The present study investigated the mechanism of the Tibetan medicine Ershiwuwei Songshi Pills(ESP) against the liver injury induced by acetaminophen(APAP) in mice based on the kelch-like ECH-associated protein 1(Keap1)/nuclear transcription factor E2 related factor 2(Nrf2) and Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) p65 signaling pathways. Kunming mice were randomly divided into a blank control group, a model group, an N-acetyl-L-cysteine(NAC) group, and high-(400 mg·kg~(-1)), medium-(200 mg·kg~(-1)), and low-dose(100 mg·kg~(-1)) ESP groups. After 14 days of continuous administration, except for those in the control group, the mice were intraperitoneally injected with 200 mg·kg~(-1) APAP. After 12 h, the serum and liver tissues of mice were collected. Hematoxylin-eosin(HE) staining was performed on pathological sections of the liver, and the levels of aspartate aminotransferase(AST) and alanine aminotransferase(ALT) in the serum and the levels of glutathione(GSH), malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), myeloperoxidase(MPO), and total antioxidant capacity(T-AOC) in liver tissue homogenate were detected to observe and analyze the protective effect of ESP on APAP-induced liver injury in mice. The serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1β), and interleukin-6(IL-6) were determined by enzyme-linked immunosorbent assay(ELISA). The protein expression of Nrf2, Keap1, TLR4, and NF-κB p65 in the liver was determined by Western blot. Quantitative real-time was used to determine the mRNA expression of glutamate-cysteine ligase catalytic subunit(GCLC), glutamate-cysteine ligase regulatory subunit(GCLM), heme oxygenase-1(HO-1), and NAD(P)H dehydrogenase quinone 1(NQO-1) in the liver to explore the mechanism of ESP in improving APAP-induced liver damage in mice. As revealed by results, compared with the model group, the ESP groups showed improved liver pathological damage, decreased ALT and AST levels in the serum and MDA and MPO content in the liver, increased GSH, SOD, CAT, and T-AOC in the liver, reduced TNF-α and IL-6 levels in the serum, down-regulated expression of Keap1 in the liver cytoplasm and NF-κB p65 in the liver nucleus, up-regulated expression of Nrf2 in the liver nucleus, insignificant change in TLR4 expression, and elevated relative mRNA expression levels of antioxidant genes GCLC, GCLM, HO-1, and NQO-1. ESP can reduce the oxidative damage and inflammation caused by APAP, and the mechanism may be related to the Keap1/Nrf2 signaling pathway and the signal transduction factors on the TLR4/NF-κB p65 pathway.
Acetaminophen/toxicity* ; Animals ; Antioxidants/pharmacology* ; Glutamate-Cysteine Ligase/pharmacology* ; Glutathione ; Interleukin-6/metabolism* ; Kelch-Like ECH-Associated Protein 1/metabolism* ; Liver ; Medicine, Tibetan Traditional ; Mice ; NF-E2-Related Factor 2/metabolism* ; NF-kappa B/metabolism* ; RNA, Messenger/metabolism* ; Signal Transduction ; Superoxide Dismutase/metabolism* ; Toll-Like Receptor 4/metabolism* ; Tumor Necrosis Factor-alpha/metabolism*

Objective:To analyze the clinical characteristics and prognosis of patients infected with novel coronavirus Omicron variant in Shanghai, as to provide a reference for epidemic prevention, clinical diagnosis, and treatment.Methods:Altogether 4 264 novel coronavirus Omicron variant-infected patients with positive results of nucleic acid admitted to Shanghai New International Expo Center N3 Mobile Cabin Hospital from April 2 to May 7, 2022, were included. The demographic and baseline clinical characteristics, treatment strategy, prognosis, and different factors affecting the length of hospital stay were analyzed.Results:A total of 4 264 novel coronavirus variant Omicron-infected cases were collected, including 3 111 cases (73.0%) asymptomatic infections and 1 153 cases (27.0%) mild infections. The overall median age was 45 (33, 55) years old with a range from 2 years old to 81 years old. The male to female ratio was 1.37∶1. Altogether 3 305 cases (77.5%) had been vaccinated, of which 3 166 cases completed more than 2 doses. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical manifestations of these infected patients. During the course of the disease, patients with asymptomatic infection were mainly treated with traditional Chinese medicine (TCM, 55.1%) and clinical observation (36.8%), and those with mild infection were mainly treated with TCM (42.2%) or integrated Chinese and Western medicine (30.4%). All patients were cured and discharged. The overall median length of hospital stay and the negative conversion time of nucleic acid were 9 (6, 10) days and 8 (5, 9) days, respectively. Compared with the asymptomatic infected patients, the hospitalization duration and the nucleic acid negative conversion time of the mildly infected patients were slightly longer [days: 10 (8, 11) vs. 9 (5, 10); 8 (6, 10) vs. 7 (4, 9), both P < 0.001]. Multiple linear regression analysis showed that the increasing age and mild infection were associated with longer hospitalization duration, and the treatment of TCM or integrated Chinese and Western medicine was associated with shortened length of hospital stay (all P < 0.05). Conclusions:The current novel coronavirus Omicron variant epidemic in Shanghai mainly caused asymptomatic and mild infections. The young and middle-aged population had a relatively high infection rate. The upper respiratory tract symptoms such as cough and expectoration were the most common clinical symptoms. Elderly and confirmed patients had prolonged hospitalization duration, while for patients receiving TCM treatment, the hospitalization duration was shortened.

Objective: To summarize the application experience and the therapeutic effect of Nirmatrelvir-Ritonavir (trade name: Paxlovid) for COVID-19 in children. Methods: A retrospective analysis was performed on the clinical data, including collecting the clinical manifestations and clinical outcomes, dynamically monitoring the blood routine, hepatic and renal function and SARS-CoV-2 nucleic acid results, and observing the related side effects during the treatment, etc, of 3 cases with COVID-19 treated with Paxlovid admitted to Shanghai Children's Hospital (designated referral hospital for SARS-CoV-2 infection in Shanghai) from May 1^st to June 1^st, 2022. Results: The 3 cases were 12, 14, 17 years of age, among which 2 cases were males, 1 case was female. All 3 cases were mild cases with underlying diseases and risk of developing into severe COVID-19, with symptoms of high fever, sore throat and dry cough. The treatment of Paxlovid at 3^rd day of symptom onset contributed to the symptom-free after 1-2 days and negative results of SARS-CoV-2 nucleic acid after 2-4 days. All patients had no adverse manifestations of gastrointestinal tract and nervous system but a case had little skin rashes, which recovered after the withdrawal of Paxlovid. Three cases had normal hepatic and renal function during the Paxlovid treatment. At 3 months after discharge, no clinical manifestations of post-COVID syndrome were found in all 3 cases. Conclusion: Paxlovid was effective and relatively safe in the treatment of 3 children with COVID-19.
Child ; Male ; Humans ; Female ; COVID-19 ; SARS-CoV-2 ; Ritonavir/therapeutic use* ; Retrospective Studies ; China ; Nucleic Acids ; COVID-19 Drug Treatment

Objective Coronavirus disease 2019 (COVID-19) and tuberculosis (TB) are major public health and social issues worldwide. The long-term follow-up of COVID-19 with pulmonary TB (PTB) survivors after discharge is unclear. This study aimed to comprehensively describe clinical outcomes, including sequela and recurrence at 3, 12, and 24 months after discharge, among COVID-19 with PTB survivors. Methods From January 22, 2020 to May 6, 2022, with a follow-up by August 26, 2022, a prospective, multicenter follow-up study was conducted on COVID-19 with PTB survivors after discharge in 13hospitals from four provinces in China. Clinical outcomes, including sequela, recurrence of COVID-19, and PTB survivors, were collected via telephone and face-to-face interviews at 3, 12, and 24 months after discharge. Results Thirty-two COVID-19 with PTB survivors were included. The median age was 52 (45, 59) years, and 23 (71.9％) were men. Among them, nearly two-thirds (62.5％) of the survivors were moderate, three (9.4％) were severe, and more than half (59.4％) had at least one comorbidity (PTB excluded). The proportion of COVID-19 survivors with at least one sequela symptom decreased from 40.6％ at 3 months to 15.8％ at 24 months, with anxiety having a higher proportion over a follow-up. Cough and amnesia recovered at the 12-month follow-up, while anxiety, fatigue, and trouble sleeping remained after 24 months. Additionally, one (3.1％) case presented two recurrences of PTB and no re-positive COVID-19 during the follow-up period. Conclusion The proportion of long symptoms in COVID-19 with PTB survivors decreased over time, while nearly one in six still experience persistent symptoms with a higher proportion of anxiety. The recurrence of PTB and the psychological support of COVID-19 with PTB after discharge require more attention.

Additional sex combs-like 1 (ASXL1) interacts with BRCA1-associated protein 1 (BAP1) deubiquitinase to oppose the polycomb repressive complex 1 (PRC1)-mediated histone H2A ubiquitylation. Germline BAP1 mutations are found in a spectrum of human malignancies, while ASXL1 mutations recurrently occur in myeloid neoplasm and are associated with poor prognosis. Nearly all ASXL1 mutations are heterozygous frameshift or nonsense mutations in the middle or to a less extent the C-terminal region, resulting in the production of C-terminally truncated mutant ASXL1 proteins. How ASXL1 regulates specific target genes and how the C-terminal truncation of ASXL1 promotes leukemogenesis are unclear. Here, we report that ASXL1 interacts with forkhead transcription factors FOXK1 and FOXK2 to regulate a subset of FOXK1/K2 target genes. We show that the C-terminally truncated mutant ASXL1 proteins are expressed at much higher levels than the wild-type protein in ASXL1 heterozygous leukemia cells, and lose the ability to interact with FOXK1/K2. Specific deletion of the mutant allele eliminates the expression of C-terminally truncated ASXL1 and increases the association of wild-type ASXL1 with BAP1, thereby restoring the expression of BAP1-ASXL1-FOXK1/K2 target genes, particularly those involved in glucose metabolism, oxygen sensing, and JAK-STAT3 signaling pathways. In addition to FOXK1/K2, we also identify other DNA-binding transcription regulators including transcription factors (TFs) which interact with wild-type ASXL1, but not C-terminally truncated mutant. Our results suggest that ASXL1 mutations result in neomorphic alleles that contribute to leukemogenesis at least in part through dominantly inhibiting the wild-type ASXL1 from interacting with BAP1 and thereby impairing the function of ASXL1-BAP1-TF in regulating target genes and leukemia cell growth.

Background: Mental stress-induced myocardial ischemia (MSIMI) is closely associated with adverse cardiac events in patients with coronary artery disease (CAD) and we aimed to determine whether biomarkers and blood pressure could be potential predictors of MSIMI. Methods: This study enrolled 82 patients with documented CAD between June 1, 2017 and November 9, 2017. Patient blood samples were obtained at resting period and at the end of mental arithmetic. Then, patients were assigned to MSIMI positive group and MSIMI negative group. The main statistical methods included linear regression, receiver operating characteristic (ROC) curves, and logistic regression. Results: Patients with CAD with MSIMI had significantly greater median resting N-terminal pro-brain natriuretic peptide (NT-proBNP, 141.02 [45.85–202.76] pg/mL vs. 57.95 [27.06–117.64] pg/mL; Z = -2.23, P = 0.03) and mean systolic blood pressure (SBP) (145.56 ± 16.87 mmHg vs. 134.92 ± 18.16 mmHg, Z = -2.13, P = 0.04) when compared with those without MSIMI. After 5-min mental stress task, those who developed MSIMI presented higher elevation of median post-stressor high sensitivity cardiac troponin I (hs-cTnI, 0.020 [0.009–0.100] ng/mL vs. 0.009 [0.009–0.010] ng/mL; Z = -2.45, P = 0.01), post-stressor NT-proBNP (138.96 [39.93–201.56] pg/mL vs. 61.55 [25.66–86.50] pg/mL; Z = -2.15, P = 0.03) compared with those without MSIMI. Using the ROC curves, and after the adjustment for basic characteristics, the multiple logistic regression analysis showed that patients presenting a post-stressor hs-cTnI ≥ 0.015 ng/mL had seven-fold increase in the risk of developing MSIMI (odds ratio [OR]: 7.09; 95% confidence interval [CI]: 1.65–30.48; P = 0.009), a rest NT-proBNP ≥ 80.51 pg/mL had nearly eight-fold increase (OR: 7.85; 95% CI: 1.51–40.82; P = 0.014), a post-stressor NT-proBNP ≥ 98.80 pg/mL had 35-fold increase (OR: 34.96; 95% CI: 3.72– 328.50; P = 0.002), a rest SBP ≥ 129.50 mmHg had 11-fold increase (OR: 11.42; 95% CI: 1.21–108.17; P = 0.034). Conclusions The present study shows that CAD patients with higher hs-cTnI level, and/or greater NT-proBNP and/or SBP are at higher risk of suffering from MSIMI when compared with those without MSIMI, indicating that hs-cTnI, NT-proBNP, SBP might be potential predictors of MSIMI.

Upper urinary surgery is an important area of urology surgery. Open surgery used to be the gold standard of upper urinary surgery. With the development of medical techniques, minimal invasive surgeries including laparoscopic and robot assisted-laparoscopic surgery have gradually replaced the open surgery. Because of the complexity and diversity of upper urinary diseases, surgeries sometimes are difficult, and minimal invasive surgeries require higher surgical abilities of urologists than open surgeries. In recent years, depending on our surgical experience and international reports, our team from three Chinese medical centers summarizes techniques of upper urinary minimal invasive surgeries. For malignant diseases, such as renal and ureteral carcinomas, it's important to totally remove the tumor first, and then to avoid the surgical injuries. We summarize surgical experience of retroperitoneal laparoscopic partial nephrectomy for moderately complex renal hilar tumors. Our team modified minimal invasive techniques for some complex tumors, including ring suture technique for renal hilar tumors, internal suspension technique for renal ventral tumors, and combination retroperitoneal laparoscopic surgery with mini-flank incision for complex renal tumors. While for begin diseases, urologists should focus on the resections and surgical injuries at the same time. We have reported the novel technique of laparoscopic aspiration for central renal angiomyolipoma, making the surgery simple and available. For reconstruction surgeries, operations should be based on several principals. We generalize it as "4TB principals", which include "tension-free", "water-tight", "thin suture", "no touch of the key area" and "protecting the blood supply". Depending on the localization, length, and etiology of the strictures, different techniques are required. Our team summarize the pyeloplasty, ureteral reimplantation and ileal ureter replacement based on our surgical experience. For infant upper urinary surgeries, our team has made invasive surgeries that can be used in complex diseases, such as duplex kidney. Based on years of surgical techniques, our modified surgeries achieve a better subjective cosmetic result than the traditional surgeries. In the future, the standardized, practical, simple and individual minimal invasive surgical technique will become the main direction in the future researches.
Humans ; Kidney ; Laparoscopy ; Nephrectomy ; Ureter ; Urologic Surgical Procedures

Objective:To investigate the analgesic time-effect characteristics and changes in concentrations of rabbit's hypothalamic 5-hydroxytryptamine (5-HT) and noradrenaline (NE) caused by buccal acupuncture in the rheumatoid arthritis (RA) rabbits,and to reveal the analgesic central mechanism of buccal acupuncture,thereby providing a theoretical basis for the treatment of pain by buccal acupuncture.Methods:Forty rabbits were randomly divided into a normal group,a model group,a body acupuncture group,and a buccal acupuncture group,with 10 rabbits in each group.No model was established in the normal group,while equal dose of normal saline was injected at the matched site and time point;rabbits in other groups were subjected to the establishment of RA models using egg protein.From the 27th day of the experiment,rabbits in each group received the designated intervention.Rabbits in the normal group and the model group were fixed for 30 min every day using the same method as those in the other groups.In the acupuncture group,Dubi (ST 35) and Zusanli (ST 36) on bilateral hind limbs were selected.Perpendicular needling (using the needles with 0.25 mm in diameter and 25 mm in length) was performed with twirling manipulation for 15 s at intervals of 5 min.The needles were retained for 30 min and acupuncture was performed once a day.In the buccal acupuncture group,the knee point in the buccal acupuncture and needles with a diameter of 0.25 mm and a length of 15 mm were selected.Oblique needling was performed with twirling manipulation for 15 s at intervals of 5 min.The needles were retained for 30 min and acupuncture was performed once a day.The thermal pain thresholds at the 0,5,15,30,60,120 and 240 min after the 1st and 10th acupuncture therapy were measured with a PL-200 thermal-inducing pain meter.After the 10th acupuncture therapy,rabbit's hypothalamus was removed,and the 5-HT and NE concentrations in the hypothalamus at the peak point of the acupuncture pain threshold curve were determined by high performance liquid chromatography (HPLC).Results:The analgesic effect was obvious at 5 min after buccal acupuncture started,peaked at 30 min,and decreased to the lowest value at 240 min.Rabbits in the body acupuncture group began to show significant analgesic effect at 15 min,which was peaked at 30 min,and began to decline at 60 min.The pain threshold at 240 min was still higher than that at 0 min.Compared with the model group,the concentrations of hypothalamic 5-HT in the buccal acupuncture group and the body acupuncture group was significantly increased,and the between-group differences were statistically significant (both P＜0.05).The NE/5-HT ratios in hypothalamus in the buccal acupuncture group and the body acupuncture group were significantly lower than the ratio in the model group,and the differences were statistically significant (both P＜0.05);difference in the decrease was statistically significant between the buccal acupuncture group and the body acupuncture group (P＜0.05).Conclusion:The analgesic effect of buccal acupuncture shows an obvious time-dependent curve.It is characterized by rapid onset of pain relief,rapid increase and decline in pain threshold.5-HT and NE levels in rabbit's hypothalamus can be affected by buccal acupuncture,with increased 5-HT concentration and reduced NE/5-HT ratio.

OBJECTIVETo investigate regulation function of anodonta glucan HBP-A on chondrocytes through Wnt pathway in vitro.

METHODSRat chondrocytes were cultured and differentiated induced with IL-1beta (10 ng/ml) in vitro. Chondrocytes were divided into five groups:IL-13 group,IL-1beta + IWP-2 (5 microM,Wnt pathway inhibitor) group, IL-1beta + HBP-A (0.3 mg/ml) group and IL-1beta + IWP-2 + HBP-A group. Wnt-3a, beta-catenin (24 h,48 h,72 h) and MMP-13(72 h) genes expression were detected by Rt-PCR, while beta-catenin, MMP-13, Sox-9 and coll-II (48 h) protein expression were measured by Western-blot.

RESULTSAfter induction of IL-1beta, gene expression of Wnt-3a, beta-catenin and MMP-13 were increased,so were the protein expression of beta-catenin and MMP-13. In contrast,protein expression of Sox-9 and Coll-II were declined. Following addition of HBP-A, Wnt-3a, beta-catenin and MMP-13 were shown as induction of IL-1beta, but protein expression of Sox-9 and Coll-II were upgraded. Combining HBP-A with IWP-2 led to the lowest level in Wnt-3a, beta-catenin gene and beta-catenin protein expression and highest expression of Sox-9 protein.

CONCLUSIONHBP-A could not only delay the differentiation of chondrocytes through downgrading the signal expression of Wnt/beta-catenin,but also adjust the expression of Wnt-3a, beta-catenin and Sox-9 when combinated with the Wnt inhibitor.

Animals ; Anodonta ; chemistry ; Cell Differentiation ; drug effects ; Cells, Cultured ; Chondrocytes ; cytology ; drug effects ; metabolism ; Glucans ; pharmacology ; Interleukin-1beta ; metabolism ; Rats ; Wnt Signaling Pathway ; drug effects ; Wnt3A Protein ; genetics ; metabolism ; beta Catenin ; metabolism

Objective:To investigate regulation function of anodonta glucan HBP-A on chondrocytes through Wnt path-way in vitro. Methods:Rat chondrocytes were cultured and differentiated induced with IL-1β (10 ng/ml) in vitro. Chondro-cytes were divided into five groups:IL-1βgroup,IL-1β+IWP-2 (5μM,Wnt pathway inhibitor) group,IL-1β+HBP-A (0.3 mg/ml) group and IL-1β+IWP-2+HBP-A group. Wnt-3a,β-catenin (24 h,48 h,72 h) and MMP-13(72 h) genes expres-sion were detected by Rt-PCR,whileβ-catenin,MMP-13,Sox-9 and coll-Ⅱ (48 h) protein expression were measured by Western-blot. Results:After induction of IL-1β,gene expression of Wnt-3a,β-catenin and MMP-13 were increased,so were the protein expression ofβ-catenin and MMP-13. In contrast,protein expression of Sox-9 and Coll-Ⅱwere declined. Follow-ing addition of HBP-A,Wnt-3a,β-catenin and MMP-13 were shown as induction of IL-1β,but protein expression of Sox-9 and Coll-Ⅱwere upgraded . Combining HBP-A with IWP-2 led to the lowest level in Wnt-3a ,β-catenin gene andβ-catenin protein expression and highest expression of Sox-9 protein. Conclusion:HBP-A could not only delay the differentiation of chondrocytes through downgrading the signal expression of Wnt/β-catenin,but also adjust the expression of Wnt-3a,β-catenin and Sox-9 when combinated with the Wnt inhibitor.