[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 median age of onset was 12 years old (range 10-18 yearsold). 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.

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.

[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.

[Comparison of the efficacy of different surgical strategies in the treatment of patients with initially resectable gastric cancer liver metastases].

Objective: To examine the impact of varied surgical treatment strategies on the prognosis of patients with initial resectable gastric cancer liver metastases (IR-GCLM). Methods: This is a retrospective cohort study. Employing a retrospective cohort design, the study selected clinicopathological data from the national multi-center retrospective cohort study database, focusing on 282 patients with IR-GCLM who underwent surgical intervention between January 2010 and December 2019. There were 231 males and 51 males, aging (M(IQR)) 61 (14) years (range: 27 to 80 years). These patients were stratified into radical and palliative treatment groups based on treatment decisions. Survival curves were generated using the Kaplan-Meier method and distinctions in survival rates were assessed using the Log-rank test. The Cox risk regression model evaluated HR for various factors, controlling for confounders through multivariate analysis to comprehensively evaluate the influence of surgery on the prognosis of IR-GCLM patients. A restricted cubic spline Cox proportional hazard model assessed and delineated intricate associations between measured variables and prognosis. At the same time, the X-tile served as an auxiliary tool to identify critical thresholds in the survival analysis for IR-GCLM patients. Subgroup analysis was then conducted to identify potential beneficiary populations in different surgical treatments. Results: (1) The radical group comprised 118 patients, all undergoing R0 resection or local physical therapy of primary and metastatic lesions. The palliative group comprised 164 patients, with 52 cases undergoing palliative resections for gastric primary tumors and liver metastases, 56 cases undergoing radical resections for gastric primary tumors only, 45 cases undergoing palliative resections for gastric primary tumors, and 11 cases receiving palliative treatments for liver metastases. A statistically significant distinction was observed between the groups regarding the site and the number of liver metastases (both P<0.05). (2) The median overall survival (OS) of the 282 patients was 22.7 months (95%CI: 17.8 to 27.6 months), with 1-year and 3-year OS rates were 65.4% and 35.6%, respectively. The 1-year OS rates for patients in the radical surgical group and palliative surgical group were 68.3% and 63.1%, while the corresponding 3-year OS rates were 42.2% and 29.9%, respectively. A comparison of OS between the two groups showed no statistically significant difference (P=0.254). Further analysis indicated that patients undergoing palliative gastric cancer resection alone had a significantly worse prognosis compared to other surgical options (HR=1.98, 95%CI: 1.21 to 3.24, P=0.006). (3) The size of the primary gastric tumor significantly influenced the patients' prognosis (HR=2.01, 95%CI: 1.45 to 2.79, P<0.01), with HR showing a progressively increasing trend as tumor size increased. (4) Subgroup analysis indicates that radical treatment may be more effective compared to palliative treatment in the following specific cases: well/moderately differentiated tumors (HR=2.84, 95%CI 1.49 to 5.41, P=0.001), and patients with liver metastases located in the left lobe of the liver (HR=2.06, 95%CI 1.19 to 3.57, P=0.010). Conclusions: In patients with IR-GCLM, radical surgery did not produce a significant improvement in the overall prognosis compared to palliative surgery. However, within specific patient subgroups (well/moderately differentiated tumors, and patients with liver metastases located in the left lobe of the liver), radical treatment can significantly improve prognosis compared to palliative approaches.

Effects of robot-assisted gait training on motor performance of lower limb in poststroke survivors: a systematic review with meta-analysis.

OBJECTIVE: This study aimed to investigate the effects of robot-assisted gait training (RAGT) on improving walking ability, and to determine the optimal dosage of task-specific training based on RAGT for stroke patients. MATERIALS AND METHODS: Two investigators independently searched electronic databases, including PubMed, Embase, Cochrane Library, and Physiotherapy Evidence Database (PEDro) from inception to 31 January 2020. The study design was a systematic review with meta-analysis of randomized controlled trials (RCTs), comparing the intervention of RAGT plus conventional therapy to conventional therapy alone. RCTs mainly focus on lower limb motor function as the primary outcomes, while the secondary outcomes involve gait speed, walking distance, cadence, balance, and activities of daily living (ADL). Pooled effect estimates were calculated by comparing the change from baseline to the end of the study in each group. RESULTS: Twenty-eight RCTs were included. The pooled analysis showed that RAGT had a significantly short-term effect on improving lower limb function [standardized mean difference (SMD) 0.32, 95% CI 0.10 to 0.55]. Additionally, there were significant improvements in gait speed (MD 0.10, 95% CI 0.06 to 0.14) and ADL (SMD 0.17, 95% CI 0.02 to 0.32). Subgroup analyses indicated that RAGT lasting for 30-60 minutes per day over 4 weeks yielded a moderate effect size (SMD 0.53, 95% CI 0.16 to 0.90). Additionally, RAGT significantly promoted lower limb function recovery in the early stage after a stroke (SMD 0.33, 95% CI 0.07 to 0.58) or in non-ambulatory patients (SMD 0.35, 95% CI 0.10 to 0.59). CONCLUSIONS: RAGT demonstrated significant positive effects on lower limb function post-stroke. Our results provide additional evidence to support that RAGT is a potentially appropriate intervention to promote lower limb recovery in individuals who have had a stroke.

Remifentanil for tracheal intubation without neuromuscular blocking drugs in adult patients: a systematic review and meta-analysis.

There is increasing interest in the use of short-acting opioids such as remifentanil to facilitate tracheal intubation. The aim of this systematic review was to determine the efficacy and safety of remifentanil for tracheal intubation compared with neuromuscular blocking drugs in adult patients. We conducted a systematic search for randomised controlled trials evaluating remifentanil for tracheal intubation. Primary outcomes included tracheal intubation conditions and adverse events. Twenty-one studies evaluating 1945 participants were included in the analysis. Use of remifentanil (1.5-4.0 µg.kg-1 ) showed no evidence of a difference in tracheal intubation success rate compared with neuromuscular blocking drugs (risk ratio (95%CI) 0.97 (0.94-1.01); six studies; 1232 participants; I2 28%; p = 0.16; moderate-certainty evidence). Compared with neuromuscular blocking drugs, the use of remifentanil (2.0-4.0 µg.kg-1 ) makes little to no difference in terms of producing excellent tracheal intubation conditions (risk ratio (95%CI) 1.16 (0.72-1.87); two studies; 121 participants; I2 31%, p = 0.54; moderate-certainty of evidence). There was no evidence of an effect between remifentanil (2.0-4.0 µg.kg-1 ) and neuromuscular blocking drugs for bradycardia (risk ratio (95%CI) 0.44 (0.01-13.90); two studies; 997 participants; I2 81%; p = 0.64) and hypotension (risk ratio (95%CI) 1.05 (0.44-2.49); three studies; 1071 participants; I2 92%; p = 0.92). However, the evidence for these two outcomes was judged to be of very low-certainty. We conclude that remifentanil may be used as an alternative drug for tracheal intubation in cases where neuromuscular blocking drugs are best avoided, but more studies are required to evaluate the haemodynamic adverse events of remifentanil at different doses.

[Quality control of gastric resection range in laparoscopic locally advanced gastric cancer].

After nearly 30 years of exploration and practice, minimally invasive surgical techniques represented by laparoscopic technology have become an important means for the surgical treatment of gastric cancer. In China, laparoscopic radical resection for locally advanced gastric cancer has been extensively carried out. However, there are still controversies regarding the gastric resection range and methods for advanced gastric cancer. By reviewing relevant domestic and foreign guideline documents and combining team practice experience, this article elaborates on the key points of quality control of laparoscopic gastric resection range for locally advanced gastric cancer from aspects such as tumor localization and gastric resection range for upper, middle and lower gastric tumors. It aims to provide reference for carrying out and promoting laparoscopic radical gastrectomy more safely.

[Prioritizing the integrated management of cancer pain to comprehensively enhance the diagnosis and treatment proficiency in cancer pain].

As one of the most common complications of cancer or its treatment, cancer-related pain can negatively affect the functional status and quality of life of patients. Pain management for cancer patients in China started later than that in developed countries. After 30 years of efforts by health authorities and medical professionals, cancer pain management in China has made great progress. However, with the accelerated aging of the Chinese population, the increasing incidence of cancer, the prolonged survival of cancer patients, and the strengthening of people's expectations for high-quality life, there is still a gap between the development level of cancer pain management in China and the actual health needs of cancer patients. This article provides a comprehensive overview of the current state and future challenges facing the integrated management of cancer pain in China. Simultaneously, it offers a prospective outlook on future developments, thereby furnishing vital information for professionals engaged in the field of cancer pain management.

[Hepatitis B virus infection status and clinical characteristics in patients with rheumatoid arthritis].

Objective: To investigate the epidemiology of hepatitis B virus (HBV) infection in patients with rheumatoid arthritis (RA) in China and its association with RA disease characteristics. Methods: A cross-sectional study. A retrospective study was conducted on RA patients recruited from January 2001 to February 2023 in the Department of Rheumatology and Immunology, Sun Yat-Sen Memorial Hospital. Demographic and clinical data were collected including age, gender, disease duration, active smoking, RA disease activity, physical function, radiographic assessment, serological markers of HBV infection and liver function indicators. According to the status of HBV infection, RA patients were grouped as chronic HBV infection, resolved HBV infection and no HBV infection groups. The distribution of each group and the clinical characteristics of RA patients were analyzed. Results: Among 1 941 RA patients, 1 461 (75.3%) completed HBV screening, including 335 males (22.9%) and 1 126 females (77.1%), with a mean age of (55.4±13.1) years. The prevalence of chronic HBV infection was 10.1%(148/1 461), which was significantly higher in male patients than in females [14.6%(49/335) vs 8.8%(99/1 126), P<0.001], especially among those males born from 1970 to 1979[20.0%(7/35) vs 8.5%(17/201), P=0.037] and 1980-1989 [31.8%(7/22) vs 10.5%(14/133), P=0.007]. Among 148 RA patients with chronic HBV infection, there were 5 cases (3.4%) of chronic hepatitis B, 2 cases (1.4%) of HBV-associated cirrhosis and 1 case (0.7%) of hepatocellular carcinoma. The prevalence of resolved HBV infection was 57.6%(841/1 461). There were 472(32.3%) patients with no HBV infection and 267(56.6%) of them showed negative anti-HBs. Among all RA patients, 15 (1.0%) patients had abnormal liver function, of which 7 cases were drug-induced liver injury, 5 cases were chronic hepatitis B, 2 cases were non-alcoholic fatty liver disease, and 1 case was primary biliary cholangitis. Conclusion: Chronic HBV infection remains a common complication in RA patients in China, the infection rate is 10.1%, and the screening and management of HBV infection should be strengthened in clinical practice.

New insights on the association of weight loss with the reduction in carotid intima-media thickness among patients with obesity: an updated systematic review and meta-analysis.

OBJECTIVES: Carotid intima-media thickness (CIMT) is a noninvasive marker of atherosclerosis, a typical pathologic process underlying cardiovascular diseases (CVDs). It is essential to explore the relationships between weight loss and the reduction of CIMT. STUDY DESIGN: This was an updated systematic review and meta-analysis. METHODS: A systematic literature search was conducted to collect relevant clinical trials. The pooled results of meta-analyses were assessed by weighted mean difference (WMD) and the corresponding 95 % confidence interval (95% CI). RESULTS: Thirty-three articles involving 2273 participants were collected in this meta-analysis. Among all participants with obesity, the pooled mean of weight loss was -23.26 kg (95% CI: -27.71 to -18.81), and the pooled mean change of CIMT was -0.06 mm (95% CI: -0.08 to -0.04). Compared with Non-surgical interventions, Surgical ones could lead to much higher weight loss (Pbetween groups < 0.001). A more significant CIMT reduction was identified among Surgical intervention patients than among Non-surgical intervention participants (Pbetween groups < 0.001). CONCLUSIONS: Effective interventions, especially Surgical interventions, could reduce the weight of patients with obesity, followed by the decline of CIMT, which might further disturb atherosclerosis progression and lower CVD risk.

Phase II clinical trial of neoadjuvant anti-PD-1 (toripalimab) combined with axitinib in resectable mucosal melanoma.

BACKGROUND: The outcome of patients with resectable mucosal melanoma is poor. Toripalimab combined with axitinib has shown impressive results in metastatic mucosal melanoma with an objective response rate of 48.3% and a median progression-free survival of 7.5 months in a phase Ib trial. It was hypothesized that this combination administered in the neoadjuvant setting might induce a pathologic response in resectable mucosal melanoma, so we conducted this trial. PATIENTS AND METHODS: This single-arm phase II trial enrolled patients with resectable mucosal melanoma. Patients received toripalimab 3 mg/kg once every 2 weeks (Q2W) plus axitinib 5 mg two times a day (b.i.d.) for 8 weeks as neoadjuvant therapy, then surgery and adjuvant toripalimab 3 mg/kg Q2W starting 2 ± 1weeks after surgery for 44 weeks. The primary endpoint was the pathologic response rate according to the International Neoadjuvant Melanoma Consortium recommendations. RESULTS: Between August 2019 and October 2021, 29 patients were enrolled and received treatment, of whom 24 underwent resection. The median follow-up time was 34.2 months (95% confidence interval 20.4-48.0 months). The pathologic response rate was 33.3% (8/24; 4 pathological complete responses and 4 pathological partial responses). The median event-free survival for all patients was 11.1 months (95% confidence interval 5.3-16.9 months). The median overall survival was not reached. Neoadjuvant therapy was tolerable with 8 (27.5%) grade 3-4 treatment-related adverse events and no treatment-related deaths. Tissue samples of 17 patients at baseline and after surgery were collected (5 responders and 12 nonresponders). Multiplex immunohistochemistry demonstrated a significant increase in CD3+ (P = 0.0032) and CD3+CD8+ (P = 0.0038) tumor-infiltrating lymphocytes after neoadjuvant therapy, particularly in pathological responders. CONCLUSIONS: Neoadjuvant toripalimab combined with axitinib in resectable mucosal melanoma demonstrated a promising pathologic response rate with significantly increased infiltrating CD3+ and CD3+CD8+ T cells after therapy.

[Clinical characteristics and prognosis of 28 cases of infant acute lymphoblastic leukemia].

Objective: To analyze the clinical characteristics and prognosis of patients with infant acute lymphoblastic leukemia (IALL). Methods: A retrospective cohort study.Clinical data, treatment and prognosis of 28 cases of IALL who have been treated at Beijing Children's Hospital, Capital Medical University and Baoding Children's Hospital from October 2013 to May 2023 were analyzed retrospectively. Based on the results of fluorescence in situ hybridization (FISH), all patients were divided into KMT2A gene rearrangement (KMT2A-R) positive group and KMT2A-R negative group. The prognosis of two groups were compared. Kaplan-Meier method and Log-Rank test were used to analyze the survival of the patients. Results: Among 28 cases of IALL, there were 10 males and 18 females, with the onset age of 10.9 (9.4,11.8) months. In terms of immune classification, 25 cases were B-ALL (89%), while the remaining 3 cases were T-ALL (11%). Most infant B-ALL showed pro-B lymphocyte phenotype (16/25,64%). A total of 22 cases (79%) obtained chromosome karyotype results, of which 7 were normal karyotypes, no complex karyotypes and 15 were abnormal karyotypes were found. Among abnormal karyotypes, there were 4 cases of t (9; 11), 2 cases of t (4; 11), 2 cases of t (11; 19), 1 case of t (1; 11) and 6 cases of other abnormal karyotypes. A total of 19 cases (68%) were positive for KMT2A-R detected by FISH. The KMT2A fusion gene was detected by real-time PCR in 16 cases (57%). A total of 24 patients completed standardized induction chemotherapy and were able to undergo efficacy evaluation, 23 cases (96%) achieved complete remission through induction chemotherapy, 4 cases (17%) died of relapse. The 5-year event free survival rate (EFS) was (46±13)%, and the 5-year overall survival rate (OS) was (73±10)%.The survival time was 31.3 (3.3, 62.5) months. There was no significant statistical difference in 5-year EFS ((46±14)% vs. (61±18)%) and 5-year OS ((64±13)% vs. (86±13)%) between the KMT2A-R positive group (15 cases) and the KMT2A-R negative group (9 cases) (χ2=1.88, 1.47, P=0.170, 0.224). Conclusions: Most IALL patients were accompanied by KMT2A-R. They had poor tolerance to traditional chemotherapy, the relapse rate during treatment was high and the prognosis was poor.

Use of TSAR, Thermal Shift Analysis in R, to identify Folic Acid as a Molecule that Interacts with HIV-1 Capsid.

Thermal shift assay (TSA) is a versatile biophysical technique for studying protein interactions. Here, we report a free, open-source software tool TSAR (Thermal Shift Analysis in R) to expedite and automate the analysis of thermal shift data derived either from individual experiments or large screens of chemical libraries. The TSAR package incorporates multiple, dynamic workflows to facilitate the analysis of TSA data and returns publication-ready graphics or processed results. Further, the package includes a graphic user interface (GUI) that enables easy use by non-programmers, aiming to simplify TSA analysis while diversifying visualization. To exemplify the utility of TSAR we screened a chemical library of vitamins to identify molecules that interact with the capsid protein (CA) of human immunodeficiency virus type 1 (HIV-1). Our data show that hexameric CA interacts with folic acid in vitro.

Estrogen as a guardian of auditory health: Tsp1-CD47 axis regulation and noise-induced hearing loss.

OBJECTIVES: This study aimed to analyze the role of estrogen in noise-induced hearing loss (NIHL) and uncover underlying mechanisms. METHODS: An ovariectomized Sprague-Dawley rat model (OVX) was constructed to investigate the hearing threshold and auditory latency before and after noise exposure using the auditory brainstem response (ABR) test. The morphological changes were assessed using immunofluorescence, scanning electron microscopy and transmission electron microscopy. Proteomics and bioinformatics were used to analyze the mechanism. The findings were further verified through western blot and Luminex liquid suspension chip technology. RESULTS: After noise exposure, OVX rats exhibited substantially elevated hearing thresholds. A conspicuous delay in ABR wave I latency was observed, alongside increased loss of outer hair cells, severe collapse of stereocilia and pronounced deformation of the epidermal plate. Accordingly, OVX rats with estrogen supplementation exhibited tolerance to NIHL. Additionally, a remarkable upregulation of the thrombospondin 1 (Tsp1)-CD47 axis in OVX rats was discovered and verified. CONCLUSIONS: OVX rats were more susceptible to NIHL, and the protective effect of estrogen was achieved through regulation of the Tsp1-CD47 axis. This study presents a novel mechanism through which estrogen regulates NIHL and offers a potential intervention strategy for the clinical treatment of NIHL.