Objective To explore the effect of Endoanal advancement flap(ERAF)and transanal opening of interphincteric space(TROPIS)in the treatment of complex anal fistula and their impact on anorectal pressure,so as to provide a reference for clinical selection of surgical methods.Methods Eighty-four patients with complex anal fistula admitted from October 2018 to October 2022 were divided into group E received ERAF treatment(n=48)and group T received TROPIS treatment(n=36).The clinical efficacy,operation,wound surface and anorectal pressure of the two groups were compared.Results The effective rate of treatment in Group T was 97.22％,which was higher than that in Group E(87.50％),with no statistically significant difference(P＞0.05).The surgical time[(31.53 ±7.29)minutes],intraoperative bleeding volume[(29.56±7.37)ml],and wound area[(10.03± 0.96)cm2,(8.76±0.87)cm2,(6.20±0.77)cm2]on the day of surgery,7 and 14 days after surgery in Group T were all smaller than those in Group E[(35.36±8.54)min,(36.86±8.04)ml,(12.09± 1.23)cm2,(10.52±1.09)cm2 and(7.36±0.85)cm2](P＜0.05).After surgery,the VAS score and Wexner incontinence score of Group T were(1.38±0.27)and(0.21±0.08),respectively.Group E was(1.56±0.29)and(0.33±0.09),respectively.In group T,the anorectal systolic pressure at 20 mm and 30 mm and the anorectal resting pressure at 20 mm and 30 mm were(138.18±29.58)mmHg,(136.22±35.41)mmHg,(35.47±6.58)mmHg,and(32.97±8.01)mmHg,respectively.In Group E,the data was(152.78±31.53)mmHg,(156.29±32.74)mmHg,(38.29±7.62)mmHg and(36.41±7.63)mmHg,respectively.Both groups showed a decrease in score and anorectal pressure,and group T was lower than group E(P＜0.05).The incidence of adverse reactions in Group E was 20.83％,which was higher than that in Group T(11.11％),but the difference was not statistically significant(P＞0.05).Conclusion TROPIS has a better effect in the treatment of complex anal fistula,which can shorten the operation time,reduce intraoperative bleeding,reduce postoperative pain,and protect anal function.

Traumatic supraorbital fissure syndrome (TSOFS) is a symptom complex caused by nerve entrapment in the supraorbital fissure after skull base trauma. If the compressed cranial nerve in the supraorbital fissure is not decompressed surgically, ptosis, diplopia and eye movement disorder may exist for a long time and seriously affect the patients′ quality of life. Since its overall incidence is not high, it is not familiarized with the majority of neurosurgeons and some TSOFS may be complicated with skull base vascular injury. If the supraorbital fissure surgery is performed without treatment of vascular injury, it may cause massive hemorrhage, and disability and even life-threatening in severe cases. At present, there is no consensus or guideline on the diagnosis and treatment of TSOFS that can be referred to both domestically and internationally. To improve the understanding of TSOFS among clinical physicians and establish standardized diagnosis and treatment plans, the Skull Base Trauma Group of the Neurorepair Professional Committee of the Chinese Medical Doctor Association, Neurotrauma Group of the Neurosurgery Branch of the Chinese Medical Association, Neurotrauma Group of the Traumatology Branch of the Chinese Medical Association, and Editorial Committee of Chinese Journal of Trauma organized relevant experts to formulate Chinese expert consensus on the diagnosis and treatment of traumatic supraorbital fissure syndrome ( version 2024) based on evidence of evidence-based medicine and clinical experience of diagnosis and treatment. This consensus puts forward 12 recommendations on the diagnosis, classification, treatment, efficacy evaluation and follow-up of TSOFS, aiming to provide references for neurosurgeons from hospitals of all levels to standardize the diagnosis and treatment of TSOFS.

Objective:To investigate the pregnancy outcomes of different treatment methods for triplet pregnancies with different chorionicities.Methods:A retrospective study was conducted on 97 triplet pregnancies who visited and delivered at the Department of Obstetrics, the Third Affiliated Hospital of Zhengzhou University, from January 1, 2017, to November 30, 2023. The pregnancies were categorized based on chorionicity into monochorionic triamniotic (MCTA) ( n=24), dichorionic triamniotic (DCTA) ( n=33), and trichorionic triamniotic (TCTA) ( n=40). They were further divided into expectant management group ( n=46), reduction to twins group ( n=40), and reduction to singleton group ( n=11) based on the treatment method. Pregnancy outcomes were compared among the groups. Statistical analysis were performed using t-test, corrected t-test, one-way analysis of variance and LSD test, Kruskal-Wallis test and Mann-Whitney U test, Chi-square test, continuity correction Chi-square test, Fisher's exact test, and Bonferroni correction. Results:(1) Comparison of pregnancy outcomes with different treatment methods for the same chorionicity: In MCTA, there were no statistically significant differences in gestational age at delivery, live birth rate before 37 weeks, live birth rate before 32 weeks, neonatal birth weight, and incidence of severe neonatal complications between the expectant management group and the reduction to monochorionic diamniotic (MCDA) group (all P>0.05). In DCTA, compared to the reduction to singleton group, the expectant management group had lower gestational age at delivery [(31.8±2.7) vs. (37.9±1.3) weeks, U=－3.66] and neonatal birth weight [(1 604.3±422.6) vs. (2 997.1±598.9) g, U=－3.84] (both P<0.05), but higher live birth rate before 37 weeks (9/10 vs.1/8, Bonferroni correction, P<0.017). The expectant management group showed a trend towards higher rates of pregnancy complications (5/10 vs. 2/15 and 0/8) and severe neonatal complications [37.0% (10/27) vs. 10.7% (3/28) and 0/7] compared to the groups reduced to dichorionic diamniotic (DCDA) twins and singletons. However, the differences between the groups were not statistically significant (all P>0.017). In TCTA, compared to the expectant management group, the reduction to DCDA group had a higher gestational age at delivery [(37.1±0.9) vs. (34.1±2.7) weeks, t'=－4.36], and increased neonatal birth weight [(2 647.5±377.8) vs. (1 902.5±459.9) g, t'=－6.98] (both P<0.05). The incidence of maternal pregnancy complications [3/15 vs. 54.2% (13/24)] and live birth rate before 37 weeks [3/15 vs. 66.7% (16/24)] were lower (Fisher's exact test, both P<0.05). (2) Comparison of pregnancy outcomes with different chorionicities for the same treatment method: In the expectant management group, the DCTA group had the lower neonatal birth weight compared to the MCTA and TCTA groups [(1 604.3±422.6) vs. (1 948.3±573.4) and (1 902.5±459.9) g, LSD test, both P<0.05]. In the fetal reduction group, the TCTA group had higher neonatal birth weight compared to the MCTA and DCTA groups [(2 657.6±373.3) vs. (2 000.8±443.3) and (2 078.8±799.9) g, U=－2.91 and U=－3.12] (both P<0.05). Conclusions:The appropriate treatment method for triplet pregnancies should be selected based on chorionicity. Expectant management is recommended for MCTA, fetal reduction is suggested for DCTA to improve pregnancy outcomes. For TCTA, the pregnant woman should be informed of the risks of preterm birth associated with expectant management, who should then decide whether to undergo fetal reduction.

Objective: To understand social anxiety of Tibetan adolescents aged 10-15 years old in high altitude areas and its correlation with sleep duration, so as to provide a reference and support for social anxiety prevention and mental health interventions for Tibetan adolescents in high altitude areas. Methods: A total of 2 426 Tibetan adolescents from the Lhasa, Chamdo, and Nagchu regions of Tibet were surveyed. From April to June 2022, basic demographics, social anxiety, and sleep status were obtained and analyzed using class based, stratified whole group sampling, and the correlations detected between the two were analyzed by logistic regression analysis. Results: The average social anxiety score of Tibetan adolescents aged 10-15 years in high altitude areas was (6.51±4.32), and the detection rate of social anxiety was 5.23%. The mean sleep duration was (7.42±1.18) hours/day. The differences were statistically significant when compared across gender, overweight/obesity status, level of physically activity, and sleep duration ( χ 2=19.44, 14.39, 7.83, 7.21, P <0.05). After adjusting for relevant variables, the Logistic regression analysis showed that sleep deprivation among boys ( OR =2.91, 95% CI =1.82-4.61), sleep deprivation among girls ( OR = 3.51 , 95% CI =2.01-6.04), and overall sleep deprivation among Tibetan adolescents ( OR =3.12, 95% CI =1.91-4.58) were positively associated with social anxiety( P <0.01). Conclusions A positive association was found between social anxiety and sleep deprivation, indicating that social anxiety is an issue among Tibetan adolescents living in high altitude regions. Sufficient sleep duration plays a positive protective role in reducing social anxiety among Tibetan adolescents in high altitude areas, and the findings provide a reference for future mental health interventions.

Objective:To investigate the application value of domestic robotic surgical system in radical resection of hilar cholangiocarcinoma (hCCA).Methods:The retrospective and descriptive study was constructed. The clinicopathological data of a 66-year-old male patient with hCCA who was admitted to the Second Hospital of Shandong University in November 2022 were collected. Radical resection of hCCA was performed using the Toumai? laparoscopic surgical robot system. Observation indicators: (1) intraoperative conditions; (2) postoperative conditions; (3) follow-up. Count data were represented as absolute numbers and (or) percentages.Results:(1) Intraoperative conditions. The patient underwent radical resection of hCCA successfully using robotic surgical system, including tumor resection, lymph node dissection, and gastrointestinal reconstruc-tion. The operation time and volume of intraoperative blood loss were 400 minutes and 100 mL, respectively, and no intraoperative blood transfusion was required. (2) Postoperative conditions. The patient began ambulation on postoperative day 1 and began taking liquid food on postoperative day 4. Liver function examination and abdominal computed tomograph (CT) on postoperative day 5 showed a decrease in serum bilirubin, no biliary or intestinal leakage, and no edema or necrosis at the anastomotic site. The abdominal pre-anastomotic and post-anastomotic drainage tubes were removed on the 7th and 9th day after the surgery respectively, and the patient was discharged on the 10th day after surgery. Results of postoperative pathological examination showed moderately to poorly differentiated adenocarcinoma of the bile duct. Immunostaining was positive for CK7 and CK19. The Ki-67 proliferation index was 35%. The proximal and distal resection margin of bile duct were negative. The tumor diameter was 30 mm. Perineural invasion was positive. The surgical specimen margin was negative. Two lymph nodes were identified containing tumor cells positive for malignancy. No tumor cell metastasis was detected in the No.8, No.12 or gastric lesser curvature lymph nodes submitted for pathological examination. (3) Follow-up. The patient was followed up at postoperative 1-, 3-, 5-month after discharge. During follow-up period, results of liver function examination and abdominal CT showed liver function restore to normal levels, no complication such as biliary fistula, intestinal fistula, gastroparesis or tumor metastasis.Conclusion:The Domestic Toumai ? laparoscopic surgical robot system can be applied to radical resection of hCCA.

Downstaging treatment by local therapy combined with systemic therapy before liver transplantation for patients with recurrent hepatocellular carcinoma (HCC) can control tumor progression and reduce tumor burden, which resulting in reducing the push-out rate of patients during the waiting period for liver transplantation, providing an oncological observation window, enabling patients of beyond Milan criteria downstaged with better survival benefit. The authors introduce the clinical experience of a case with recurrent HCC of beyond Milan criteria who under-went liver transplantation after receiving atezolizumab plus bevacizumab combined with local therapy. Results show the patient achieving pathological complete remission without postoperative rejection and obtaining a good prognosis with life status improved.

Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers, including lung cancer; however, targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need. In this study, we tested the anticancer activity of orlistat, an FDA-approved anti-obesity drug, in human and mouse cancer cells in vitro and in vivo, and we found that orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. In addition, we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2, a molecule regulating the lipid droplet homeostasis, as a novel target of orlistat. Moreover, in a mouse xenograft model, orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control (P < 0.05). Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.
Animals ; Cell Death ; Cell Line, Tumor ; Ferroptosis ; Lung Neoplasms/drug therapy* ; Mice ; Orlistat

COVID-19 has swept globally and Pakistan is no exception.To investigate the initial introductions and transmissions of the SARS-CoV-2 in Pakistan,we performed the largest genomic epidemiology study of COVID-19 in Pakistan and generated 150 complete SARS-CoV-2 genome sequences from samples collected from March 16 to June 1,2020.We identified a total of 347 mutated positions,31 of which were over-represented in Pakistan.Meanwhile,we found over 1000 intra-host single-nucleotide variants(iSNVs).Several of them occurred concurrently,indicating possible interactions among them or coevolution.Some of the high-frequency iSNVs in Pakistan were not observed in the global population,suggesting strong purifying selections.The genomic epidemiology revealed five distinctive spreading clusters.The largest cluster consisted of 74 viruses which were derived from different geographic locations of Pakistan and formed a deep hierarchical structure,indicating an extensive and persistent nation-wide transmission of the virus that was probably attributed to a signature mutation(G8371T in ORF 1ab)of this cluster.Further-more,28 putative international introductions were identified,several of which are consistent with the epidemiological investigations.In all,this study has inferred the possible pathways of introduc-tions and transmissions of SARS-CoV-2 in Pakistan,which could aid ongoing and future viral surveillance and COVID-19 control.

Objective To evaluate the effect of three different doses of oxycodone hydrochloride injection on uterine cramping pain and emotion in patients of artificial abortion.Methods Four hundred female patients, aged 17-38 years, BMI 18.5-23.9 kg/m2, falling into ASA physical statusⅠ orⅡ, undergoing elective artificial abortion were randomized into four groups using a random number table:group O1 (oxycodone 0.06 mg/kg), group O2 (oxycodone 0.08 mg/kg), group O3 (oxycodone 0.1 mg/kg), and group F, 100 cases in each.In group O1, group O2 and group O3, oxycodone 0.06, 0.08, 0.1 mg/kg were intravenously injected respectively, while in group F fentanyl1μg/kg was intravenously injected.Then, propofol 2.5 mg/kg was intravenously injected as induced dose.The operation was started when eyelash reflexes disappeared, propofol 0.4 mg/kg was intravenously injected when body movement appeared during the operation.The propofol doses, operation time and recovery time were recorded.HR, MAP, RR before anesthesia (T0), when loss of eyelash reflex (T1), operation (T2) and recovery (T3) were recorded.The uterine cramping pain was assessed with numerical rating scale (NRS) at recovery, 10, 30, 60 min after operation.Patients'satisfaction was recorded after operation.Patients'emotion was assessed with positive and negative affect scale (PANAS) both before and after operation in one hour.Rescue analgesia, nausea and vomiting, dizziness, respiratory depression, pruritus, uroschesis, cognitive dysfunction, sweatiness were recorded.Results The propofol doses and recovery time in groups O2, O3 and F were significantly lower than those in group O1 (P<0.05).The NRS score of uterine cramping pain in groups O1, O2 and O3 were significantly lower than that in group F (P<0.05).Patients'satisfaction in groups O1, O2 and O3 were significantly higher than that in group F (P<0.05).The positive affective score after operation in one hour among the four groups were significantly higher than that before operation (P<0.05), and the negative affective score after operation in one hour among the four groups were significantly lower than that before operation (P<0.05).The positive affective score after operation in one hour in groups O1, O2 and O3 were significantly higher than that in group F (P<0.05), and the rescue analgesia in groups O1, O2 and O3 were significantly lower than that in group F (P<0.05).There were no significant differences among the four groups as to the dizziness, nausea and vomiting.No respiratory depression, pruritus, emergence agitation, cognitive dysfunction, uroschesis and sweatiness were reported.Conclusion Oxycodone 0.08 mg/kg combined with propofol in patients undergoing artificial abortion is effective in preventing uterine cramping pain.Furthermore, the patients'satisfaction and positive affective score can also be improved.

OBJECTIVETo investigate the protective effect of bone marrow mesenchymal stem cells (BMSCs)-derived exosomesagainst testicular ischemia-reperfusion injury (IRI) in rats.

METHODSRat BMSCs were isolated, cultured and identified in theprimary culture. The exosomes were extracted from the BMSCs and characterized using nanoparticle tracking analysis, transmission electron microscopy, and Western blotting. Twenty-four healthy male SD rats were randomly divided into shamoperation group, testicular IRI with saline treatment group and IRI with exosome treatment group. The contralateral testes ofthe rats were collected for pathological observation, aseessment of superoxide dismutase (SOD) and malondialdehyde (MDA), and detection of HMGB1, caspases-3 and cleaved caspase-3 expressions using Western blotting.

RESULTSWe successfullyobtained exosomes from rat BMSCs. Testicular IRI significantly impaired testicular spermatogenesis, which was markedlyimproved by treatment with the exosomes ( < 0.05). Testicular IRI also caused significant increase in the protein expression ofHMGB1, caspase-3 and cleaved caspase-3 in the testicular tissue, and treatment with the exosomes obviously amelioratedthese changes ( < 0.05).

CONCLUSIONSBMSCs-derived exosomes protects against testicular IRI due to the anti-oxidant, antiinflammatory and anti-apoptosis activities of the exosomes.