ObjectiveTo explore the correlation between general anesthesia and mild cognitive impairment in older adults so as to provide new ideas for early prevention and timely intervention of mild cognitive impairment（MCI）. MethodsBased on the baseline survey of the Hubei memory and aging cohort study（2018-2023）， the participants completed a thorough neuropsychological assessment and physical examination， and self-reported a history of general anesthesia and surgery. The association of general anesthesia and MCI in the elderly was analyzed using the logistic regression model. In addition， the stratification and interaction analysis of anesthesia history， anesthesia number and physical intellectual exercise were conducted separately. ResultsA total of 5 069 older adults aged 65 and above were included in this study， including 3 692 city dwellers and 1 377 rural people， among whom were 2 584 women （51%）. Out of the 1 472 participants with history of general anesthesia， 249 people （17.4%） had MCI. After controlling for confounding factors， there was a 39.6% increased risk of MCI in older adults who underwent general anesthesia ［OR=1.396，95%CI（1.169，1.668），P<0.001］， suggesting that general anesthesia may be an independent influence on MCI. For the older adults who had one general anesthesia ［OR=1.235，95%CI（1.001，1.523），P=0.049］， two general anesthesia ［OR=1.779，95%CI （1.292，2.450），P<0.001］， and three OR more general anesthesia ［OR=2.395，95%CI （1.589，3.610），P<0.001］， their risks of MCI were increased by 23.5%， 77.9%， and 139.5%， respectively. Compared with the older adults without a history of general anesthesia who did not exercise， the risk of developing MCI was significantly negatively correlated with the exercise group， cognitive exercise group， and combined exercise and cognitive exercise groups （all P<0.001）. The risk of developing MCI in the exercise group was 60.2% of that in the no exercise group ［OR = 0.602， 95% CI（0.456， 0.795）］， the risk in the cognitive exercise group was 42.4% of that in the no exercise group ［OR = 0.424， 95% CI（0.294， 0.613）］， and the risk in the combined exercise and cognitive exercise group was 27.0% of that in the no exercise group ［OR = 0.270， 95% CI （0.208， 0.353）］. In the older adults with a history of general anesthesia， compared with the no exercise group， the risk of developing MCI was significantly negatively correlated with the cognitive exercise group and the combined exercise and cognitive exercise group （all P < 0.05）. The risk of developing MCI in the cognitive exercise group was 47.7% of that in the no exercise group ［OR=0.477， 95% CI （0.256，0.892）］， the risk in the combined exercise and cognitive exercise group was 34.5% of that in the no exercise group ［OR=0.345， 95% CI （0.220， 0.540）］， while the risk in the exercise-only group did not show a significant difference. ConclusionThe risk of MCI increased significantly in older adults with a history of general anesthesia， and this risk increased with the times of anesthesia. Physical and mental exercise reduces the risk of MCI. it is recommended that older adults with a history of anesthesia incorporate physical and mental exercise into their daily lives to prevent mild cognitive impairment.

Trials within cohorts （TwiCs） are design methods derived from randomized controlled trials （RCTS）. They have been widely used in chronic disease areas such as tumors and cardiovascular diseases. The basis of the TwiCs design is a prospective cohort of specific diseases. When RCTS need to be implemented， some patients meeting the inclusion and exclusion criteria are randomly sampled from the cohort to receive "trial interventions"， while the remaining patients in the cohort who meet the inclusion and exclusion criteria continue to receive conventional treatment as control groups. By comparing the efficacy differences between the intervention measures of the trial group and the control group， the efficacy of intervention measures was evaluated. Within the cohort， the same process could be repeated to carry out multiple RCTS， so as to evaluate different intervention measures or compare the efficacy of different doses or timing of interventions. Compared with classical RCTS， TwiCs make it easier to recruit patients from the cohort and have higher external validity， providing a new research paradigm for improving the efficiency and applicability of RCTS in clinical practice. However， TwiCs may also face the challenge of poor compliance of patients in the cohort. Researchers need to take effective measures to control these patients in the design and operation of TwiCs. This article focused on the methodological key points during the implementation of TwiCs， including multi-stage informed consent （patients are informed of consent at three stages： entering the cohort， entering the trial group， and after the trial）， randomization procedures （only random sampling of patients from the cohort to receive "trial interventions"）， sample size calculation， and statistical analysis methods. The article also compared the differences between TwiCs and traditional RCTS and illustrated TwiCs research design and analysis with examples， so as to provide new research ideas and methods for clinical researchers.

The syndrome/pattern of defensive qi deficiency is a common basic syndrome of traditional Chinese medicine in clinical practice. However,there is a lack of standardized and operable diagnostic specifications in practical applications. Based on the previous literature,this study proposed the idea of starting from the elements of the syndrome,qualitative diagnostic criteria for the syndrome/pattern of defensive qi deficiency oriented to the entire region of the disease were constructed based on the two dimensions of " deficient defensive qi failing to consolidate the exterior" and " qi deficiency" and constructing a set of quantitative evaluation criteria as the supporting content for the diagnostic items. The core members of the research group attempted to formulate the draft standard,then reached a consensus through the Delphi method expert questionnaire consultation and the Nominal group technique,and finally evaluated the reliability and validity of the standard through clinical verification to provide ideas for the standardization and normalization of research on syndromes.

Objective:To investigate the effects of Wumei-Fangfeng drug on Treg/Th17 immune balance in allergic rhinitis(AR)mice via regulating MMP9 derived from mast cell exosomes.Methods:Potential targets of Wumei and Fangfeng were screened,and the intersection was taken from the targets and AR risk genes,subsequently GO analysis and protein-protein interaction analysis were performed to screen therapeutic targets.AR mice model were constructed,mast cells and exosomes were separate from femurs of mice.Wumei-Fangfeng drug and exosomes were used to treat mice.The behavioral scores of mice in each group were evaluated,mRNA expressions of Foxp3,RORγt were detected in nasal mucosa of mice.After knocking down of MMP9 in exosomes,the behavioral score,Foxp3 and RORγt mRNA expressions were observed in AR mice.Results:Bioinformatics results showed that Wumei-Fangfeng drug may act on AR by mast cell exosomes derived IL-1β and MMP9.Compared with normal mice,mRNA expression of Foxp3 in AR mice was decreased,while RORγt mRNA expression was increased,and MMP9 expression was increased(all P<0.05).Expression of Foxp3 mRNA was increased,and expressions of RORγt and MMP9 were decreased in AR mice treated with Wumei-Fangfeng drug,however,mast cell exosomes could further counteract the effects of Wumei-Fangfeng drug,and the effects of mast cell exosomes was weakened after MMP9 knockdown.Conclusion:Wumei-Fangfeng drug regulates the imbalance of Treg/Th17 in AR mice by inhibiting the exosomal MMP9 of bone marrow-derived mast cells.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Objective:To evaluate the effect of white noise on reducing procedural pain of premature infants.Methods:Randomized controlled trials (RCTs) on the effect of white noise on reducing procedural pain in premature infants were searched for in PubMed, Embase, Web of Science, Cochrane Library, CINAHL, CNKI, VIP, Wanfang database and China Biology Medicine disc. The retrieval time was from the establishment of the databases to January 12, 2023. After independent literature screening, data extraction and bias risk assessment by two researchers, Meta-analysis was conducted using RevMan 5.3 software.Results:A total of 8 RCTs with 689 premature infants were finally included. The Meta-analysis results showed that compared with conventional procedures, the use of white noise alone could reduce the pain score ( SMD=-2.29, 95% CI: -2.78--1.79, P<0.000 01) in preterm infants during and after procedures ( SMD=-2.55, 95% CI: -4.52--0.58, P=0.01) , reduce the heart rate ( MD=-7.38, 95% CI: -7.97--6.80, P<0.000 01) during and after procedures ( MD=-10.36, 95% CI: -13.58--7.14, P<0.000 01) , and increase blood oxygen saturation during operation ( MD=3.78, 95% CI: 3.54-4.02, P<0.000 01) and after operation ( MD=2.19, 95% CI: 1.84-2.54, P<0.000 01) . Conclusions:White noise can effectively relieve the procedural pain of premature infants and maintain the stability of physiological indicators. In the future, more high-quality and large sample randomized controlled trials should be conducted to verify the application effect of white noise in relieving pain of premature infants.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

ObjectiveTo analyze the current research status， research hotspots and main features of the literature related to metacognitive therapy and metacognitive training， and to explore the similarities and differences in research approaches of the two intervention techniques and their research directions in the future. MethodsCitespace-based visualization analysis was carried out on the relevant literature of "metacognitive therapy" and "metacognitive training" published in 2011-2020 in the Web of Science database. Results① Adrian Wells was the core author and the author of highly cited papers in the research field of metacognitive therapy. Steffen Moritz is the core author and the author of highly cited papers in the research field of metacognitive training. Aaron T Beck was a highly cited researcher in both fields. ② The analysis of research hotspots showed that the two intervention techniques were mainly reflected in the "maturity and expansion of techniques"， "the evaluation and testing of the effects of techniques" and "the comparative analysis of techniques". ③ The key literature characteristics analysis showed that both techniques involved the aspects of "effectiveness"， "validity"， "meta-analysis" and "variation". ConclusionBoth metacognitive therapy and metacognitive training studies in 2011-2020 highlight their respective core researchers， with similarities and distinctive features in terms of research hotspots and key literature features.

Objective:To survey the status quo of community practice bases for general practice residency training in Wuhan city.Methods:A questionnaire survey was conducted in 12 community general practice training bases affiliated to 11 tertiary hospitals in Wuhan city from March to June 2021. A total of 123 general practice residents and 41 instructors participated in the survey using the different questionnaires. The contents of questionnaires included the basic conditions of the training base and the current status of training at community base, as well as their satisfaction on the program and related problems. The statistical analysis was performed with SPSS software.Results:The conditions of the 12 primary practice bases met the requirements of the Standard for Standardized Training Bases for General Practice Residents (2019 Revision) in terms of size of community hospitals, qualification of the person in charge and faculty team. The survey showed that only 3 bases had psychiatric department; 7 bases had literature retrieval system; all 12 bases had a teaching secretary, but only 1 had a full-time teaching secretary; all 12 bases had established formal assistant relationship with higher-level hospitals, but the frequency of communication was low in some bases. Survey also showed that 68.3% (28/41) instructors were aged 40-50 years; 90.2% (37/41) of instructors participated in epidemic prevention and control; 36.6% (15/41) thought that instructing work was related to professional promotion; 87.8% (36/41) of instructors were generally satisfied with the work performance. Most of trainees (92.7%, 114/123) were satisfied with the training at the primary base, and there was a difference in satisfaction degree between trainees with different enrollment sources (χ 2=6.92, P=0.032). The proportion of trainees with confidence for future career increased from 39.8% (49/123) before training in community bases to 60.2% (74/123) after training. Conclusions:The survey shows that primary practice bases for general practice residency training in Wuhan have met the basic requirements; however, the evaluation and motivation of teachers need to be improved, the opportunities for trainees to practice in general outpatient clinics should be increased, research and teaching need to be emphasized, and the management of trainees needs to be strengthened.

Objective:To investigate the diagnostic value of independent and combined subtests of the psychometric hepatic encephalopathy score (PHES) in mild hepatic encephalopathy(MHE) of patients with liver cirrhosis, so as to optimize the PHES.Methods:This was a prospective, multicenter and real-world study which was sponsored by the National Clinical Research Center of Infectious Diseases and the Portal Hypertension Consortium. Twenty-six hospitals from 13 provinces, autonomous regions and municipalities countrywide participated in this study, induding Tianjin Third Central Hospital, the Fourth People′s Hospital of Qinghai Province, the Second Affiliated Hospital of Baotou Medical College, the Third People′s Hospital of Taiyuan, the Fifth Medical Center of PLA General Hospital and so on. From October 2021 to February 2022, outpatients and hospitalized patients with liver cirrhosis and no obvious hepatic encephalopathy were consecutively enrolled. All patients received 5 PHES subjects in the same order: number connection test(NCT)-A, NCT-B, digit symbol test(DST), line tracing test(LTT) and serial dotting test(SDT), and the scores were calculated. The total score of PHES <-4 was taken as the cut-off value for diagnosing MHE. Compare the differences in each subtest between MHE group and non-MHE group. Receiver operating characteristic curve(ROC) and area under the curve(AUC) was performed to assess the diagnostic value of independent and combined subtests in MHE. Mann-Whitney U test and DeLong test were used for statistical analysis. Results:A total of 581 patients with liver cirrhosis were enrolled, 457 were diagnosed as MHE, and the incidence of MHE was 78.7%. The results of NCT-A, NCT-B, SDT, LTT, DST of MHE group were 60.00 s(47.01 s, 88.00 s), 90.45 s(69.32 s, 125.35 s), 74.00 s(57.65 s, 96.60 s), 74.72(60.00, 98.61) and 27.00(20.00, 36.00), respectively. Compared those of non-MHE group(34.00 s(29.15 s, 44.48 s), 50.00 s(40.98 s, 60.77 s), 50.00 s(41.07 s, 63.03 s), 46.23(38.55, 59.42) and 42.00(34.00, 50.75)), the differences were statistically significant( Z=12.37, 12.98, 9.83, 11.56, 10.66; all P<0.001). The AUC(95% confidence interval(95% CI)) of subtests of PHES NCT-B, NCT-A, LTT, DST and SDT alone in MHE diagnosis were 0.880(0.849 to 0.910), 0.862(0.828 to 0.896), 0.838(0.799 to 0.877), 0.812(0.772 to 0.851) and 0.788(0.743 to 0.832), respectively. The combination of 2 PHES subtests significantly increased the diagnostic efficacy. Among them the diagnostic efficacy of the combination of NCT-B and LTT was the best, the AUC(95% CI) was 0.924(0.902 to 0.947), the specificity was 91.9% and the sensitivity was 79.2%, which was better than a single PHES subtest (NCT-A, NCT-B, SDT, LTT and DST) and the combination of NCT-A and DST(AUC was 0.879, 95% CI0.847 to 0.910) which was recommended by guidelines on the management of hepatic encephalopathy in cirrhosis, the differences were statistically significant ( Z=3.78, 3.83, 5.57, 5.51, 5.38, 2.93; all P<0.01). Furthermore, compared between the combination of NCT-B and LTT and the combination of 3 subests of PHES, only the diagnostic efficacy of combination of NCT-B, LTT and SDT (AUC was 0.936, 95% CI 0.916 to 0.956) was better than that of the combination of NCT-B and LTT, the difference was statistically significant( Z=2.32, P=0.020). Conclusion:Based on the diagnostic efficacy and clinical feasibility of PHES subtests and their combinations, the combination of NCT-B and LTT is recommended for the diagnosis of MHE.