[Analysis on incidence trend of meningococcal meningitis and major pathogenic serogroups of Neisseria meningitidis in China, 1990-2023].

Objective: To understand the incidence trend of meningococcal meningitis from 1990 to 2023 and major pathogenic serogroups of Neisseria (N.) meningitidis from 2006 to 2023 in China and the time trend of the incidence of meningococcal meningitis caused by main pathogenic serogroups, and provide reference for the prevention and control of meningococcal meningitis. Methods: The study used the data from "National Epidemic Data Compile" from 1990 to 2003 and the data from China Notifiable Infectious Disease Reporting System from 2004 to 2023 to analyze the incidence trend of meningococcal meningitis in China from 1990 to 2023 by Joinpoint regression method. Based on the data of the national meningococcal meningitis surveillance information reporting and management system from 2006 to 2023, the incidence of meningococcal meningitis caused by different serogroups of N. meningitidis was described and analyzed, and the trend χ2 test was performed to analyze the change of the incidence of meningococcal meningitis caused by N. meningitidis A, B, and C. Results: The overall incidence of meningococcal meningitis in China showed a downward trend from 1990 to 2023 [average annual percent change (AAPC)=-14.80%, P<0.001], with the most obvious decline from 2005 to 2012 [annual percent change (APC)=-31.01%, P<0.001]. The incidence of meningococcal meningitis decreased in both men and women (AAPC=-14.69% and -15.05%, both P<0.001). A total of 1 178 serogroup specific cases of meningococcal meningitis were reported in China from 2006 to 2023, the proportion of serogroup C was highest (32.5%), followed by unclassified (22.3%), B (20.1%), A (18.4%), W (4.5%), Y (2.0%) and X (0.2%). The results of trend χ2 test indicated that the incidence of meningococcal meningitis caused by N. meningitidis A and C showed downward trends (both P<0.001) and the incidence of meningococcal meningitis caused by N. meningitidis B showed an upward trend in general population and young children (0-4 years old group) from 2006 to 2023 (both P<0.05). Conclusion: The incidence of meningococcal meningitis showed a downward trend in China from 1990 to 2023, but it is still necessary to pay more attention to the incidence of meningococcal meningitis caused by N. meningitidis B in age group aged 0-4 years and by multi serogroups at same time in general population.

[Discussion on aesthetic and chemical characteristics of drinking water quality in emergencies].

The Standards for drinking water quality(GB 5749-2022), which has taken effect on April 1, 2023, stipulates that limit values of aesthetic and chemical characteristics of drinking water can be temporarily adjusted in emergencies. However, the national standard does not clearly specify the adjusted period and limit values. This study is based on the principle that the human body will not cause acute toxic damage during short-term exposure, considering the acceptability such as chromaticity, smell, and taste in drinking water, referring to the drinking water quality standards of different countries and regions including the World Health Organization, the United States, the European Union, Japan, Australia, etc. We discussed the limited values during emergencies for 21 aesthetic and chemical characteristics from GB 5749-2022 to guaranine the drinking water safety and human health in emergencies.

[Prenatal screening and prenatal diagnosis clinical laboratory diagnostic pathway].

Congenital defects and genetic diseases in the fetus are the focus of prenatal screening and prenatal diagnosis. Obstetrics and gynecology, pediatrics, medical imaging (ultrasound and magnetic resonance imaging), clinical laboratory, pathology, and other disciplines are mostly involved in this multidisciplinary work on maternal and infant health care, which aims to prevent birth defects in strict accordance with laws, regulations, and pertinent industry standards, such as the Notice of the National Health Commission on Issuing the Basic Standards for Prenatal Screening Technical Medical Institutions and the Basic Standards for Prenatal Diagnosis Technical Medical Institutions (Guowei Maternal and Child Letter [2019] No. 297). To further support the implementation of prenatal screening and diagnosis work and streamline workflow, this study has compiled the timing, inspection, and testing procedures of various projects in each link from the standpoint of the disease clinical laboratory diagnostic pathway. This approach improves communication amongst various disciplines in prenatal screening and diagnosis work and offers clinical service quality, and it also helps improve the standard of the birth population and prevent and controll severe birth defects.

[Sanguinarine alleviates ulcerative colitis in mice by regulating the Nrf2/NF-κB pathway].

OBJECTIVE: To investigate the mechanism of sanguinarine (SA) for alleviating ulcerative colitis (UC) induced by dextran sodium sulfate (DSS) in mice. METHODS: Male C57BL/6 mouse models of 3.5% DSS-induced UC were randomized for treatment with 1, 5 and 10 mg/kg SA by gavage, 400 mg/kg sulfasalazine by gavage, or 10 mg/kg SA combined with intraperitoneal injection of 30 mg/kg ML385 (a Nrf2 inhibitor). The changes in intestinal inflammation was assessed by monitoring weight changes, disease activity index (DAI) score, colon length measurement, and HE staining. After the treatments, the colon tissues were collected for detection of malondialdehyde (MDA) content using colorimetry, mRNA expressions of inflammatory factors using RT-qPCR, and the expressions of Nrf2, HO-1, Keap-1, p-p65, p65, occludin, and ZO-1 proteins were detected using Western blotting. RESULTS: SA treatment obviously alleviated weight loss, colon length shortening and DAI score increase and ameliorated structural destruction of the colon glands and colonic crypts in mice with DSSinduced UC. SA intervention significantly decreased the levels of TNF-α, IL-1ß and IL-6 mRNA and lowered ROS and MDA levels in the colon tissue of UC mice. The mouse models receiving SA treatment showed significantly increased expressions of Nrf2, HO-1, occludin and ZO-1 and lowered expressions of Keap-1 and P-P65 in the colon tissue without significant changes of p65 expression, and these changes were SA dose-dependent. Treatment with ML385 obviously attenuated the effect of highdose SA for improving UC in the mouse models. CONCLUSION: SA can improve UC-like enteritis in mice possibly by activating the Nrf2 pathway and inhibiting the NF-κB pathway in the colon tissue.

[Sanguinarine induces ferroptosis of colorectal cancer cells by upregulating STUB1 and downregulating GPX4].

OBJECTIVE: To investigate the effect of sanguinarine (SAN) on proliferation and ferroptosis of colorectal cancer cells. METHODS: SW620 and HCT-116 cells treated with different concentrations of SAN were examined for cell viability changes using CCK8 assay to determine the IC50 of SAN in the two cells. The inhibitory effects of SAN on proliferation, invasion and migration of the cells were evaluated using colony-forming assay and Transwell assays. ROS production in the treated cells was analyzed with flow cytometry, and lipid peroxide production was assessed by detecting malondialdehyde (MDA) level. Glutathione (GSH) levels in the cells were detected, and Western blotting was used to detect the expressions of ferroptosis-related proteins STUB1 and GPX4. RESULTS: SAN significantly inhibited the proliferation, invasion and migration of SW620 and HCT-116 cells. SAN treatment significantly promoted ROS production, increased intracellular MDA level, and lowered GSH level in the two cells (P<0.05). Western blotting showed that SAN significantly upregulated the expression of STUB1 and down-regulated the expression of its downstream protein GPX4 (P<0.05). CONCLUSION: SAN induces ferroptosis in colorectal cancer cells by regulating STUB1/GPX4, which may serve as a new therapeutic target for colorectal cancer.

[Clinical characteristics of perimenopausal female patients with rheumatoid arthritis].

Objective: To explore the menopause status of patients with rheumatoid arthritis (RA) and clinical characteristics of perimenopausal RA patients. Methods: A cross-sectional study. Female RA patients were recruited retrospectively in the Sun Yat-Sen Memorial Hospital from August 2015 to August 2023. Clinical data were collected, including onset age, disease duration, RA disease activity indicators, functional assessment, and radiographic scores. According to menopausal status, the patients were categorized as pre-menopausal, perimenopausal and post-menopausal groups to explore their menopausal and clinical characteristics. Results: A total of 1 151 female patients were enrolled, with a mean age of (50.2±13.0) years. At enrollment, there were 470 (40.8%), 140 (12.2%) and 541 (47.0%) patients in pre-menopause, perimenopause and post-menopause status, respectively. The mean age of menopause was (49.0±4.2) years. Compared with pre-menopausal group, perimenopausal RA patients had higher disease activity indicators [clinical disease activity index (CDAI) 17 (6, 26) vs 10 (3, 19) ], higher levels of inflammation [erythrocyte sedimentation rate (ESR) 35 (21, 65) vs 26 (14, 44) mm/1h, C-reactive protein (CRP) 6.2 (3.2, 16.8) vs 3.3 (3.2, 13.6) mg/L], and a higher proportion of functional limitation [25.0%(35/140) vs 10.4%(49/470)] (all P<0.016 7); while there was no significant differences in disease activity[M(Q1, Q3)] [CDAI 17 (6, 26) vs 14 (6, 25)], levels of inflammation [ESR 35(21, 65) vs 42 (23, 72) mm/1h, CRP 6.2 (3.2, 16.8) vs 6.2 (3.3, 23.9) mg/L] and functional limitation [25.0%(35/140) vs 28.8%(156/541)] when compared with those in post-menopausal group (all P>0.016 7). In RA patients during the perimenopausal period, 49 cases (35.0%) developed RA during this period. Compared with patients with RA onset during reproductive age, patients with RA onset during the perimenopausal period had higher numbers of 28-joint tender joints [7 (2, 10) vs 4 (0, 8)], higher CDAI [20 (12, 29) vs 14 (4, 24)], and higher ESR [45 (25, 72) vs 32 (18, 56) mm/1h] (all P<0.05). Conclusion: Perimenopausal patients with RA have severe disease activity and functional limitation.

[Efficacy of venetoclax-based induction regimen in newly diagnosed pediatric acute myeloid leukemia].

Objective: To explore the efficacy of venetoclax-based induction regimen for children with newly diagnosed acute myeloid leukemia (AML). Methods: Children with newly diagnosed AML in Beijing Children's Hospital Affiliated to Capital Medical University and Baoding Hospital Affliliated to Capital Medical University from November 2019 and December 2023 were prospectively included. The patients were divided into DAH group (daunorubicin, cytarabine and homoharringtonine) and VAH group (venetoclax, cytarabine and homoharringtonine) according to induction regimen. The clinical data of the children were collected, the clinical characteristics and induced remission rate between the two groups were compared, and multivariate logistic regression was used to analyze the related factors affecting the induced remission rate. Results: A total of 135 patients were enrolled, including 96 cases in the DAH group (54 males and 42 females), aged [M (Q1, Q3)] 6.4 (3.9, 11.6) years and 39 cases in the VAH group (26 males and 13 females), aged 8.0 (6.2, 13.2) years. Among patients initially diagnosed with low-medium risk AML, the morphologic complete remission rates were 94.7% (18/19) in the VAH group and 84.4% (38/45) in the DAH group, respectively, and the negativity conversion rates of minirnal residual disease (MRD) were 57.9% (11/19) and 46.7% (21/45), respectively, with no statistically difference (all P>0.05). Among patients initially diagnoised with high-risk AML, the morphologic complete remission rates in the VAH group was higher than that in the DAH group [95.0% (19/20) vs 70.6% (36/51), P=0.027], and negativity conversion rates of MRD were 45.0% (9/20) and 33.3% (17/51), respectively, with no statistically difference (P=0.359). The induction regimen (venetoclax, cytarabine and homoharringtonin) was beneficial to morphological remission (OR=0.126, 95%CI: 0.025-0.629). FLT3 mutation was not conducive to morphological remission (OR=5.832, 95%CI: 1.778-19.124) and negative MRD (OR=4.166, 95%CI: 1.396-12.433). Conclusion: Venetoclax-based induction regimen is more effective than traditional chemotherapy regimen for newly diagnosed pediatric AML.

MiR-539-3p Alleviates Apoptosis and Extracellular Matrix Degradation in Chondrocytes of Childhood-Onset Osteoarthritis by Targeting RUNX2.

Recent research has identified that miR-539-3p impedes chondrogenic differentiation, yet its specific role and underlying mechanisms in childhood-onset osteoarthritis (OA) remain unclear. This study found that miR-539-3p levels were considerably lower in cartilage samples derived from childhood-onset OA patients compared to the control group. Enhancing miR-539-3p expression or suppressing RUNX2 expression notably reduced apoptosis, inflammation, and extracellular matrix (ECM) degradation in OA chondrocytes. In contrast, reducing miR-539-3p or increasing RUNX2 had the opposite effects. RUNX2 was confirmed as a direct target of miR-539-3p. Further experiments demonstrated that miR-539-3p targeting RUNX2 effectively lessened apoptosis, inflammation, and ECM degradation in OA chondrocytes, accompanied by changes in key molecular markers like reduced caspase-3 and matrix etallopeptidase 13 (MMP-13) levels, and increased B-cell lymphoma 2 (Bcl-2) and collagen type X alpha 1 chain (COL2A1). This study underscores the pivotal role of miR-539-3p in alleviating inflammation and ECM degradation in childhood-onset OA through targeting RUNX2, offering new insights for potential therapeutic strategies against this disease.

[Analysis of loss to follow-up status and influencing factors of children born to pregnant women with HIV infection in China in 2019].

Objective: To understand the loss to follow-up of children born to pregnant women with HIV infection (HIV-exposed children) and analyze its influencing factors in China in 2019. Methods: The data were collected from the follow-up records of pregnant women with HIV infection and their children reported by the national "Management Information System for the Prevention of HIV, syphilis and Hepatitis B Mother-to-Child Transmission" in 2019. HIV-exposed children were defined as those who were not followed up after birth or who were not followed up at 18 months of age and who were not followed up at 21 months of age. The univariate and multivariate influencing factors of loss to follow-up of children born to HIV-infected pregnant women were analyzed by χ2 test and logistic regression model. SPSS 25.0 software was used for statistical analysis. Results: The number of HIV-infected pregnant women was 5 039, the number of live-born children was 5 035, the number of loss to follow-up children within 18 months of age was 283, and the loss to follow-up rate children was 5.62%(283/5 035). The results of multivariate logistic regression analysis showed that the rate of loss to follow-up of exposed children born to pregnant women who worked as farmers (animal husbandry and fishery) (aOR=0.34, 95%CI: 0.22-0.53), unmarried (aOR=0.47, 95%CI: 0.24-0.93), first marriage (aOR=0.38, 95%CI: 0.22-0.67), remarriage (aOR=0.36, 95%CI: 0.20-0.67) and cohabiting (aOR=0.47, 95%CI: 0.23-0.97), and knew they had HIV infection before this pregnancy (aOR=0.53, 95%CI: 0.40-0.70) was lower. Han nationality (aOR=1.52, 95%CI: 1.09-2.13), primary school (aOR=2.06, 95%CI: 1.10-3.89) and junior middle school (aOR=1.81, 95%CI: 1.03-3.17) educational level, non-use of antiviral drugs (aOR=6.21, 95%CI: 4.32-8.93) and delivery in township (street) level midwifery institutions (aOR=5.72, 95%CI: 1.61-20.27) had higher rates of loss to follow-up among infants born to HIV-infected pregnant women. Conclusions: HIV-exposed children still have a specific rate of loss to follow-up in China in 2019. In order to further reduce the rate of loss to follow-up, it is of great significance to improve the detection rate of HIV before pregnancy and the rate of antiviral drugs used in pregnant women with HIV infection, which is of great significance for the effective implementation of comprehensive intervention measures of prevention of mother-to-child transmission of HIV.

Fabrication and evaluation of porous coatings doped with bioactive elements on titanium surfaces.

OBJECTIVE: Although pure titanium (PT) and its alloys exhibit excellent mechanical properties, they lack biological activity as implants. The purpose of this study was to improve the biological activity of titanium implants through surface modification. MATERIALS AND METHODS: Titanium was processed into titanium discs, where the titanium discs served as anodes and stainless steel served as cathodes, and a copper- and cobalt-doped porous coating [pure titanium model (PTM)] was prepared on the surface of titanium via plasma electrolytic oxidation. The surface characteristics of the coating were evaluated using field emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), X-ray photoelectron spectroscopy (XPS), atomic force microscopy (AFM), and profilometry. The corrosion resistance of PTM was evaluated with an electrochemical workstation. The biocompatibility and bioactivity of coated bone marrow mesenchymal stem cells (BMSCs) were evaluated through in vitro cell experiments. RESULTS: A copper- and cobalt-doped porous coating was successfully prepared on the surface of titanium, and the doping of copper and cobalt did not change the surface topography of the coating. The porous coating increased the surface roughness of titanium and improved its resistance to corrosion. In addition, the porous coating doped with copper and cobalt promoted the adhesion and spreading of BMSCs. CONCLUSIONS: A porous coating doped with copper and cobalt was prepared on the surface of titanium through plasma electrolytic oxidation. The coating not only improved the roughness and corrosion resistance of titanium but also exhibited good biological activity.

Low Temperature Dynamic Polaron Liquid in a Manganite Exhibiting Colossal Magnetoresistance.

Polarons-fermionic charge carriers bearing a strong companion lattice deformation-exhibit a natural tendency for self-localization due to the recursive interaction between electrons and the lattice. While polarons are ubiquitous in insulators, how they evolve in transitions to metallic and superconducting states in quantum materials remains an open question. Here, we use resonant inelastic x-ray scattering to track the electron-lattice coupling in the colossal magneto-resistive bi-layer manganite La_{1.2}Sr_{1.8}Mn_{2}O_{7} across its metal-to-insulator transition. The response in the insulating high-temperature state features harmonic emissions of a dispersionless oxygen phonon at small energy transfer. Upon cooling into the metallic state, we observe a drastic redistribution of spectral weight from the region of these harmonic emissions to a broad high energy continuum. In concert with theoretical calculations, we show that this evolution implies a shift in electron-lattice coupling from static to dynamic lattice distortions that leads to a distinct polaronic ground state in the low temperature metallic phase-a dynamic polaron liquid.

[Opportunities and challenges in accurate early diagnosis and treatment of lung cancer/pulmonary nodules].

Lung cancer remains the most prevalent and lethal malignancy in our country. Early diagnosis and treatment are crucial for improving patient prognosis in lung cancer/pulmonary nodules. Recent advancements in non-invasive/minimally invasive liquid biopsy, multi-omics, and artificial intelligence technologies have significantly enhanced the accuracy of early lung cancer/pulmonary nodule diagnosis. However, an early diagnostic method with both high sensitivity and specificity is yet to be established. Furthermore, addressing the methods and extent of early precision surgery, local precision therapy, perioperative combined treatment, and postoperative recurrence and metastasis monitoring are urgent challenges in the early management of lung cancer/pulmonary nodules. Integrating the advantages of various treatment strategies and formulating personalized and precise treatment plans is key to further improving patient survival. In the future, while exploring new therapeutic strategies, it is necessary to continuously search for biomarkers to identify the population that will benefit from the treatment effectively. Additionally, large-sample randomized controlled clinical studies should be conducted to investigate the benefits of long-term patient survival under a diverse range of treatment strategies.

[Impact of obesity on the incidence of postoperative pulmonary complications following laparoscopic colorectal surgery].

Objective: To evaluate the effects of obesity on the incidence of postoperative pulmonary complications (PPCs) following laparoscopic colorectal surgery. Methods: A total of 150 patients with pathological diagnosis of colorectal cancer who accepted laparoscopic colorectal excision from January to May 2023 were retrospectively recruited. All the patients scored 26 points or more in the Assess Respiratory Risk in Surgical Patients in Catalonia (ARISCAT) model, making them all in intermediate to high risks of PPCs. Patients were divided into obesity group and non-obesity group depending on whether they were obese or not. Propensity score matching (1∶1) was performed to achieve the balance of clinicopathological characteristics with the matching factors of age, sex, respiratory complications and ARISCAT score. A total of 96 patients were eventually enrolled, with 48 patients in obesity group and 48 patients in non-obesity group. Besides, the patients were divided into 25°-30° Trendelenburg subgroup and ±10°-15° Trendelenburg subgroup according to surgical sites for further analysis. The incidence of PPCs, the intraoperative airway pressure and blood biomarker expression of lung injury, including soluble receptor for advanced glycation end products (sRAGE) and angiopoietin-2 (ANG2) at postoperative day (POD) 1 and POD3 between the two groups were compared. The relationship between obesity and incidence of PPCs within 30 postoperative days were analyzed with unifactorial Cox proportional hazard model. Results: The obesity group was comprised of 35 males and 13 females with a median age of 60 (49, 69) years, and the non-obesity group was comprised of 35 males and 13 females with a median age of 60 (52, 67) years. The incidence of PPCs was 50.0% (24/48) in the obesity group, which was higher than 20.8% (10/48) in the non-obesity group and the incidence of grade Ⅰ PPCs and microatelectasis were 31.3% (15/48) and 33.3% (16/48), higher than the 12.5% (6/48) and 12.5% (6/48) of the non-obesity group (all P<0.05). The peak airway pressure (Ppeak) and plateau airway pressure (Pplat) of patients in obesity group were 34.0(31.5, 36.5) and 30.0(27.0, 32.0) cmH2O(1 cmH2O=0.098 kPa), which were significantly higher than the 26.0 (24.0, 29.5) and 22.0 (21.0, 26.5) cmH2O of the non-obesity group (all P<0.001). The ANG2 level of the obesity group at POD3 was 11.9 (8.4, 16.5) µg/L, which was higher than 9.2 (6.0, 12.3) µg/L of the non-obesity group (P=0.045). In 25°-30°Trendelenburg subgroup, the incidence of PPCs in obese patients were significantly higher than that of non-obese patients [41.4% (12/29) vs 11.4% (4/35), P=0.005]. In ±10°-15°Trendelenburg subgroup, no significant difference was found in PPCs incidence between obese and non-obese patients [63.2% (12/19) vs 46.2% (6/13), P=0.215]. The unifactorial Cox proportional hazard model analysis showed that obesity was a risk factor of PPCs in 30 postoperative days (HR=3.015, 95%CI: 1.438-6.321, P=0.001). Conclusion: In patients undergoing laparoscopic colorectal surgery with intermediate to high risk of PPCs, obesity raises intraoperative airway pressure and aggravates intraoperative lung endothelial injury. Obesity is a risk factor of PPCs in 30 postoperative days.

[Clinical features and follow-up study on 55 patients with adolescence-onset methylmalonic acidemia].

Objective: To investigate the clinical features and outcomes of adolescence-onset methylmalonic acidemia (MMA) and explore preventive strategies. Methods: This was a retrospective case analysis of the phenotypes, genotypes and prognoses of adolescence-onset MMA patients. There were 55 patients diagnosed in Peking University First Hospital from January 2002 to June 2023, the data of symptoms, signs, laboratory results, gene variations, and outcomes was collected. The follow-ups were done through WeChat, telephone, or clinic visits every 3 to 6 months. Results: Among the 55 patients, 31 were males and 24 were females. The age of onset was 12 years old (range 10-18 years old). They visited clinics at Tanner stages 2 to 5 with typical secondary sexual characteristics. Nine cases (16%) were trigged by infection and 5 cases (9%) were triggered by insidious exercises. The period from onset to diagnosis was between 2 months and 6 years. Forty-five cases (82%) had neuropsychiatric symptoms as the main symptoms, followed by cardiovascular symptoms in 12 cases (22%), kidney damage in 7 cases (13%), and eye disease in 12 cases (22%). Fifty-four cases (98%) had the biochemical characteristics of methylmalonic acidemia combined with homocysteinemia, and 1 case (2%) had the isolated methylmalonic acidemia. Genetic diagnosis was obtained in 54 cases, with 20 variants identified in MMACHC gene and 2 in MMUT gene. In 53 children with MMACHC gene mutation,1 case had dual gene variants of PRDX1 and MMACHC, with 105 alleles. The top 5 frequent variants in MMACHC were c.482G>A in 39 alleles (37%), c.609G>A in 17 alleles (16%), c.658_660delAAG in 11 alleles (10%), c.80A>G in 10 alleles (10%), c.567dupT and c.394C>T both are 4 alleles (4%). All patients recovered using cobalamin, L-carnitine, betaine, and symptomatic therapy, and 54 patients (98%) returned to school or work. Conclusions: Patients with adolescence-onset MMA may triggered by fatigue or infection. The diagnosis is often delayed due to non-specific symptoms. Metabolic and genetic tests are crucial for a definite diagnosis. Treatment with cobalamin, L-carnitine, and betaine can effectively reverse the prognosis of MMA in adolescence-onset patients.

[The effect of deep neuromuscular block combined with low pneumoperitoneum pressure on postoperative pain in patients undergoing laparoscopic radical colorectal surgery].

Objective: To investigate the effect of deep neuromuscular blockade (DNMB) combined with low pneumoperitoneum pressure anesthesia strategy on postoperative pain in patients undergoing laparoscopic colorectal surgery. Methods: This study was a randomized controlled trial. One hundred and twenty patients who underwent laparoscopic colorectal surgery at Cancer Hospital of Chinese Academy of Medical Sciences from December 1, 2022 to May 31, 2023 were selected and randomly divided into two groups by random number table method. Moderate neuromuscular blockade [train of four stimulations count (TOFC)=1-2] was maintained in patients of the control group (group C, n=60) and pneumoperitoneum pressure level was set at 15 mmHg(1 mmHg=0.133 kPa). DNMB [post-tonic stimulation count (PTC)=1-2] was maintained in patients of the DNMB combined with low pneumoperitoneum pressuregroup (group D, n=60) and pneumoperitoneum pressure level was set at 10 mmHg. The primary measurement was incidence of moderate to severe pain at 1 h after surgery. The secondary measurements the included incidence of moderate to severe pain at 1, 2, 3, 5 d and 3 months after surgery, the incidence of rescue analgesic drug use, the doses of sufentanil in analgesic pumps, surgical rating scale (SRS) score, the incidence of postoperative residual neuromuscular block, postoperative recovery [evaluated with length of post anesthesia care unit (PACU) stay, time of first exhaust and defecation after surgery and length of hospital stay] and postoperative inflammation conditions [evaluated with serum concentration of interleukin (IL)-1ß and IL-6 at 1 d and 3 d after surgery]. Results: The incidence of moderate to severe pain in group D 1 h after surgery was 13.3% (8/60), lower than 30.0% (18/60) of group C (P<0.05). The incidence of rescue analgesia in group D at 1 h and 1 d after surgery were 13.3% (8/60) and 4.2% (5/120), respectively, lower than 30.0% (18/60) and 12.5% (15/120) of group C (both P<0.05). The IL-1ß level in group D was (4.1±1.8)ng/L at 1 d after surgery, which was lower than (4.9±2.6) ng/L of group C (P=0.048). The IL-6 level in group D was (2.0±0.7)ng/L at 3 d after surgery, which was lower than (2.4±1.1) ng/L of group C (P=0.018). There was no significant difference in the doses of sufentanil in analgesic pumps, intraoperative SRS score, incidence of neuromuscular block residue, time spent in PACU, time of first exhaust and defecation after surgery, incidence of nausea and vomiting, and length of hospitalization between the two groups (all P>0.05). Conclusion: DNMB combined with low pneumoperitoneum pressure anesthesia strategy alleviates the early-stage pain in patients after laparoscopic colorectal surgery.

[Relationship between gut microbiota and its metabolite dysregulation and postoperative cognitive dysfunction in elderly male C57BL/6J mice after laparotomy exploration].

Objective: To explore the relationship between gut microbiota and its metabolite dysregulation and postoperative cognitive dysfunction in elderly male C57BL/6J mice after laparotomy exploration. Methods: A total of 48 specific pathogen-free (SPF) male C57BL/6J mice, aged 16-17 months, were divided into two groups by random number table method: control group (n=24) and operation group (n=24). Mice in the operation group were induced with 1.4% isoflurane for 15 minutes, followed by a 10 minutes exploratory laparotomy anesthetized with 1.4% isoflurane and 100% oxygen, and anesthesia continued for 2 hours after surgery. Mice in control group were put in 100% oxygen for 2 hours. Feces and venous blood samples of both groups were collected 48 hours after surgery. Changes in the abundance and diversity of intestinal bacteria in the feces were detected by 16S rDNA gene sequencing. Functional changes of fecal metabolic profiles were detected by liquid chromatography tandem mass spectrometry (LC/MS) metabolomics and differential metabolite functions were analyzed. The serum level of interleukin (IL)-6, IL-1ß and tumor necrosis factor-α (TNF-α) were detected by Enzyme-linked immunosorbent assay (ELISA). The cognitive function of the mice was detected by Morris water maze test 3 days after operation. Results: The postoperative escape latency of mice in control group and operation group was (22.0±4.9) and (35.0±5.1) s, and the target quadrant residence time was (26.0±3.7) and (16.0±2.9) s, respectively. Compared with the control group, the postoperative escape latency of mice in the operation group was prolonged (P=0.035), and the residence time in the target quadrant was reduced (P=0.006). The difference of intestinal flora between the two groups was comparable. The expression levels of Escherichia coli, shigella and clostridium in the operation group were up-regulated, while the expression levels of rumen bacteria and butyricobacteria were down-regulated. Fecal metabolic profiles of mice in control group and operation group were obtained by LC/MS, and 14 and 21 different metabolites were screened in positive and negative ion modes, respectively. The different metabolites in positive ion mode were glutamic acid, 2-indoleic acid, kynuuric acid and glyceraldehyde. The negative ion pattern differential metabolites are methionine, aspartic acid, L-threonine, tyrosyl-threonine and 5-hydroxyindole-3-acetic acid. The identified differential metabolite pathways are mainly involved in amino acid, fatty acid and tryptophan metabolism and nucleotide synthesis. There were no significant differences in serum levels of IL-1ß, IL-6 and TNF-α between the two groups (all P>0.05). Conclusion: The dysregulated changes of gut microbiota and its metabolites are correlated with the occurrence of postoperative cognitive dysfunction in elderly male C57BL/6J mice. Anesthesia and surgery alter the structure of mice intestinal bacteria on the level of abundance, and change the metabolic balance and feces metabolomic phenotype.

[Analysis of 9 patients with adolescence-onset methylenetetrahydrofolate reductase deficiency].

Objective: To explore the diagnosis and treatment of adolescence-onset methylenetetrahydrofolate reductase (MTHFR) deficiency. Methods: This was a retrospective case study. Nine patients with adolescence-onset MTHFR deficiency were diagnosed at Peking University First Hospital from January 2016 to December 2022, and followed up for more than 1 year. Their general information, clinical manifestations, laboratory tests, cranial images, MTHFR gene variants, diagnosis, treatment, and outcome were analyzed retrospectively. Results: The 9 patients came from 8 families. They had symptoms at age of 8.0 years to 17.0 years and diagnosed at 9.0 years to 17.5 years. Eight were male and 1 was female. Two patients were brothers, the elder brother developed abnormal gait at 17.0 years; and the younger brother was then diagnosed at 15.0 years of age and treated at the asymptomatic stage, who was 18.0 years old with normal condition during this study. The main manifestations of the 8 symptomatic patients included progressive dyskinesia and spastic paralysis of the lower limbs, with or without intellectual decline, cognitive impairment and behavioral abnormalities. Totally, 15 variants of MTHFR gene were identified in the 9 patients, including 8 novel variants. Five patients had brain image abnormalities. Increased plasma total homocysteine level (65-221 µmol/L) was found in all patients, and decreased to 20-70 µmol/L after treatment with betaine and calcium folinate. Besides, the 8 symptomatic patients had their behavior and cognitive problems significantly improved, with a legacy of lower limb motor disorders. Conclusions: Late-onset MTHFR deficiency can occur in adolescence. The diagnosis is usually delayed because of non-specific clinical symptoms. The test of blood total homocysteine could be used as a selective screening test. Eight novel varients of MTHFR gene were identified. Timely treatment can improve clinical condition significantly, and pre-symptomatic treatment may prevent brain damage.