal disorders (FGIDs) are associated with the long-term risk of chronic kidney disease (CKD) remains unclear. We aimed to investigate the prospective association of FGIDs with CKD and examine whether mental health mediated the association.Methods::About 416,258 participants without a prior CKD diagnosis enrolled in the UK Biobank between 2006 and 2010 were included. Participants with FGIDs (including irritable bowel syndrome [IBS], dyspepsia, and other functional intestinal disorders [FIDs; mainly composed of constipation]) were the exposure group, and non-FGID participants were the non-exposure group. The primary outcome was incident CKD, ascertained from hospital admission and death registry records. A Cox proportional hazard regression model was used to investigate the association between FGIDs and CKD, and the mediation analysis was performed to investigate the mediation proportions of mental health.Results::At baseline, 33,156 (8.0%) participants were diagnosed with FGIDs, including 21,060 (5.1%), 8262 (2.0%), and 6437 (1.6%) cases of IBS, dyspepsia, and other FIDs, respectively. During a mean follow-up period of 12.1 years, 11,001 (2.6%) participants developed CKD. FGIDs were significantly associated with a higher risk of incident CKD compared to the absence of FGIDs (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.28–1.44). Similar results were observed for IBS (HR, 1.27; 95% CI, 1.17–1.38), dyspepsia (HR, 1.30; 95% CI, 1.17–1.44), and other FIDs (HR, 1.60; 95% CI, 1.43–1.79). Mediation analyses suggested that the mental health score significantly mediated 9.05% of the association of FGIDs with incident CKD and 5.63–13.97% of the associations of FGID subtypes with CKD. Specifically, the positive associations of FGIDs and FGID subtypes with CKD were more pronounced in participants with a high genetic risk of CKD.Conclusion::Participants with FGIDs had a higher risk of incident CKD, which was partly explained by mental health scores and was more pronounced in those with high genetic susceptibility to CKD.

We aimed to investigate the relationship of dietary zinc intake with new-onset hypertension among Chinese adults. A total of 12,177 participants who were free of hypertension at baseline from the China Health and Nutrition Survey were included. Dietary intake was assessed by three consecutive 24-h dietary recalls combined with a household food inventory. Participants with systolic blood pressure ≽ 140 mmHg or diastolic blood pressure ≽ 90 mmHg or diagnosed by a physician or under antihypertensive treatment during the follow-up were defined as having new-onset hypertension. During a median follow-up duration of 6.1 years, 4269 participants developed new-onset hypertension. Overall, the association between dietary zinc intake and new-onset hypertension followed a J-shape (P for non-linearity < 0.001). The risk of new-onset hypertension significantly decreased with the increment of dietary zinc intake (per mg/day: hazard ratio (HR) 0.93; 95% confidence interval (CI) 0.88-0.98) in participants with zinc intake < 10.9 mg/day, and increased with the increment of zinc intake (per mg/day: HR 1.14; 95% CI 1.11-1.16) in participants with zinc intake ≽ 10.9 mg/day. In conclusion, there was a J-shaped association between dietary zinc intake and new-onset hypertension in general Chinese adults, with an inflection point at about 10.9 mg/day.
Adult ; Humans ; Cohort Studies ; Zinc ; Diet ; Hypertension/epidemiology* ; Eating ; China/epidemiology*

Objective:To explore the efficacy and safety of anti-B cell maturation antigen (BCMA) chimeric antigen receptor T-cell (CAR-T) for the retreatment of relapsed and refractory multiple myeloma (RRMM).Methods:The clinical data of 10 RRMM patients who received anti-BCMA CAR-T therapy for the second time (CART2) in Henan Province Hospital of Traditional Chinese Medicine due to failure or recurrence after their first anti-BCMA CAR-T (CART1) therapy from January 2017 to June 2021 were retrospectively analyzed. The treatment, efficacy and adverse events of patients receiving CART2 therapy were summarized; and the objective response rate (ORR), median duration of response (DOR) and incidence of adverse reactions were compared between CART1 and CART2.Results:Among 10 patients, 8 were males and 2 were females, with a median age of 57 years (41-70 years). Patients' 3-month ORR after CART1 therapy was 90%, and the median DOR was 16.0 months (3.0-27.0 months). CART2 used human-derived anti-BCMA CAR-T to treat 6 cases and mouse-derived anti-BCMA CAR-T to treat 4 cases. The 3-month ORR of patients receiving CART2 therapy was 40%, and the median DOR was 8.5 months (3.0-11.0 months). Among 9 patients who received mouse-derived anti-BCMA CAR-T in CART1 therapy, 4 of them received the same product again and none of them showed curative effect. Among 6 patients retreated with human-derived anti-BCMA CAR-T, 4 patients (66.7%) of them achieved partial remission (PR) or better. During CART1 therapy, 10 patients developed grade 1-2 cytokine release syndrome (CRS), and 7 patients developed different degrees of decrease in leukocyte, neutrophil absolute count (ANC) and platelet. Among patients who achieved effective outcomes after receiving CART2 therapy, 4 patients of them developed grade 1-2 CRS, and different degrees of decrease in white blood cell, ANC and thrombocytopenia. Immune effector cell-related neurotoxicity syndrome was not observed.Conclusions:Anti-BCMA CAR-T is effective and safe to retreat RRMM. The ORR and DOR of patients receiving CART2 therapy are lower than those of patients receiving CART1 therapy. CRS and cytopenia are common adverse reactions.

Objective:To analyze the risk factors for keratoconus through a systematic review of secondary literature.Methods:Analytical studies from Cochrane Library, PubMed, Embase database, CNKI, Wanfang Periodicals Database, VIP Chinese Science and Technology Journal Database published from January 2000 to May 2021 were searched, most of which were about the keratoconus occurrence and progression and the valid data were extracted.The case-control and the cohort studies were evaluated according to the Newcastle-Ottawa Scale.The categorical variables for combined effect size were odds ratio( OR) and 95% confidence interval ( CI). The heterogeneity was evaluated via the Q test and I2 test.The fixed-effect model was adopted when P>0.1 or I2≤50%, while the random effect model was adopted when I2>50%.The sources of heterogeneity in included evaluation indexes were analyzed through subgroup and sensitivity analysis.The publication bias was evaluated by Egger tests, Harbord tests, Peters tests and funnel plots. Results:A total of 21 papers with 30 124 keratoconus cases and 59 012 control cases enrolled, including 18 case-control studies and 3 cohort studies, whose data were from 10 countries, were included.The NOS scores of the studies were not less than 7 points.The Meta-analysis results indicated that family history ( OR: 8.68, 95% CI: 6.30-11.97), eye rubbing ( OR: 4.62, 95% CI: 3.75-5.70), allergy ( OR: 2.34, 95% CI: 1.73-3.16), obstructive sleep apnea ( OR: 1.53, 95% CI: 1.12-2.10) and Down syndrome ( OR: 7.09, 95% CI: 4.19-11.99) were the risk factors for keratoconus, and mitral valve prolapse ( P>0.05) was not a risk factor for keratoconus, and diabetes ( OR: 0.63, 95% CI: 0.50-0.79) was a protective factor for keratoconus.The subgroup analysis results indicated that the heterogeneity in allergy was partially due to the specific disease classification, and the heterogeneity in diabetes and obstructive sleep apnea was totally owing to the source of the cases.The sensitivity study showed that the results were robust after changing the analysis model.There was no bias in the included studies. Conclusions:Family history, eye rubbing, allergy, obstructive sleep apnea and Down syndrome are risk factors for keratoconus, and diabetes is a protective factor for keratoconus.

OBJECTIVE: To summarize the clinical phenotype and genotypic characteristics of 3 patients with KBG syndrome and epileptic seizure. METHODS: Clinical data of the patients were collected. Family-trio whole exon sequencing (WES) was carried out. Candidate variants were verified by Sanger sequencing. RESULTS: Patients 1 and 2 were boys, and patient 3 was an adult woman. All patients had epileptic seizures and mental deficiency. Their facial features included triangular face, low hair line, hypertelorism, large forward leaning auricles, broad nasal bridge, upturned nostrils, long philtrum, arched upper lip, and macrodontia. The two boys also had bilateral Simian creases. WES revealed that the three patients all harbored heterozygous de novo frameshift variants in exon 9 of the ANKRD11 gene including c.2948delG (p.Ser983Metfs*335), c.5397_c.5398insC (p.Glu1800Argfs*150) and c.1180_c.1184delAATAA (p.Asn394Hisfs*42). So far 291 patients with ANKRD11 gene variants or 16q24.3 microdeletions were reported, with over 75% being de novo mutations. CONCLUSION Above findings have enriched the spectrum of ANKRD11 gene mutations underlying KBG syndrome. WES is helpful for the early diagnosis of KBG, and provided reference for genetic counseling of this disease.
Abnormalities, Multiple/genetics* ; Bone Diseases, Developmental/genetics* ; Epilepsy/genetics* ; Facies ; Humans ; Intellectual Disability/genetics* ; Phenotype ; Repressor Proteins/genetics* ; Seizures/genetics* ; Tooth Abnormalities/genetics*

Objective:To evaluate the effect of esmolol on the expression of phosphorylated extracellular signal-regulated kinase 1/2 (p-ERK1/2) during cerebral ischemia-reperfusion (I/R) in rats.Methods:Forty-eight clean-grade healthy adult male Sprague-Dawley rats, were allocated into 3 groups ( n=16 each) using a random number table method: sham operation group (Sham group), cerebral I/R group (I/R group) and esmolol group (E group). Cerebral I/R was induced by 3 cycles of 20-min occlusion of bilateral common carotid arteries followed by 10-min reperfusion in anesthetized rats.Esmolol 200 g·kg -1·min -1 was intravenously infused for 1 h starting from 30 min before ischemia, and the model was established after 30-min infusion in E group.The equal volume of normal saline was given at 30 min before ischemia in I/R group.Bilateral common carotid arteries were only isolated but not clamped, and the equal volume of normal saline was given after isolating bilateral common carotid arteries in Sham group.Learning and memory function was tested by Morris water maze test before ischemia and at 1, 3 and 7 days of reperfusion.Rats were sacrificed after Morris water maze test, and the hippocampus was excised for determination of wet to dry weight ratio (W/D ratio), permeability of blood-brain barrier (using Evans blue method), expression of ERK1/2 mRNA (by real-time polymerase chain reaction ), and expression of p-ERK1/2 (by Western blot). Results:Compared with Sham group, the escape latency and swimming distance were significantly prolonged at 1, 3 and 7 days of reperfusion, the W/D ratio and EB content in brain tissues were increased, and the expression of ERK1/2 mRNA and p-ERK1/2 was up-regulated in I/R and E groups ( P<0.05). Compared with I/R group, the escape latency and swimming distance were significantly shortened at 1, 3 and 7 days of reperfusion, the W/D ratio and EB content in brain tissues were decreased, and the expression of ERK1/2 mRNA and p-ERK1/2 was down-regulated in E group ( P<0.05). Conclusion:The mechanism by which esmolol alleviates cerebral I/R injury and improves cognitive function is related to inhibiting the up-regulated expression of ERK1/2 in rats.

Objective To evaluate the effects of dexmedetomidine on perioperative inflammatory response and cellular immune function in patients undergoing posterior lumbar interbody fusion. Methods Eighty American Society of Anesthesiologists physical statusⅠorⅡpatients of either sex, aged 40-60 yr, scheduled for elective posterior lumbar interbody fusion, were divided into dexmedetomidine group(group Dex)and control group(group C)using a random number table with 40 patients in each group. In group D, dexmedetomidine at a loading dose of 0.5 μg∕kg was intravenously infused starting from 10 min before anesthesia induction, followed by continuous infusion of 0.5 μg·kg-1·h-1until 15 min before the end of operation. The equal volume of normal saline was given at the same time points in group C. Before induc?tion, at 30 min after beginning of operation and at 1 h and 1, 3 and 5 days after the end of operation (T1?6), arterial blood samples were collected for determination of the plasma CD42a+∕CD14+ratio, HLA?DR+∕CD14+ratio, concentration of C?reactive protein(CRP)and white blood cell(WBC)count. Re?sults Compared with the baseline at T1, the plasma CD42a+∕CD14+ratio was significantly increased at T2?6, the HLA?DR+∕CD14+ratio was decreased at T3?6, the plasma CRP concentrations were increased at T4?6, and the WBC count was increased at T3?5in group C, and the plasma CD42a+∕CD14+ratio was signifi?cantly increased at T6, the HLA?DR+∕CD14+ratio was decreased at T3?5, and the plasma CRP concentra?tions were increased at T2?5in group D(P<0.05). Compared with group C, the plasma CD42a+∕CD14+ra?tio was significantly decreased at T2?4, the HLA?DR+∕CD14+ratio was increased at T4?5, and the plasma CRP concentrations and WBC count were decreased at T2?5in group D(P<0.05). Conclusion Dexme?detomidine can decrease perioperative inflammatory response and improve cellular immune function in the patients undergoing posterior lumbar interbody fusion.

Objective To study the treatment outcomes using transcatheter arterial chemoemboliza tion (TACE) followed by hepatic resection (HR) in patients with BCLC stage B hepatocellular carcinoma (HCC).Methods The clinical data of 46 patients with intermediate stage HCC in the Third Affiliated Hospital of Sun Yat-sen University from Jan.2004 to Jul.2013 were analyzed retrospectively.The baseline characteristics of these 46 patients were recorded.The levels of serum aspartate transaminase (AST),ala nine aminotransferase (ALT),total bilirubin (TBil),and albumin (Alb),and the prothrombin time (PT) at 1 week and 1 month after HR were compared with those at the baseline.The overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan-Meier method.The effect on PFS by the changes in the alpha-fetal protein level and the modified Response Evaluation Criteria In Solid Tumors (mRECIST) after TACE were analyzed using the log-rank test.Results The number of cycles of TACE given before HR was 1.7 ± 1.1.The mean time interval between TACE and HR was 3.0 ± 3.2 months.The levels of serum AST,ALT,TBil,Alb and PT at 1 week after HR were significantly different from the baseline levels (P ＜ 0.05),while those levels at 1 months after HR showed no significant difference from the baseline levels (P＞0.05).The mean OS was 72.1 ±6.0 (95％ CI 60.36 ～83.86) months.The median PFS was 46.0 (95％ CI:42.60～49.40) months.Using the log-rank test,the decrease in AFP (P ＜ 0.001) and the improvement in mRECIST (CR + PR) (P ＜ 0.001) after TACE were significantly associated with better PFS.Conclusions HR after TACE was safe for patients with BCLC stage B HCC and might prolong the PFS and OS.Decreases in AFP level and improvement in mRECIST (CR + PR) after TACE were factors they could be used to predict the survival outcomes of HR.

Objective To investigate the experiences in observation and nursing care during perioperative period of cavernous sinus dural arteriovenous fistulas(DAVFS) embolized with coil and ONYX glue. Methods In the course of the operation,17 cases of cavernous sinus DAVFS were treated with psychological nursing, perioperation disease observation and complications preventive nursing. Results All patients with DAVFS could be embolized successfully using interventional techniques and without complications. Conclusions The therapeutic method of embolizing cavernous sinus DAVFS with coil and ONYX glue is secure and cost-effective.The key steps of the patients convalescence lie in comprehensive perioperative nursing,observing symptoms carefully and preventing complications.

Objective To evaluate the association between LDL-C and ischemic stroke in patients with nonvalvular atrial fibrillation (AF).Method A total of 2 470 patients with nonvalvular AF were included in the present study.The clinical data and laboratory examination results of the patients in the hospital were collected.The subjects were either divided into the ischemic stroke history (n =560),and non-ischemic stroke history groups (n =1 910),or divided into the low-middle risk (n =566) and high risk groups (n =1 904) based on CHA2 DS2-VASc score.Results There were significant differences in the proportion of Han,the ratio of gender,age,hemoglobin,hematocrit,ALT,serum uric acid,HDL-C and LDL-C between the patients with ischemic stroke history and without (all P ＜ 0.05).Similarly,there were significant differences in the proportion of Han,the ratio of gender,age,white blood cell count,hemoglobin,hematocrit,platelet count,ALT,albumin,TG and LDL-C between subjects in the low-middle risk group and those in the high risk group (all P ＜ 0.05).A logistical regression analysis showed that LDL-C was an independent risk factor for both the ischemic stroke history (OR 2.089,95％ CI 1.860-2.347,P ＜0.05),and future ischemic stroke risk (OR 1.270,95％ CI 1.079-1.494,P ＜ 0.05) in patients with nonvalvular AF.Conclusion LDL-C is associated with ischemic stroke in patients with nonvalvular AF,and it is also an independent risk factor for future ischemic stroke in these patients.