A 20-year-old male patient presented to the Department of Dermatology of Peking Union Medical College Hospital with complaints of an 8-year history of facial scarring, swelling of the lower limbs, and a 4-year history of scalp thickening. Physical examination showed thickening furrowing wrinkling of the skin on the face and behind the ears, ciliary body hirsutism, blepharoptosis, and cutis verticis gyrate. Both lower limbs were swollen, especially the knees and ankles. The skin of the palms and soles of the feet was keratinized and thickened. Laboratory examination using bone and joint X-ray showed periostosis of the proximal middle phalanges and metacarpals of both hands, distal ulna and radius, tibia and fibula, distal femurs, and metatarsals.Genetic testing revealed two variants in SLCO2A1, c.1658T > A and c.96+4A > C.Through multidisciplinary consultation, we confirmed the diagnosis of pachydermoperiostosis.

Aim To explore the role of SIRT1/Nrf2 / HO-1 in alleviating the cognitive function impairment by sevoflurane treatment in a mouse model of postoperative cerebral reperfusion. Methods C57BL/6J mice were randomly divided into five groups: sham operation group, hemorrhagic shock reperfusion group, sevoflurane postconditioning group, sevoflurane postcondition-ing + SIRT1 inhibitor group and sevoflurane postconditioning + Nrf2 inhibitor group. Mice were subjected to Morris water maze test after cerebral ischemia reperfusion. The ATP, superoxide dismutase (SOD), ROS and MDA contents in tissue of mice were detected. SIRT1, Nrf2 and HO-1 proteins in tissue were detected by Western blot. Results After hemorrhagic shock, the learning and memory ability of mice was reduced.ATP and SOD concentration in hippocampus was reduced , MDA and ROS concentration increased, and the SIRT, Nrf2 and HO-1 concentration was reduced. Sevoflurane improved the cognitive dysfunction and oxi-dative damage in postoperative mice, and the neuro-protective effect of sevoflurane on hemorrhagic shock and resuscitation mice was weakened followed with SIRT1 and Nrf2 inhibitors. Conclusion Sevoflurane probably alleviates the oxidative reaction damage and cognitive impairment caused by cerebral reperfusion in mice through SIRT1/Nrf2/H0-1 pathway.

Objective To establish a method of LC-MS/MS for determining cordycepin(Cor)and 3′-deoxyinosine(3′-Deo)concentration in rat plasma,and to study their pharmacokinetics in rats.Methods Protein was precipitated with methanol using 2-chloadenosine(2-Chl)as an internal standard.The chromatography was performed on Kinetex C18(3 mm×100 mm,2.6 μm,Phenomenex,USA)with gradient elution in aqueous(5 mmol·L-1 ammonium acetate)-methanol solution as mobile phase.ESI ion source was used for mass spectrometry,and positive ion multiple reaction monitoring(MRM)was used for scanning detection.The pharmacokinetics of Cor and 3′-Deo after oral administration of Cor(10 mg·kg-1)were studied in rats.Results Cor at 0.5-100 ng·mL-1 and 3′-Deo at 1-200 ng·mL-1 had good linearity,and the lower limits of quantification were 0.5 and 1 ng·mL-1,respectively.After oral administration of Cor in rats,the plasma concentration of Cor was low,which was mainly converted into the metabolite 3′-Deo.The Cmax of Cor and 3′-Deo were(5.4±3.4)and(142.0±50.0)ng·mL-1,and AUC0-360min min were(658.4±459.3)and(18 034.9±4 981.1)ng·min·mL-1,respectively.Conclusion The method is simple,sensi-tive,and accurate,which is suitable for determining Cor and 3′-Deo concentration in plasma and the pharmacokinetic study.

Objective To understand the consumption of hand hygiene(HH)products and HH compliance in in-tensive care units(ICUs)of secondary and higher grade medical institutions(MIs)in Shanghai,and provide basis for further monitoring of HH among health care workers(HCWs).Methods Through healthcare-associated infec-tion surveillance system,the consumption of HH products and HH compliance in ICUs from secondary and higher grade MIs in Shanghai in 2017-2021 were analyzed.Results 105 ICUs from 74 MIs were included in analysis,the average consumption of HH products was 79.24(44.88-258.63)mL/(bed·day),with statistically significant difference among different types of ICUs(P＜0.001).The average consumption of HH products increased from 65.75 mL/(bed·day)in 2017 to 87.55 mL/(bed·day)in 2021,showing an increasing trend year by year(P＜0.001).HCWs'HH compliance rate was 82.13％,with the highest in nurses(86.59％)and the lowest(48.90％)in medical technicians,HH compliance rates of HCWs of different occupations were statistically significant different(P＜0.001).Among the implementation modes of HH,39.86％used running water for hand washing,42.27％used alcohol-based hand rub to wipe hands,13.22％didn't take HH measures,and 4.65％didn't take HH mea-sures when wearing gloves,with statistically significant differences among different HH implementation modes of HCWs(P＜0.001).There was a positive correlation between the average consumption of HH products per bed·day and HCWs'HH compliance rate(r=0.703,P＜0.05).Conclusion The average consumption of HH products per bed·day and HH compliance rate of HCWs in ICUs in Shanghai presents an increasing trend year by year.There are differences in the average consumption of HH products per bed·day and HH compliance rate among different types of ICUs.The implementation of HH can be evaluated by continuously surveillance on the average consumption of HH products per bed·day.

With the advancement of comprehensive treatment and minimally invasive technology, patients with originally unresectable gallbladder cancer are expected to undergo surgical treatment after transformational therapy, which can achieve the effect of increasing R0 resection rate and improving long-term prognosis. Conversion therapy as a new option for patients with gallbladder cancer who are difficult to undergo radical surgery is still subject to much debate. Patients with locally progressive gallbladder cancer at the initial diagnosis may be the target population for conversion therapy. Gemcitabine+ cisplatin is still used as the standard first-line chemotherapy regimen. The use of multiple chemotherapeutic agents in combination also shows new vitality. High-throughput sequencing and the use of precision targeting drugs will become new trends in the future. The use of immune drugs is still needed. And the use of immunotherapy drugs is still in demand. High-throughput sequencing and the use of precision-targeted drugs will become a new trend in the future, the use of immunologic drugs still needs more evidence-based medical support, and the use of post-translational minimally invasive techniques may bring benefits to patients.

ObjectiveTo observe the clinical efficacy of Tongdu Huoxue decoction in the treatment of acute lumbar disc herniation （LDH）. MethodA total of 316 patients with acute LDH admitted to the orthopedic outpatient department of Hubei Provincial Hospital of Traditional Chinese Medicine and Honghu City Hospital of Traditional Chinese Medicine from January 2020 to June 2023 were randomly divided into two groups. 156 cases in the control group （two cases with stopped follow-up） were treated with meloxicam tablets， while 153 cases in the observation group （five cases with stopped follow-up） were treated with Tongdu Huoxue decoction. Both groups were treated for three months. The clinical efficacy， McGill Pain Score Scale （SF-MPQ）， Oswestry Dysfunction Index （ODI） score， and the Japanese Orthopaedic Association （JOA） scores of the two groups before and after treatment were compared. The serum levels of interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-α （TNF-α） of the patients before and after treatment were determined by using enzyme-linked immunosorbent assay （ELISA）. The NDI-092 type electromyography-evoked potential instrument was adopted to measure the motor conduction velocity and clinical efficacy of the tibial and common peroneal nerves in patients of the two groups before and after treatment， and the clinical safety of the two groups of patients was compared. ResultAfter treatment， the total effective rate in the observation group was 95.4% （146/153）， significantly higher than that in the control group of 76.3% （119/156） （χ² =23.18， P<0.05）. After treatment， both groups showed significant reductions in SF-MPQ and ODI scores， as well as the levels of IL-1β， IL-6， and TNF-α （P<0.05）， with the observation group showing a more significant reduction （P<0.05）. Both groups showed a significant increase in JOA scores and motor conduction velocities of the tibial and common peroneal nerves after treatment （P<0.05）， with the observation group showing a more significant increase （P<0.05）. ConclusionTongdu Huoxue decoction can alleviate lumbar and leg pain in acute LDH， improve lumbar spine function， and suppress inflammatory reactions. It is highly safe and is worthy of clinical promotion.

Celastrol and wilforlide A are the main active triterpenoids of the traditional Chinese medicine Lei Gong Teng, which have anti-tumour, anti-inflammatory and immunosuppressive activities, and are the material basis for the clinical efficacy of Lei Gong Teng-related Chinese medicinal preparations. By analysing the biosynthetic pathway of active ingredients, optimizing genetic elements and utilizing "cell factory" to produce triterpenoids heterologously will be an effective way to obtain from Tripterygium wilfordii in the future in a "low-cost and high-efficient" manner. CYP712Ks are the first cytochrome P450s involved in the skeleton modification of friedelane-type and oleanane-type triterpenoids in T. wilfordii, and they can catalyse the generation of polpunonic acid from friedelin and 3-epi-katonic acid from β-amyrin by carboxylation at C-29 position. In this study, four multifunctional TwCYP712K1/2/3/5 were used to clarify the catalytic function and substrate selection preference using in vivo functional characterization in Saccharomyces cerevisiae. The spatial structure of the protein-substrate binding was clarified through homology modeling and molecular docking, and then the differential amino acids in the active pocket of the protein were mutated to clarify the crucial amino acids determining the catalytic function and the selection of substrate structure. A total of 63 mutant elements were constructed, and the amino acid sites affecting the carboxylation function of TwCYP712Ks were analyzed. In particular, the key amino acids affecting the substrate selectivity of TwCYP712K2 towards oleanane-type and friedelane-type triterpenoids were revealed and the TwCYP712K2^F127I and TwCYP712K2^A227T mutants would result in a reversal of the product ratio. In conclusion, four proteins of TwCYP712Ks were semi-rationally designed by homologous protein alignment and mutual mutation to elucidate multiple amino acid sites determining the catalytic function of the proteins, and a series of activity-enhancing or altering mutants were obtained, which provide abundant catalytic elements for the biosynthesis of active triterpenoids from T. wilfordii, and the mechanism of carboxylation in the C-29 position was initially elucidated.

italic>Acanthopanax senticosus is one of the genuine regional herb in Northeast China. In this study, we identified the germplasm resources of commercial A. senticosus samples based on atpI and atpB_rbcL according to the previous chloroplast genome sequencing results, and determinated the content of syringin by HPLC to evaluated the quality of commercial samples. A total of 80 A. senticosus samples were collected from 47 cities in 24 provinces. DNA was extracted to amplify the products of atpI and atpB_rbcL by PCR. The results showed that 7 haplotypes (H2, H5, H8, H10, H12, H14, H23) were formed by the combined analysis of the two gene fragments. H2 from Yichun in Heilongjiang, Shangzhi in Harbin, Suihua in Heilongjiang, Fushun in Liaoning, Benxi in Liaoning, Changbai in Jilin and Jingyu in Jilin were the dominant genotype, representing 58.75% of the total samples. H14 and H23 were the unique haplotypes of the producing area. It is speculated that the commercial A. senticosus samples with haplotypes of H14 and H23 are from Raohe, Shuangyashan, Heilongjiang and Mingshui, Suihua, Heilongjiang, respectively. HPLC analysis indicated that the content of syringin in 73.96% of the samples met the Pharmacopoeia standards. There was a significant difference in the content of syringin among the samples, ranging from 0.003 7% to 0.524 5%, with a difference of 0.520 8%, indicating that the quality of the samples in the market of A. senticosus was uneven. However, there were no significant differences in the contents of syringin in the commercial A. senticosus among different haplotypes. The content of syringin in the haplotype H23 in the market sample is relatively high, so it may be a germplasm with better quality. This study researched the germplasm resources and medicinal materials quality of commercial A. senticosus samples and will help guide the commercial circulation, reasonable medication of A. senticosus, and the screening of excellent germplasm.

Objective To explore clinical effect of the fifth metatarsal head excision and non-excision in rheumatoid arthritis(RA)forefoot deformity reconstruction.Methods Retrospective analysis was performed on 50 patients(76 feet)with moderate to severe forefoot deformity caused by RA treated from May 2015 to January 2019.According to degeneration of the fifth metatarsophalangeal joint,the fifth metatarsal head was retained or excised by wind-like forefoot reconstruction,and divid-ed into the fifth metatarsal head preservation group(preservation group)and the fifth metatarsal head resection group(resec-tion group).Twenty-four female patients in preservation group,aged from 47 to 81 years old with an average of(60.37±8.60)years old;the course of disease ranged from 13 to 22 years with an average of(19.00±3.06)years;body mass index(BMI)ranged from 21 to 28 kg·m-2 with an average of(23.53±2.47)kg·m-2;six patients(6 feet)with moderate hallux valgus defor-mity and 18 patients(30 feet)with severe hallux valgus deformity;treated with the first metatarsophalangeal joint fusion com-bined with the second th the fourth metatarsophalangeal joint arthroplasty and the fifth metatarsophalangeal joint cleanup.Twenty-six female patients in resection group were female,aged from 30 to 80 years old with an average of(58.53±13.70)years old;the course of disease ranged from 8 to 25 years with an average of(17.94±3.92)years;BMI raged from 20 to 28 kg·m-2 with an average of(24.60±2.03)kg·m-2;4 patients(4 feet)with moderate bunion valgus deformity and 22 patients(36 feet)with severe bunion valgus deformity;treated by the first metatarsophalangeal joint fusion combined with the second th the fifth metatarsophalangeal joint resection of the metatarsophalangeal head.Operation time and postoperative complications between two groups were observed,hallux valgus angle(HVA),intermetatarsal angles between the first and the second metatarsals(I-MAFS),intermetatarsal angles between the first and fifth metatarsals(IMAFF),Japanese Society for Surgery of Foot(JSSF)score before surgery and at the latest follow-up were compared.Results Fifty patients were followed-up from 14 to 46(25.30± 8.83)months in resection group and 12 to 48 with an average of(24.30±1 1.12)months in preservation group,while no signifi-cant difference between two groups(P＞0.05).There were no significant difference in operation time and postoperative compli-cations between two groups(P＞0.05).JSSF scores,HVA,IMAFS and IMAFF in fesection group were improved from(45.09± 3.35)points,(38.90±13.67)°,(12.88±1.72)°,(32.50±2.99)° before operation to(81.60±3.27)points,(15.40±0.90),(9.06±2.27)°,(22.20±1.98)° at the latest follow-up(P＜0.05);preservation group were improved from(47.09±3.96)points,(43.30±12.65)°,(13.99±3.13)°,(33.20±6.14)° to(83.10±3.66)points,(15.20±1.54)°,(8.99±1.02)°,(24.70±1.88)°,respectively.There were no significant difference in JSSF score,HVA,IMAFS and IMAFF between two groups before opera-tion and the latest follow-up(P＞0.05).At the latest follow-up,there were statistically significant differences in pain and defor-mity in JSSF scores between two groups(P＜0.05).Conclusion Both rheumatoid anterior foot reconstruction and anterior foot reconstruction fifth metatarsophalangeal joint debridement showed significant improvement in clinical efficacy and imaging re-sults.Compared with rheumatoid prefoot reconstruction,the fifth metatarsophalangeal joint reconstruction for the treatment of moderate and severe deformity of rheumatoid prefoot showed better improvement in pain,but worse improvement in deformity.For the moderate to severe deformity of the forefoot caused by rheumatoid disease,patients with mild to moderate degenerative deformity of the articular surface of the fifth metatarsal phalanges may be considered for use.

ObjectiveThe purpose of this study was to investigate the effects of transcutaneous electrical acupoint stimulation (TEAS) on cognitive function of vascular dementia (VD) rats and its mechanism. MethodsVD rat model was established by modified two-vessel occlusion (2-VO). After modeling, TEAS and electroacupuncture (EA) were used to stimulate Baihui and Zusanli points of rats respectively for 14 d. After treatment, novel object recognition test, Morris water maze test, and Y maze test were used to evaluate the spatial memory and learning ability of rats. Hematoxylin and eosin staining was used to observe the morphology of hippocampal neurons. Transmission electron microscopy was used to observe the ultrastructure of hippocampal mitochondria. Enzyme-linked immunosorbent assay kits were used to detected the levels of SOD, CAT, GSH-Px, MDA and ROS in serum of rats. Western blot was used to detect the expression of PGC-1α, TFAM, HO-1, NQO1 proteins in the hippocampus, Keap1 protein in the cytoplasm and Nrf2, NRF1 proteins in the nucleus. ResultsAfter treatment for 14 d, compared to the model group, the escape latency of VD rats decreased, while the discrimination index, the times of rats crossing the original platform area, the residence time in the original platform quadrant, and the percentage of alternation increased. TEAS can improve the structure of hippocampal neurons and mitochondria of VD rats, showing that neurons were arranged more regularly and distributed more evenly, nuclear membrane and nucleoli were clearer, and mitochondrial swelling were reduced, mitochondrial matrix density were increased, and mitochondrial cristae were more obvious. The levels of SOD, GSH-Px and CAT in serum increased significantly, while the concentration of MDA and ROS decreased. TEAS also up-regulated the expression levels of PGC-1α TFAM, NQO1 and HO-1 proteins in the hippocampus and Nrf2, NRF1 proteins in the nucleus, but down-regulated the Keap1 protein in the cytoplasm. ConclusionTEAS can improve cognition, hippocampal neurons and mitochondrial structure of VD rats, and the effect is better than EA. The mechanism may be the activation of PGC-1α mediated mitochondrial biogenesis and antioxidant stress, which also provides a potential therapeutic technology and experimental basis for the treatment of VD.