Over three years have passed since the COVID-19 pandemic started. The dangerousness and impact of COVID-19 should definitely not be ignored or underestimated. Other than the symptoms of acute infection, the long-term symptoms associated with SARS-CoV-2 infection, which are referred to here as "sequelae of long COVID (LC)", are also a conspicuous global public health concern. Although such sequelae were well-documented, the understanding of and insights regarding LC-related sequelae remain inadequate due to the limitations of previous studies (the follow-up, methodological flaws, heterogeneity among studies, etc.). Notably, robust evidence regarding diagnosis and treatment of certain LC sequelae remain insufficient and has been a stumbling block to better management of these patients. This awkward situation motivated us to conduct this review. Here, we comprehensively reviewed the updated information, particularly focusing on clinical issues. We attempt to provide the latest information regarding LC-related sequelae by systematically reviewing the involvement of main organ systems. We also propose paths for future exploration based on available knowledge and the authors' clinical experience. We believe that these take-home messages will be helpful to gain insights into LC and ultimately benefit clinical practice in treating LC-related sequelae.

Power laws have been observed in various fields and help us understand natural phenomena. Power laws have also been observed in ultrasound images. This study used the power spectrum of the signal identified from the reflected ultrasound signal observed in ultrasonography based on the power-law shot noise (PLSN) model. The power spectrum follows a power law, which has a scaling factor that depends on the characteristics of the tissue in the region where the ultrasound wave propagates. To distinguish between a tumor and blood vessels in the liver, we propose a classification model that includes a scaling factor based on ResNet, a deep learning model for image classification. In a task to classify 6 types of tissue - a tumor, the inferior vena cava, the descending aorta, the Gleason sheath, the hepatic vein, and small blood vessels – tumor sensitivity increased 3.8% and the F-score for a tumor improved 2% while precision was maintained. The scaling factor obtained using the PLSN model was validated for classification of liver tumors.

Gaucher disease (GD), one of the most common lysosomal storage diseases, is caused by GBA1 mutations resulting in defective glucocerebrosidase (GCase) and consequent accumulation of its substrates β-glucosylceramide (β-GlcCer). We reported progranulin (PGRN), a secretary growth factor-like molecule and an intracellular lysosomal protein was a crucial co-factor of GCase. PGRN binds to GCase and recruits Heat Shock Protein 70 (Hsp70) to GCase through its C-terminal Granulin (Grn) E domain, termed as ND7. In addition, both PGRN and ND7 are therapeutic against GD. Herein we found that both PGRN and its derived ND7 still displayed significant protective effects against GD in Hsp70 deficient cells. To delineate the molecular mechanisms underlying PGRN's Hsp70-independent regulation of GD, we performed a biochemical co-purification and mass spectrometry with His-tagged PGRN and His-tagged ND7 in Hsp70 deficient cells, which led to the identification of ERp57, also referred to as protein disulfide isomerase A3 (PDIA3), as a protein that binds to both PGRN and ND7. Within type 2 neuropathic GD patient fibroblasts L444P, bearing GBA1 L444P mutation, deletion of ERp57 largely abolished the therapeutic effects of PGRN and ND7, as manifested by loss of effects on lysosomal storage, GCase activity, and β-GlcCer accumulation. Additionally, recombinant ERp57 effectively restored the therapeutic effects of PGRN and ND7 in ERp57 knockout L444P fibroblasts. Collectively, this study reports ERp57 as a previously unrecognized binding partner of PGRN that contributes to PGRN regulation of GD.

Hepatic forkhead box protein A2 (FOXA2) is a crucial transcription factor for liver development and metabolic homeostasis. However, its role in hepatocellular carcinoma (HCC) progression and lenvatinib-related drug resistance remains unknown. In this study, the level of FOXA2 expression was found to be lower in HCC tissues than in paired adjacent tumor tissues. A low level of FOXA2 expression was associated with aggressive tumor characteristics (vascular invasion and poor differentiation). A low level of FOXA2 expression was found to be an independent risk factor for tumor recurrence (hazard ratio (HR): 1.899, P < 0.001) and long-term survival (HR: 2.011, P = 0.003) in HCC patients after hepatectomy. In xenograft animal models, FOXA2 overexpression significantly inhibited tumor growth. Moreover, FOXA2 overexpression was found to enhance the inhibitory effect of lenvatinib on HCC cells by upregulating the adenosine monophosphate-activated protein kinase-mechanistic target of rapamycin (AMPK-mTOR) pathway. Conversely, inhibition of adenosine monophosphate-activated protein kinase (AMPK) or stimulation of mechanistic target of rapamycin (mTOR) attenuated the sensitization of cells overexpressing FOXA2 to lenvatinib. Similarly, FOXA2 overexpression augmented the antitumor effect of lenvatinib in animal models with xenograft tumors. FOXA2 overexpression increased autophagy in HCC cells treated with lenvatinib. Lenvatinib treatment activated the platelet-derived growth factor receptor-extracellular regulated protein kinase (PDGFR-ERK) pathway in HCC. FOXA2 overexpression further downregulated the PDGFR-ERK pathway through the activation of the AMPK-mTOR axis. In conclusion, FOXA2 was identified as an independent risk factor for HCC after hepatectomy. FOXA2 was found to be closely associated with the biological progression of HCC. By modulating the AMPK-mTOR-autophagy signaling pathway, FOX2 significantly augmented antitumor effect of lenvatinib in HCC.

Concurrent screening has been proven to provide a comprehensive approach for management of congenital deafness and prevention of ototoxicity. The SLC26A4 gene is associated with late-onset hearing loss and is of great clinical concern. For much earlier detection of newborns with deafness-causing mutations in the SLC26A4 gene, the Beijing Municipal Government launched a chip for optimized genetic screening of 15 variants of 4 genes causing deafness based on a chip to screen for 9 variants of 4 genes, and 6 variants of the SLC26A4 gene have now been added. To ascertain the advantage of a screening chip including 15 variants of 4 genes, the trends in concurrent hearing and genetic screening were analyzed in 2019 and 2020. Subjects were 76,460 newborns who underwent concurrent hearing and genetic screening at 24 maternal and child care centers in Beijing from January 2019 to December 2020. Hearing screening was conducted using transiently evoked otoacoustic emissions (TEOAEs), distortion product otoacoustic emissions (DPOAE), or the automated auditory brainstem response (AABR). Dried blood spots were collected for genetic testing and 15 variants of 4 genes, namely GJB2, SLC26A4, mtDNA 12S rRNA, and GJB3, were screened for using a DNA microarray platform. The initial referral rate for hearing screening decreased from 3.60% (1,502/41,690) in 2019 to 3.23% (1,124/34,770) in 2020, and the total referral rate for hearing screening dropped form 0.57% (236/41,690) in 2019 to 0.54% (187/34,770) in 2020, indicating the reduced false positive rate of newborn hearing screening and policies to prevent hearing loss conducted by the Beijing Municipal Government have had a significant effect. Positivity according to genetic screening was similar in 2019 (4.970%, 2,072/41,690) and 2020 (4.863%,1,691/34,770), and the most frequent mutant alleles were c.235 del C in the GJB2 gene, followed by c.919-2 A > G in the SLC26A4 gene, and c.299 del AT in the GJB2 gene. In this cohort study, 71.43% (5/7) of newborns with 2 variants of the SLC26A4 gene were screened for newly added mutations, and 28.57% (2/7) of newborns with 2 variants of the SLC26A4 gene passed hearing screening, suggesting that a screening chip including 15 variants of 4 genes was superior at early detection of hearing loss, and especially in early identification of newborns with deafness-causing mutations in the SLC26A4 gene. These findings have clinical significance.

Neoadjuvant chemotherapy (NAC) is generally accepted for treatment of liver metastasis of colorectal cancer (CRLM), but what is a reasonable interval between the latest NAC and surgery is still unknown. The aim of the current study was to investigate the proper timing of surgery after NAC. Subjects were 141 patients with CRLM who underwent NAC and then surgery were retrospectively identified from 2008 to 2020. They were divided into a short interval group (SIG, ≤ 4 weeks) and long interval group (LIG, > 4 weeks) using the software X-tile. The SIG was subclassified group into 3 time periods (1-2 weeks, 2-3 weeks, and 3-4 weeks) to assess the incidence of complications. Patients in the SIG were more likely to have significantly better recurrence-free survival (RFS) (3-year RFS of 47.4% vs. 20.5%, P = 0.043) and no difference in overall survival (OS) (3-year OS 76.1% vs. 79.9%, P = 0.635). The postoperative complication rate was 23.5% in the SIG and 14.0% in the LIG (P = 0.198). The postoperative complication rate in the 1-2 weeks subgroup was marginally higher than that in the > 4 weeks subgroup (35% vs. 14.3% P = 0.055). Multivariate analysis revealed that chemotherapy-free intervals of 1-2 weeks were an independent predictor of increased postoperative complications (OR = 0.263, 95% CI 0.7-0.985 P = 0.048). Patients who underwent surgery within 4 weeks of NAC had better RFS. In addition, 1-2 weeks was an independent factor influencing the development of more complications. For patients with CRLM, performing surgery within 2-4weeks of NAC was feasible and safe, and it did not increase the incidence of postoperative complications but it did prolong RFS.

Endometriosis is a chronic inflammatory disease. The immune-checkpoint molecules CD226 and TIGIT play an important role in regulating T cells' function. However, little is known about the proportion and function of CD226 and TIGIT on CD4⁺ T cells in endometriosis. The current study found no significant differences in the TIGIT percentage on peripheral CD4⁺ T cells between patients with endometriosis and the control group. However, CD226 was lower in patients with endometriosis than that in the control group (P < 0.01). The cytokines TNF-α, IL10, and IFN-γ were significantly elevated in TIGIT⁺ CD4⁺ T cells compared to TIGIT- CD4⁺ T cells. HLA-DR⁺ cells were more numerous among TIGIT⁺ CD4⁺ T cells than among the TIGIT- subset (P <0.001). Similarly, the cytokines TNF-α, IL10, and IFN-γ were significantly elevated in CD226⁺ CD4⁺ T cells compared to levels in CD226- CD4⁺ T cells. The proportion of HLA-DR⁺ CD4⁺ T cells among CD226⁺ CD4⁺ T cells was also significantly higher than that among the CD226- subset (P < 0.001). After TIGIT was blocked, the level of IL-10 in TIGIT⁺ CD4⁺ T cells was higher than that in cells with unblocked TIGIT. There were no differences in TNF-α and IFN-γ. After CD226 was blocked, TNF-α and IFN-γwere lower while IL-10 was higher. In conclusion, there is a diminution of CD226 in CD4⁺ T cells in patients with endometriosis. This is correlated with the effector function of CD4⁺ T cells, and blocking CD226 can suppress this function.

We conducted a study to assess the characteristics, scope of activity, and negative emotions in elderly women with urinary incontinence (UI) based on a longitudinal follow-up conducted in Shanghai, China from 2013 to 2019. A total of 3,531 elderly women were included in the final analysis, and 697 women who experienced UI during follow-up were included in the UI group. Subjects with UI were subdivided into those with partial UI (UI once a day or less) and UI (frequent UI). Two thousand eight hundred and thirty-four women who did not have UI during the same period served as the control group. The prevalence of UI was 19.74% in this study. Logistic regression analysis revealed that being older (> 80 years of age), having a high level of education (> 12 years; elderly people with a high level of education may pay more attention to their health and notice UI more readily), a low personal monthly income (≤ 3,000 RMB), more gravidity/parity, and having a chronic disease (chronic obstructive pulmonary disease (COPD), dementia, or Parkinson's disease) were risk factors for UI (p < 0.05). About 60% of women in the partial UI group engaged in daily activities outdoors, while this number decreased sharply to 3.6% in the UI group. Women in the UI group were more likely to have negative emotions, such as depression, anxiety, irritability, or feeling worthless (p < 0.001). Among elderly women with dementia, those with UI had defects in terms of judgment in everyday life, the ability of convey information, and the ability to understand information (p < 0.05). More attention needs to be paid to the adverse effects of UI on activities of daily living (ADL) and mental health in the future.

We conducted a study to analyze the unmet needs of and risk factors for use of assistive walking devices by the elderly based on sample survey data from Shanghai, China from July to October 2019. Among a total sample size of 11,193 people age 55 and older, 1,947 people (17.39%) needed assistive walking devices, 829 (42.58%) of whom needed but did not use those devices. Multivariate analysis indicated that residence, living alone or cohabitating, indoor handrails, the number of diseases, and IADL were factors influencing the unmet need for assistive walking devices (p < 0.05, respectively). People who lived in community health centers (p = 0.0104, OR = 1.956, 95% CI: 1.171-3.267) and those who lived only with their spouse (p = 0.0002, OR = 2.901, 95% CI: 1.641-5.126) were more likely to have an unmet need for assistive walking devices. People without indoor handrails (p = 0.0481, OR = 0.718, 95% CI: 0.517-0.997), those with 3 or more diseases (p = 0.0008, OR = 0.577, 95% CI: 0.418-0.796), and those with severely impaired IADL (p = 0.0002, OR = 0.139, 95% CI: 0.05-0.386) were less likely to have an unmet need for assistive walking devices. Self-perceived needs of the elderly, the diversity and performance of assistive devices, and the accessibility and affordability of assistive walking devices may lead to unmet needs.

We conducted a study to explore how one's emotional state affects attempted suicide among the elderly in Shanghai, China. Random sampling was used to select people age 55 and older in Shanghai from 2013 to 2019. A questionnaire was used to collect relevant data, including attempted suicide and emotional status. Subjects were a total of 783 elderly people who participated in this study for two years and more, and they consisted of 569 elderly people did not commit suicide during the study period and 214 elderly people who attempted suicide. Cumulative logistic regression indicated that feeling less interested than usual in hobbies (p < 0.001, OR = 2.805, 95% CI: 0.941-8.360) and being more easily angered (p < 0.0001, OR = 11.972, 95% CI: 6.275-22.843) increase the risk of attempted suicide.