This paper summarized Professor PENG Peichu's experience in the differentiation and treatment of prostate cancer in three phases and four stages. It is considered that prostatic cancer is categorized into root deficiency and branch excess， with depletion of healthy qi as the root， and the accumulation of cancer toxin as the minifestation. Clinical diagnosis and treatment of prostatic cancer can be divided into three phases and four stages according to the exuberance and decline of pathogenic and healthy qi and the changes of deficiency and excess of yin and yang. In the initial accumulation phase of cancer toxin （yang excess stage）， the key pathogenesis is the accumulation of dampness， heat and static blood， and internal generation of cancer toxin， and the treatment should be resolving toxins， fighting cancer and dispelling yang excess. In the phase of healthy qi deficiency and toxin accumulation （yin deficiency stage）， with the lung and kidney yin deficiency， dampness， heat and static toxin accumulation as the key pathogenesis， the treatment should be centered on mutual generation between metal and water to nourish kidney yin， supplemented with the method of clearing heat and draining dampness， activating blood and resolving toxins， for which self-made Nanbei Formula（南北方）is usually used. In the phase of yang deficiency and cold stagnation （yang deficiency stage and yin excess stage）， with the spleen and kidney yang deficiency， cold dampness stagnation， static heat and toxin accumulation as the key pathogenesis， the treatment should be warming and tonifying spleen and kidney to dissipate cold accumulation； for deficiency of both yin and yang， and excess pathogen obstruction， modified Yanghe Decoction（阳和汤） is recommended， while for yang deficiency， cold congealing and blood stasis， self-made Wenshen Sanjie Formula（温肾散结方） can be used， and for cold dampness binding with cancer toxin， and cold complex with heat， self-made Quanan Formula （泉安方） is advised.

Objective To investigate the reliability and validity of the assessment tools of Brief ICF Core Sets for Arthroplasty of Knee Osteoarthritis in Perioperative Period(ICSAKOPP). Methods From May,2022 to April,2023,320 patients undergoing knee arthroplasty were selected in Peking University Third Hospital,China-Japan Friendship Hospital,Peking University First Hospital and Chinese PLA General Hospital.Trained assessors used Brief ICSAKOPP to evaluate all enrolled patients before arthroplasty,three days(±one day)after arthroplasty,three weeks(±one week)after arthroplasty,and three months(±one month)after ar-throplasty.Western Ontario and McMaster Universities Osteoarthritis Index(WOMAC)scores were recorded at the same time.Five professionals were asked to score all the items of Brief ICSAKOPP,and the content validity index(CVI)was caculated. Results A total of 64 cases were dropped down.CVI of all the items of the Brief ICSAKOPP were above 0.8,with a av-erage CVI of the scale of 0.938.The Cronbach's α coefficient of the Brief ICSAKOPP was 0.813.There was a moderate correlation(r=0.681,P<0.001)between the overall Brief ICSAKOPP and WOMAC scores,as well as body functional dimension score(r=0.668,P<0.001)and activities and participation dimension score(r=0.657,P<0.001). Conclusion Brief ICSAKOPP is good in content validity,internal consistency reliability and criterion validity.

Objective To evaluate the value of SOX1 and PAX1 gene methylation detection in the sec-ondary triage of high-grade cervical lesions.Methods Exfoliated cervical cells were collected from 122 patients tested positive for human papilloma virus(HPV)and subjected to thin-prep cytologic test(TCT)and SOX1/PAX1 gene methylation tests.Results The HPV test combined with TCT showed the sensitivity of 95.24％and the specificity of 23.75％for detecting cervical intraepithelial neoplasia(CIN)grade 2 and above(CIN2+).After the addition of the SOX1/PAX1 gene methylation detection in secondary triage,the sensitivity for detecting CIN2+was 83.33％,which had no statistically significant difference from the sensitivity of TCT combined with HPV test(P=0.078).However,the specificity reached 77.50％,which was significantly higher than that of HPV test combined with TCT(P＜0.001).The SOX1/PAX1 gene methylation level in the CIN2+group was higher than those in the normal cervical tissue and the CIN1 group(P＜0.001).The cut-off values of SOX1 and PAX1 gene methylation for CIN2+detection were-11.81 and-11.98,respectively.Conclusion Adding the detection of SOX1/PAX1 gene methylation in secondary triage significantly improves the efficiency and accuracy of CIN2+detection.

Objective:To investigate the influence of neoadjuvant chemotherapy on safety and prognosis of patients undergoing multivisceral resection for gastric cancer.Methods:The pro-pensity score matching (PSM) and retrospective cohort study was conducted. The clinicopathological data of 144 patients with gastric cancer who underwent multivisceral resection in the Fudan University Shanghai Cancer Center from December 2011 to December 2020 were collected. There were 95 males and 49 females, aged (56±13)years. Of 144 patients, 27 cases undergoing neoadjuvant chemotherapy and postoperative adjuvant chemotherapy were divided into the neoadjuvant chemotherapy group, and 117 cases undergoing postoperative adjuvant chemotherapy were divided into the adjuvant chemotherapy group. Observation indicators: (1) PSM and comparison of general data of patients between the two groups after matching; (2) surgical and postoperative conditions; (3) prognosis. PSM was done by the 1∶1 nearest neighbor matching method, with the caliper setting as 0.02. Measurement data with normal distribution were expressed as Mean± SD. Measurement data with skewed distribution were expressed as M(range), and comparison between groups was conducted using the rank sum test. Count data were expressed as absolute numbers, comparison between groups was conducted using the chi-square test. Comparison of ordinal data was conducted using the non-parameter test. The Kaplan-Meier method was used to draw survival curves and calculate survival rate, and the Log-Rank test was used for survival analysis. Results:(1) PSM and comparison of general data of patients between the two groups after matching. Of 144 patients, 46 cases were successfully matched, including 23 cases in the neoadjuvant chemotherapy group and 23 cases in the adjuvant chemotherapy group, respectively. The elimination of preoperative hemoglobin, clinical TNM staging confounding bias ensured comparability between the two groups after PSM. (2) Surgical and postoperative conditions. Of 46 patients, 26 cases underwent gastrectomy with one organ resection, 16 cases underwent gastrectomy with two organs resection, and 4 cases underwent gastrectomy with three organs resection. Of the patients with multivisceral resection, the proportion of patients undergoing combined splenectomy, pancreatectomy, colon resection, liver resection, and small intes-tinal resection was 69.6%(32/46), 39.1%(18/46), 32.6%(15/46), 8.7%(4/46), 2.2%(1/46), respectively. Cases with D 1 lymph node dissection, cases with D 2 lymph node dissection, cases with R 0 resection, cases with R 1 resection in the neoadjuvant chemotherapy group and the adjuvant chemotherapy group were 1, 22, 23, 0 and 0, 23, 23, 0, respectively, showing no significant difference in the above indicators between the two groups ( P>0.05). The number of lymph node dissected, the volume of intraoperative blood loss, duration of postoperative hospital stay in the neoadjuvant chemotherapy group and the adjuvant chemotherapy group were 28(range, 22-37), 150 (range, 100-200)mL, 11(range, 8-16)days and 25(range, 18-32), 150(range, 100-200)mL, 11(range, 9-18)days, respec-tively, showing no significant difference in the above indicators between the two groups ( Z=-1.13, -0.32, -0.50, P>0.05). Cases with complications ≥grade Ⅱ of Clavien-Dindo classification during the postoperative 30 days were 2 in the neoadjuvant chemotherapy group, including 1 case of abdominal abscess and 1 case of pneumonia. Cases with complications ≥grade Ⅱ of Clavien-Dindo classification during the postoperative 30 days were 8 in the adjuvant chemotherapy group, including 3 cases of abdominal abscess, 2 cases of anastomotic fistula, 1 case of pneumonia, 1 case of pancreatic fistula, 1 case of gastric emptying disability. There were significant differences in the complications ≥grade Ⅱ of Clavien-Dindo classification between the neoadjuvant chemotherapy group and the adjuvant chemotherapy group ( χ2=4.60, P<0.05). There was no significant difference in the abdominal abscess, anastomotic fistula, pneumonia, pancreatic fistula, gastric emptying disability between the two groups ( P>0.05). None of patient died in either of the neoadjuvant chemotherapy group and the adjuvant chemotherapy group. (3) Prognosis. Of 46 patients, 43 cases were followed up for 15.4(range, 3.0-84.0)months. The overall survival time of patients in the neoadjuvant chemotherapy group and the adjuvant chemotherapy group were (14±10)months and (24±22)months, showing no significant difference between them ( hazard ratio=0.82, 95% confidence interval as 0.28-2.40, P>0.05). Conclusion:Compared with postoperative adjuvant chemotherapy, neoadjuvant chemotherapy does not increase the surgical risk of locally advanced gastric cancer patients undergoing multivisceral and radical resection, and can reduce the incidence of complications ≥grade Ⅱ of Clavien-Dindo classification during the postoperative 30 days, but does not improve patient survival.

METTL3 and METTL14 are two components that form the core heterodimer of the main RNA m6A methyltransferase complex (MTC) that installs m6A. Surprisingly, depletion of METTL3 or METTL14 displayed distinct effects on stemness maintenance of mouse embryonic stem cell (mESC). While comparable global hypo-methylation in RNA m6A was observed in Mettl3 or Mettl14 knockout mESCs, respectively. Mettl14 knockout led to a globally decreased nascent RNA synthesis, whereas Mettl3 depletion resulted in transcription upregulation, suggesting that METTL14 might possess an m6A-independent role in gene regulation. We found that METTL14 colocalizes with the repressive H3K27me3 modification. Mechanistically, METTL14, but not METTL3, binds H3K27me3 and recruits KDM6B to induce H3K27me3 demethylation independent of METTL3. Depletion of METTL14 thus led to a global increase in H3K27me3 level along with a global gene suppression. The effects of METTL14 on regulation of H3K27me3 is essential for the transition from self-renewal to differentiation of mESCs. This work reveals a regulatory mechanism on heterochromatin by METTL14 in a manner distinct from METTL3 and independently of m6A, and critically impacts transcriptional regulation, stemness maintenance, and differentiation of mESCs.
Animals ; Mice ; Methylation ; Chromatin ; Histones/metabolism* ; RNA, Messenger/genetics* ; Methyltransferases/metabolism* ; RNA/metabolism*

In addition to the essential pharmacologi-cal effects of opioids,situational cues associated with drug addiction memory are key triggers for drug seeking.CircRNAs,an emerging hotspot regulator in crown genet-ics-play an important role in central nervous system-relat-ed diseases.However,the internal mediating mechanism of circRNA in the field of drug reward and addiction mem-ory remains unknown.Here,we trained mice on a condi-tional place preference(CPP)model and collected nucle-us accumbens(NAc)tissues from day 1(T0)and day 8(T1)for high-throughput RNA sequencing.qRT-PCR revealed that circTmeff-1 was highly expressed in the NAc core but not in the NAc shell,suggesting that it plays a role in addiction memory formation.Meanwhile,the reverse regulation of circTmeff-1 by adeno-associated viruses could both inhibit the formation of addiction mem-ory in the NAc core or shell.Subsequently,the GO and KEGG analyses indicated 21 that circTmeff-1 might regu-late the addiction memory via the MAPK and AMPK path-ways.These findings suggest that circTmeff-1 in NAc plays a crucial role in morphine-dependent memory for-mation.

ObjectiveTo investigate rehabilitation competence among trainers and trainees whom participated in the training program entitled National Training Program of Shortage Rehabilitation Physicians (NTPSRP) using World Health Organization rehabilitation competency framework (RCF). MethodsBased on RCF, a questionnaire was developed and administrated through network using Questionnaire Star. All the trainers and trainees who participated in NTPSRP were investigated in September, 2023. ResultsA total of 911 subjects were collected from 27 provinces, including 426 trainers (teachers) and 485 trainees (students). The average age of the teachers was older, with more years of work experience and professional experience in rehabilitation medicine. The degree and professional title of the teachers was also higher. The overall internal consistency reliability of the questionnaire was good (Cronbach's α = 0.988), and all the internal consistency reliability in five fields was good (Cronbach's α > 0.9). The five dimensional structure of RCF in the results was consistent with the prior model established by RCF theory. The self-ratings of all physicians in the five fields were higher than the median level, and was higher in the teachers than in the students [(3.42±0.68) vs. (2.73±0.80), P < 0.001]. Gender and years of experience in rehabilitation medicine were independent factors for the total score of the questionnaire. The total self-rating of female students was 9.65 points lower than that of the male (95%CI 4.386 to 14.914); and one more year in rehabilitation medicine would increase 1.78 points in self-rating (95%CI 1.140 to 2.419). ConclusionThe structure and content of RCF can be used to evaluate the competence of rehabilitation physicians. The teachers and students of NTPSRP are eligible to RCF. RCF-based evaluation can be used to guide the development of continuing education courses for rehabilitation professionals.

Pulmonary endothelial barrier dysfunction is a hallmark of clinical pulmonary edema and contributes to the development of acute lung injury (ALI). Here we reported that ruscogenin (RUS), an effective steroidal sapogenin of Radix Ophiopogon japonicus, attenuated lipopolysaccharides (LPS)-induced pulmonary endothelial barrier disruption through mediating non-muscle myosin heavy chain IIA (NMMHC IIA)‒Toll-like receptor 4 (TLR4) interactions. By in vivo and in vitro experiments, we observed that RUS administration significantly ameliorated LPS-triggered pulmonary endothelial barrier dysfunction and ALI. Moreover, we identified that RUS directly targeted NMMHC IIA on its N-terminal and head domain by serial affinity chromatography, molecular docking, biolayer interferometry, and microscale thermophoresis analyses. Downregulation of endothelial NMMHC IIA expression in vivo and in vitro abolished the protective effect of RUS. It was also observed that NMMHC IIA was dissociated from TLR4 and then activating TLR4 downstream Src/vascular endothelial cadherin (VE-cadherin) signaling in pulmonary vascular endothelial cells after LPS treatment, which could be restored by RUS. Collectively, these findings provide pharmacological evidence showing that RUS attenuates LPS-induced pulmonary endothelial barrier dysfunction by inhibiting TLR4/Src/VE-cadherin pathway through targeting NMMHC IIA and mediating NMMHC IIA‒TLR4 interactions.

[This corrects the article DOI: 10.1016/j.apsb.2021.09.017.].

Objective:To establish Sprague-Dawley (SD) rat models of cognitive impairment through repeated stimulation of lipopolysaccharide (LPS) in the early brain development, and to inquire into the effect of " multi-hits" mediated by inflammatory response on the histology and behavior of SD rat models and related molecular mechanisms.Methods:This study adopted a group design for experiments.The " multi-hits" SD rat models were established by intraperitoneal injection of LPS.According to the random number table method, 24 pregnant rats were randomly divided into 4 groups: control group, LPS1 group, LPS2 group and LPS3 group, 6 rats in each group.In the control group, saline was intraperitoneally injected into rats with gestational age of 18 days and 20-day-old neonatal rats.Rats with gestational age of 18 days were intraperitoneally injected with saline in the LPS1 group, 0.05 mg/kg LPS in the LPS2 group, and 0.1 mg/kg LPS in the LPS3 group.The pups in LPS1-3 groups were all injected intraperitoneally with 1 mg/kg LPS at the postnatal age of 20 days.The motor and cognitive function of the pups were evaluated overall by behavioral experiments such as forelimb suspension tests, grid tests and water maze tests.The relative expression of glial fibrillary acidic protein (GFAP), Notch1 and Jagged1 in brain tissue of pups was mainly detected by Western blot (WB) and histological experiments.One-way ANOVA analysis of variance and independent samples t- test were used to compare data among groups and between groups, respectively. Results:(1) Behavioral experiments: compared with the control group, LPS1-3 groups showed progressive decrease in forelimb suspension time [(34.81±5.66) s, (22.47±4.35) s, and (13.20±4.25) s vs.(43.88 ± 4.85) s], and the number of missteps in the grid experiment increased progressively (16.13±2.90, 20.75±3.10, 25.13±4.45 vs.9.00±2.72). The differences were statistically significant ( F=69.77, 35.59, all P<0.001). Both the escape latency and total distance in Morri′s water maze test increased progressively ( P<0.05). (2) WB experiment: the relative expression levels of GFAP, Notch1 and Jagged1 proteins in LPS1-3 groups were significantly higher than that in the control group ( P<0.05). (3) Hematoxylin-eosin (HE) staining and electron microscope pathology: compared with the control group, LPS1-3 groups had more loosely arranged frontal cortices and more obvious cell pyknosis.Under the electron microscope, the cytoplasm was swelling to varying degrees, mitochondrial cristae were broken, and part of the nuclear membrane was damaged. Conclusions:In the " multi-hits" cognitive impairment model, the damage to the brain tissue structure and behavioral changes of pups may be related to the up-regulation of Notch1/Jagged1 pathway mediated by repeated exposure to LPS.