Impact of preoperative balance training on postoperative functional recovery of patients after total knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: Previous studies' results on the impact of preoperative balance training on postoperative functional recovery after total knee arthroplasty (TKA) appeared to be ambiguous. Thus, this systematic review and meta-analysis were performed to investigate the effects of preoperative balance training on walking ability, balance-specific performance, and other functional indicators in elderly patients post-TKA. MATERIALS AND METHODS: Patient data were obtained from databases including PubMed, Physiotherapy Evidence Database (PEDro), CINAHL, SPORTDiscus, and Scopus. The inclusion criteria followed the Population-Intervention-Comparison-Outcome (PICO) principle. The assessment process involved meticulous screening, judicious data extraction, and rigorous evaluation of trial method quality, conducted by two independent researchers. Based on standardized mean differences and 95% confidence intervals, meta-analysis was performed employing a random-effects model or fixed-effects model. RESULTS: Preoperative balance training appears to be a potentially effective intervention for enhancing the knee osteoarthritis (KOA) patients' knee joint function (RR = 1.16, 95% CI: -2.58, 4.91), isometric knee flexion (RR = 2.49, 95% CI: -2.53, 7.50), knee extension (RR = -0.13, 95% CI: -0.45, 0.18), knee society score (KSS) (RR = 2.18, 95% CI: -1.51, 5.88), stair test (RR = -0.73, 95% CI: -1.84, 0.37), and timed up and go (RR = -1.18, 95% CI: -1.60, -0.76). CONCLUSIONS: Compared to interventions with less emphasis on balance training, rehabilitation programs highly emphasizing balance training significantly enhance the walking ability, balance specificity, and functional indicators of elderly patients post-TKA. This includes rehabilitation programs for senior TKA patients, with a focus on activities meant to improve the sensory system, balance in particular.

Modulation of the microRNA-6089/E2F transcription factor2 axis by querceting: implications for osteoblast viability, proliferation, migration, and osteogenic differentiation in fracture healing.

Quercetin is widely distributed in plants as a flavonol compound with multiple biological activities. It has been found that quercetin can regulate bone homeostasis through multiple pathways and targets. This study investigated the role and specific molecular mechanisms of quercetin in regulating osteoblast viability, proliferation, migration and osteogenic differentiation. A mouse model of traumatic fracture was established and then 100 mg/kg quercetin corn oil suspension was gavaged at the same time every day for 28 days. miR-6089 and E2F transcription factor 2 (E2F2) expression levels in mice were measured. Fracture healing in mice was observed. MC3T3-E1 cells were transfected with plasmids targeting miR-6089 and E2F2, and cell viability, proliferation, migration, apoptosis, and osteogenic differentiation were determined. The targeting relationship between miR-6089 and E2F2 was verified. In vivo experiments showed that quercetin significantly increased osteocalcin (OCN) expression (P<0.05) and promoted fracture healing in traumatic fracture (TF) mice. miR-6089 expression was down-regulated (P<0.05) and E2F2 expression was up-regulated (P<0.05) in TF mice. Quercetin promoted miR-6089 expression and inhibited E2F2 expression (both P<0.05). In vitro results showed that quercetin promoted miR-6089 expression and inhibited E2F2 expression in a dose-dependent manner (both P<0.05). Quercetin dose-dependently promoted MC3T3-E1 cell viability, proliferation, migration, and osteogenic differentiation, and inhibited MC3T3-E1 cell apoptosis (all P<0.05). Up-regulating miR-6089 further promoted MC3T3-E1 cell viability, proliferation, migration and osteogenic differentiation, and inhibited MC3T3-E1 cell apoptosis (all P<0.05). miR-6089 targeted and regulated E2F2 expression. Up-regulating E2F2 attenuated the promoting effect of up-regulated miR-6089 on MC3T3-E1 cell viability, proliferation, migration, osteogenic differentiation, and inhibition of apoptosis (all P<0.05). We conclude that quercetin enhances osteoblast viability, proliferation, migration, and osteogenic differentiation by modulating the miR-6089/E2F2 axis, thereby promoting fracture healing.

[A prospective cohort study of factors associated with longevity in older adults in 10 areas of China].

Objective: To evaluate the associations of sociodemographic characteristics and lifestyle factors with longevity status in older adults in China. Methods: After excluding those born after 31st December 1938, a total of 51 870 older adults from the China Kadoorie Biobank (CKB) were included. The attained age was defined according to the survival age or age on 31st December 2018. According to the attained age, the old persons were categorized into non-longevity (died before age 80 years) and longevity (attained age ≥80 years). The longevity group was further divided into two groups: longevity with death occurring before 2019, and longevity and survival to 2019. The information about socio-demographic characteristics and lifestyles was collected at the 2004-2008 baseline survey. Multinomial logistic regression models were used to analyze the associations between exposure factors and outcomes by taking the non-longevity group as the reference group. Results: A total of 51 870 older adults aged 65-79 years in the baseline survey were included for analysis. During a follow-up for (10.2±3.5) years, 38 841 participants were longevity, and 30 354 participants still survived at the end of 2018. Compared to men, rural populations, non-married individuals, those with an annual household income of less than 10 000 yuan, and those with education levels of primary school or below, the adjusted ORs(95%CI) for longevity and survival to 2019 in women, urban residents, married individuals, those with annual household incomes ≥20 000 yuan, and those with education levels of college or university were 1.68 (1.58-1.78), 1.69 (1.61-1.78), 1.15 (1.10-1.21), 1.44 (1.36-1.53), and 1.32 (1.19-1.48), respectively. The OR (95%CI) for longevity and survival to 2019 was 1.09 (1.08-1.10) for those with an increase of 4 MET-hour/day in total physical activity level. With those who never or almost never smoked, had no alcohol drinking every week, had normal weight (BMI: 18.5-23.9 kg/m2), and WC <85 cm (man)/<80 cm (woman) as the reference groups, the ORs(95%CI) of longevity and survival to 2019 were 0.64 (0.60-0.69) for those smoking ≥20 cigarettes per day, 1.29 (1.14-1.46) for those with alcohol drinking every week, 1.13 (1.01-1.26) for those with pure alcohol drinking <30 g per day, 0.56 (0.52-0.61) for those being underweight, 1.27 (1.19-1.36) for those being overweight, 1.23 (1.11-1.36) for those with obesity, and 0.86 (0.79-0.93) for those with central obesity. Further stratified analysis by WC was performed. In the older adults with WC <85 cm (man)/<80 cm (woman), the ORs (95%CI) of longevity and survival was 1.80 (1.69-1.92) for those with each 5 kg/m2 increase in BMI and 1.02 (0.96-1.08) for those with WC ≥85 cm (man)/≥80 cm (woman). There was a statistically significant difference in the association between BMI and longevity between the two WC groups (interaction test P<0.001). Conclusion: This study showed that women, the married, those with higher socioeconomic status and education level, and those with healthy lifestyles were more likely to achieve longevity.

Clinically Oriented CBCT Periapical Lesion Evaluation via 3D CNN Algorithm.

Apical periodontitis (AP) is one of the most prevalent disorders in dentistry. However, it can be underdiagnosed in asymptomatic patients. In addition, the perioperative evaluation of 3-dimensional (3D) lesion volume is of great clinical relevance, but the required slice-by-slice manual delineation method is time- and labor-intensive. Here, for quickly and accurately detecting and segmenting periapical lesions (PALs) associated with AP on cone beam computed tomography (CBCT) images, we proposed and geographically validated a novel 3D deep convolutional neural network algorithm, named PAL-Net. On the internal 5-fold cross-validation set, our PAL-Net achieved an area under the receiver operating characteristic curve (AUC) of 0.98. The algorithm also improved the diagnostic performance of dentists with varying levels of experience, as evidenced by their enhanced average AUC values (junior dentists: 0.89-0.94; senior dentists: 0.91-0.93), and significantly reduced the diagnostic time (junior dentists: 69.3 min faster; senior dentists: 32.4 min faster). Moreover, our PAL-Net achieved an average Dice similarity coefficient over 0.87 (0.85-0.88), which is superior or comparable to that of other existing state-of-the-art PAL segmentation algorithms. Furthermore, we validated the generalizability of the PAL-Net system using multiple external data sets from Central, East, and North China, showing that our PAL-Net has strong robustness. Our PAL-Net can help improve the diagnostic performance and speed of dentists working from CBCT images, provide clinically relevant volume information to dentists, and can potentially be applied in dental clinics, especially without expert-level dentists or radiologists.

[Analysis of 9 cases of pediatric-type follicular lymphoma].

Objective: To summarize the pathological diagnosis, clinical features, treatment methods and outcomes of pediatric-type follicular lymphoma (PTFL). Methods: Clinical data including the pathology, clinical features, treatment methods, and follow-up results of 9 PTFL patients admitted to Henan Cancer Hospital from February 2017 to February 2023 were analyzed retrospectively. Results: The age of onset in 9 children was 6 to 18 years, all the patients were males. The clinical manifestation was local painless lymph node enlargement in the head and neck, with a stage of Ⅰ-Ⅱ. The histomorphological characteristics of PTFL were similar to those of classic follicular lymphoma (FL). The germinal center of most follicles were enlarged, the mantle zone disappeared, centroblasts were easily visible, and the histological grade were mostly grade Ⅲ, which may be accompanied by the "starry sky" phenomenon. Monoclonal peaks can be seen in B cell clonal rearrangements (BCR). Immunohistochemistry (IHC) showed CD20 positive, CD10 positive, Bcl-6 positive, Bcl-2 negative, C-myc negative, and Ki-67 was 70%-95%. Fluorescence in situ hybridization (FISH) test was negative for t (14, 18), Bcl-2 translocation, and C-myc translocation. Six cases underwent surgical resection, and 3 cases underwent surgical resection combined with chemotherapy. Up to February 2023, with a follow-up time of 45 to 72 months, all children survived without any recurrence and were in a complete remission state. Conclusions: PTFL is mainly characterized by adolescent male onset, with early clinical manifestations and pathological manifestations of high-level histological status, high proliferation index, and lack of t (14; 18)/Bcl-2 translocation and Bcl-2 expression. It is mainly treated by localized surgical excision and has a good prognosis.

[A case report of ocular monkeypox].

A 35-year-old male patient arrived at the clinic, reporting a persistent issue of his right eye being difficult to open for the past three weeks. Alongside this, he had been experiencing a gradual development of lesions around the eye. Notably, about a month prior to the onset of these symptoms, the patient had engaged in unprotected intercourse with a male partner. The initial manifestation was a papule near the eye, which then rapidly progressed. Laboratory analysis of samples taken from the lesions confirmed the presence of monkeypox through polymerase chain reaction testing. Furthermore, this patient received positive diagnoses for both HIV and syphilis infections. Notably, his absolute CD4 count was measured at an extremely low level of 2 cells/µl.(This article was published ahead of print on the official website of Chinese Journal of Ophthalmology on September 18, 2023).

[Hemophagocytic syndrome secondary to COVID-19: a case report and literature review].

Objective: To improve the awareness of hemophagocytic syndrome(HPS) secondary to COVID-19 (COVID-sHPS). Methods: We reported an adult case of COVID-sHPS, including clinical presentation, laboratory examinations, histopathological findings, treatment strategy, and outcome. We also conducted literature research in PubMed database and Wanfang database using the keywords "COVID-19" and "hemophagocytic syndrome" and subsequently summarized relevant literature. Results: A 49-year-old man was admitted to our hospital after 4 weeks of recurrent fever. Prior to this hospitalization, he had received an empiric combination therapy with antibiotics and antiviral drugs against SARS-CoV-2. His vital signs were within the normal range and no abnormalities were found on physical examination on admission. After admission, throat swab nucleic acid tests were weakly positive for SARS-CoV-2, and negative for influenza and respiratory syncytial virus. Blood nucleic acid tests for cytomegalovirus and EB virus were negative, as was blood mNGS. Laboratory tests showed a series of abnormalities, including leukopenia, thrombocytopenia, low fibrinogen, elevated serum ferritin, elevated transaminase, decreased NK cell activity, and hemophagocytosis in bone marrow. According to the HPS-2004 diagnostic criteria, he was diagnosed with hemophagocytic syndrome, which was high likely to be caused by COVID-19 infection due to the lack of evidence of genetic risk factors and other clear triggers. He was initially treated with dexamethasone at a dose of 10 mg·m-2·d-1 and his condition improved rapidly. The literature search identified twenty-three articles on COVID-sHPS, 22 of which were in English. A total of 89 patients had COVID-sHPS and 55 (61.7%) were male. COVID-sHPS could occur at any age, but mainly in adults (86/89, 96%). Fever was reported in the literature with a clear description of the course of the disease. Most HPS occurred during the acute phase of COVID-19, but 3 patients developed HPS during the convalescent phase. Almost all reported cases presented with increased ferritin, elevated transaminases, elevated triglycerides, and cytopenia, mainly anemia and thrombocytopenia. In the retrieved literature, HS-score≥169 was frequently used to diagnose COVID-sHPS, and glucocorticoid in combination with immunoglobulin was the most common treatment strategy. COVID-sHPS had a poor prognosis and a high mortality rate (84.2%, 75/89). Conclusions: The prognosis of COVID-sHPS is poor, so clinicians should raise their awareness of the disease, identify high-risk suspected populations, and arrange reasonable relevant examinations for definite diagnosis and early initial treatment to improve their outcome.

[Association between cardiometabolic diseases and quality of life and the mediation effect of perceived stress].

Objective: To explore the association between cardiometabolic diseases (CMD) and quality of life, the association between CMD and perceived stress, and the mediation effect of perceived stress on the association between CMD and quality of life, and to provide evidence for the prevention and treatment of CMD and the improvement of quality of life in these patients. Methods: This is a cross-sectional study. Data were collected by the employees' physical examination of a company in Xi'an in 2021. Multiple linear regression models were used to analyze the association between the status of CMD (divided into three categories: no CMD, presence of one kind of CMD, and with≥2 kinds of CMD (≥2 kinds of CMD were defined as cardiometabolic multimorbidity (CMM)), quality of life, and perceived stress. Mediation analysis with a multi-categorical independent variable was conducted to determine the mediation effect of perceived stress on the association between CMD and quality of life. Results: Among all 4 272 participants, 1 457 (34.1%) participants had one kind of CMD and 677 (15.8%) participants had CMM. The average scores for quality of life and perceived stress were (57.5±15.7) and (16.9±7.9), respectively. Compared with participants without CMD, after adjusting for demographic and lifestyle factors, no statistically significant associations were observed between one kind of CMD and perceived stress or quality of life (both P>0.05). Perceived stress did not mediate the association between one kind of CMD and quality of life. However, participants with CMM had lower quality of life and higher perceived stress than participants without CMD. The relative total effect coefficient c (95%CI) and the relative direct effect coefficient c' (95%CI) between CMM and quality of life were -3.71 (-5.04--2.37) and -2.52 (-3.81--1.24) (both P<0.05), respectively. The relative indirect effect coefficient a2b (95%CI) of perceived stress on the association between CMM and quality of life was -1.18 (-1.62--0.77) (P<0.05). The mediation effect size was 31.8%. Conclusions: CMM is negatively associated with quality of life and positively associated with perceived stress. Perceived stress partially mediates the association between CMM and quality of life. Our results suggest that, in addition to preventing and treating CMM actively, efforts should be taken to relieve the perceived stress of people with CMM to improve their quality of life.

[Association of outdoor artificial light at night exposure with overweight and obesity among children and adolescents aged 9 to 18 years in China].

OBJECTIVE: To analyze the association between outdoor artificial light-at-night (ALAN) exposure and overweight and obesity among children and adolescents aged 9 to 18 years in China. METHODS: Using follow-up data of 5 540 children and adolescents aged 9 to 18 years conducted from November 2019 to November 2020 in eight provinces of China, latitude and longitude were determined based on school addresses, and the mean monthly average nighttime irradiance at the location of 116 schools was extracted by the nearest neighbor method to obtain the mean outdoor ALAN exposure [unit: nW/(cm2·sr)] for each school. Four indicators of overweight and obesity outcomes were included: Baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence. Mixed effects Logistic regression was used to explore the association between ALAN exposure levels (divided into quintiles Q1-Q5) and baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence. In addition, a natural cubic spline function was used to explore the exposure response association between ALAN exposure (a continuous variable) and the outcomes. RESULTS: The prevalence of baseline overweight and obesity, persistent overweight and obesity, overweight and obesity progression and overweight and obesity incidence among the children and adolescents in this study were 21.6%, 16.3%, 2.9% and 12.8%, respectively. The OR value for the association between ALAN exposure and baseline overweight and obesity was statistically significant when ALAN exposure levels reached Q4 or Q5, 1.90 (95%CI: 1.26-2.86) and 1.77 (95%CI: 1.11-2.83), respectively, compared with the children and adolescents in the Q1 group of ALAN exposure. Similar to the results for baseline overweight and obesity, the OR values for the association with persistent overweight and obesity were 1.89 (95%CI: 1.20-2.99) and 1.82 (95%CI: 1.08-3.06) when ALAN exposure levels reached Q4 or Q5, respectively, but none of the OR values for the association between ALAN and overweight and obesity progression and overweight and obesity incidence were statistically significant. Fitting a natural cubic spline function showed a non-linear trend between ALAN exposure and persistent overweight and obesity. CONCLUSION: There is a positive association between ALAN exposure and overweight and obesity in children and adolescents, and the promotion of overweight obesity in children and adolescents by ALAN tends to have a cumulative effect rather than an immediate effect. In the future, while focusing on the common risk factors for overweight and obesity in children and adolescents, there is a need to improve the overweight and obesity-causing nighttime light exposure environment.

A quinary WTaCrVHf nanocrystalline refractory high-entropy alloy withholding extreme irradiation environments.

In the quest of new materials that can withstand severe irradiation and mechanical extremes for advanced applications (e.g. fission & fusion reactors, space applications, etc.), design, prediction and control of advanced materials beyond current material designs become paramount. Here, through a combined experimental and simulation methodology, we design a nanocrystalline refractory high entropy alloy (RHEA) system. Compositions assessed under extreme environments and in situ electron-microscopy reveal both high thermal stability and radiation resistance. We observe grain refinement under heavy ion irradiation and resistance to dual-beam irradiation and helium implantation in the form of low defect generation and evolution, as well as no detectable grain growth. The experimental and modeling results-showing a good agreement-can be applied to design and rapidly assess other alloys subjected to extreme environmental conditions.

ABCC1 is a predictive biomarker for prognosis and therapy in hepatocellular carcinoma.

OBJECTIVE: Liver neoplasm is one of the most fatal malignancies worldwide, among which hepatocellular carcinoma (HCC) (MIM #114550, https://omim.org/) is the most prevalent type. ABCC1 (MIM *158343) is a membrane-bound protein that relies on ATP hydrolysis to transport substrates and is associated with tumour drug resistance and malignant potential. However, the relationship between ABCC1, HCC prognosis, and immune infiltration remains elusive. MATERIALS AND METHODS: We analysed the mRNA expression of ABCC1 using data from public databases. Immunohistochemistry staining was performed to identify ABCC1 expression in tumour samples. We further investigated the correlation between ABCC1 and clinicopathological features. We investigated the connection between ABCC1 and HCC prognosis using survival and Cox regression analyses. We investigated the underlying pathways of ABCC1 in HCC using functional enrichment analysis and GSEA. We determine the relationship between ABCC1 and immune cell infiltration via an integrated immune landscape analysis. RESULTS: Our investigation revealed the upregulation of ABCC1 expression in HCC (p < 0.01), which was verified in clinical samples (p < 0.01). In addition, ABCC1 is adversely associated with HCC clinical features and prognosis (p < 0.05). GO/KEGG analysis and GSEA identified that ABCC1 participates in multiple immune- and tumour-related pathways (p < 0.05). Immune cell infiltration analysis indicated that ABCC1 was positively correlated with various immune cells, among which, the strongest correlation was with macrophages (p < 0.001). Furthermore, we observed significant variations in immune checkpoints between the ABCC1-low and ABCC1-high groups (p < 0.01). This indicated that patients with a high expression of ABCC1 might respond poorly to immune checkpoint blockade (ICB) therapy (p = 9.2e-07). CONCLUSIONS: Our study identified ABCC1 as a predictor of HCC prognosis and response to therapy.

[Quantitative study of supraspinatus tendon injury grading based on synthetic magnetic resonance imaging].

Objective: To investigate the diagnostic value of quantitative parameters of synthetic magnetic resonance imaging (SyMRI) in the grade of supraspinatus tendon injury. Methods: Ninety-seven patients with clinical definite of supraspinatus tendon injury from July 2021 to July 2022 in General Hospital of Ningxia Medical University were prospectively collected (case group), including 54 males and 43 females, with an age of 29 to 56 (37.4±9.6) years. According to the results of shoulder arthroscopy, the case group were divided into three subgroups included tendinopathy group (37 cases, grade Ⅱ), partial tear group (34 cases, grade Ⅲ) and complete tear group (26 cases, grade Ⅳ). During the same period, 28 normal rotator cuff volunteers without supraspinatus tendon injury were recruited (control group), including 16 males and 12 females, aged 23 to 49 (36.1±7.2) years, and marked as grade Ⅰ. All the subjects underwent MRI scan of articulatio humeri included T1-weighted imaging(T1WI) fast spin echo(FSE) sequences in axial view, T2-weighted imaging(T2WI) fat suppression(FS) sequences in axial view, T2WI FS sequences in oblique coronal view, proton density-weighted (PDW) imaging in oblique sagittal view and SyMRI in oblique coronal view. The supraspinatus tendon was divided into lateral, medial and middle subregions according to its shape in oblique coronal T2WI view, two radiologists measured the T1, T2 and PD values of the supraspinatus tendon. The interclass correlation coefficient (ICC) were used to compare the consistency between and within observers. One-way analysis of variance or Kruskal-Wallis H test were used to compare the differences of quantitative parameters in different grades, the multivariate logistic regression model was used to analyze the risk factors of supraspinatus tendon injury grade, and the receiver operating characteristic (ROC) curves and area under curve (AUC) was drawn and calculated to evaluate the diagnostic efficacy. The Spearman correlation was used to analyze the correlation between the quantitative values and grades of supraspinatus tendon injury. Results: The ICC values of T1, T2 and PD values for the three subregions of the supraspinatus tendon were greater than 0. 700. The differences of T1 values in the lateral subregion, T2 values in the lateral and middle subregions were statistically significant in the overall comparison across different grades (all P<0. 001).The differences of T1 values in the middle and medial subregions, T2 values in the medial subregion and PD values in the lateral, middle and medial subregions were not statistically significant in the overall comparison of different grades (all P>0. 05). Multiple logistic regression model analysis showed that T2 values in the lateral and middle subregions were related factors for the grade of supraspinatus tendon injury[ OR (95%CI):1.123 (1.037-1.216), 0.122 (1.151-1.197);all P<0.001 ]. The AUC of the T2 values in lateral subregion diagnosing grade Ⅰ vs grade Ⅳ, grade Ⅱ vs grade Ⅳ and grade Ⅲ vs grade Ⅳ were 0.891(95%CI: 0.801-0.981), 0.797(95%CI: 0.680-0.914), 0.723(95%CI: 0.594-0.853) (all P<0.001), and the AUC of the T2 values in middle subregion diagnosing grade Ⅰ vs Ⅳ, grade Ⅱ vs Ⅳ, grade Ⅱ vs Ⅲ, and grade Ⅰ vs Ⅲ were 0.946 (95%CI: 0.849-0.989), 0.886 (95%CI: 0.809-0.962), 0.746 (95%CI: 0.631-0.861), 0.843 (95%CI: 0.745-0.941)(all P<0.001). The T2 values in the lateral and middle subregions were positively correlated with the grade of supraspinatus tendon injury (r=0.542, 0.615; both P<0.001), while T1 values and T2 values in the medial subregions were not significantly correlated with the grade of supraspinatus tendon injury (both P>0.05). Conclusion: SyMRI has high clinical application value in the grading of supraspinatus tendon injury, especially T2 value can be used as an effective quantitative parameter for the grading of supraspinatus tendon injury.

[Short-course radiotherapy combined with CAPOX and PD-1 inhibitor for the total neoadjuvant therapy of locally advanced rectal cancer: the preliminary single-center findings of a prospective, multicentre, randomized phase II trial (TORCH)].

Objective: Total neoadjuvant therapy has been used to improve tumor responses and prevent distant metastases in patients with locally advanced rectal cancer (LARC). Patients with complete clinical responses (cCR) then have the option of choosing a watch and wait (W&W) strategy and organ preservation. It has recently been shown that hypofractionated radiotherapy has better synergistic effects with PD-1/PD-L1 inhibitors than does conventionally fractionated radiotherapy, increasing the sensitivity of microsatellite stable (MSS) colorectal cancer to immunotherapy. Thus, in this trial we aimed to determine whether total neoadjuvant therapy comprising short-course radiotherapy (SCRT) combined with a PD-1 inhibitor improves the degree of tumor regression in patients with LARC. Methods: TORCH is a prospective, multicenter, randomized, phase II trial (TORCH Registration No. NCT04518280). Patients with LARC (T3-4/N+M0, distance from anus ≤10 cm) are eligible and are randomly assigned to consolidation or induction arms. Those in the consolidation arm receive SCRT (25Gy/5 Fx), followed by six cycles of toripalimab plus capecitabine and oxaliplatin (ToriCAPOX). Those in the induction arm receive two cycles of ToriCAPOX, then undergo SCRT, followed by four cycles of ToriCAPOX. Patients in both groups undergo total mesorectal excision (TME) or can choose a W&W strategy if cCR has been achieved. The primary endpoint is the complete response rate (CR, pathological complete response [pCR] plus continuous cCR for more than 1 year). The secondary endpoints include rates of Grade 3-4 acute adverse effects (AEs) etc. Results: Up to 30 September 2022, 62 patients attending our center were enrolled (Consolidation arm: 34, Induction arm:28). Their median age was 53 (27-69) years. Fifty-nine of them had MSS/pMMR type cancer (95.2%), and only three MSI-H/dMMR. Additionally, 55 patients (88.7%) had Stage III disease. The following important characteristics were distributed as follows: lower location (≤5 cm from anus, 48/62, 77.4%), deeper invasion by primary lesion (cT4 7/62, 11.3%; mesorectal fascia involved 17/62, 27.4%), and high risk of distant metastasis (cN2 26/62, 41.9%; EMVI+ 11/62, 17.7%). All 62 patients completed the SCRT and at least five cycles of ToriCAPOX, 52/62 (83.9%) completing six cycles of ToriCAPOX. Finally, 29 patients achieved cCR (46.8%, 29/62), 18 of whom decided to adopt a W&W strategy. TME was performed on 32 patients. Pathological examination showed 18 had achieved pCR, four TRG 1, and 10 TRG 2-3. The three patients with MSI-H disease all achieved cCR. One of these patients was found to have pCR after surgery whereas the other two adopted a W&W strategy. Thus, the pCR and CR rates were 56.2% (18/32) and 58.1% (36/62), respectively. The TRG 0-1 rate was 68.8% (22/32). The most common non-hematologic AEs were poor appetite (49/60, 81.7%), numbness (49/60, 81.7%), nausea (47/60, 78.3%) and asthenia (43/60, 71.7%); two patients did not complete this survey. The most common hematologic AEs were thrombocytopenia (48/62, 77.4%), anemia (47/62, 75.8%), leukopenia/neutropenia (44/62, 71.0%) and high transaminase (39/62, 62.9%). The main Grade III-IV AE was thrombocytopenia (22/62, 35.5%), with three patients (3/62, 4.8%) having Grade IV thrombocytopenia. No Grade V AEs were noted. Conclusions: SCRT-based total neoadjuvant therapy combined with toripalimab can achieve a surprisingly good CR rate in patients with LARC and thus has the potential to offer new treatment options for organ preservation in patients with MSS and lower-location rectal cancer. Meanwhile, the preliminary findings of a single center show good tolerability, the main Grade III-IV AE being thrombocytopenia. The significant efficacy and long-term prognostic benefit need to be determined by further follow-up.

[Study on HBV-related acute-on-chronic liver failure risk factors and novel predictive survival model].

Objective: To identify the predisposing factors, clinical characteristics, and risk factors of disease progression to establish a novel predictive survival model and evaluate its application value for hepatitis B virus-related acute-on-chronic liver failure. Methods: 153 cases of HBV-ACLF were selected according to the guidelines for the diagnosis and treatment of liver failure (2018 edition) of the Chinese Medical Association Hepatology Branch. Predisposing factors, the basic liver disease stage, therapeutic drugs, clinical characteristics, and factors affecting survival status were analyzed. Cox proportional hazards regression analysis was used to screen prognostic factors and establish a novel predictive survival model. The receiver operating characteristic curve (ROC) was used to evaluate predictive value with the Model for End-Stage Liver Disease (MELD) and the Chronic Liver Failure Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLF). Results: 80.39% (123/153) based on hepatitis B cirrhosis had developed ACLF. HBV-ACLF's main inducing factors were the discontinuation of nucleos(t)ide analogues (NAs) and the application of hepatotoxic drugs, including Chinese patent medicine/Chinese herbal medicine, non-steroidal anti-inflammatory drugs, anti-tuberculosis drugs, central nervous system drugs, anti-tumor drugs, etc. 34.64% of cases had an unknown inducement. The most common clinical symptoms at onset were progressive jaundice, poor appetite, and fatigue. The short-term mortality rate was significantly higher in patients complicated with hepatic encephalopathy, upper gastrointestinal hemorrhage, hepatorenal syndrome, and infection (P < 0.05). Lactate dehydrogenase, albumin, the international normalized ratio, the neutrophil-to-lymphocyte ratio, hepatic encephalopathy, and upper gastrointestinal bleeding were the independent predictors for the survival status of patients. The LAINeu model was established. The area under the curve for evaluating the survival of HBV-ACLF was 0.886, which was significantly higher than the MELD and CLIF-C ACLF scores (P < 0.05), and the prognosis was worse when the LAINeu score ≥ -3.75. Conclusion: Discontinuation of NAs and the application of hepatotoxic drugs are common predisposing factors for HBV-ACLF. Hepatic decompensation-related complications and infection accelerate the disease's progression. The LAINeu model can predict patient survival conditions more accurately.

[Daratumumab maintenance after autologous hematopoietic stem cell transplantation for newly diagnosed multiple myeloma].

Objective: This study aimed to evaluate the efficacy and safety of daratumumab as a maintenance treatment after autologous hematopoietic stem cell transplantation (auto-HSCT) in patients with newly diagnosed multiple myeloma (NDMM) . Methods: The clinical data, hematological and renal response, and safety of 15 post-transplant patients with NDMM who had received daratumumab maintenance between May 1, 2022 and June 30, 2023 were retrospectively analyzed. Results: Fifteen patients (11 males and 4 females) with a median age of 58 (41-72) years were included. Thirteen patients did not receive daratumumab during induction therapy and auto-HSCT, 6 patients had renal impairment, and nine patients had high-risk cytogenetics. The median infusion of daratumumab was 12 (6-17) times, and the median duration of maintenance was 6 (1.5-12) months. The treatment efficacy was evaluated in all 15 patients, and daratumumab maintenance therapy increased the rate of stringent complete response from 40% to 60%. The renal response rate and median estimated glomerular filtration rate of six patients with RI-NDMM were also improved. During daratumumab maintenance therapy, the most common hematological grade 3 adverse event (AE) was lymphopenia [4 of 15 patients (26.67%) ], whereas the most common nonhematologic AEs were infusion-related reactions [7 of 15 patients (46.67%) ] and grade 3 pneumonia [5 of 15 patients (33.33%) ]. The five patients with pneumonia were daratumumab naive [5 of 13 patients (38.46%) ], with a median of 8 (6-10) infusions. Among them, the chest computed tomography of three patients showed interstitial infiltrates, and treatment with methylprednisolone was effective. With a median follow-up of 12 months, the 1-year overall survival rate was 93.33%, and only one patient died (which was not related to daratumumab treatment) . Conclusions: Daratumumab was safe and effective as a maintenance agent for post-auto-HSCT patients with NDMM, and AEs were controllable. The most common nonhematologic AE was grade 3 pneumonia, and a less dose-intense maintenance regimen for the first 8 weeks could reduce the incidence of pneumonia.

[Relationship between metastasis in the para-aortic lymph nodes of cervical cancer and pathological features].

Objective: To investigate the incidence and the related risk factors of para-aortic lymph node metastasis in cervical cancer. Methods: The pathological data of 727 patients with cervical cancer who underwent radical hysterectomy and pelvic and para-aortic lymph node dissection were retrospectively analyzed. The relative postoperative pathological parameters of para-aortic lymph node metastasis were statistically analyzed. Results: Among the 727 patients with cervical cancer, 123(16.9%) had para-aortic lymph node metastasis. Univariate analysis showed that the tumor size, the depth of muscular invasion, the vessel invasion, the uterine body invasion, the vaginal invasion, the parametrial invasion, positive surgical margin, the ovary metastasis, the fallopian tubes metastasis, the pelvic lymph node metastasis, and the common iliac lymph node metastasis were associated with para-aortic lymph node metastasis. While the multivariate logistic regression analysis showed that the diameter of primary tumor >4.2 cm, the parametrial invasion, the pelvic lymph node metastasis, and the common iliac lymph node metastasis were the independent risk factors of para-aortic lymph node metastasis. Conclusions: The diameter of primary tumor >4.2 cm, the parametrial invasion, the pelvic lymph node metastasis, and the common iliac lymph node metastasis are the independent risk factors of para-aortic lymph node metastasis in cervical cancer. The tumor size and the common iliac lymph node status should be fully evaluated before the initial operation. Additionally, assessment of the postoperative pelvic lymph node status and the parametrial status will help reduce the rate of misdiagnosis and missed diagnosis, providing a basis for individualized treatment and prognostic judgment.